Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

To characterize human antibodies against low-calcium response V(LcrV)antigen of Yersinia pestis,the mono-clonal antibodies were screened and assayed.Antibody gene was derived from peripheral blood mononuclear cells of the vaccin-ees immunized by plague subunit vaccine in phase Ⅱb clinical trial.Human ScFv antibody library was constructed by phage dis-play.After panning library by using recombinant LcrV antigen,antibody variable genes were sequenced and converted into IgG1 format to evaluate its binding specificity and relevant parameters.An anti-plague human ScFv antibody library was estab-lished contained 7.54× 108 independent clones.After panning by LcrV antigen,3 human antibodies named as RV-B4,RV-D1 and RV-E8,respectively,were identified.Using indirect enzyme-linked immunosorbent assay(ELISA)and Western blot(WB),the specific bindings of the mAbs to LcrV antigen were confirmed.The dissociation constant(KD)of them to LcrV is 2.1 nmol/L,1.24 nmol/L and 42 nmol/L,respectively.Minor protective efficacy was found among 3 human antibodies in Y.pestis 141-infected mice.Three anti-LcrV monoclonal antibodies generated from immunized vaccinees were binding specific antibod-ies and could not block plague infection in mice.These antibodies are the potential candidate reagents for basic research of plague immunity and the application of plague diagnosis.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objective:To describe the epidemiological characteristics and trends of leukemia incidence in Qidong between 1972 and 2021, and provide guidelines for prevention and control measures and strategies.Methods:The cancer registry data was collected and analyzed on leukemia incidence during 1972—2021 in Qidong by sex, age and time. Crude incidence rate (CR), China age-standardized rate (ASRC), world age-standardized rate (ASRW), and average annual change percentage (AAPC) was calculated by Joinpoint software. Age-period-cohort (APC) model was used to analyze the influence of age, period and birth cohort on the changes in the incidence trend of leukemia patients.Results:From 1972 to 2021, there were 2 948 patients with leukemia in Qidong, accounting for 2.00% of all cancer new cases, CR of leukemia was 5.26/10 5, ASRC was 4.34/10 5, ASRW was 4.35/10 5. The truncated incidence of 35—64 years old was 5.29/10 5, the cumulative incidence rate between the ages of 0 and 74 years old was 0.40%, the cumulative risk was 0.40%. There were 1 608 male patients, the CR, ASRC, and the ASRW were 5.81/10 5, 4.88/10 5 and 4.85/10 5. The number of female patients were 1 340, and the CR, ASRC, and the ASRW were 4.71/10 5, 3.86/10 5 and 3.91/10 5, respectively. Temporal trends indicated significant upward trends in ASRC among both gender, males and females with AAPC values of 1.41% ( P＜0.001), 1.15% ( P＜0.001), and 1.73% ( P＜0.001), respectively. The results of the APC model showed that the average net drift value of leukemia incidence in all age groups was 1.57% (95% CI, 1.24%-1.89%), and the highest value of local drift was 3.20% (95% CI, 1.63%-4.78%) in the 80~ years old group. The incidence of leukemia increased with age. With the passage of time, the risk of leukemia incidence increased gradually compared with the rate ratio of leukemia incidence (risk ratio [ RR], 1.00) in 1992—1996, the RR of leukemia incidence increased from 0.70 during 1972—1976 to 1.57 during 2017—2021. The later the cohort was born, the greater the risk of leukemia incidence compared with the relative risk of leukemia incidence ( RR, 1.00) in 1952—1956 cohort, the RR of leukemia incidence increased from 0.24 in the 1892—1896 cohort to 2.73 in the 2017—2021 cohort. Conclusions:The incidence of the leukemia has presented a rising trend in the past fifty years. Leukemia incidence increased with age, and the period and cohort effects on the risk of incidence increase. Further research is needed to investigate the risk factors related to leukemia.

Objective:To describe the epidemiological characteristics and trends of leukemia incidence in Qidong between 1972 and 2021, and provide guidelines for prevention and control measures and strategies.Methods:The cancer registry data was collected and analyzed on leukemia incidence during 1972—2021 in Qidong by sex, age and time. Crude incidence rate (CR), China age-standardized rate (ASRC), world age-standardized rate (ASRW), and average annual change percentage (AAPC) was calculated by Joinpoint software. Age-period-cohort (APC) model was used to analyze the influence of age, period and birth cohort on the changes in the incidence trend of leukemia patients.Results:From 1972 to 2021, there were 2 948 patients with leukemia in Qidong, accounting for 2.00% of all cancer new cases, CR of leukemia was 5.26/10 5, ASRC was 4.34/10 5, ASRW was 4.35/10 5. The truncated incidence of 35—64 years old was 5.29/10 5, the cumulative incidence rate between the ages of 0 and 74 years old was 0.40%, the cumulative risk was 0.40%. There were 1 608 male patients, the CR, ASRC, and the ASRW were 5.81/10 5, 4.88/10 5 and 4.85/10 5. The number of female patients were 1 340, and the CR, ASRC, and the ASRW were 4.71/10 5, 3.86/10 5 and 3.91/10 5, respectively. Temporal trends indicated significant upward trends in ASRC among both gender, males and females with AAPC values of 1.41% ( P＜0.001), 1.15% ( P＜0.001), and 1.73% ( P＜0.001), respectively. The results of the APC model showed that the average net drift value of leukemia incidence in all age groups was 1.57% (95% CI, 1.24%-1.89%), and the highest value of local drift was 3.20% (95% CI, 1.63%-4.78%) in the 80~ years old group. The incidence of leukemia increased with age. With the passage of time, the risk of leukemia incidence increased gradually compared with the rate ratio of leukemia incidence (risk ratio [ RR], 1.00) in 1992—1996, the RR of leukemia incidence increased from 0.70 during 1972—1976 to 1.57 during 2017—2021. The later the cohort was born, the greater the risk of leukemia incidence compared with the relative risk of leukemia incidence ( RR, 1.00) in 1952—1956 cohort, the RR of leukemia incidence increased from 0.24 in the 1892—1896 cohort to 2.73 in the 2017—2021 cohort. Conclusions:The incidence of the leukemia has presented a rising trend in the past fifty years. Leukemia incidence increased with age, and the period and cohort effects on the risk of incidence increase. Further research is needed to investigate the risk factors related to leukemia.

Objective To investigate the efficacy and safety of tyrosine kinase inhibitor(TKI)combined with immune checkpoint inhibitor as the second-line therapy for advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the clinical data of 63 patients with advanced HCC who were admitted to Department of Interventional Radiology,The First Affiliated Hospital of Soochow University,from January 2018 to December 2022,and all patients experienced progression/intolerance after transcatheter arterial chemoembolization combined with first-line TKI and were switched to second-line TKI with or without immune checkpoint inhibitor.The 32 patients receiving second-line TKI with immune checkpoint inhibitor were enrolled as combination group,and the 31 patients receiving second-line TKI alone were enrolled as single treatment group.Modified Response Evaluation Criteria in Solid Tumors was used to evaluate tumor response,and Common Terminology Criteria for Adverse Events 5.0 was used to evaluate adverse events.The Kaplan-Meier method was used to calculate median overall survival(mOS)and median progression-free survival(mPFS)for the two groups,and the two groups were compared in terms of objective response rate(ORR)and disease control rate(DCR).The chi-square test was used for comparison of baseline data and follow-up results between groups.Results The median follow-up time was 16.5(3.2-53.4)months for the 63 patients.The combination group had an mOS of 24.3(95%confidence interval[CI]:20.0-28.6)months and an mPFS of 9.8(95%CI:7.5-12.1)months,while the single treatment group had an mOS of 15.8(95%CI:11.4-20.1)months and an mPFS of 4.1(95%CI:3.2-4.9)months,and there were significant differences in mOS and mPFS between the two groups(P=0.029 and 0.038).The combination group had an ORR of 47%and a DCR of 84%,while the single treatment group had an ORR of 19%and a DCR of 65%;there was a significant difference in ORR between the two groups(P=0.021),but with no significant difference in DCR between the two groups(P=0.070).As for adverse events,4 patients(12.5%)in the combination group and 3(10.0%)in the single treatment group experienced grade Ⅲ-Ⅳ serious adverse events,with no fatal drug reactions in either group,and there was no significant difference in the incidence rate of adverse events between the two groups(P=0.783).Conclusion Compared with TKI alone,TKI combined with immune checkpoint inhibitor has a more significant therapeutic effect as the second-line therapy for advanced HCC,without increasing serious adverse reactions.

Background and aims:Liver cirrhosis is a complex disease that may result in increased morbidity and mortality following bariatric surgery(BS).This study aimed to explore the outcome of BS in patients with unexpected cirrhosis,focusing on postoperative complications and the progression of liver disease. Methods:A retrospective study of bariatric patients with cirrhosis from four centers in China between 2016 and 2023 was conducted,with follow-up for one year after BS.The primary outcome was the safety of BS in patients with unexpected cirrhosis,while the secondary outcome was the metabolic efficacy of BS in this group postoperatively. Results:A total of 47 patients met the study criteria,including 46 cases of Child-Pugh class A cirrhosis and 1 case of Child-Pugh B.Pathological examination confirmed nodular cirrhosis in 21 patients(44.68％),pseudolobule formation in 1 patient(2.13％),lipedema degeneration with inflammatory cell infiltration in 3 patients(6.38％),and chronic hepatitis in 1 patient(2.13％).The average percentage of total weight loss was 29.73±6.53％at one year postoperatively.During the 30-day postoperative period,the complication rate was 6.38％,which included portal vein thrombosis,gastrointestinal bleeding,and intra-abdominal infection.Moreover,no cases of liver decompensation or mortality were reported during the follow-up period.The remission rates of comorbidities among 41 patients one year after surgery were as fol-lows:dyslipidemia 100％,type 2 diabetes 82.61％,hypertension 84.62％,and obstructive sleep apnea syndrome 85.71％. Conclusions:BS can be safely performed in patients with unexpected cirrhosis in the compensated stage of liver disease,with low postoperative morbidity and no mortality observed during one-year follow-up.

Objective To elucidate the molecular genetic etiology of patients with disorders of sex development(DSD)using whole exome sequencing(WES),thereby enhancing our understanding of the underlying mechanisms of sexual development abnormalities.Methods Retrospective analysis was conducted on clinical data of 60 DSD patients diagnosed in the First People's Hospital of Yunnan Province between March 2008 and August 2021,with an additional family study for one proband.Genomic DNA was extracted from patients for WES analysis.Single nucleotide polymorphism(SNP)and insertions/deletion(InDel)tests were identified using SAMtools software in conjunction with established SNP and InDel databases.Copy number variations(CNVs)at the exon level were detected using ExomeDepth,while the potential pathogenicity of mutations was predicted with PolyPhen-2,Mutation taster and PyMol software,with Sanger sequencing employed for confirmation.Results The study included 22 patients with 46,XX DSD and 38 with 46,XY DSD.Among the 46,XX DSD patients,the SRY gene was detected in 14 patients.In the remaining 8 patients and a proband's families,single nucleotide site variations(SNVs)of NR5A1,PROKR2 and ANOS1 genes were identified in 2 patients,and CNVs in CYP21A2 gene were found in 4 patients.The pathogenicity of CYP21A2 EX1 Dup has been previously reported,while the remaining 3 CNVs were of uncertain significance,and no DSD-related mutations were detected in 2 patients.In the WES analysis of 46,XY DSD patients,10 pathogenic or likely pathogenic SNVs across 5 genes(SRY,AR,SRD5A2,CYP17A1,and NR5A1)were identified in 14 patients.Additionally,5 likely pathogenic CNVs involving the CYP21A2,AKR1C2,CBX2,and NR5A1 genes were detected in 5 patients,comprising 3 deletions and 2 duplications.Novel SNVs in NR5A1(c.722G>T,c.48C>G)and ANOS1 c.564A>T were identified,with no prior reports in relevant databases.The pathogenicity of CYP21A2 EX1 Dup is documented in related databases,while the remaining CNVs have not been previously reported.Conclusion The utilization of WES technology has enhanced the diagnostic potential for DSD,broadened the spectrum of known DSD-related gene mutations,and deepened our comprehension of DSD pathogenesis,offering valuable support for genetic counseling.

The biological clock(also known as the circadian rhythm)is the fundamental reliance for all organisms on Earth to adapt and survive in the Earth's rotation environment.Circadian rhythm is the most basic regulatory mechanism of life activities,and plays a key role in maintaining normal physiological and biochemical homeostasis,disease occurrence and treatment.Recent studies have shown that the biologi-cal clock plays an important role in the development of oral tissues and in the occurrence and treatment of oral diseases.Since there is cur-rently no guiding literature on the research methods of biological clock in stomatology,researchers mainly conduct research based on pub-lished references,which has led to controversy about the research methods of biological clock in stomatology,and there are many confusions about how to rationally apply the research methods of circadia rhythms.In view of this,this expert consensus summarizes the characteristics of the biological clock and analyzes the shortcomings of the current biological clock research in stomatology,and organizes relevant experts to summarize and recommend 10 principles as a reference for the rational implementation of the biological clock in stomatology research.