Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, we demonstrated that a GsMTx4-based 17-residue peptide, which we call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.

Immunotherapy has become a pivotal modality in clinical cancer treatment. However, its effectiveness is limited to a small subset of patients due to the low antigenicity, impaired innate response, and various adaptive immune resistance mechanisms of the tumor microenvironment (TME). Accumulating evidence reveals the critical roles of metal elements in shaping immunity against tumor progression and metastasis. The marriage of metalloimmunotherapy and nanotechnology further presents new opportunities to optimize the physicochemical and pharmacokinetic properties of metal ions in a precise spatiotemporal control manner. Several metallodrugs have demonstrated encouraging immunotherapeutic potential in preliminary studies and are currently undergoing clinical trials at different stages, yet challenges persist in scaling up production and addressing long-term biosafety concerns. This review delineates how metal materials modulate biological activities across diverse cell types to orchestrate antitumor immunity. Moreover, it summarizes recent progress in smart drug delivery-release systems integrating metal elements, either as cargo or vehicles, to enhance antitumor immune responses. Finally, the review introduces current clinical applications of nanomedicines in metalloimmunotherapy and discusses potential challenges that impede its widespread translation into clinical practice.

OBJECTIVE To evaluate the effects of different functional dyspepsia(FD)modeling methods and explore the thera-peutic effect and potential mechanism of Banxia Xiexin Decoction on FD.METHODS BALB/c mice were randomly divided into the blank group,iodoacetamide group,loperamide group,tail clamp group and vinegar group.After 1 week of intervention,the status of mice in each group was observed and their gastrointestinal motility,hormone levels and pathological changes were detected.A more i-deal FD modeling method was evaluated and determined.After modeling,different doses of Banxia Xiexin Decoction were given to in-tervene,and the changes in the gastrointestinal function of mice were observed.The expression of related proteins was studied by im-munohistochemistry,ELISA,Western Blot and other experimental methods.RESULTS Comparing the four modeling methods,it was found that the mice in the iodoacetamide group,loperamide group,and vinegar group showed weight loss compared to the blank group;the gastric emptying rate and small intestinal propulsion rate of mice in the iodoacetamide group and vinegar group decreased;changes in gastrointestinal hormones were found in the serum of mice in the tail clip group and vinegar group.Finally,the iodoacetamide meth-od was evaluated as the optimal FD modeling method.The administration results showed that Banxia Xiexin Decoction had no signifi-cant effect on the food intake and body weight of FD mice,while medium and high doses could improve the physical condition of FD mice,increase their gastric emptying rate and small intestine propulsion rate.The experimental results of immunohistochemistry,West-ern blotting,and ELISA confirmed that medium and high doses of Banxia Xiexin Decoction can significantly reduce the expression lev-els of TNF-α and IL-6 in the duodenum and serum of FD mice.CONCLUSION The iodoacetamide method is a better FD modeling method.Banxia Xiexin Decoction can improve the condition of FD mice,increase gastrointestinal motility,reduce the secretion of in-flammatory factor,thereby achieving the therapeutic effect of treating FD.

Objective:To investigate the effects of prophylactic flow restriction for brachiocephalic arteriovenous fistula on postoperative high-flow-related complications and patency rate in patients undergoing hemodialysis.Methods:Clinical data of patients with end-stage renal disease who underwent brachiocephalic arteriovenous fistula surgery for hemodialysis from February 2017 to May 2022 in Department of Nephrology,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine were retrospectively analyzed.During surgery,a 4-5 mm vascular suture loop was placed around the vein near the anastomosis as a flow restriction device in 43 patients(flow restriction group),while 42 patients did not receive the prophylactic flow restriction ring(control group).All patients were followed up for 1 to 5 years.The incidence rates of complications related to the hemodialysis access pathway,including distal ischemia syndrome,the formation of arteriovenous fistula aneurysms,thrombus,high-flow congestive heart failure,anastomosis of the vein within 1 cm of the anastomosis and cephalic arch stenosis,were compared between the two groups.The natural blood flow rate of the arteriovenous fistula,anastomosis size,the internal diameter of the vein near the anastomosis,primary patency rate,assisted primary patency rate,and secondary patency rate of the arteriovenous fistula,were also evaluated and compared between the two groups.Logistic regression analysis was used to investigate the factors affecting arteriovenous fistula patency rates,as well as the impact of the flow-restricting ring on postoperative factors.Results:Ultrasound measurements showed that the internal diameter of the vein at the site of the flow restriction ring in the flow restriction group was(3.7±0.6)mm at three months postoperatively,which was significantly smaller than the internal diameter of the narrowest part of the vein near the anastomosis in the control group[(4.1±1.0)mm,t=-2.416,P＜0.01].The postoperative anastomotic diameter and natural blood flow rate of the arteriovenous fistula in the flow restriction group were both significantly lower than those in the control group(both P＜0.05).Furthermore,the incidence rates of various complications in the flow restriction group were significantly lower than those in the control group(all P＜0.05).At 6,12,and 24 months postoperatively,the primary patency rate and assisted primary patency rate in the flow restriction group were significantly higher than those in the control group(both P＜0.05),while there was no significant difference in secondary patency rates between the two groups(P＞0.05).Binary logistic regression analysis indicated that age,diabetes,and natural blood flow rate of the arteriovenous fistula at 3 months postoperatively were independent risk factors for primary patency rate,while the flow restriction for brachiocephalic arteriovenous fistula was an independent protective factor for primary patency rate(P＜0.01 or P＜0.05).The application of flow restriction was negatively correlated with anastomotic diameter at 6 and 12 months,natural arteriovenous fistula blood flow,and the incidence rates of cephalic arch stenosis and aneurysm formation(all P＜0.05).Conclusion:The prophylactic constriction during brachiocephalic arteriovenous fistula surgery in patients undergoing hemodialysis can limit the size of the anastomosis and postoperative arteriovenous fistula blood flow,reducing complications such as cephalic arch stenosis and high-flow heart failure,and increasing primary patency rates of arteriovenous fistula and delay the reintervention of the fistula.

Objective: To investigate the epidemiological characteristics of influenza in Yuhang District, Hangzhou City from 2019 to 2023, so as to provide the reference for formulating influenza prevention and control measures. Methods: Influenza case data with current address in Yuhang District was collected through the Chinese Disease Prevention and Control Information System from 2019 to 2023. Influenza-like illness data was collected through the Hangzhou Epidemiological Investigation System. Time distribution, population distribution and pathogen detection of influenza-like illness were descriptively analyzed. Results: There were 118 319 influenza cases reported in Yuhang District from 2019 to 2023, with an average annual reported incidence rate of 2 316.80/105. The highest incidence rate was seen in 2023, with a reported incidence rate of 5 736.82/105. The peak incidence of influenza occurred from November to March of the following year, presenting the winter and spring epidemic. The cases were mainly distributed in the age groups of 7 to 14 years and 25 to 59 years, with 31 310 and 34 470 cases, accounting for 26.46% and 29.13%, respectively. Influenza cases were reported in all 12 towns (streets) in Yuhang District, with the top two being Wuchang Street and Liangzhu Street, with the average annual incidence rates of 17 346.08/105 and 14 945.80/105, respectively. From 2019 to 2023, there were 103 868 cases of influenza-like illness, and 1 482 throat swab samples were collected. Among them, 260 positive samples of influenza virus were detected, with a positive rate of 17.54%. The peak detection period for positive specimens was from November to March of the following year, with 222 influenza virus positive specimens detected. The influenza virus types included H1N1, H3N2, and Victoria B, accounting for 25.77%, 38.85% and 35.38%, respectively. Conclusions The peak of influenza outbreak in Yuhang District from 2019 to 2023 was in winter and spring, with children and adolescents being the main affected objectives. H1N1, H3N2 and Victoria B were alternately prevalent. Prevention and control measures such as influenza vaccination should be strengthened.

BACKGROUND:Cartilage defects are one of the major clinical challenges faced by orthopedic surgeons.Tissue engineering is an interdisciplinary approach that combines knowledge of engineering and cell biology to provide new ideas and approaches for the repair of cartilage defects. OBJECTIVE:To prepare a multi-component composite scaffold based on silk fibroin,gelatin,and chitosan to screen for a three-dimensional porous scaffold suitable for cartilage regeneration by evaluating its physicochemical properties and biological performance. METHODS:Four groups of porous scaffolds were prepared by vacuum freeze-drying method using silk fibroin,gelatin and chitosan as the base materials,namely chitosan/gelatin scaffold,silk fibroin/chitosan scaffold,silk fibroin/gelatin scaffold and silk fibroin/chitosan/gelatin scaffold.The suitable cartilage scaffolds were screened by scanning electron microscopy,X-ray diffractometer,porosity,water absorption and swelling rate,biodegradation rate and mechanical property detection.Then cartilage scaffolds were co-cultured with chondrocytes isolated and extracted from patients with osteoarthritis.The feasibility of porous scaffolds for cartilage injury repair was evaluated in vitro by cell adhesion rate assay,cell live-dead staining and cell activity proliferation assay. RESULTS AND CONCLUSION:(1)All four groups of scaffolds had porous structures.The comprehensive physical performance test results showed that the silk fibroin/gelatin/chitosan scaffold was more in line with the requirements of cartilage defect repair.This scaffold had a pore size of(176.00±53.68)μm,the porosity of(80.15±2.57)%,and water absorption and swelling rate of(3 712±358)%.After immersion in PBS containing lysozyme for 28 days in vitro,the biodegradation rate was(46.87±3.25)%,and it had good mechanical properties.(2)Chondrocytes could adhere well on the silk fibroin/gelatin/chitosan scaffold,and the cell adhesion rate increased with time.CCK8 and live/dead cell double staining results showed that silk fibroin/gelatin/chitosan scaffold had good biocompatibility and low cytotoxicity.(3)The results showed that silk fibroin/gelatin/chitosan scaffold had a highly hydrated 3D structure,suitable pore size and porosity,good biodegradability and superior mechanical properties,which can provide a good reticular skeleton and microenvironment for nutrient transport and chondrocyte attachment and proliferation.

This paper interprets the background, content overview and characteristics, clinical practice significance and disciplinary development of Nursing Standards for Clinical Operation Techniques in Critical Care Ultrasound (hereinafter referred to as the Standards) and puts forward reflections on the clinical application of the Standards, aiming to improve the critical care ultrasound techniques of clinical nursing staff, solve nursing challenges and make clinical nursing ultrasound techniques more scientific, standardized and homogenized.

Objective:To comprehensively search and summarize the evidence on critical ultrasound nursing practice training courses, with the aim of providing a basis for critical ultrasound nursing practice training.Methods:Taking the evidence-based clinical translation model of Fudan University Centre for Evidence-based Nursing as the theoretical framework, the evidence was retrieved, evaluated, and summarized to determine the evidence to be introduced into clinical practice, forming a training program for critical ultrasound nursing practice. From July to August 2023, 25 experts from 10 provinces/municipalities across the country were selected for two rounds of consultation to determine the practical training course system for critical ultrasound nursing.Results:A total of 14 articles were included, including one clinical decision, nine expert consensus, and four systematic reviews. In the two rounds of consultation, the positive coefficients of experts were 90.0% (27/30) and 92.6% (25/27), the authority coefficients of experts were 0.956 and 0.964, and the coefficients of Kendall's harmony were 0.303 and 0.350 ( P<0.01), respectively. The final practical training course system for critical ultrasound nursing included five first-level indicators, 25 second-level indicators, and 67 third-level indicators. Conclusions:Ultrasound examination is a complex skill. The construction method of the practical training course system for critical ultrasound nursing is scientific, reasonable, with strong practicality in content, which can provide reference for the development and evaluation of critical ultrasound nursing training courses.

Objective:To formulate the Nursing standards of clinical practice of critical care ultrasonography (referred to as the Standards), so as to provide recommendations for the application of ultrasound in intensive care nursing practice. Methods:Based on the experience of intensive care ultrasound nursing practice and literature research, combined with the consensus recommendations of intensive care ultrasound, the critical care ultrasound study group formed the first draft of the Standards. After expert interview, consensus discussion, two rounds of Delphi expert letter consultation and other methods, the content of the Standards was revised and improved, and the final draft of the Standards was formed. Results:The Standards included four parts, such as basic application of intensive care ultrasound, nursing evaluation standard of intensive care ultrasound guidance, nursing operation process guided by ultrasound and intensive care ultrasound training. Conclusions:The establishment of Standards is scientific and practical, which can provide guidance for nursing practice of clinical operation technology of critical care ultrasonography.

Objective:To identify the prevalence of multimorbidity among a Chinese population, analyze the risk of all-cause mortality with different multimorbidity patterns, and the impact of exercise on the risk of multimorbidity-related mortality and life lost.Methods:The study was based on 437 408 MJ Health Management Center participants. The classification decision tree was used to explore multimorbidity patterns composed of hypertension, diabetes, chronic kidney disease (CKD), and chronic obstructive pulmonary disease (COPD). The Cox proportional hazards model was used to calculate the all-cause mortality hazard ratio ( HR) for different multimorbidity patterns. Using Chiang's life table method, years of life lost were the difference in life expectancy for those with and without multimorbidity. Results:The prevalence rate of multimorbidity was 8.7%. Among multivariate patterns, the most common ones were "hypertension+CKD" (3.6%), "hypertension + diabetes + CKD" (1.1%) and "hypertension+diabetes+CKD+COPD" (0.1%). Compared with a healthy population, patterns with the highest mortality risk were "diabetes+CKD" ( HR=3.80, 95% CI: 3.45-4.18), "diabetes+CKD+COPD" ( HR=4.34, 95% CI: 3.43-5.49) and "hypertension+ diabetes+CKD+COPD" ( HR=4.75,95% CI:4.15-5.43). Through low-intensity and moderate to high-intensity exercise, the increased HRs were attenuatedcompared with the inactive population. People with single disease and multimorbidity shortened life by 4.6 and 13.4 years, while exercise attenuated 2.3 and 4.6 years of life lost, of which low-intensity and moderate to high-intensity exercise saved 1.5 and 3.7 years of life lost due to chronic diseases. Conclusions:Multimorbidity patterns based on "diabetes + CKD" cause the highest mortality risk, and physical activity in reducing mortality was significant for either with or without multimorbidity. Higher exercise intensity leads to a greater relative reduction of mortality risk.