Objective To investigate the bone protective effects and underlying mechanisms of 900MHz radiofrequency radiation (RF) at different power densities (50, 150, and 450 μW/cm²) on an ovariectomy-induced osteoporosis mouse model. Methods Sixty 3-month-old C57BL/6 female mice were randomly divided into Sham group (sham exposure), OVX group (ovariectomy), OVX + LRF group (OVX + 50 μW/cm² RF), OVX + MRF group (OVX + 150 μW/cm² RF), OVX + HRF group (OVX + 450 μW/cm² RF), and OVX + E2 group (OVX + estradiol). Ovariectomized mice in the OVX + RF groups were exposed to RF of varying power densities for 4 hours daily. Ovariectomized mice in the OVX + E2 group received intramuscular injections of estradiol (0.04 mg/kg) every two days. After four weeks of intervention, Micro-CT, ELISA, RT-PCR, and immunohistochemistry were employed to analyze bone density, bone microstructure, serum bone metabolic markers, and the expression of related genes and proteins. Results Compared with the Sham group, the OVX group showed significantly decreased bone mineral density (BMD) and bone microstructure indicators such as BV, BV/TV, Tb.Th, and Tb.N, significantly increased bone microstructure indicator Tb.Sp, significantly decreased serum estradiol, significantly increased serum CTX-I, TRACP-5b, BGP, and OPG, significantly increased Nfatc1 and Runx2 mRNAs, and significantly increased OPG and RANKL. Compared with the OVX group, the OVX + MRF group and OVX + E2 group exhibited significantly increased BMD, BV, BV/TV, Tb.Th, and Tb.N, significantly decreased Tb.Sp, significantly increased serum OPG, Runx2 mRNA, and OPG, and significantly decreased serum CTX-I, TRACP-5b, Nfatc1 mRNA, and RANKL. Compared with the OVX group, the OVX + LRF group showed significantly increased cortical bone BMD and Tb.Th, the OVX + HRF group showed significantly increased cortical bone BMD and serum CTX-I and TRACP-5b, and the OVX + MRF group showed significantly increased serum BGP. Among the three power densities, the 150 μW/cm² RF showed the most significant effect. Conclusion The 150 μw/cm² 900 MHz RF can counteract the abnormalities in serum bone metabolism biomarkers, the decrease in BMD, the degeneration of bone microstructure, and the increase in bone resorption caused by ovariectomy in mice.

Sinisan is a classical prescription developed and applied by ancient medical experts and it is first recorded in the Treatise on Cold Damage written by ZHANG Zhongjing in the Eastern Han Dynasty. Later physicians have modified this prescription based on this original one. The bibliometrics methods were used to analyze the key information and research trend of Sinisan. According to the inclusion and exclusion criteria， 69 pieces of effective data were extracted， involving 67 ancient traditional Chinese medicine （TCM） books. The results showed that the name， composition， and decocting methods of Sinisan in later generations were inherited from the original record in the Treatise on Cold Damage. The original plants of medicinal materials used in Sinisan are basically clear. We recommend Bupleuri Radix as the dried root of Bupleurem scorzonerifolium， Paeoniae Radix Alba as the dried root of Paeonia lactiflora， Aurantii Fructus as the dried fruit of Citrus aurantium， Glycyrrhizae Radix et Rhizoma as the dry root and rhizome of Glycyrrhiza uralensis. Raw materials of Bupleuri Radix and Paeoniae Radix Alba， Aurantii Fructus stir-fried with bran， and stir-fried Glycyrrhizae Radix et Rhizoma should be used for preparation of Sinisan. According to measurement system in the Han Dynasty， a bag of Sinisan is composed of 1.25 g Bupleuri Radix， 1.25 g Paeoniae Radix Alba， 1.25 g Aurantii Fructus， and 1.25 g Glycyrrhizae Radix et Rhizoma. The materials should be grounded into coarse powder and taken with a proper amount of rice soup， 3 times a day. Sinisan has the effects of regulating qi movement and harmonizing the liver and spleen. It can be used for treating reversal cold in limbs and cold damage. In modern clinical practice， Sinisan can be used to treat chronic gastritis， irritable bowel syndrome， and dyspepsia. The above research results provide scientific reference for the future research and development of Sinisan.

Anti-CD20 monoclonal antibodies for the treatment of refractory nephrotic syndrome （RNS） in children. The first- generation rituximab is the most widely used in clinical practice； it shows definite efficacy in children with RNS， is recommended by guidelines， particularly for achieving a high remission rate in minimal change nephrosis， and can significantly reduce the cumulative use of glucocorticoids and immunosuppressants. The second-generation ofatumumab has potential as an alternative treatment for patients who are intolerant or resistant to rituximab， while the third-generation obinutuzumab has shown efficacy in complex cases such as rituximab resistance or post-transplant recurrence. However， there is still controversy regarding the optimization of rituximab treatment dosage and whether ofatumumab and obinutuzumab offer greater advantages than rituximab for the treatment of RNS in children. The most common adverse reaction induced by anti-CD20 monoclonal antibodies is infusion reactions， and long-term adverse events mainly include increased risks of sustained immunosuppression and infections. Rituximab has significant economic advantages for the treatment of RNS， but additional pharmacoeconomic research based on China’s healthcare environment is needed to evaluate the cost-effectiveness of ofatumumab and obinutuzumab in this population. Given that the current use of ofatumumab and obinutuzumab in this field is considered off-label use， clinical application should only proceed after a rigorous evaluation of the patient’s benefits and risks.

ObjectiveTo investigate the therapeutic effects of direct-acting antiviral agents (DAAs) combined regimens for hepatitis C virus (HCV) patients in Dehong Prefecture, Yunnan Province from 2022 to 2024, to analyze the characteristics of treatment failure patients, so as to provide a basis for discovering more effective treatment regimens in the future. MethodsData on HCV prevention and treatment in Dehong Prefecture was extracted from the China Disease Control and Prevention Information System. A total of 617 patients with HCV antiviral therapy were included, and the differences in variable characteristics among patients with different genotypes were analyzed using comparative statistical tests, including basic socio-demographic characteristics, biochemical testing indicators, and information on previous treatment and current treatment. In addition, the cure rate of HCV patients with diverse characteristics was compared, and the potential causes of treatment failure were explored simultaneously. ResultsThe cure rate of HCV was 96.8%, and statistically significant differences were observed in aspartate transaminase (AST) and alanine transaminase (ALT) levels, previous antiviral therapy history and initial treatment regimens among patients with different HCV genotypes (all P<0.05). Among the multi-type combination regimens, the cure rate of sofosbuvir (SOF)-containing regimens was 97.00%, that of velpatasvir (VEL)-containing regimens was 95.45%, and the cure rate of other treatment regimens, including the regimens with ribavirin (RIB) intervention, was 93.10%. Among the patients with treatment failure, 45.00% had genotype 3, 40.00% had abnormal abdominal ultrasound results, and all presented with elevated baseline AST test levels. ConclusionThe clinical treatment of HCV patients should consider the differences in genotype and biochemical test results. DAAs combined regimens for HCV have achieved a high cure rate in Dehong Prefecture and are applicable to HCV patients with diverse clinical characteristics, providing research evidence for wider application.

[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。

AIM: To investigate and analyze the current situation and needs of clinical research nurses in China, in order to provide scientific basis for constructing a training system for research nurses, promoting standardized training, and achieving standardized management for them. METHODS:A self-made questionnaire was used to investigate 102 research nurses from nearly 70 well-known clinical trial institutions in China. The contents of the questionnaire mainly included the general information, professional experience and work content of the research nurses, the sense of accomplishment and training needs of clinical trial work. RESULTS: Among the 102 research nurses surveyed, 92.15% have a bachelor's degree or above; 53.92% of those have intermediate or higher professional titles; 74.51% of them are part-time research nurse. Among professional experiences, 19.61% have more than 10 years of clinical trial experience; 47.06%, 40.20%, and 21.17% of surveyed research nurses were authorized to participate in clinical trial drug management, sample management, and quality control; 70.59% of research nurses have a high sense of achievement in their daily work. In terms of education and training needs, clinical trial related laws and regulations, standardized training for clinical trial protocol implementation, and good clinical practice (GCP) are the three most important aspects. CONCLUSION: Clinical research nurses in China have a relatively high level of education and nursing experience, but there is still a large gap in the amount of professional full-time clinical research nurses in China. Due to the rapid development of innovative drugs and devices, as well as the urgent need to improve the clinical research system, it is necessary to establish a training, assessment, and evaluation system for research nurses that is in line with China's national conditions in order to improve the professional level of research nurses, and improve the quantity and quality of clinical trial research on innovative drugs and devices in China.

Objective To evaluate the safety, effectiveness and feasibility of robotic-assisted kidney transplantation (RAKT). Methods Clinical data of 16 patients who underwent kidney transplantation were collected. Among them, 8 recipients received RAKT (RAKT group) and 8 cases underwent open kidney transplantation (OKT) with the contralateral kidney from the same donor (OKT group). Perioperative status and the recovery of renal allograft function were compared between two groups. Results All patients successfully completed the surgery. In the RAKT group, no patient was converted to open surgery. The operation time in the RAKT group was longer than that in the OKT group (P=0.015). No significant differences were observed in the serum creatinine levels before surgery and upon discharge between two groups (both P>0.05). In the OKT group, one recipient developed delayed graft function (DGF), and the remaining recipients did not experience perioperative complications. No significant difference was noted in the short-term recovery of renal allograft function between two groups (P>0.05). Conclusions Postoperative recovery of the recipients in the RAKT group is equivalent to that of their counterparts in the OKT group. RAKT is a safe and effective procedure for the team expertise in kidney transplantation.

Objective To analyze the diagnostic utility of combining susceptibility-weighted imaging(SWI)with arterial spin labeling(ASL)in patients with acute ischemic stroke(AIS).Methods Fifty AIS patients who admitted to Yongchuan Hospital,Chongqing Medical University from July 2020 to July 2021 were selected.Scans were performed using a 3.0T MRI scanner,including sequences such as FLAIR,DWI,3D-TOF-MRA,3D-ASL,and SWI.The perfusion status of the infarction core,the grading of draining veins around the infarction core,compensation by collateral circulation,the occurrence of hemorrhagic transformation,and prognosis were assessed.Results The grading of draining veins around the infarction core was significantly correlated with NIHSS scores(r=0.869,P＜0.05)and prognosis(r=0.825,P＜0.05).In addition,significant correlations were found between the perfusion status of the infarction core and the occurrence of hemorrhagic transformation(r=0.873,P＜0.05),compensation by collateral circulation and prognosis(r=0.883,P＜0.05).Conclusion The combination of SWI and ASL provides accurate indications of the hemodynamic conditions around the infarction core in AIS patients,and it can accurately assess the prognosis of AIS patients,contributing valuable information for clinical diagnosis and the selection of treatment strategies.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective To investigate the effect and mechanism of Feixin Decoction(Astragali Radix,Pericae Semen,Carthami Flos,Descurainiae Semen Lepidii Semen,Paeoniae Radix Rubra,etc.)on monocrotaline-induced pulmonary arterial hypertension(PAH)rats based on peroxisome proliferator-activated receptor-γ/nuclear factor-κB(PPAR-γ/NF-κB)signaling pathway.Methods Forty-eight male SD rats were randomly divided into normal group,model group,Sildenafil group(0.025 g·kg-1)and low-,medium-and high-dose of Feixin Decoction groups(11.7,23.4,46.8 g·kg-1).PAH rat model was established by single intraperitoneal injection of monocrotaline solution(60 mg·kg-1).After 1 hour of modeling,the rats were given intragastric administration once a day for 28 days.Hemodynamic and echocardiographic parameters including right ventricular systolic pressure(RVSP),mean pulmonary artery pressure(mPAP),right ventricular hypertrophy index(RVHI),pulmonary artery acceleration time(PAAT),pulmonary artery ejection time(PET),tricuspid annular plane systolic excursion(TAPSE),right ventricular internal diameter(RVIDd)and right ventricular anterior wall thickness(RVAWT)were measured in each group.The pathological changes of pulmonary arterioles were observed by HE staining.The expression level of α-smooth muscle actin(α-SMA)in rat pulmonary artery was detected by immunofluorescence.The levels of plasma interleukin-1β(IL-1β),IL-6 and tumor necrosis factor-α(TNF-α)were detected by ELISA.The expression levels of PPAR-γ/NF-κB signaling pathway-related proteins were detected by immunohistochemistry and Western Blot.Results Compared with the normal group,the RVSP,mPAP,RVHI,RVIDd and RVAWT of the model group were significantly increased(P＜0.01).PAAT,PAAT/PET and TAPSE were significantly decreased(P＜0.01).The wall of pulmonary arterioles was significantly thickened,and the percentage of wall thickness of pulmonary arterioles to vascular diameter and the percentage of vascular wall area to total cross-sectional area of pulmonary arterioles were significantly increased(P＜0.01).The positive expression rate of α-SMA protein in pulmonary artery was significantly increased(P＜0.01).The levels of plasma IL-1β,IL-6 and TNF-α were significantly increased(P＜0.01).The positive expression rate of PPAR-γ protein in lung tissue was significantly decreased(P＜0.01),and the positive expression rate of NF-κB protein was significantly increased(P＜0.01).The protein expressions of PPAR-γ and IκB-α in lung tissue were significantly down-regulated(P＜0.01).The protein expression ratio of p-NF-κB/NF-κB was significantly increased(P＜0.01).Compared with the model group,RVSP,mPAP,RVHI,RVIDd and RVAWT in each administration group were significantly decreased(P＜0.05,P＜0.01),while PAAT,PAAT/PET and TAPSE were significantly increased(P＜0.05,P＜0.01).The thickness of the vascular wall was significantly reduced,and the percentage of the wall thickness of the pulmonary arterioles to the diameter of the blood vessels and the percentage of the vascular wall area to the total cross-sectional area of the small arteries were significantly reduced(P＜0.05,P＜0.01).The positive expression rate of α-SMA protein in pulmonary artery was significantly decreased(P＜0.05,P＜0.01).The plasma levels of IL-1β,IL-6 and TNF-α were significantly decreased(P＜0.05,P＜0.01).The positive expression rate of PPAR-γ protein in lung tissue was significantly increased(P＜0.05,P＜0.01),and the positive expression rate of NF-κB protein was significantly decreased(P＜0.05,P＜0.01).The protein expression of PPAR-γ in lung tissue was significantly up-regulated(P＜0.05,P＜0.01),and the protein expression ratio of p-NF-κB/NF-κB was significantly decreased(P＜0.01).The protein expression of IκB-α in the lung tissue of rats in the high-dose group of Feixin Decoction was significantly up-regulated(P＜0.01).Conclusion Feixin Decoction can improve pulmonary artery pressure,right ventricular dysfunction and pulmonary vascular remodeling in PAH rats induced by monocrotaline.The mechanism may be related to the regulation of PPAR-γ/NF-κB signaling pathway to inhibit inflammatory response.