Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

Objective:To systematically evaluate of the efficacy and safety of Tip-flexible suction ureteral access sheath and ordinary ureteral access sheath combined with flexible ureteroscopy to treat upper urinary tract stones.Methods:The databases CNKI, Wanfang, VIP, CBM, PubMed, Cochrane, Embase, Web of Science, MEDLINE and Google Scholar were searched from their inception to May 31, 2024 for related studies about Tip-flexible suction ureteral access sheath compared with ordinary ureteral sheath combined with flexible ureteroscopy to treat upper urinary tract stones. Literature screening and data extraction were performed independently by two researchers, the quality assessment of randomized controlled trials was assessed using the Cochrane risk of bias assessment scale, the Newcastle-Ottawa risk of bias assessment scale was used to assess the quality of retrospective studies, and finally Meta-analysis of data was conducted using Review Manager 5.3 software.Results:A total of 14 literatures involving 1947 patients with upper urinary tract stones (1017 in the Tip-flexible suction sheath group and 930 in the ordinary sheath group) were included. Meta-analysis showed that the stone free rate of the Tip-flexible suction sheath group was higher than that of the ordinary sheath group (immediate postoperative stone free rate 80.7% vs. 60.0%, OR = 3.04, 95% CI 2.30-4.03, P<0.05; 1 month after surgery stone free rate 94.4% vs. 79.4%, OR=4.39, 95% CI 3.12-6.19, P<0.05). The total complication rate of the Tip-flexible suction sheath group was lower than that of the ordinary sheath group (5.4% vs. 17.3%, OR=0.29, 95% CI 0.21~0.40, P<0.05). There was no significant difference in the decrease of hemoglobin level between the Tip-flexible suction sheath group and the ordinary sheath group at 1 day after surgery( MD=-0.30, 95% CI -2.61-2.02, P>0.05). The postoperative fever in the Tip-flexible suction sheath group was less than that in the ordinary sheath group (1.9% vs. 7.5%, OR=0.28, 95% CI 0.15-0.54, P<0.05). There was no significant difference in operation time between the Tip-flexible suction sheath group and the ordinary sheath group( MD=-4.93, 95% CI -11.48-1.62, P>0.05). The postoperative hospital stay in the Tip-flexible suction sheath group was shorter than that in the ordinary sheath group ( MD=-0.20, 95% CI -0.25--0.16, P <0.05). Conclusions:Compared with ordinary ureteral access sheath combined with flexible ureteroscope to treat upper urinary tract stones, Tip-flexible suction ureteral access sheath has a higher stone free rate, less postoperative fever, low total complication rate, shorter postoperative hospital stay, which is conducive to postoperative recovery and is safer and more effective.

Objective To examine the characteristics of the prevalence of congenital cleft lip with/without cleft palate in the ethnic Tibetan population and to provide support for the precise prevention and treatment of cleft lip with/without cleft palate in the Tibetan population.Methods The clinical data of Tibetan patients with cleft lip with/without cleft palate were collected and the clinical characteristics of the patients were analyzed.The patients'age ranged from 2 months to 51 years old.All the subjects were admitted to West China Stomatology Hospital,Sichuan University for the treatment of cleft lip with/without cleft palate between January 2016 and August 2023.Most of the subjects came from Sichuan Province and the Tibet Autonomous Region.Results A total of 1 051 patients were enrolled and children aged under 12 months(460 cases)accounted for the largest proportion.Among the subjects,383 had cleft lip only(36.44%),140 had cleft palate only(13.32%),and 528 had cleft lip with cleft palate(50.24%).The male-to-female ratios of patients with cleft lip only(0.99∶1),cleft palate only(0.54∶1),and cleft lip with cleft palate(1.67∶1)exhibited significant differences(P＜0.001).However,there was no significant difference in the male-to-female ratio in patients with cleft lip only or those with cleft lip with cleft palate when the subjects were divided into two groups according to whether they had unilateral or bilateral cleft lip with/without cleft palate.Most of the patients with bilateral cleft lip were female,while most of the patients with unilateral cleft lip and unilateral or bilateral cleft lip with cleft palate were male.The unilateral cleft lip with/without cleft palate was located predominantly on the left side.Syndromic cleft lip with/without cleft palate accounted for 3.43%of all the cases and the most common concomitant deformity was congenital heart disease.3.81%(40 cases)of the patients had a family history.In the patients with cleft lip only and those with cleft palate only,the proportion of patients having parents with corresponding phenotypes was higher than those of other phenotypes of cleft lip with/without cleft palate.Regarding the birth time distribution of the children with cleft lip with/without cleft palate,Spring saw the highest number of births of these children(311 cases,29.59%),while Winter saw the lowest number of births(231 cases,21.98%).Conclusion The cases of cleft lip with/without cleft palate in the ethnic Tibetan population are predominantly cleft lip and palate.Unilateral cleft lip only or cleft lip with palate is predominantly located on the left side.Lip disease phenotypes may be more heritable.

Objective Congenital cleft lip and palate is a common birth defect that seriously affects the lives of the afflicted children and their families.Previously,no research has been done to investigate the pathogenic characteristics of cleft lip and palate among ethnic minorities,for example,Tibetans,a minority ethnic group with a large population in China.This study aims to investigate the relationship between the occurrence of cleft lip and palate in Tibetans and Han Chinese in western China and the distribution of ABO blood groups and Rh blood groups to provide a theoretical basis for the precise prevention and treatment of cleft lip and palate.Methods In this study,statistics on Tibetan patients with cleft lip and palate,some Han patients with cleft lip and palate,and normal controls from western China were retrospectively collected.All participants were patients from West China Stomatology Hospital,Sichuan University.All patients with cleft lip and palate received treatment at the hospital between January 2016 and September 2023.The normal controls were outpatients or inpatients who did not have cleft lip and palate,and who received treatment at the hospital between January 2020 and October 2023.Information on the A,B,O,and AB blood groups and Rh positive and negative blood groups of the patients was collected and compared with that of the normal controls.The incidence of different phenotypes,including cleft lip alone,cleft palate alone,and cleft lip with cleft palate,in patients of blood groups A,B,O and AB were statistically analyzed by Chi-square test.Results A total of 1227 Tibetan patients with cleft lip and palate,4064 Han patients with cleft lip and palate,and 5360 normal controls were included in the study.Among all the patients with cleft lip and palate,1863 had cleft lip alone,1425 had cleft palate alone,and 2003 had cleft lip with cleft palate.The ABO blood group distribution of Tibetan patients with cleft lip and palate was characterized as O＞B＞A＞AB,with Rh positive blood group accounting for 100%,blood type O accounting for 41.15%,and blood type B accounting for 30.64%.The blood group distribution of the Han patients with cleft lip and palate was characterized as O＞A＞B＞AB,with Rh positive blood group accounting for 99.58%,blood type O accounting for 35.78%,and type A accounting for 30.54%.There was a significant difference in ABO blood groups between Tibetan and Han patients with cleft lip and palate(P＜0.005),but no significant difference in Rh blood groups.The ABO blood group distribution of the Tibetan patients with cleft lip and palate showed an obvious difference from that of the control group,while those of the Han patients with cleft lip and cleft palate and the control group did not show obvious differences.In the analysis of the subtypes,it was found that the blood group distribution in the subtypes of cleft lip alone,cleft palate alone,and cleft lip with cleft palate in the Tibetan population was O＞B＞A＞AB,while that in the Han Chinese population was O＞A＞B＞AB.There were differences in blood group distribution between Tibetans and Hans of the subtypes of cleft lip alone and cleft lip with cleft palate(P＜0.001),but there was no difference in blood group distribution in the population of cleft palate-only subtype.The proportion of blood type O in Tibetan patients with cleft lip and palate was significantly higher than that in the Han patients with cleft lip and palate.The blood group distribution of Tibetan patients with cleft lip and palate in Sichuan Province,Xizang Autonomous Region,and Qinghai Province was always O＞B＞A＞AB.Tibetan patients from Shiqu County and Baiyu County,Ganzi Tibetan Autonomous Prefecture and Chaya County,Qamdo City were predominantly of blood type B,and those from other regions were mainly of blood type O.Conclusion There were significant differences in the phenotype composition and ABO blood group distribution between the Tibetan and Han populations with cleft lip and palate in western China.The distribution of blood group O in the population with cleft lip and palate was higher than that in the normal population,and the same trend was observed for different phenotypes.However,differences between Tibetan and Han populations in ABO blood group distribution were only found in the phenotypes of cleft lip only and cleft lip with palate.Tibetans with blood type O are more prone to cleft lip deformity than Han people,and the effect in the phenotype of cleft lip with palate is less pronounced than that in the phenotype of cleft lip only.

Objective:To systematically evaluate of the efficacy and safety of Tip-flexible suction ureteral access sheath and ordinary ureteral access sheath combined with flexible ureteroscopy to treat upper urinary tract stones.Methods:The databases CNKI, Wanfang, VIP, CBM, PubMed, Cochrane, Embase, Web of Science, MEDLINE and Google Scholar were searched from their inception to May 31, 2024 for related studies about Tip-flexible suction ureteral access sheath compared with ordinary ureteral sheath combined with flexible ureteroscopy to treat upper urinary tract stones. Literature screening and data extraction were performed independently by two researchers, the quality assessment of randomized controlled trials was assessed using the Cochrane risk of bias assessment scale, the Newcastle-Ottawa risk of bias assessment scale was used to assess the quality of retrospective studies, and finally Meta-analysis of data was conducted using Review Manager 5.3 software.Results:A total of 14 literatures involving 1947 patients with upper urinary tract stones (1017 in the Tip-flexible suction sheath group and 930 in the ordinary sheath group) were included. Meta-analysis showed that the stone free rate of the Tip-flexible suction sheath group was higher than that of the ordinary sheath group (immediate postoperative stone free rate 80.7% vs. 60.0%, OR = 3.04, 95% CI 2.30-4.03, P<0.05; 1 month after surgery stone free rate 94.4% vs. 79.4%, OR=4.39, 95% CI 3.12-6.19, P<0.05). The total complication rate of the Tip-flexible suction sheath group was lower than that of the ordinary sheath group (5.4% vs. 17.3%, OR=0.29, 95% CI 0.21~0.40, P<0.05). There was no significant difference in the decrease of hemoglobin level between the Tip-flexible suction sheath group and the ordinary sheath group at 1 day after surgery( MD=-0.30, 95% CI -2.61-2.02, P>0.05). The postoperative fever in the Tip-flexible suction sheath group was less than that in the ordinary sheath group (1.9% vs. 7.5%, OR=0.28, 95% CI 0.15-0.54, P<0.05). There was no significant difference in operation time between the Tip-flexible suction sheath group and the ordinary sheath group( MD=-4.93, 95% CI -11.48-1.62, P>0.05). The postoperative hospital stay in the Tip-flexible suction sheath group was shorter than that in the ordinary sheath group ( MD=-0.20, 95% CI -0.25--0.16, P <0.05). Conclusions:Compared with ordinary ureteral access sheath combined with flexible ureteroscope to treat upper urinary tract stones, Tip-flexible suction ureteral access sheath has a higher stone free rate, less postoperative fever, low total complication rate, shorter postoperative hospital stay, which is conducive to postoperative recovery and is safer and more effective.

Objective: To analyze the clinical and genetic characteristics of 33 children with congenital lipoid adrenal hyperplasia (CLAH) caused by StAR gene defects. Methods: The clinical, biochemical, genetic, and follow-up (until December 2021) data of 33 children diagnosed with CLAH from 2006 to 2021 were retrospectively analyzed in Xinhua Hospital, Shanghai Jiao Tong University School of Medicine. Results: Of the 33 children with CLAH, 17 had a karyotype of 46, XX and 16 had a karyotype of 46, XY; 31 were female and 2 were male by social gender. Classic type and non-classic type were found in 30 and 3 children respectively. The age at diagnosis was 9.0 (3.0, 34.5) months. All the 30 cases with classic CLAH presented within the first year of life with skin hyperpigmentation (28 cases, 93%), vomiting and(or) diarrhea (19 cases, 63%), no increase in body weight (8 cases, 27%), elevated adrenocorticotropic hormone levels (21cases (70%)>275 pmol/L), decreased cortisol levels (47 (31,126) nmol/L), hyponatremia ((126±13) mmol/L), hyperkalemia ((5.7±1.1) mmol/L), and normal 17α-hydroxyprogesterone levels (30 cases, 100%). All these with classic CLAH exhibited female external genitalia. Three children with non-classic CLAH (including 2 cases of 46, XY and 1 case of 46, XX) also showed signs and symptoms of adrenal insufficiency, but 2 of them had an age of onset later than 1 year of age, including 1 case of 46, XY with male external genitalia and 1 case of 46, XX with female external genitalia. The other 46, XY patient with non-classic CLAH presented with adrenal insufficiency at 2 months of age, showing micropenis and hypospadias. In the 17 females with 46, XX, 4 older than 10 years of age showed spontaneous pubertal development. A total of 25 StAR gene pathogenic variants were identified in 33 patients, with p.Q258* (18/66, 27%), p.K236Tfs*47 (8/66, 12%) and p.Q77* (6/66, 9%) being the common variantion. Six novel variants were found, including c.358T>G, c.713_714del, c.125del, c.745-1G>A, c.179-2A>C, and exon 1 deletion. Conclusions: Patients with classic CLAH typically present with signs and symptoms of primary adrenal insufficiency in the early infancy period and female external genitalia. p.Q258*, p.K236Tfs*47 and p.Q77* are common variants in CLAH patients.
Adrenal Hyperplasia, Congenital/genetics* ; Adrenal Insufficiency ; Adrenocorticotropic Hormone ; Child, Preschool ; China ; Disorder of Sex Development, 46,XY ; Female ; Humans ; Hydrocortisone ; Hydroxyprogesterones ; Hyperplasia ; Infant ; Male ; Mutation ; Phosphoproteins/genetics* ; Retrospective Studies

Drug instructions,the statutory and technical documents recording effectiveness and safety information,are an important basis for guiding doctors,pharmacists,and patients to use drugs rationally,and their scientificity,standardization,and accuracy directly affect the medication safety of the public. The sections of adverse drug events,contraindications,precautions,warnings,and application for specific populations in drug instructions directly express safety information and measures for rational use of drugs. In the drug life cycle,marketing authorization holders( MAHs) need to update safety information in the instructions promptly to ensure the safety and effectiveness of clinical drug medication. At present,revising instructions is an important measure to control drug risks. In the drug life cycle,in order to standardize the revision of safety information in the instructions by MAHs and eliminate inexact terms such as " unclear",the Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions,a series of group standards,have been established under the guidance of Standardization Department,China Association of Chinese Medicine. Therefore,on the basis of the existing rules and regulations,the standardized technical procedures for revising instructions came into being to help clinical safe and rational medication of drugs,and implement the strategy of " Healthy China".
China ; Drug-Related Side Effects and Adverse Reactions ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Medicine, Chinese Traditional ; Nonprescription Drugs/adverse effects* ; Reference Standards

Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions,a series of group standards,were proposed by Professor ZHANG Bing from Research Center for Pharmacovigilance and Rational Use of Traditional Chinese Medicine,and underwent centralized management by Chinese Association of Chinese Medicine. They were officially released on July 23 and implemented on July 31,2021. The series of group standards consist of six sections,including general principles,adverse drug events,contraindications,precautions,application for special populations,and warnings. The section of general principles is comprised of holistic and programmatic expressions,which explain the general technical requirements for revising the marketed Chinese patent medicine instructions. The other five sections focus on information collection,screening,transformation,and illustration of specific items,forming a standardized revision technical process. This series of standards is the result of multiple rounds of research and the suggestions of more than 200 experts in different professional fields of " medicine-pharmacy-management-law-enterprise" have been gathered therein to reach a consensus. With the purposes of establishing standardized technical specifications for the revision of safety information in the marketed Chinese patent medicine instructions,guiding marketing authorization holders in revising the instructions,filling the gaps in the research of Chinese patent medicine instructions,promoting the deve-lopment of pharmaceutical care and academic research,and encouraging the rational and safe medication of Chinese patent medicine,the series of group standards is of great significance.
China ; Drug-Related Side Effects and Adverse Reactions ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Medicine, Chinese Traditional ; Nonprescription Drugs/adverse effects* ; Pharmacovigilance