Baokang Hospital Affiliated to Tianjin University of Traditional Chinese Medicine

Childhood community-acquired pneumonia (CAP) is a common illness; however, comprehensive studies of hospitalizations for CAP among children in China based on prospective and multicenter data collection are limited. The aim of this investigation was to determine the respiratory pathogens responsible for CAP in hospitalized children. From January to December 2015, oropharyngeal swabs and blood serum were collected from hospitalized children with CAP symptoms ranging in age from 6 months to 14 years at 10 hospitals across China. We used immunofluorescence to detect antibodies for eight respiratory viruses and passive agglutination to detect specific IgM against Mycoplasma pneumoniae (M. pneumoniae). Of 1500 children presenting with CAP, 691 (46.1%) tested positive for at least one pathogen (virus or M. pneumoniae). M. pneumoniae (32.4%) was detected most frequently, followed by respiratory syncytial virus (11.5%), adenovirus (5.0%), influenza A virus (4.1 %), influenza B virus (3.4%), parainfluenza virus types 2 and 3 type (3.1 %), parainfluenza virus type 1 (2.9%), and human metapneumovirus (0.3%). Co-infections were identified in 128 (18.5%) of the 691 cases. These data provide a better understanding of viral etiology and M. pneumoniae in CAP in children between 6 months and 14 years in China. More study of the etiologic investigations that would further aid the management of pneumonia is required. With effective immunization for RSV, ADV, and M. pneumoniae infections, more than one-half of the pneumonia cases in this study could have been prevented.

As an important component of traditional medicine, Traditional Chinese Medicine (TCM) is widely spread and applied in more than 100 countries across the world. The standardization of TCM is very important for the international application of Chinese medicine. In this paper, we have explained and analyzed the standardization situations of TCM in China with the purpose of providing reference for standardization and international development of TCM.

To systematically evaluate the efficacy and safety of berberine for the treatment of hyperlipidemia, six electronic literature databases including SinoMed, CNKI, WanFang Data, PubMed, Embase and The Cochrane Library were searched to collect clinical randomized controlled trials (RCTs) of berberine alone or combined with statins for the treatment of hyperlipidemia from the inception to 8 March 2018. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included RCTs. Then, meta-analysis was performed by using RevMan 5.3 software. A total of 11 RCTs involving 1386 patients were finally included. The results of meta-analysis showed that compared with the placebo group, berberine could significantly reduce the total cholesterol and low-density lipoprotein levels and elevate the high density lipoprotein level ([Formula: see text]). Compared with the simvastatin group, berberine was effective only in reducing the level of triglyceride ([Formula: see text], 95% CI: [Formula: see text]0.66, [Formula: see text]0.07, [Formula: see text]). There, however, was no statistical significance between the BBR group and simvastatin group in the low density lipoprotein and high density lipoprotein levels. Compared with the simvastatin group, berberine plus simvastatin was more effective in reducing the level of triglyceride ([Formula: see text], 95% CI: [Formula: see text]0.46, [Formula: see text]0.20, [Formula: see text]) and total cholesterol ([Formula: see text], 95% CI: [Formula: see text]0.60, [Formula: see text]0.12, [Formula: see text]). In terms of adverse reactions, the incidence of adverse reactions including transaminase elevation and muscle aches was lower in the berberine alone or combined with simvastatin group than that in the control group, while the instance of constipation was higher. This study suggests that berberine is effective for hyperlipidemia. The quality and quantity of included studies, however, were dissatisfactory, which might decrease the reliability of the results. Higher quality studies are needed to provide more high quality evidence.

BACKGROUND: Delirium is a very common condition associated with significant morbidity, mortality, and costs. Current critical care guidelines recommend first and foremost the use of nonpharmacological strategies in both the prevention and treatment of delirium. Pharmacological interventions may augment these approaches and they are currently used widely in clinical practice to manage the symptoms of delirium. Benzodiazepines are currently used in clinical practice to treat behavioural disturbances associated with delirium but current guidelines do not recommend their use for this indication. The use of these medicines is controversial because there is uncertainty about whether they are effective for patients or have the potential to harm them. OBJECTIVES: To assess the effectiveness and safety of benzodiazepines in the treatment of delirium (excluding delirium related to withdrawal from alcohol or benzodiazepines) in any healthcare settings other than intensive care units (ICU). SEARCH METHODS: We searched ALOIS: the Cochrane Dementia and Cognitive Improvement Group's Specialized Register up to 10 April 2019. ALOIS contains records of clinical trials identified from monthly searches of a number of major healthcare databases (including MEDLINE, Embase, PsycINFO, CINAHL, LILACS), numerous trial registries (including national, international and pharmaceutical registries), and grey literature sources. SELECTION CRITERIA: We included randomised controlled trials (RCTs) conducted in healthcare settings that ranged from nursing homes and long-term care facilities to any hospital setting except for ICUs, involving adult patients with delirium excluding those with delirium related to alcohol or benzodiazepine withdrawal. Included RCTs had to assess the effect of benzodiazepines, at any dose and given by any route, compared with placebo or another drug intended to treat delirium. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data, and assessed the risk of bias of included studies. We decided whether or not to pool data on the basis of clinical heterogeneity between studies. We used GRADE (Grades of Recommendation, Assessment, Development and Evaluation) methods to assess the quality of evidence. MAIN RESULTS: We identified only two trials that satisfied the selection criteria. We did not pool the data because of the substantial clinical differences between the trials. In one trial, participants (n = 58) were patients in an acute palliative care unit with advanced cancer who had a mean age of 64 years. All of the participants had delirium, were treated with haloperidol, and were randomised to receive either lorazepam or placebo in combination with it. Due to very serious imprecision, all evidence was of low certainty. We were unable to determine whether there were clinically important differences in the severity of delirium (mean difference (MD) 2.10, 95% CI -0.96 to 5.16; n = 50), length of hospital admission (MD 0.00, 95% CI -3.45 to 3.45; n = 58), mortality from all causes (risk ratio (RR) 0.33, 95% CI 0.04 to 3.02; participants = 58) or any of a number of adverse events. Important effects could not be confirmed or excluded. The study authors did not report the length of the delirium episode. In the other trial, participants (n = 30) were patients in general medical wards with acquired immune deficiency syndrome (AIDS) who had a mean age of 39.2 years. Investigators compared three drug treatments: all participants had delirium, and were randomised to receive lorazepam, chlorpromazine, or haloperidol. Very low-certainty evidence was identified, and we could not determine whether lorazepam differed from either of the other treatments in the effect on severity of delirium, any adverse event, or mortality from all causes. The study authors did not report the length of the delirium episode or the length of hospital admission. AUTHORS' CONCLUSIONS: There is no enough evidence to determine whether benzodiazepines are effective when used to treat patients with delirium who are cared for in non-ICU settings. The available evidence does not support their routine use for this indication. Because of the scarcity of data from randomised controlled trials, further research is required to determine whether or not there is a role for benzodiazepines in the treatment of delirium in non-ICU settings.

The proteasome inhibitor is a target therapy for multiple myeloma (MM) patients, which has increased the overall survival rate of multiple myeloma in clinic. However, relapse and toxicity are major challenges for almost all MM patients. Thus, there is an urgent need for an effective and less toxic combination therapy. Here, we demonstrated that a natural compound, resveratrol (RSV) displayed anti-proliferative activity in a dose- and time-dependent manner in a panel of MM cell lines. More importantly, a low concentration of RSV was synergistic with a low dose of the proteasome inhibitor carfilzomib (CFZ) to induce apoptosis in myeloma cells. Further studies showed that mitochondria was a key regulatory site after RSV/CFZ combination treatment. RSV induced the release of second mitochondria-derived activator of caspase (Smac) in a dose-dependent manner and kept the Smac in a high level after combination with CFZ. Also, RSV was additive with CFZ to increase reactive oxygen species (ROS) production. Moreover, a stress sensor SIRT1, with deacetylase enzyme activity, was remarkably downregulated after RSV/CFZ combination, thereby significantly decreasing its target protein, survivin in MM cells. Simultaneously, autophagy was invoked after RSV/CFZ combination treatment in myeloma cells. Further inhibition of autophagy could increase more ROS production and apoptosis, indicating a close linkage between autophagy and proteasome to modulate the oxidative stress. Together, these findings suggest that induction of multiple stress responses after RSV/CFZ combination is a major mechanism to synergistically inhibit MM cell growth and reduce the toxicity of CFZ in MM cells. This study also provides an important rationale for the clinic to consider an autophagy inhibitor for the combination therapy in MM patients.

Background: Development of a core outcome set (COS) for clinical trials for COVID-19 is urgent because of the pandemic wreaking havoc worldwide and the heterogeneity of outcomes in clinical trials. Methods: A preliminary list of outcomes was developed after a systematic review of protocols of clinical trials for COVID-19. Then, two rounds of the Delphi survey were conducted. Stakeholders were traditional Chinese medicine (TCM) experts, Western medicine (WM) experts, nurses and the public. Patients with confirmed COVID-19 were also invited to participate in a questionnaire written in understandable language. Then different stakeholders participated a consensus meeting by video conference to vote. Results: Ninety-seven eligible study protocols were identified from 160 clinical trials. Seventy-six outcomes were identified from TCM clinical trials and 126 outcomes were identified from WM clinical trials. Finally, 145 outcomes were included in the first round of the Delphi survey. Then, a COS for clinical trials of TCM and WM was developed. The COS include clinical outcomes (recovery/improvement/progression/death), etiology (SARS-CoV-2 nucleic-acid tests, viral load), inflammatory factor (C-reactive protein), vital signs (temperature, respiration), blood and lymphatic-system parameters (lymphocytes, virus antibody), respiratory outcomes (Pulmonary imaging, blood oxygen saturation, PaO2/FiO2 ratio, arterial blood gas analysis, mechanical ventilation, oxygen intake, pneumonia severity index), clinical efficacy (prevalence of preventing patients with mild-to-moderate disease progressing to severe disease), symptoms (clinical symptom score). Outcomes were recommended according to different types of disease. Outcome measurement instrument/definition were also recommended. Conclusion: Though there are some limitations for the research, such as insufficient patients and the public involvement, the unbalanced stakeholders’ region, the COS for COVID-19 may improve consistency of outcome reporting in clinical trials. It also should be updated with research progression. Key words: COVID-19; core outcome set; traditional Chinese medicine; Western medicine; methodology.

Zuojin Pill (ZJP), a traditional Chinese medicine formula, consists of Coptis chinensis Franch. and Evodia rutaecarpa (Juss.) Benth. in a ratio of 6:1 (w/w) and was first recorded in "Danxi's experiential therapy" for treating gastrointestinal disorders in the 15th century. However, the poor solubility of alkaloids from ZJP restricted the protective effect in treating gastritis and gastric ulcer. The aim of the study was to investigate the protective mechanism of mucoadhesive microspheres loaded with alkaloids from C. chinensis Franch. and E. rutaecarpa (Juss.) Benth. on ethanol-induced acute gastric mucosal injury in rats. Surface morphology, particle size, drug loading, encapsulation efficiency, in vitro drug release, mucoadhesiveness, and fluorescent imaging of the microspheres in gastrointestinal tract were studied. The results showed that the mucoadhesive microspheres loaded with alkaloids could sustain the release of drugs beyond 12 hours and had gastric mucoadhesive property with 82.63% retention rate in vitro. The fluorescence tracer indicated high retention of mucoadhesive microspheres within 12 hours in vivo. The mucoadhesive microspheres loaded with alkaloids could reduce the gastric injury by decreasing the mucosal lesion index, increasing the percentage of inhibition and increasing the amount of mucus in the gastric mucosa in an ethanol-induced gastric mucosal injury rat model. Moreover, the mucoadhesive microspheres loaded with alkaloids reduce the inflammatory response by decreasing the levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), downregulating the mRNA expression of inducible nitric oxide synthase, TNF-α, and IL-1β in gastric mucosa. All the results indicate that mucoadhesive microspheres loaded with alkaloids could not only increase the residence time of alkaloids in rat stomach, but also exert gastroprotective effects through reducing the inflammatory response on ethanol-induced gastric mucosal damage. Thus, these microspheres could be developed as a potential controlled release drug for treatment of gastric ulcer.

AngII (angiotensin II)-induced excessive ROS (reactive oxygen species) generation and proliferation of VSMCs (vascular smooth muscle cells) is a critical contributor to the pathogenesis of atherosclerosis. PGC-1α [PPARγ (peroxisome-proliferator-activated receptor γ) co-activator-1α] is involved in the regulation of ROS generation, VSMC proliferation and energy metabolism. The aim of the present study was to investigate whether PGC-1α mediates AngII-induced ROS generation and VSMC hyperplasia. Our results showed that the protein content of PGC-1α was negatively correlated with an increase in cell proliferation and migration induced by AngII. Overexpression of PGC-1α inhibited AngII-induced proliferation and migration, ROS generation and NADPH oxidase activity in VSMCs. Conversely, Ad-shPGC-1α (adenovirus-mediated PGC-1α-specific shRNA) led to the opposite effects. Furthermore, the stimulatory effect of Ad-shPGC-1α on VSMC proliferation was significantly attenuated by antioxidant and NADPH oxidase inhibitors. Analysis of several key subunits of NADPH oxidase (Rac1, p22(phox), p40(phox), p47(phox) and p67(phox)) and mitochondrial ROS revealed that these mechanisms were not responsible for the observed effects of PGC-1α. However, we found that overexpression of PGC-1α promoted NOX1 degradation through the proteasome degradation pathway under AngII stimulation and consequently attenuated NOX1 (NADPH oxidase 1) expression. These alterations underlie the inhibitory effect of PGC-1α on NADPH oxidase activity. Our data support a critical role for PGC-1α in the regulation of proliferation and migration of VSMCs, and provide a useful strategy to protect vessels against atherosclerosis.

IMPORTANCE The incidence of Bradyarrhythmias is high among the population. However, at early stages of the disease, it cannot always get enough attention and is lack of safe and effective therapies, until it is serious enough to resort to pacemaker implantation. Traditional Chinese Medicine(TCM) has a long history of treating Bradyarrhythmia, with a lot of formulas being widely used in clinical practice. While the effectiveness and the underlying mechanisms of these formulas have not yet been clearly identified. OBJECTIVE To evaluate the effectiveness of some common TCM formulas in treating patients with Bradyarrhythmia and to summarise the current evidence as to their mechanisms. DATA SOURCES Relevant studies were identified by searching for papers published from January 2000 to August 2017 in Pubmed; EMBASE; the Cochrane Library (Cochrane Central Register of Controlled Trials); the China National Knowledge Internet; and the China biology medicine, Wanfang, and VIP databases. The following medical subject heading (MeSH) terms were included for Pubmed search and adapted for other databases as needed-“TCM”、“Chinese medicine”、“traditional Chinese medicine”、“Bradycardia”、“Bradyarrhythmia”. STUDY SELECTION Randomized clinical trials investigating treatment outcomes in Bradyarrhythmia patients with one of the six TCM formulas (Shenxian-shengmai oral liquid, Shensong Yangxin capsule, XinBao pill, Mahuang-Fuzi-Xixin decoction, Zhigancao decoction and Shengmai injection). DATA EXTRACTION AND SYNTHESIS Two independent reviewers performed the data extraction and assessed study quality. A meta-analysis was performed to calculate risk ratio (RR) and 95% confidence index (CI) using random-effects and fixed-effects model. RESULTS A total of 121 clinical trials with 11138 patients were included. Of the six TCM formulas, SXSM (RR:1.33, 95% CI 1.27 to 1.39, P＜0.00001), SSYX (RR:1.52, 95% CI 1.40 to 1.66, P＜0.00001), XB can be more effective than common treatment (RR 1.18, 95％CI 1.11 to 1.26, P＜0.00001), as well as placebo (RR 5.33, 95％CI 2.88-9.87, P＜0.00001), but less effective than TCM dialectical therapy (RR:0.75, 95％CI 0.68 to 0.82, P＜0.00001). MFX (RR:1.30, 95%CI 1.23 to 1.37, P＜0.00001), (RR:1.35, 95%CI 1.23 to 1.48, P＜0.00001), SMI (RR:1.36, 95%CI 1.21 to 1.52, P＜0.00001). CONCLUSIONS AND RELEVANCE There are evidence that some TCM formulas might help to relieve Bradyarrhythmias. But with the relatively low quality of the clinical

BACKGROUND: Pre-diabetes is a growing health concern where a large percentage of these patients develop full type 2 diabetes. Effective interventions on pre-diabetes can prevent or delay the occurrence or development of diabetes. Pharmacodynamics and pre-clinical of JinQi-Jiangtang tablets (JQJT) suggest that it could be benefit for pre-diabetes. METHODS/DESIGN: Randomized controlled trial (RCT) is implemented in this study. The study term is 24 months (12 months for intervention and 12 months for follow up). Participants are recruited from four cities of China: Beijing, Tianjin, Xi'an and Nanning. Four hundred participants are randomized to treatment group (JQJT tablets) and control group (Placebo); two hundred participants each. People being included in this study must have been diagnosed as pre-diabetes via western medicine criteria and traditional Chinese medicine (TCM) criteria. The end-point indexes include: incidence of diabetes mellitus and reversion rate. Primary outcome indexes include: oral glucose tolerance test; insulin releasing test; glycosylated hemoglobin (HA1c). Secondary outcome indexes include: score of the Short Form 36 Health Survey Questionnaire (SF-36); score of TCM symptoms; blood lipid test. Indexes of safety include: general medical examination; blood and urine regular test; electrocardiogram (ECG), liver function (ALT) and renal function (BUN, Creatinine) test; record of adverse event, such as headache, faint, etc. Qualitative control will be implemented and a number of standard operating processes (SOPs) will be formed throughout the study: laboratory quality control measures; compliance control for researchers and participants; researcher training before study; supervision; investigational drug management and others. DISCUSSION: The aim of this study is to evaluate the effectiveness and safety of JinQi JiangTang (JQJT) tablets for the treatment of patients with pre-diabetes. TRIAL REGISTRATION: Chinese clinical trials register ChiCTR-TRC-00000401.

// Ning Liu 1 , Zhigang Yang 2 , Xiaozhen Liu 3 and Yun Niu 3 1 Department of Pathology, Bao Di Hospital, Bao Di Clinical College of Tianjin Medical University, Tianjin, China 2 Tianjin Baodi Hospital of Traditional Chinese Medicine, Tianjin, China 3 Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, China Correspondence to: Ning Liu, email: // Keywords : breast cancer, molecular subtype, triple negative subtype, lymph node status, prognosis Received : October 25, 2016 Accepted : January 09, 2017 Published : February 02, 2017 Abstract Background and Objectives: To investigate the association between different molecular subtype (MST) and the axillary lymph nodal (ALN) status. Materials and Methods: A total of 528 female patients with primary breast cancer were collected. Survival estimates were calculated using the Kaplan-Meier method, univariate and multivariate logistic regression models. Results: Triple negative and Luminal A breast cancers were more frequently node-negative (N0) when compared to Luminal B and Her-2 positive cancers (77.4% and 73.4% vs. 45.3% and 40.0%, respectively; P < 0.0001). We observed a clearly significant difference among ALN status in patients with Her-2 positive (P = 0.001) and Luminal B (P < 0.0001) breast cancer. While no significant prognostic diffreence among different LN status was detected in the Triple negative (P = 0.070) and Luminal A subtype (P = 0.660). On the other hand, we detected no prognostic diffreence among different MST in N1 and N3 subgroups (P = 0.569 and P = 0.484, respectively). Multivariate analysis showed that lymph node status (P < 0.01), molecular subtype (P < 0.01), and tumor size (P < 0.01) were significantly and independently prognostic factors. The c-index of the prognosis nomogram for recurrence prediction was 0.70. Conclusion: Triple negative breast cancer is not associated more frequently with a higher number of involved nodes. The prognosis nomogram can predict the probability of recurrence patients within 3 or 5 years.

The aim of the study was to investigate the effect of Ginkgo biloba extract 50 (GBE50), a well-known natural antioxidant, against immunity and antioxidant enzyme activities in ischemia reperfusion (IR) rats. Rats were then divided into six groups fed for 15 days with the same diet: three groups (IV, V, VI) were treated by different doses of GBE50 suspension [20, 40, or 60 mg/kg body weight by oral gavage every day at a fixed time (10.00 a.m.)] (equal to 5, 10 and 20 times, respectively, the maximum recommended human dose), and three groups (I, II, III) were untreated. At the end of the experiment, rats' hearts were subjected to 30 min of ischemia followed by 90 min of reperfusion. Results showed that IR significantly enhanced heart rate, S-T height, myocardium (myeloperoxidase) MPO activity and blood interleukin-8 (IL-8), tumor necrosis factor Alpha (TNF-a), interleukin-1β (IL-1β) levels, blood aspartate transaminase (AST), lactate dehydrogenase (LDH), and creatinine kinase (CK) activities, reduced myocardium sodium-potassium adenosine triphosphatase (Na(+)-K(+)-ATPase), calcium-magnesium adenosine triphosphatase (Ca(2+)-Mg(2+)-ATPase) activities and antioxidant enzyme activities in IR group (III) compared to sham control group (II). Pretreatment of GBE50 markedly significantly reduced heart rate, S-T height, myocardium MPO activity and blood IL-8, TNF-a, IL-1β levels, blood AST, LDH, and CK activities, enhanced myocardium Na(+)-K(+)-ATPase, Ca(2+)-Mg(2+)-ATPase activities and antioxidant enzyme activities in IR group (II) compared to IR group (III). The results suggested that the GBE50 may reduce the oxidative stress in the reperfused myocardium, and increased immunity and antioxidant activities in IR rats.

Objectives To examine heterogeneity of outcomes in protocols of clinical trials of Coronavirus Disease 2019 (COVID-19) and to identify outcomes for prioritization in developing a core outcome set (COS) in this field. Design This study is a review. Data sources Databases of ICMJE-accepted clinical trial registry platform were searched on February 14, 2020. Eligibility Criteria Randomized controlled trials (RCTs) and non-RCTs of COVID-19 were considered. Conditions of patients include common type, severe type or critical type. Interventions include traditional Chinese medicine (TCM) and Western medicine. We excluded trials that for discharged patients, psychological intervention and complications of COVID-19. Data extraction and synthesis The general information and outcomes, outcome measurement instruments and measurement times were extracted. The results were analysed by descriptive analysis. Results 19 registry platforms were searched. A total of 97 protocols were included from 160 protocols. For protocols of TCM clinical trials, 76 outcomes from 16 outcome domains were reported, and almost half (34/76, 44.74%) of outcomes were reported only once; the most frequently reported outcome was time of SARS-CoV-2 RNA turns to negative. 27 (27/76, 35.53%) outcomes were provided one or more outcome measurement instruments. 10 outcomes were provided one or more measurement time frame. For protocols of western medicine clinical trials, 126 outcomes from 17 outcome domains were reported; almost half (62/126, 49.21%) of outcomes were reported only once; the most frequently reported outcome was proportion of patients with negative SARS-CoV-2. 27 outcomes were provided one or more outcome measurement instruments. 40 (40/126, 31.75%) outcomes were provided one or more measurement time frame. Conclusion Outcome reporting in protocols of clinical trials of COVID-19 is inconsistent. Thus, developing a core outcome set is necessary. Strengths and limitations of this study 1. This review is the first to describe variation in outcomes, outcome measurement instruments and outcome measurement time reporting in clinical trials for Coronavirus Disease 2019 (COVID-19). 2. All the database of ICMJE-accepted clinical trial registry platform were searched, and randomized controlled trials and observational studies were considered. 4. The aim of this review was to provide a list of outcomes for clinical trials of COVID-19, both interventions of Traditional Chinese Medicine and western medicine were considered. 5. When the searching was conducted, no clinical trials were registered by countries out of China, so all of included protocols were from China.

Human prolactin (hPRL) plays multiple roles in growth, metabolism, development, reproduction, and immunoregulation, which is an important protein synthesized in a pituitary. Two-dimensional gel electrophoresis (2DE) is an effective method in identity of protein variants for in-depth insight into functions of that protein. 2DE, 2DE-based PRL-immunoblot, mass spectrometry, and bioinformatics were used to analyze hPRL variants in human normal (control; n = 8) pituitaries and in five subtypes of pituitary adenomas [NF- (n = 3)-, FSH+ (n = 3)-, LH+ (n = 3)-, FSH+/LH+ (n = 3)-, and PRL+ (n = 3)-adenomas]. Six hPRL variants were identified with different isoelectric point (pI)-relative molecular mass (Mr) distribution on a 2DE pattern, including variants V1 (pI 6.1; 26.0 kDa), V2 (pI 6.3; 26.4 kDa), V3 (pI 6.3; 27.9 kDa), V4 (pI 6.5; 26.1 kDa), V5 (pI 6.8; 25.9 kDa), and V6 (pI 6.7; 25.9 kDa). Compared to controls, except for variants V2-V6 in PRL-adenomas, V2 in FSH+-adenomas, and V3 in NF--adenomas, the other PRL variants were significantly downregulated in each subtype of pituitary adenomas. Moreover, the pattern of those six PRL variants was significantly different among five subtypes of pituitary adenomas relative to control pituitaries. Different hPRL variants might be involved in different types of PRL receptor-signaling pathways in a given condition. Those findings clearly revealed the existence of six hPRL variants in human pituitaries, and the pattern changes of six hPRL variants among different subtypes of pituitary adenomas, which provide novel clues to further study the functions, and mechanisms of action, of hPRL in human pituitary and in PRL-related diseases, and the potential clinical value in pituitary adenomas.

-glycolic acid) (mPEG-PLGA) nanoparticles (BA LCH NPs) for the treatment of cataract. mPEG-PLGA NPs were optimized by the Box-Behnken design and the central composite design based on the encapsulation efficiency and drug loading. Then, the BA LCH NPs were characterized based on morphology, particle size, and zeta potentials. The analytical data of differential scanning calorimetry, X-ray diffraction, and transmission electron microscopy depicted the drug excipient compatibility. In vitro, we evaluated cell viability, cellular uptake, potential ocular irritation, transcorneal permeability, and the precorneal retention of BA LCH NPs. In vivo, the chronic selenium cataract model was selected to assess the therapeutic effect of BA LCH NPs. The size of BA LCH NPs was within the range from 148 to 219 nm and the zeta potential was 19-25 mV. Cellular uptake results showed that the fluorescence intensity of the preparations in each group increased with time, and the fluorescence intensity of the LCH NP group was significantly higher than that of the solution group. The optimized BA LCH NPs improved precorneal residence time without causing eye irritation and also showed a sustained release of BA through the cornea for effective management of cataract. Also, fluorescence tracking on the rabbit cornea showed increased corneal retention of the LCH NPs. In addition, the results of therapeutic efficacy demonstrated that BA LCH NPs can significantly reduce the content of malondialdehyde and enhanced the activities of catalase, superoxide dismutase, and glutathione peroxidase, which was comparable to positive control and better than the BA solution group. Thus, it can be inferred that the BA LCH NPs are a promising drug delivery system for enhancing the ophthalmic administration of BA to the posterior segment of the eye and improving cataract symptoms.

PURPOSE: The objective of this study was to investigate the effects of the solid lipid nanoparticles of baicalin (BA-SLNs) on an experimental cataract model and explore the molecular mechanism combined with bioinformatics analysis. MATERIALS AND METHODS: The transparency of lens was observed daily by slit-lamp and photography. Lenticular opacity was graded. Two-dimensional gel electrophoresis (2-DE) was employed to analyze the differential protein expression modes in each group. Proteins of interest were subjected to protein identification by nano-liquid chromatography tandem mass spectrometry (LC-MS/MS). Bioinformatics analysis was performed using the Ingenuity Pathway Analysis (IPA) online software to comprehend the biological implications of the proteins identified by proteomics. RESULTS: At the end of the sodium selenite-induced cataract progression, almost all lenses from the model group developed partial nuclear opacity; however, all lenses were clear and normal in the blank group. There was no significant difference between the BA-SLNs group and the blank group. Many protein spots were differently expressed in 2-DE patterns of total proteins of lenses from each group, and 65 highly different protein spots were selected to be identified between the BA-SLNs group and the model group. A total of 23 proteins were identified, and 12 of which were crystalline proteins. CONCLUSION: We considered crystalline proteins to play important roles in preserving the normal expression levels of proteins and the transparency of lenses. The general trend in the BA-SLN-treated lenses' data showed that BA-SLNs regulated the protein expression mode of cataract lenses to normal lenses. Our findings suggest that BA-SLNs may be a potential therapeutic agent in treating cataract by regulating protein expression and may also be a strong candidate for future clinical research.

BACKGROUND: At present, diabetes is a chronic disease of great cost and heavy burdens. The International Diabetes Federation has repeatedly warned that by 2025, the global number of diabetics would rise to 333 million from 194 million in 2003. Although the occurrence of diabetes in developing countries is lower, China has a large population, so that the number of cases is increased. At the same time, more people have prediabetes, a growing health concern where a large percentage of the patients develop full type 2 diabetes. In addition, the patients of diabetes easily incur complications such as blindness, kidney failure, and cardiovascular diseases that can seriously affect the patients' quality of life and cause great economic burdens to family and society. Therefore, effective interventions for prediabetes are needed to prevent or delay the occurrence and development of diabetes. METHODS: A randomized controlled trial that was assessed with pharmacoeconomic methods was undertaken in this study. The study term was 24 months (12 months for the intervention and 12 months for follow up). Four hundred participants, recruited from four cities in China: Beijing, Tianjin, Xian, and Naning, were randomized to the treatment group (JQJT tablets) and the control group (placebo). Participants included in this study had been diagnosed with prediabetes according to the criteria for western medicine and Traditional Chinese Medicine (TCM). The end-point effectiveness indexes included the incidence of diabetes and the reversion rate. The drug costs and lifestyle intervention costs were included in the total costs. The study used the cost-effectiveness analysis to discuss the economic advantage of the JQJT tablets. RESULTS: The outcomes of the study contained 2 sections,namely clinical outcomes and cost-effectiveness analysis outcomes. The clinical outcomes: the treatment group and control group had no significant statistical difference P> 0.05) on the baseline of situation; Jinqi Jiangtang tablet effectively reduced the incidence of diabetes mellitus and enhanced reversion rate. compared with the control group (p< 0.05); the scores of SF-36 of two groups had no significant difference P> 0.05); finally the compliance of participants between the two groups had no significant difference. The cost-effectiveness analysis outcomes:in the intervention period of 12 months,on the aspect of reversion rate, the treatment group had better economic advantage by using cost-effectiveness ratio and the incremental cost-effectiveness ratio;on the aspect of the incidence of diabetes, the control group had better economic advantage by using cost-effectiveness ratio and the incremental cost-effectiveness ratio; in the follow-up period of 24 months, on the aspect of reversion rate, the treatment group had better economic advantage by using cost-effectiveness ratio and the incremental cost-effectiveness ratio, on the aspect of the incidence of diabetes, the control group had better economic advantage by using cost-effectivenes ratio and the incremental cost-effectiveness ratio.At the same time, these outcomes remained the same by sensitivity analysis. Assuming that prices and resident incomes rose 5%, the sensitiveness analysis shows that the two group affected by the paremeters changed little. CONCLUSION: The importance and effectiveness of lifestyle education and JinQi Jiangtang tablets was proven. In both the intervention period and follow-up, JinQi Jiangtang tablets combined with lifestyle education had a greater cost advantage effect than the lifestyle education alone on the reversion rate; the lifestyle education had a greater cost advantage effect than the JinQi Jiangtang tablets combined with lifestyle education on the incidence of diabetes. TRIAL REGISTRATION: Chinese Clinical Trials ChiCTR-TRC-09000401 ) , registered on 25 May 2009.

Background: Enhanced recovery after surgery (ERAS) protocol has been implemented in surgeries for more than 20 years, this study investigated the global states and hotspots of ERAS research. Methods: Based on the Web of Science database, a bibliometric and visualized study of original ERAS research from 2000 to 2020 was performed, including the trends of publications and citations; distribution of countries, authors, institutions, sources; study design, level of evidence, served surgeries and surgical disciplines. Hotspots were revealed by research interests and keywords. Results: Within the field of original ERAS research, there was a rising trend in annual publications and citations. The USA was the greatest contributor. Kehlet, H, University of Copenhagen were the most influential author and institution, respectively. British Journal of Surgery and Annals of Surgery were the most cited journals. Though there were more prospective designs, more than half of the studies presented level IV evidence and had fewer citations and citation densities compared to that of level II and level III. ERAS protocol was overwhelmingly implemented in colorectal surgeries. Most studies focused on elements of ERAS, the top three research interests were "length of stay," "pain management," and "complications." In recent years, bariatric surgery, compliance with ERAS, and feasibility in the elderly were new hotspots. Conclusion: Revealing the global states and hotspots can help researchers better understand the trends in ERAS research. The USA was the greatest contributor to ERAS research. Kehlet, H, was the most influential author in the field. Bariatric surgery, compliance with ERAS, and feasibility in the elderly represent the new trend of ERAS research. Most of the ERAS research had a low evidence levels, studies with high-level evidence are still required in this field.

Osteoporosis is a disease characterized by low bone mass and progressive destruction of bone microstructure, resulting in increasing the risk of fracture. Icariin (ICA) as a phytoestrogen shows osteogenic effects, and the mechanical stimulation has been demonstrated the improving effect on osteoporosis. The objective of this study was to investigate the effect of ICA in combination with constrained dynamic loading (CDL) stimulation on osteoporosis in ovariectomized (OVX) mice. The serum hormone levels, bone turnover markers, trabecular architecture, ulnar biomechanical properties, and the expression of osteoblast-related gene (alkaline phosphatase, ALP; osteocalcin, OCN; bone morphogenetic protein-2, BMP-2; Collagen I (α1), COL1; osteoprotegerin, OPG) and osteoclast-related genes (receptor activators of NF-κB ligand, RANKL; tartrate-resistant acid phosphatase, TRAP) were analyzed. The results showed that ICA + CDL treatment could increase the osteocalcin (20.85%), estradiol levels (20.61%) and decrease the TRAP activity (26.27%) significantly than CDL treatment. The combined treatment attenuated bone loss and biomechanical decrease more than single use of CDL treatment. ICA + CDL treatment significantly up-regulated the level of osteoblast-related gene expression and down-regulated the osteoclast-related genes expression; moreover, the combined treatment increased the ratio of OPG/RANKL significantly compared to ICA (72.83%) or CDL (65.63%) treatment alone. The present study demonstrates that icariin in combination with constrained dynamic loading treatment may have a therapeutic advantage over constrained dynamic loading treatment alone for the treatment of osteoporosis, which would provide new evidence for the clinical treatment of osteoporosis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1415-1424, 2018.

BACKGROUND: An increasing number of network meta-analyses (NMAs) in traditional Chinese medicine (TCM) have been published recently, but the quality of them was lack of assessment. This study aims to evaluate the methodological and reporting quality of NMAs in TCM. METHODS: Six electronic databases, including PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, China National Knowledge Infrastructure (CNKI), Wanfang and Chinese Biomedical Literature Database (CBM) from inception to January 2018, were searched. NMAs of TCM were included. A measurement tool to assess the methodological quality of systematic reviews (AMSTAR) and the PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-analyses of Health Care Interventions (PRISMA-NMA) were used to assess the methodological and reporting quality of the included NMAs. RESULTS: A total of 40 NMAs, including 2535 randomized controlled trials (RCTs), were included. They were published between December 2012 and November 2017. The median score and interquartile range of methodological and reporting quality was 7 (6-8) and 22 (19.1-27.1). Serious methodological flaws existed in the following aspects: the status of publication (22.5%), a list of studies provided (0%), assessment of publication bias (37.5%), and conflicts of interest (12.5%). Several items need to be improved in reporting, especially for Protocol and registration (2.5%), Data items (22.5%), Risk of bias across studies (Methods section) (37.5%), Results of individual studies (27.5%), Risk of bias across studies (Results section) (40%), Results of additional analyses (35%), and Funding (15%). CONCLUSIONS: The methodological and reporting quality of NMAs in TCM is moderate. Identified shortcomings of published NMAs should be taken into consideration in further trainings of authors and editors of NMAs in TCM. Future researchers should be encouraged to apply PRISMA-NMA, and a recognized tool for the assessment of NMA methodology was wanted.