[摘 要] 目的：探究虎杖苷通过Hippo/Yes相关蛋白（YAP）通路对人甲状腺癌8505C细胞的恶性生物学行为和顺铂（DDP）敏感性的影响。方法：体外培养8505C细胞，构建其DDP耐药细胞8505C/DDP，用CCK-8法检测0、25、50、75、100 nmol/L虎杖苷处理8505C和8505C/DDP细胞的增殖能力，以筛选虎杖苷的最佳作用浓度。将8505C细胞分为对照组、虎杖苷组、空载组、虎杖苷+YAP1过表达组；将8505C/DDP细胞分为对照组、DDP组、DDP+虎杖苷组、DDP+空载组、DDP+虎杖苷+YAP1过表达组。WB法检测各组8505C细胞中Hippo/YAP通路[YAP1、转录辅激活因子（TAZ）]和EMT（E-cadherin、N-cadherin）相关蛋白，8505C/DDP细胞中YAP1、TAZ、耐药相关蛋白[P-糖蛋白（P-gp）、多药耐药相关蛋白1（MRP1）]、凋亡相关蛋白（C-caspase-3、BAX、Bcl-2）的表达。Transwell小室和细胞划痕实验分别检测各组8505C、8505C/DDP细胞的侵袭、迁移能力。结果：虎杖苷可显著抑制8505C细胞的增殖活性（P<0.05）明显抑制8505C细胞中YAP1、TAZ蛋白、N-cadherin的表达（均P<0.05），提升E-caderin蛋白的表达（P<0.05），显著抑制8505C细胞的迁移和侵袭能力（均P<0.05），而8505C/DDP细胞对低浓度的虎杖苷具有耐药性（P<0.05）；过表达YAP1则可逆转虎杖苷对8505C细胞的影响。50 nmol/L虎杖苷明显抑制DDP处理的8505C/DDP细胞中YAP1、TAZ、P-gp、MRP1、Bcl-2的蛋白的表达（均P<0.05），提升cleaved caspase-3、BAX蛋白的表达（均P<0.05）并诱导其细胞凋亡（P<0.05），过表达YAP1则可逆转虎杖苷对8505C/DDP细胞的影响。结论：虎杖苷抑制Hippo/YAP信号通路，从而抑制8505C细胞的恶性生物学行为和增强其对的DDP敏感性。

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective To explore the effect of the diagnosis and endoscopic minimally invasive surgical treatment of non-cystic congenital pyriform sinus fistula(CPSF)in children.Methods Clinical data of 76 children with non-cystic CPSF were retrospectively analyzed from October 2017 to May 2022.Larygoscope,neck color ultrasound,esophageal barium meal,neck CT,and magnetic resonance imaging(MRI)were performed,and temperature-controlled ablation radio-frequency was performed under general anesthesia supported by laryngoscope guidance.Results The internal fistula in the pyriform fossa was seen under laryngoscope.Imaging examination shows that the fistula was connected to the pharynx.Postoperative complications:hoarseness in 3 cases and deciduous tooth loss in 3 cases.After a follow-up period of 12～40 months,there was 1 recurrence in 46 newly treated patients and 1 recurrence in 30 non newly treated patients.No recurrence was observed during the follow-up period after re-endoscopic radiofrequency plasma surgical electrodes plasma cauterization.Conclusion The symptoms of CPSF are non-specific.The discovery of the internal fistula under endoscopy is the gold standard for diagnosis.Ultrasound can be used as the initial screening method for diagnosis.Esophageal barium meal combined with CT examination can improve the diagnostic rate,and MRI can assist in diagnosis.The temperature-controlled ablation radio-frequency technique under supportive laryngoscope has the advantages of safety,minimally invasive,aesthetic,convenient,and repeatable operation,and can be used as the preferred method for the treatment of non-cystic CPSF in children.

Cytochrome P450 family 3 subfamily A(CYP3A),a major member of cytochrome P450(CYP)family,is one of the most important drug metabolizing enzymes in human.CYP3A includes 4 gene subtypes(CYP3A4,CYP3A5,CYP3A7,and CYP3A43),which is involved in 60%of drug metabolism in the human.It is not only widely distributed in normal tissues,but also significantly overexpressed in various tumor tissues.Recently,CYP3A has attracted great attention due to its involvement in the progression from chronic atrophic gastritis to gastric cancer,as well as the differential metabolism and resistance of chemotherapeutic drugs.Targeting CYP3A gene mediated-prodrug provides new ideas for the treatment of gastric cancer and is expected to become a new target for the diagnosis and treatment of gastric cancer.

Objective:To investigate the effect of interleukin (IL)-7 receptor α (IL-7Rα) antibody on the immune inflammation and renal injury in MRL/lpr lupus mice.Methods:Fifteen 3-4-week-old female MRL/lpr lupus mice (specific pathogen free) weighing 15-16 g were bred to 14-week-old and randomly divided into three groups: IL-7Rα antibody intervention group, isotype antibody (positive control) group and normal saline (negative control) group. The mice in the threc groups were intraperitoneally injected with IL-7Rα antibody, isotype antibody and normal saline respectively, with 100 μg three times a week for 4 weeks. At the age of 18-week old, the mice were sacrificed. Twenty-four-hour urinary protein was detected by Coomassie brilliant blue method, serum creatinine was detected by peroxidase method, and the expression of autoantibody (anti-double strand DNA antibody) and inflammatory factors such as tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and IL-21 was detected by enzyme-linked immunosorbent assay method. Renal pathology was detected by PAS and Sirius red staining, and CD3 and F4/80 in renal tissues were detected by immunohistochemistry method. Regulatory T cells, follicullar helper T cells (Tfh) and follicular regulatory T cells (Tfr) were detected by flow cytometry.Results:The 24-hour urinary protein, serum creatinine, serum anti-double strand DNA antibody and serum IFN-γ and IL-21 in the IL-7Rα antibody intervention group were significantly lower than those in the control groups (all P<0.01). However, there was no significant difference in serum TNF-α among the three groups ( F=0.39, P>0.05). The positive infiltrating cells of CD3 and F4/F80, and the ratio of type Ⅰ/Ⅲ collagen fibers ( F=41.11, P<0.01) of renal tissues in the IL-7Rα antibody intervention group were lower than those in the other two groups. Compared with the control groups, the ratio of regulatory T cells (CD4 +CD25 +Foxp3 +)/effector T cells (CD4 +CD25 +) in blood of IL-7Rα antibody intervention group increased ( F=21.64, P<0.01), while the ratio of Tfr (CD4 +CXCR5 +Foxp3 +)/Tfh (CD4 +CXCR5 +) in peripheral blood and spleen increased ( F=38.95, P<0.01; F=12.90, P<0.01). Conclusion:IL-7Rα antibody can reduce the production of autoantibodies such as anti-double strand DNA antibody and inflammatory factors by increasing the ratio of regulatory T cells and Tfr/Tfh, thus alleviating immune inflammation and renal damage in MRL/lpr lupus mice.

Osteoporotic thoracolumbar fracture in the elderly will seriously reduce their quality of life and life expectancy. For osteoporotic thoracolumbar fracture in the elderly, spinal reconstruction is necessary, which should comprehensively consider factors such as the physical condition, fracture type, clinical characteristics and osteoporosis degree. While there lacks relevant clinical norms or guidelines on selection of spinal reconstruction strategies. In order to standardize the concept of spinal reconstruction for osteoporotic thoracolumbar fracture in the elderly, based on the principles of scientificity, practicality and progressiveness, the authors formulated the Clinical guideline for spinal reconstruction of osteoporotic thoracolumbar fracture in elderly patients ( version 2022), in which suggestions based on evidence of evidence-based medicine were put forward upon 10 important issues related to the fracture classification, non-operative treatment strategies and surgical treatment strategies in spinal reconstruction after osteoporosis thoracolumbar fracture in the elderly, hoping to provide a reference for clinical treatment.

Background::Urticaria is a common skin disease characterized by episodes of wheals, and it has a negative effect on patients’ quality of life. Large-scale population-based epidemiological studies of urticaria are scarce in China. The aim of this survey was to determine the prevalence, clinical forms, and risk factors of urticaria in the Chinese population.Methods::This survey was conducted in 35 cities from 31 provinces, autonomous regions, and municipalities of China. Two to three communities in each city were selected in this investigation. Participants completed questionnaires and received dermatological examinations. We analyzed the prevalence, clinical forms, and risk factors of urticaria.Results::In total, 44,875 questionnaires were distributed and 41,041 valid questionnaires were collected (17,563 male and 23,478 female participants). The lifetime prevalence of urticaria was 7.30%, with 8.26% in female and 6.34% in male individuals ( P < 0.05). The point prevalence of urticaria was 0.75%, with 0.79% in female and 0.71% in male individuals ( P < 0.05). Concomitant angioedema was found in 6.16% of patients. Adults had a higher prevalence of urticaria than adolescents and children. Living in urban areas, exposure to pollutants, an anxious or depressed psychological status, a personal and family history of allergy, thyroid diseases, and Helicobacter pylori infection were associated with a higher prevalence of urticaria. Smoking was correlated with a reduced risk of urticaria. Conclusion::This study demonstrated that the lifetime prevalence of urticaria was 7.30% and the point prevalence was 0.75% in the Chinese population; women had a higher prevalence of urticaria than men. Various factors were correlated with urticaria.

Objective:To investigate the distribution and antimicrobial resistance profile of clinical bacteria isolated from blood culture in China.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2018 to December 2019. Antibiotic susceptibility tests were conducted with agar dilution or broth dilution methods recommended by US Clinical and Laboratory Standards Institute (CLSI). WHONET 5.6 was used to analyze data.Results:During the study period, 14 778 bacterial strains were collected from 50 hospitals, of which 4 117 (27.9%) were Gram-positive bacteria and 10 661(72.1%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (37.2%), Klebsiella pneumoniae (17.0%), Staphylococcus aureus (9.7%), coagulase-negative Staphylococci (8.7%), Pseudomonas aeruginosa (3.7%), Enterococcus faecium (3.4%), Acinetobacter baumannii(3.4%), Enterobacter cloacae (2.9%), Streptococci(2.8%) and Enterococcus faecalis (2.3%). The the prevalence of methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus were 27.4% (394/1 438) and 70.4% (905/1 285), respectively. No glycopeptide-resistant Staphylococcus was detected. More than 95% of S. aureus were sensitive to amikacin, rifampicin and SMZco. The resistance rate of E. faecium to vancomycin was 0.4% (2/504), and no vancomycin-resistant E. faecalis was detected. The ESBLs-producing rates in no carbapenem-resistance E. coli, carbapenem sensitive K. pneumoniae and Proteus were 50.4% (2 731/5 415), 24.6% (493/2001) and 35.2% (31/88), respectively. The prevalence of carbapenem-resistance in E. coli and K. pneumoniae were 1.5% (85/5 500), 20.6% (518/2 519), respectively. 8.3% (27/325) of carbapenem-resistance K. pneumoniae was resistant to ceftazidime/avibactam combination. The resistance rates of A. baumannii to polymyxin and tigecycline were 2.8% (14/501) and 3.4% (17/501) respectively, and that of P. aeruginosa to carbapenem were 18.9% (103/546). Conclusions:The surveillance results from 2018 to 2019 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while E. coli was the most common pathogen, and ESBLs-producing strains were in majority; the MRSA incidence is getting lower in China; carbapenem-resistant E. coli keeps at a low level, while carbapenem-resistant K. pneumoniae is on the rise obviously.

Objective:To investigate the bacterial composition and antimicrobial resistance profile of clinical isolates from bloodstream infections in China.Methods:The clinical bacterial strains isolated from blood culture were collected during January 2020 to December 2020 in member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS). Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical Laboratory Standards Institute(CLSI, USA). WHONET 5.6 was used to analyze data.Results:During the study period, 10 043 bacterial strains were collected from 54 hospitals, of which 2 664 (26.5%) were Gram-positive bacteria and 7 379 (73.5%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (38.6%), Klebsiella pneumoniae (18.4%), Staphylococcus aureus (9.9%), coagulase-negative Staphylococci (7.5%), Pseudomonas aeruginosa (3.9%), Enterococcus faecium (3.3%), Enterobacter cloacae (2.8%), Enterococcus faecalis (2.6%), Acinetobacter baumannii (2.4%) and Klebsiella spp (1.8%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus aureus were 27.6% and 74.4%, respectively. No glycopeptide- and daptomycin-resistant Staphylococci were detected. More than 95% of Staphylococcus aureus were sensitive to rifampicin and SMZco. No vancomycin-resistant Enterococci strains were detected. Extended spectrum β-lactamase (ESBL) producing Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were 48.4%, 23.6% and 36.1%, respectively. The prevalence rates of carbapenem-resistance in Escherichia coli and Klebsiella pneumoniae were 2.3% and 16.1%, respectively; 9.6% of carbapenem-resistant Klebsiella pneumoniae strains were resistant to ceftazidime/avibactam combination. The prevalence rate of carbapenem-resistance in Acinetobacter baumannii was 60.0%, while polymyxin and tigecycline showed good activity against Acinetobacter baumannii. The prevalence rate of carbapenem-resistance of Pseudomonas aeruginosa was 23.2%. Conclusions:The surveillance results in 2020 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while Escherichia coli was the most common pathogen, and ESBL-producing strains declined while carbapenem-resistant Klebsiella pneumoniae kept on high level. The proportion and the prevalence of carbapenem-resistant Pseudomonas aeruginosa were on the rise slowly. On the other side, the MRSA incidence got lower in China, while the overall prevalence of vancomycin-resistant Enterococci was low.

Objective:To investigate the distribution and antimicrobial resistance profile of clinical bacteria isolated from blood culture in China.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2016 to December 2017. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by US Clinical and Laboratory Standards Institute (CLSI) 2019. WHONET 5.6 was used to analyze data.Results:During the study period, 8 154 bacterial strains were collected from 33 hospitals, of which 2 325 (28.5%) were Gram-positive bacteria and 5 829 (71.5%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (34.7%), Klebsiella pneumoniae (15.8%), Staphylococcus aureus (11.3%), coagulase-negative Staphylococci (7.4%), Acinetobacter baumannii (4.6%), Pseudomonas aeruginosa (3.9%), Enterococcus faecium (3.8%), Streptococci (2.9%), Enterobacter cloacae (2.7%) and Enterococcus faecalis (2.5%). Methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus (MRCNS) accounted for 34.2%(315/922) and 77.7%(470/605), respectively. No vancomycin-resistant Staphylococcus was detected. The resistance rate of Enterococcus faecium to vancomycin was 0.6%(2/312), and no vancomycin-resistant Enterococcus faecium was detected. The ESBLs-producing rates in Escherichia coli, Klebsiella pneumoniae and Proteus were 55.7%(1 576/2 831), 29.9%(386/1 289) and 38.5%(15/39), respectively. The incidences of carbapenem-resistance in Escherichia coli, Klebsiella pneumoniae were 1.2%(33/2 831), 17.5%(226/1 289), respectively. The resistance rates of Acinetobacter baumannii to polymyxin and tigecycline were 14.8%(55/372) and 5.9%(22/372) respectively, and those of Pseudomonas aeruginosa to polymyxin and carbapenem were 1.3%(4/315) and 18.7%(59/315), respectively. Conclusion:The surveillance results from 2016 to 2017 showed that the main pathogens of blood stream infection in China were gram-negative bacteria, while Escherichia coli was the most common pathogen; the MRSA incidence was lower than other surveillance data in the same period in China; carbapenem-resistant Escherichia coli was at a low level during this surveillance, while carbapenem-resistant Klebsiella pneumoniae is on the rise.