Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

OBJECTIVE: Campylobacter jejuni NCTC11168 is commonly used as a standard strain for flagellar biosynthesis research. In this report, two distinguished phenotypic isolates (CJ1Z, flhA mutant strain, lawn; CJ2S, flhA complemented strain, normal colony) appeared during laboratory passages for NCTC11168. METHODS: Phenotypic assessments, including motility plates, transmission electron microscopy, biofilm formation assay, autoagglutination assay, and genome re-sequencing for these two isolates (CJ1Z, flhA mutant strain; CJ2S, flhA complemented strain) were carried out in this study. RESULTS: Transmission electron microscopy revealed that the flagellum was lost in CJ1Z. Phenotypic assessments and genome sequencing of the two isolates were performed in this study. The capacity for biofilm formation, colony auto-agglutination, and isolate motility was reduced in the mutant CJ1Z. Comparative genomic analysis indicated a unique native nucleotide insertion in flhA (nt, 2154) that caused the I719Y and I720Y mutations and early truncation in flhA. CONCLUSION FlhA has been found to influence the expression of flagella in C. jejuni. To the best of our knowledge, this is the first study to describe the function of the C-terminal of this protein.
Campylobacter jejuni/genetics* ; Bacterial Proteins/metabolism* ; Mutation ; Biological Variation, Population

With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly temporary and incomplete. Moreover, even patients with the same oncogenic driver gene can respond diversely to the same agent. Furthermore, the therapeutic role of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC remains unclear. Therefore, this review aimed to classify the management of NSCLC with driver mutations based on the gene subtype, concomitant mutation, and dynamic alternation. Then, we provide an overview of the resistant mechanism of target therapy occurring in targeted alternations ("target-dependent resistance") and in the parallel and downstream pathways ("target-independent resistance"). Thirdly, we discuss the effectiveness of ICIs for NSCLC with driver mutations and the combined therapeutic approaches that might reverse the immunosuppressive tumor immune microenvironment. Finally, we listed the emerging treatment strategies for the new oncogenic alternations, and proposed the perspective of NSCLC with driver mutations. This review will guide clinicians to design tailored treatments for NSCLC with driver mutations.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Tumor Microenvironment/genetics*

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

OBJECTIVE: To investigate whether anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes were correlated with unexplained recurrent miscarriages. METHODS: In our a single-center retrospective study, 283 patients with at least one unexplained miscarriage who visited the Third Hospital of Peking University between January 2021 and August 2023, aged between 18-40 years, and tested for anti-phosphatidylserine/prothrombin antibodies IgG or IgM subtypes, were included. The patients with either positive IgG or IgM anti-phosphatidylserine/prothrombin antibody were regarded as positive for anti-phosphatidylserine/prothrombin antibody. SPSS 26.0 software was used for statistical analysis. Chi-square test and Logistic regression analysis were used to study the correlation of anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes with unexplained recurrent miscarriages. And the diagnostic sensitivity, specificity, the positive predictive value, the negative predictive value of anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes in unexplained miscarriages was calculated with four-fold table. RESULTS: Chi-square analysis showed that anti-phosphatidylserine/prothrombin antibodies and its IgM subtypes were correlated with recurrent miscarriages (both P < 0.05), while the IgG subtype was not correlated with recurrent miscarriages (P>0.05). After adjusting with anticardiolipin antibodies, anti-β₂ glycoprotein antibodies, lupus anticoagulants, antinuclear antibodies, and age by Logistic regression analysis, anti-phosphatidylserine/prothrombin antibodies were correlated with unexplained recurrent miscarriages (OR=2.084, 95%CI 1.045-4.155, P < 0.05), and anti-phosphatidylserine/prothrombin antibody IgM subtypes were correlated with unexplained recurrent miscarriages (OR=2.368, 95%CI 1.187-4.722, P < 0.05).The sensitivity of anti-phosphatidylserine/prothrombin antibody in recurrent miscarriage was 65.43%, the specificity was 48.51%, the positive predictive value was 33.76%, and the negative predictive value was 77.78%. In the patients with recurrent miscarriages with negative classical antiphospholipid antibodies, the sensitivity of anti-phosphatidylserine/prothrombin antibody was 59.09%, the specificity was 63.23%, the positive predictive value was 40.63%, and the negative predictive value was 78.40%. The sensitivity of the anti-phosphatidylserine/prothrombin antibody IgM subtype for the diagnosis of recurrent miscarriage was 65.43%, the specificity was 50.99%, the positive predictive value was 34.87%, and the negative predictive value was 78.63%. CONCLUSION Anti-phosphatidylserine/prothrombin antibody and IgM subtype antibody are correlated with unexplained recurrent miscarriages in patients with at least one unexplained miscarriage. Whether positive anti-phosphatidylserine/prothrombin antibody or IgM subtype could predict future unexplained recurrent miscarriages warrants a prospective study.
Pregnancy ; Female ; Humans ; Adolescent ; Young Adult ; Adult ; Prothrombin ; Retrospective Studies ; Phosphatidylserines ; Prospective Studies ; beta 2-Glycoprotein I ; Antibodies, Antiphospholipid ; Antiphospholipid Syndrome/diagnosis* ; Antibodies, Anticardiolipin ; Abortion, Habitual ; Immunoglobulin G ; Immunoglobulin M

Objective: To quantitatively evaluate the association between mild cognitive impairment and all-cause mortality. Methods: The research papers of the association between cognitive impairment and all-cause mortality in the elderly in the databases of PubMed, EMBASE, Wang Fang data and CNKI published as of August 1, 2021 were comprehensively retrieved. Software R 4.02 was used for Meta-analysis. Results: A total of 9 research papers were included, involving 48 709 patients. The quality of included papers was high. The results of Meta-analysis showed that the association between mild cognitive impairment and the increased risk of all-cause mortality was statistically significant. Compared with the normal cognitive population, the risk of mortality in the elderly with mild cognitive impairment increased by 39% (HR=1.39, 95%CI: 1.18-1.63). Conclusions: The current research evidence showed that mild cognitive impairment assessed by MMSE screening scale can be used as an independent predictor of the increased risk of all-cause mortality in the elderly population in China. However, due to the limitation of the number of included studies and sample size, the conclusions need to be supported by more evidence studies.
Aged ; China/epidemiology* ; Cognition ; Cognition Disorders ; Cognitive Dysfunction/epidemiology* ; Humans ; Mass Screening

Objective:To characterize the knee gait maps of ordinary people, athletes and patients with anterior cruciate ligament (ACL) injury when walking on a level ground in order to identify potential kinematic indicators for early identification of ACL injury.Methods:From December 2021 to March 2022, 39 ordinary college students (normal group) and 39 college athletes (athlete group) were recruited in Southern Medical University, and 26 patients with ACL injury (patient group) were recruited at the Department of Orthopedics, Guangdong Provincial People＇s Hospital. The normal group consisted of 20 males and 19 females with a median age of 19 (18, 21) years; the athlete group consisted of 22 males and 17 females with a median age of 19 (18, 20) years; the patient group consisted of 23 males and 3 females with a median age of 20 (19, 20) years. A portable knee joint motion capture system was used to collect the knee gait maps of the subjects walking at a speed of 3 km/h on a treadmill. The knee varus and valgus angles, internal and external rotation angles, flexion and extension angles during the movement, and anteroposterior, medial-lateral superior-inferior displacements of the tibia relative to the femur were compared between the 3 groups.Results:There was no significant difference in the general data among the 3 groups except for gender, showing they were comparable ( P>0.05). There were significant differences in the varus and valgus angles during the whole gait cycle (1% to 100%), internal and external rotation angles during the weight-bearing response period (9% to 10%), flexion and extension angles during the stance phase and swing phase (1% to 27%, 29% to 100%), anteroposterior displacements during the weight-bearing reaction phase (1% to 3%) and at the end of the swing phase (96% to 98%), superior-inferior displacements at the middle support phase (15% to 19%), the end of the support phase (29% to 33%, 36% to 43%) and the swing phase (68% to 94%), and medial-lateral displacements at the middle stance phase and the middle swing phase (12% to 82%) among the 3 groups ( P<0.05). The maximum varus and valgus angles (-10.89°±4.55°, -12.20°±4.38°) of the subjects in the normal group and the athlete group were significantly greater than those in the patient group (-5.44°±3.72°) ( P<0.05). The medial-lateral displacement at the middle support phase [3.69 (0.13, 7.25) mm] of the subjects in the normal group was significantly larger than those in the athlete group and the patient group [-0.59 (-6.65, 5.24) mm, 0.96 (-1.54, 3.89) mm] ( P<0.05). Conclusions:The gait of college athletes is significantly different from that of ordinary college students and that of patients with ACL injury. Indexes like the varus and valgus angles and the medial-lateral displacement may be used as potential indictors for early identification of ACL injury.

OBJECTIVE: To assess the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on clinical outcomes of patients receiving anti-PD-1 immunotherapy for hepatocellular carcinoma. METHODS: We conducted a retrospective study among 215 patients with primary liver cancer receiving immunotherapy between June, 2018 and October, 2020. The patients with balanced baseline characteristics were selected based on propensity matching scores, and among them 33 patients who used NSAIDs were matched at the ratio of 1∶3 with 78 patients who did not use NSAIDs. We compared the overall survival (OS), progression-free survival (PFS), and disease control rate (DCR) between the two groups. RESULTS: There was no significant difference in OS between the patients using NSAIDs (29.7%) and those who did not use NSAIDs (70.2%). Univariate and multivariate analyses did not show an a correlation of NSAIDs use with DCR (univariate analysis: OR=0.602, 95% CI: 0.299-1.213, P=0.156; multivariate analysis: OR=0.693, 95% CI: 0.330-1.458, P=0.334), PFS (univariate analysis: HR=1.230, 95% CI: 0.789-1.916, P=0.361; multivariate analysis: HR=1.151, 95% CI: 0.732-1.810, P=9.544), or OS (univariate analysis: HR=0.552, 95% CI: 0.208-1.463, P=0.232; multivariate analysis: HR=1.085, 95% CI: 0.685-1.717, P=0.729). CONCLUSION Our results show no favorable effect of NSAIDs on the efficacy of immunotherapy in patients with advanced primary liver cancer, but this finding still needs to be verified by future prospective studies of large cohorts.
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use* ; Humans ; Immunotherapy/methods* ; Liver Neoplasms/drug therapy* ; Prospective Studies ; Retrospective Studies

ObjectiveTo explore the mechanism of Cervi Cornu Pantotrichumin in the treatment of osteoarthritis by network pharmacology. MethodThe active ingredients and the corresponding targets of Cervi Cornu Pantotrichumin were screened out by a Bioinformatics Analysis Tool of Molecular mechANism of Traditional Chinese Medicine （BATMAN-TCM）. The targets related to osteoarthritis were obtained through GeneCards and Online Mendelian Inheritance in Man （OMIM）. The targets corresponding to the active ingredients and those related to osteoarthritis were intersected to reveal the common targets， and STRING was adopted to build a protein-protein interaction （PPI） network. DAVID was used for gene ontology （GO） annotation and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment on the anti-osteoarthritis targets of Cervi Cornu Pantotrichumin， and R x64 3.6.3 was employed to produce the advanced bubble charts of GO terms and KEGG pathways. Cytoscape 3.7.2 was used to establish the “Chinese medicinal herb-active ingredient-target-signaling pathway” network. In vitro experiments were performed to detect the viability of RAW 264.7 cells exposed to oxidative stress and the tumor necrosis factor （TNF）-α level in RAW 264.7 cells with inflammation under the treatment by Cervi Cornu Pantotrichumin. ResultA total of 20 active ingredients of Cervi Cornu Pantotrichum were obtained， of which ceramide， 6'-O-β-D-glucosylgentiopicroside， cerebroside， oleuropein， sphingomyelin， and cholesterol ferulate did not meet the screening conditions. Therefore， a total of 14 active ingredients were finally screened out， and 303 and 3 093 targets of active ingredients and osteoarthritis were respectively obtained. The two target sets were taken to intersect， which revealed 92 common targets. GO annotation and KEGG pathway enrichment showed that the targets were mainly involved in redox process， positive regulation of RNA polymerase Ⅱ promoter transcription， inflammatory response， protein synthesis， osteoclast differentiation， TNF signaling pathway， signaling pathways in cancer， mammalian target of rapamycin （mTOR） signaling pathway， mitogen-activated protein kinase （MAPK） signaling pathway， and cyclic adenosine monophosphate （cAMP） signaling pathway. The results of in vitro experiments showed that a certain concentration of protein in Cervi Cornu Pantotrichum significantly increased the viability of RAW 264.7 cells exposed to H₂O₂-induced oxidative damage （P<0.05， P<0.01） and reduced the level of TNF-α in the RAW 264.7 cells experiencing lipopolysaccharide （LPS）-induced inflammation （P<0.05）. ConclusionBased on the network pharmacology method， the mechanism of the multi-component， multi-target and multi-pathway treatment of OA by antler antler was explained， and the anti-inflammatory and antioxidant activities of antler antler were confirmed， which provided theoretical guidance and scientific basis for further research on the treatment of OA by antler antler.