Yuncheng Central Hospital

AIM: The present study aimed to assess the benefits of two-stent techniques for patients with DEFINITION criteria-defined complex coronary bifurcation lesions. METHODS AND RESULTS: In total, 653 patients with complex bifurcation lesions at 49 international centres were randomly assigned to undergo the systematic two-stent technique (two-stent group) or provisional stenting (provisional group). The primary endpoint was the composite of target lesion failure (TLF) at the 1-year follow-up, including cardiac death, target vessel myocardial infarction (TVMI), and clinically driven target lesion revascularization (TLR). The safety endpoint was definite or probable stent thrombosis. At the 1-year follow-up, TLF occurred in 37 (11.4%) and 20 (6.1%) patients in the provisional and two-stent groups, respectively [77.8%: double-kissing crush; hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.30-0.90; P = 0.019], largely driven by increased TVMI (7.1%, HR 0.43, 95% CI 0.20-0.90; P = 0.025) and clinically driven TLR (5.5%, HR 0.43, 95% CI 0.19-1.00; P = 0.049) in the provisional group. At the 1 year after indexed procedures, the incidence of cardiac death was 2.5% in the provisional group, non-significant to 2.1% in the two-stent group (HR 0.86, 95% CI 0.31-2.37; P = 0.772). CONCLUSION: For DEFINITION criteria-defined complex coronary bifurcation lesions, the systematic two-stent approach was associated with a significant improvement in clinical outcomes compared with the provisional stenting approach. Further study is urgently warranted to identify the mechanisms contributing to the increased rate of TVMI after provisional stenting. STUDY REGISTRATION: http://www.clinicaltrials.com; Identifier: NCT02284750.

BACKGROUND: Mutations in GJB2 are the most common molecular defects responsible for autosomal recessive nonsyndromic hearing impairment (NSHI). The mutation spectra of this gene vary among different ethnic groups. METHODS: In order to understand the spectrum and frequency of GJB2 mutations in the Chinese population, the coding region of the GJB2 gene from 2063 unrelated patients with NSHI was PCR amplified and sequenced. RESULTS: A total of 23 pathogenic mutations were identified. Among them, five (p.W3X, c.99delT, c.155_c.158delTCTG, c.512_c.513insAACG, and p.Y152X) are novel. Three hundred and seven patients carry two confirmed pathogenic mutations, including 178 homozygotes and 129 compound heterozygotes. One hundred twenty five patients carry only one mutant allele. Thus, GJB2 mutations account for 17.9% of the mutant alleles in 2063 NSHI patients. Overall, 92.6% (684/739) of the pathogenic mutations are frame-shift truncation or nonsense mutations. The four prevalent mutations; c.235delC, c.299_c.300delAT, c.176_c.191del16, and c.35delG, account for 88.0% of all mutantalleles identified. The frequency of GJB2 mutations (alleles) varies from 4% to 30.4% among different regions of China. It also varies among different sub-ethnic groups. CONCLUSION: In some regions of China, testing of the three most common mutations can identify at least one GJB2 mutant allele in all patients. In other regions such as Tibet, the three most common mutations account for only 16% the GJB2 mutant alleles. Thus, in this region, sequencing of GJB2 would be recommended. In addition, the etiology of more than 80% of the mutant alleles for NSHI in China remains to be identified. Analysis of other NSHI related genes will be necessary.

Importance: For patients with non-small cell lung cancer whose disease progressed while receiving EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy, particularly third-generation TKIs, optimal treatment options remain limited. Objective: To compare the efficacy of ivonescimab plus chemotherapy with chemotherapy alone for patients with relapsed advanced or metastatic non-small cell lung cancer with the epidermal growth factor receptor (EGFR) variant. Design, Setting, and Participants: Double-blind, placebo-controlled, randomized, phase 3 trial at 55 sites in China enrolled participants from January 2022 to November 2022; a total of 322 eligible patients were enrolled. Interventions: Participants received ivonescimab (n = 161) or placebo (n = 161) plus pemetrexed and carboplatin once every 3 weeks for 4 cycles, followed by maintenance therapy of ivonescimab plus pemetrexed or placebo plus pemetrexed. Main Outcomes and Measures: The primary end point was progression-free survival in the intention-to-treat population assessed by an independent radiographic review committee (IRRC) per Response Evaluation Criteria in Solid Tumors version 1.1. The results of the first planned interim analysis are reported. Results: Among 322 enrolled patients in the ivonescimab and placebo groups, the median age was 59.6 vs 59.4 years and 52.2% vs 50.9% of patients were female. As of March 10, 2023, median follow-up time was 7.89 months. Median progression-free survival was 7.1 (95% CI, 5.9-8.7) months in the ivonescimab group vs 4.8 (95% CI, 4.2-5.6) months for placebo (difference, 2.3 months; hazard ratio [HR], 0.46 [95% CI, 0.34-0.62]; P < .001). The prespecified subgroup analysis showed progression-free survival benefit favoring patients receiving ivonescimab over placebo across almost all subgroups, including patients whose disease progressed while receiving third-generation EGFR-TKI therapy (HR, 0.48 [95% CI 0.35-0.66]) and those with brain metastases (HR, 0.40 [95% CI, 0.22-0.73]). The objective response rate was 50.6% (95% CI, 42.6%-58.6%) with ivonescimab and 35.4% (95% CI, 28.0%-43.3%) with placebo (difference, 15.6% [95% CI, 5.3%-26.0%]; P = .006). The median overall survival data were not mature; at data cutoff, 69 patients (21.4%) had died. Grade 3 or higher treatment-emergent adverse events occurred in 99 patients (61.5%) in the ivonescimab group vs 79 patients (49.1%) in the placebo group, the most common of which were chemotherapy-related. Grade 3 or higher immune-related adverse events occurred in 10 patients (6.2%) in the ivonescimab group vs 4 (2.5%) in the placebo group. Grade 3 or higher vascular endothelial growth factor-related adverse events occurred in 5 patients (3.1%) in the ivonescimab group vs 4 (2.5%) in the placebo group. Conclusions: Ivonescimab plus chemotherapy significantly improved progression-free survival with tolerable safety profile in TKI-treated non-small cell lung cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT05184712.

Sorafenib, an orally available kinase inhibitor, is the standard first-line systemic drug for advanced hepatocellular carcinoma (HCC), and it exerts potent inhibitory activity against epithelial-mesenchymal transition (EMT) and multidrug resistance (MDR) by inhibiting mitogen-activated protein kinase (MAPK) signaling in HCC. However, after long-term exposure to sorafenib, HCC cells exhibit EMT and resistance to sorafenib. The activation of AKT by sorafenib is thought to be responsible for the development of these characteristics. The present study aims to examine the underlying mechanism and seek potential strategies to reverse this resistance and the progression to EMT. Sorafenib-resistant cells showed increased metastatic and invasive ability, with a higher expression of P-glycoprotein (P-gp), compared with the parental cells. This phenomenon was at least partially due to EMT and the appearance of MDR in sorafenib-resistant HCC cells. Moreover, MDR was a downstream molecular event of EMT. Silencing Snail with siRNA blocked EMT and partially reversed the MDR, thereby markedly abolishing invasion and metastasis in sorafenib-resistant HCC cells, but silencing of MDR1 had no effect on the EMT phenotype. Additionally, HCC parental cells that were stably transfected with pCDNA3.1-Snail exhibited EMT and MDR. Two sorafenib-resistant HCC cell lines, established from human HCC HepG2 and Huh7 cells, were refractory to sorafenib-induced growth inhibition but were sensitive to MK-2206, a novel allosteric AKT inhibitor. Thus, the combination of sorafenib and MK-2206 led to significant reversion of the EMT phenotype and P-gp-mediated MDR by downregulating phosphorylated AKT. These findings underscore the significance of EMT, MDR and enhanced PI3K/AKT signaling in sorafenib-resistant HCC cells.

Background: While the lockdown strategies taken by many countries effectively limited the spread of COVID-19, those were thought to have a negative impact on older people. This study aimed to investigate the impact of lockdown on cognitive function and neuropsychiatric symptoms over a 1-year follow-up period in patients with mild cognitive impairment (MCI), Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). Methods: We enrolled consecutive patients with MCI, probable AD or DLB who were receiving outpatient memory care before the COVID-19 pandemic and followed-up with them after 1 year by face-to-face during the COVID-19 pandemic to assess changes in physical activity, social contact, cognitive function and neuropsychiatric symptoms (NPS). Results: Total 105 probable AD, 50 MCI and 22 probable DLB patients were included and completed the 1-year follow-up between October 31 and November 30, 2020. Among the respondents, 42% of MCI, 54.3% of AD and 72.7% of DLB patients had a decline in MMSE scores and 54.4% of DLB patients had worsening Neuropsychiatric inventory (NPI) scores. Patients with DLB showed a more rapid decline of MMSE than those with AD. Diminished physical activity and social contact might have hastened the deterioration of cognition and the worsening of NPS. Conclusion: Social isolation and physical inactivity even after strict lockdown for at least 6 months were correlated with accelerated decline of cognitive function and NPS in patients with AD and DLB.

Polycystic ovary syndrome (PCOS) is the most common endocrine diseases of fertile women and a major cause of infertility. The regulatory effects of DNA methylation on gene transcription and downstream lipid metabolism have not been explored in PCOS. In this study, MBD-seq and RNA-seq were performed on ovarian granulosa cells of PCOS patients and controls, and methylation specific PCR and quantitative polymerase chain reaction were used to validate the results. Then lipidomic profiling was conducted on serum of PCOS patients and controls using UPLC-MS. We identified 73 genes with differently methylated promoters and 830 differently expressed genes. The promoter regions of LPCAT1 and PCYT1A were hypermethylated, accompanied by downregulation of their messenger RNA expression, which may be involved in the regulation of PCOS through downstream glycerophospholipid metabolism and phosphatidylcholine synthesis. The lipid profiling results showed significant changes in 21 lipids, which demonstrated the disturbance in glycerophospholipid metabolism and glycerolipid metabolism pathways. Furthermore, the metabolites-genes interaction network was constructed to illustrate the association of aberrant methylome and transcriptome with lipidome alterations in glycerolipid and glycerophospholipid metabolism pathways. Our study suggested that the methylation silencing of LPCAT1 and PCYT1A may promote glycerophospholipids metabolism dysregulation, which provided a novel genetic and lipometabolic basis for the pathogenesis of PCOS.

Polycystic ovary syndrome (PCOS) is a prevalent heterogeneous endocrine and metabolic disorder in women of reproductive age. Epigenetic mechanisms contribute to the development of PCOS. Nevertheless, the role of DNA methylation in the development of PCOS remains unclear. To investigate the molecular mechanisms underlying the hyperandrogenic phenotype of PCOS, dihydrotestosterone (DHT)-induced prenatally androgenized (PNA) mice were used to mimic this phenotype. Ovarian samples from PNA and control mice were subjected to methyl-CpG-binding domain (MBD)-seq and RNA-seq, and validation was conducted using methylation-specific polymerase chain reaction (MSP) and quantitative real-time PCR (RT-qPCR). Immunohistochemical analysis (using anti-LC3II antibody) and transmission electron microscopy were conducted using ovarian tissue sections (which included granulosa cells) from PNA and control mice. There were 857 genes with differentially methylated promoter regions and 3,317 differentially expressed genes (DEGs) in the PNA mice compared to the control mice. Downregulation of Dnmt1 (which encodes DNA methyltransferase 1), accompanied by global hypomethylation, was observed in the PNA mice compared to the control mice. The promoter regions of Map3k1 (which encodes MEKK1) and Map1lc3a (which encodes LC3II) were hypomethylated, accompanied by upregulation of Map3k1 and Map1lc3a mRNA expression. The autophagy profiling results showed that LC3II protein expression and autophagosomes were significantly increased in the granulosa cells of PNA mice. Additionally, the mRNA expression of genes related to the mitogen-activated protein kinase (MAPK)/p53 pathway ( Mapk14 , Mapkapk3 , and Trp53 ) and the autophagy-related gene Becn1 were significantly increased. DHT could change the DNA methylation and transcription level of Map3k1 and lead to an activation of autophagy in granulosa cells. These observations indicated that the change in autophagy may be driven by MAPK/p53 pathway activation, which may have been caused by DHT-induced transcriptional, and the methylation level changed of the key upstream gene Map3k1 . Our study provides a novel genetic basis and new insights regarding the pathogenesis of PCOS.

Previous reports have indicated that microRNAs (miRNAs) have an important role in the pathogenesis of diabetic nephropathy (DN). Podocyte apoptosis induced by high glucose (HG) is characteristic of DN. However, the role of miRNAs in HG‑induced podocyte apoptosis remains poorly understood. The present study investigated the role and potential underlying mechanism of miRNA‑20b (miR‑20b) in podocyte apoptosis induced by HG. The results demonstrated that miR‑20b was significantly upregulated in HG‑treated podocytes, as determined by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Caspase‑3 activity and TUNEL assays indicated that suppression of miR‑20b using miR‑20b inhibitors significantly inhibited the podocyte apoptosis induced by HG. Sirtuin 7 (SIRT7) was identified as a functional target of miR‑20b by a Dual‑Luciferase activity reporter assay, RT‑qPCR and western blot analysis. Silencing SIRT7 promoted HG‑induced podocyte apoptosis, as determined by the caspase‑3 activity, while SIRT7 overexpression attenuated HG‑induced podocyte apoptosis. However, SIRT7 silencing significantly blocked the protective effect of miR‑20b suppression against HG‑induced apoptosis. In conclusion, these results indicate that miR‑20b may contribute to HG‑induced podocyte apoptosis by targeting SIRT7, providing a potential therapeutic target for the treatment of DN.

Introduction: Numerous countries went into lockdown to contain the COVID-19 outbreak, which has impeded follow-up of chronic diseases, such as cognitive impairment (CI). Cognitive and neuropsychiatric changes during the COVID-19 pandemic are neglected in China, which is the world's whistleblower. To investigate the cognitive and neuropsychologic changes in CI, as well as the proportions of rapid cognitive decline (RCD) before and during the COVID-19 pandemic to provide clinical evidence for CI intervention during a public health emergency. Methods: We performed a descriptive and retrospective study based on medical records from the memory clinic of Tianjin Dementia Institute collected through face-to-face evaluations. Information of 205 patients with CI, including patients with mild cognitive impairment and dementia, of whom 131 with Alzheimer's disease (AD) were analyzed and compared to a control group before the COVID-19 pandemic. Results: Among the 205 CI patients, the scores on the Chinese Mini Mental State Examination (C-MMSE), the Montreal Cognitive Assessment (MoCA), activities of daily living (ADLs), and the global Neuropsychiatric Inventory (NPI) were significantly different at the baseline and follow-up evaluations ( p &amp;lt; 0.05) after 14.07 (±2.87) months. The same findings were recorded among AD patients, and they exhibited more sleep disturbances at the follow-up than at baseline (32.8 vs. 20.6%, p = 0.035). When compared to the control group, slightly worse performance of cognitive, −1.00 (−4.00, 1.00) from the C-MMSE, −1.00 (−2.00, 0.00) on the MoCA, 1.00 (0.00, 9.00) on ADLs and neuropsychological 0.00 (−1.00, 3.50) on the global NPI profile, at the follow-up were presented, particularly for delusion, agitation, irritability, and appetite disturbances ( p &amp;lt; 0.05). Twenty-five (19.1%) AD patients and 48 (36.6%) controls suffered RCD during the COVID-19 pandemic. Moreover, AD patients during the COVID-19 pandemic were 0.408 times (95% confidence interval: 0.232–0.716) less likely to suffer RCD than the control. Conclusion: Confinement might ease the cognitive and neuropsychiatric deterioration of AD patients compared to those not in crisis and help prevent RCD in AD patients.

Osteoarthritis (OA) is the most prevalent joint disease, characterized by the degradation of articular cartilage, synovial inflammation, and changes in periarticular and subchondral bone. Recent studies have reported that Wnt signaling cascades play an important role in the development, growth, and homeostasis of joints. The Wnt signaling cascade should be tightly regulated to maintain the homeostasis of cartilage in either the over-activation or the suppression of Wnt/ β -catenin, as this could lead to OA. This review summarizes the role and mechanism of canonical Wnt cascade and noncanonical Wnt cascade experiments in vivo and in vitro . The Wnt cascade is controlled by several agonists and antagonists in the extracellular medium and the cytoplasm. These antagonists and agonists serve as key molecules in drug intervention into the Wnt pathway and may provide potential approaches for the treatment of OA. However, the complexity of the Wnt signaling cascade and the pharmaceutical effects on its mechanism are still not fully understood, which forces us to conduct further research and develop efficient therapeutic approaches to treat OA.

Ghrelin, a 28-amino acid peptide, is mainly secreted by the stomach. Ghrelin has been shown to have neuroprotective effects. However, whether ghrelin protects the spinal cord from ischemia/reperfusion (I/R) injury is unknown. To investigate this, 60 rats were randomly divided into three different groups: the sham group (n = 20), the vehicle group (n = 20), and the Ghrelin group (100 μg/kg, n = 20). Rats were sacrificed 12, 24, 48 and 72 h after ischemia. After the evaluation of neurologic function (48 h), the spinal cords were immediately removed for the determination of myeloperoxidase (MPO) activity (12-72 h). Apoptosis was quantitatively measured using the terminal transferase UTP nick end-labeling (TUNEL) method (24 h). The expression of bax and bcl-2 were evaluated by Western blot analysis (1 h), and GHSR-1a mRNA expression was detected using reverse transcriptase polymerase chain reaction (24 h). The neurological motor function was evaluated by 'Tarlov's score'. The neurologic outcomes in the ghrelin-group were significantly better than those in the vehicle group (p < 0.05). Serum tumor necrosis factor (TNF-α) levels were assessed in the peripheral venous blood. Ghrelin decreased the serum TNF-α levels and ameliorated the down regulation of spinal cord MPO activity. The expression of ghrelin receptors (GHSR-1a) in the rat spinal cord was decreased by I/R injury and increased by ghrelin. Ghrelin reduced the TUNEL-positive rate. Greater bcl-2, HSP27, HSP70, and attenuated bax expression were observed in the ghrelin-treated rats. Our results suggest that ghrelin administration may inhibit spinal I/R injury. Moreover, the improvement of neurologic function in rats was increased after the ghrelin treatment.

Taxol-based chemotherapy is a conventional therapeutic approach for the treatment of triple-negative breast cancer (TNBC). However, the insensitivity of TNBC cells to Taxol greatly limits the anticancer effect of the drug and leads to patient mortality. The present study first evaluated the expression levels of microRNA (miR)-1207-5p in human normal breast epithelial MCF-10A cells and TNBC cell lines (MDA-MB-231, MDA-MB-436 and MDA-MB-453). The results revealed that the highest miR-1207-5p level was in MDA-MB-231, which suggested an oncogenic role of miR-1207-5p in TNBC. Therefore, MDA-MB-231 served as the present study's research model in subsequent experiments. The mRNAs that functioned as tumor suppressor factors for miR-1207-5p were then determined. Leucine zipper tumor suppressor gene 1 (LZTS1), which was predicted by TargetScan 6.2 and was supported by the results of a dual luciferase assay, was identified as a target of miR-1207-5p. AntagomiR-1207-5p increased LZTS1 mRNA and protein expressions, enhanced cell growth arrest and cell apoptosis induced by Taxol in MDA-MB-231 cells. Additionally, it was observed that, when compared with Taxol treatment, the combination of Taxol and antagomiR-1207-5p induced a sharp decrease in B-cell lymphoma 2 (Bcl-2) and phosphorylated-protein kinase B expression accompanied by an increase in the Bcl-2-associated X protein expression. Finally, miR-1207-5p expression was significantly increased, while LZTS1 expression was significantly decreased, in TNBC tissues when compared with normal adjacent tissues, and there was a negative correlation between miR-1207-5p and LZTS1 expression. In addition, there was a notable elevation in the expression of miR-1207-5p and a reduction in the expression of LZTS1 in the Taxol non-responsive TNBC tissues when compared with the Taxol-responsive TNBC tissues. The results of the present study suggested that miR-1207-5p may be a promising predictor of sensitivity towards Taxol in TNBC.

MUC4 , a transmembrane mucin, plays important roles in epithelial renewal and differentiation. Recent studies suggest that MUC4 has been implicated in pancreatic cancer pathogenesis and is expressed in various normal and cancer tissues. The underlying features of MUC4 across various cancer types may allow us to ensure appropriate treatment and patient monitoring. However, the contributions of MUC4 to pan-cancer have not been well characterized. In this study, we investigated the expression pattern and prognostic value of MUC4 across multiple databases. We further explored genomic and epigenetic alterations of MUC4 , its association with proliferation and metastasis, and the correlation with immune infiltration in different cancers. Our results characterized the distinct expression profile and prognostic values of MUC4 in pan-cancer. Through examining its association with genomic alteration, tumor proliferation, and metastasis, as well as tumor infiltration, we revealed multiple function effects of MUC4 . MUC4 may influence prognosis, proliferation, metastasis, and immune response in opposite directions. In conclusion, our findings suggested the necessity to more carefully evaluate MUC4 as a biomarker and therapeutic target and develop the new antibodies for cancer detection and intervention.

Background. Myeloid-derived suppressor cells (MDSC) play an important role in tumor-mediated immune evasion. Levels of MDSC in peripheral blood are increased in patients with cancer, correlating with cancer stage and outcome. Studies have confirmed the associations between MDSC and various cytokines in the peripheral blood of murine and human cancer hosts. However, little is known about the association between parenchymal MDSC subsets and cytokines, or the mechanism drawing MDSC into tumor parenchyma.

OBJECTIVE: To compare 5-year disease-free survival (DFS) and overall survival (OS) rates of laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) for stage IB1 and tumor size <2 cm with visible or invisible tumors. METHODS: We retrospectively compared the oncological outcomes of 1,484 cervical cancer patients with IB1 and tumor size <2 cm on final pathology, who received ARH (n=899) or LRH (n=585) between January 2004 and December 2016. Patients were divided into visible tumor subgroup (ARH: n=668, LRH: n=444) and invisible tumor subgroup (ARH: n=231, LRH: n=141) according to tumor type. RESULTS: LRH and ARH showed similar 5-year DFS and OS rates (93.3% vs. 93.1%, p=0.997; 96.2% vs. 97.5%, p=0.351) in total study population. LRH was not associated with worse 5-year DFS rate (hazard ratio [HR]=0.96; 95% confidence interval [CI]=0.58-1.58; p=0.871) or OS rate (HR=1.37; 95% CI=0.65-2.89; p=0.409) by multivariable analysis. In the visible tumor subgroups, LRH and ARH showed similar 5-year DFS and OS rates (91.9% vs. 91.9%, p=0.933; 95.0% vs. 96.9%, p=0.276), and LRH was not associated with worse 5-year DFS or OS rate (p=0.804, p=0.324). In the invisible tumor subgroups, LRH and ARH also showed similar 5-year DFS and OS rates (97.3% vs. 97.1%, p=0.815; 100% vs. 99.5%, p=0.449), and LRH was not associated with worse 5-year DFS rate (p=0.723). CONCLUSIONS: Among patients with stage IB1 and tumor size <2 cm, whether the tumor is visible or not, the oncological outcomes of LRH and ARH among cervical cancer patients are comparable. This suggests that LRH may be suitable for stage IB1 and tumor size <2 cm with visible or invisible tumors. TRIAL REGISTRATION: International Clinical Trials Registry Platform Identifier: CHiCTR180017778.

evidence that matrine was able to protect PC12 cells against LPS-evoked damage. The neuroprotective properties of matrine may be due to its regulation of miR-9 expression as well as JNK and NF-κB pathways.

Tafolecimab is a novel fully human proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody, developed for the treatment of hypercholesterolemia. To assess the efficacy and safety of tafolecimab in Chinese patients at high or very high cardiovascular risk with hypercholesterolemia. Patients with diagnoses of heterozygous familial hypercholesterolemia (HeFH) by the Simon Broome criteria or at high or very high cardiovascular risk with nonfamilial hypercholesterolemia, with screening low-density lipoprotein cholesterol (LDL-C) level ≥1.8 mmol/L, were randomized 2:1 to receive tafolecimab or placebo 450 mg every 4 weeks (Q4W) in the 12-week double-blind treatment period. The primary endpoint was the percent change from baseline to week 12 in LDL-C levels. A total of 303 patients were enrolled and received at least 1 dose of tafolecimab (n = 205) or placebo (n = 98). The least squares mean percent change in LDL-C level from baseline to week 12 was –68.9% (SE 1.4%) in the tafolecimab group and –5.8% (1.8%) in the placebo group (difference: –63.0%; [95% CI: –66.5% to –59.6%]; P < 0.0001). More patients treated with tafolecimab achieved ≥50% LDL-C reductions, LDL-C <1.8 mmol/L, and LDL-C <1.4 mmol/L at week 12 than did those in the placebo group (all P < 0.0001). Furthermore, tafolecimab markedly reduced non-HDL-C, apolipoprotein B, and lipoprotein(a) levels. During the double-blind treatment period, the most commonly reported adverse events included urinary tract infection (5.9% with tafolecimab vs 4.1% with placebo) and hyperuricemia (3.4% vs 4.1%). Tafolecimab was safe and showed robust lipid-lowering efficacy in Chinese patients at high or very high cardiovascular risk with hypercholesterolemia. (A Study of IBI306 in Participants With Hypercholesterolemia; NCT04709536)

BackgroundTafolecimab, a fully human proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody developed for the treatment of hypercholesterolemia, demonstrated robust lipid-lowering efficacy and favorable safety in previous short-term studies. We aimed to assess the long-term efficacy and safety of tafolecimab in Chinese non-familial hypercholesterolemia (non-FH) patients.MethodsNon-FH patients at high or very-high cardiovascular risk with screening low-density lipoprotein cholesterol (LDL-C) level ≥1.8 mmol/L or non-FH patients with screening LDL-C level ≥3.4 mmol/L and on stable lipid-lowering therapy for at least 4 weeks, were randomized in a 2:2:1:1 ratio to receive subcutaneous tafolecimab 450 mg Q4W, tafolecimab 600 mg Q6W, placebo 450 mg Q4W, or placebo 600 mg Q6W, respectively, in the 48-week double-blind treatment period. The primary endpoint was the percent change from baseline to week 48 in LDL-C levels.FindingsA total of 618 patients were randomized and 614 patients received at least one dose of tafolecimab (n = 411) or placebo (n = 203). At week 48, tafolecimab induced significant reductions in LDL-C levels (treatment differences versus placebo [on-treatment estimand]: −65.0% [97.5% CI: −70.2%, −59.9%] for 450 mg Q4W; −57.3% [97.5% CI: −64.0%, −50.7%] for 600 mg Q6W; both P < 0.0001). Significantly more patients treated with tafolecimab achieved ≥50% LDL-C reductions, LDL-C < 1.8 mmol/L, and LDL-C < 1.4 mmol/L than placebo group at both dose regimens (all P < 0.0001). Furthermore, tafolecimab significantly reduced non-HDL-C, apolipoprotein B, and lipoprotein(a) levels. The most commonly-reported treatment emergent adverse events in the tafolecimab groups included upper respiratory infection, urinary tract infection and hyperuricemia.InterpretationTafolecimab dosed at 450 mg Q4W and 600 mg Q6W was safe and showed superior lipid-lowering efficacy versus placebo, providing a novel treatment option for Chinese hypercholesterolemia patients.FundingThis study was sponsored by Innovent Biologics, Inc.

INTRODUCTION: This randomized, double-blind trial aimed to test effect of a Chinese herbal medicine, Qinggongshoutao (QGST) pill, on the cognition and progression of amnestic mild cognitive impairment (aMCI). METHODS: extract, or placebo for 52 weeks. The primary outcome measures were progression to possible or probable Alzheimer's disease (AD) and change in Alzheimer's Disease Assessment Scale-cognitive subscale scores; secondary outcome measures included assessments for cognition and function. RESULTS: Total 350 patients were enrolled, possible or probable AD developed in 10. There were significant differences in the probability of progression to AD in the QGST group (1.15%) compared with placebo group (10%). There was significant difference in Alzheimer's Disease Assessment Scale-cognitive subscale scores in favor of QGST over the placebo group. Secondary outcome measure (Mini-Mental State Examination) also showed benefit in QGST at end point. DISCUSSION: In patients with aMCI, QGST showed lower AD progression rate than placebo at 8.85%, and may have benefit on global cognition.

PURPOSE: Studies have suggested that public health emergencies can have many psychological effects on college students, therefore, the aim of this study is to investigate current situation of college students' anxiety and its determinants in the time of an unexpected pandemic. PATIENTS AND METHODS: We conducted convenience sampling to collect the data through network-based online questionnaires in February 2020, a total of 17,876 college students were included in the analysis. Chi-square test and multivariate logistic were used to identify the associations between the outbreak experiences and anxiety detection. RESULTS: This study found that detection rate of anxiety among college students was 18.2%. The differences in male students, students whose self-perceived risk of infection were high, who were greatly affected by the outbreak, eager to go back to school, reluctant to leave home and stay at home enough were of statistical significance among different anxiety level (OR>1, P<0.05). And the severe anxiety rate of students who living in cities was significantly higher (2.337[1.468, 3.721]). CONCLUSION: Although our results show that anxiety among college students was at a low level, various universities should focus on the online activities and develop appropriate epidemic management plans to prevent their feelings of worry, tension and panic.