Objective To observe the effect of pirfenidone on myocardial fibrosis in rats and inves-tigate its underlying mechanism.Methods Twenty-four SD rats were randomly divided into sham-operation group,model group,low-and high-dose pirfenidone groups,with 6 rats in each group.Rat model of myocardial fibrosis was established by injecting isoprenaline into the tail vein,while normal saline was given to the sham operation group.Pirfenidone of 150 and 300 mg/(kg·d)were infused gastrically to the rats of low-and high-dose pirfenidone groups after modeling.Mas-son staining was used to observe the severity of myocardial fibrosis,immunohistochemical assay was employed to detect the expression of Collagen-1,NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome,cysteinyl aspartate-specific protease-1(Caspase-1),and Western blotting was performed to detect the protein levels of Collogen-1 and atrial desmo-plakin D(gasdermin D,GSDMD).Results The model group showed obvious myocardial fibrosis,and elevated expression of Collogen-1,NLRP3,Caspase-1 and GSDMD when compared with the sham operation group(P＜0.05).Low-and high-dose pirfenidone treatment resulted in signifi-cantly reduced myocardial fibrosis and reduced expression of Collogen-1,NLRP3,Caspase-1 and GSDMD[(8.14±1.40)％,(6.56±0.75)％vs(22.15±2.57)％,P＜0.05;0.14±0.03 vs 0.33±0.05,0.42±0.13,P＜0.05;(10.34±1.40)％,(10.33±3.40)％vs(23.22±1.99)％,P＜0.05;(15.67±0.56)％,(17.33±0.78)％vs(22.87±1.92)％,P＜0.05;0.43±0.06,0.46±0.11 vs 0.65±0.03,P＜0.05].Conclusion Pirfenidone inhibits cardiomyocyte pyroptosis and attenuates myocar-dial fibrosis through the NLRP3/Caspase-1/GSDMD signaling axis.

The problem of drug resistance resulting from the long-term use of antimicrobials is a serious threat to global health,and the emergence of multidrug-resistant bacteria,in particular,has greatly limited therapeutic op-tions.Therefore,the development of new or alternative antimicrobial agents has become an urgent need.Antimi-crobial peptides(AMPs)have been regarded as good alternatives to antibacterial drugs due to their strong antibac-terial activity and unique mechanism of action.At present,some AMPs have completed preclinical studies on drug-resistant bacterial infections and entered the clinical trial stage,while their stability and targeting have been signifi-cantly improved through the optimisation of amino acid modification,nano-delivery system and other technolo-gies,which have gradually become a research hotspot in this field.Therefore,this paper discusses the importance of AMPs in bacterial drug resistance from the biological properties of AMPs,the mechanism of regulating bacteri-al drug resistance and the application of AMPs in the treatment of drug-resistant bacterial infections,with a view to providing a reference for the development of drugs against drug-resistant bacteria and clinical application.

Objective To explore the application effect of the dual-track nursing intervention model in the treatment process of children with lobar pneumonia.Methods A total of 186 children with lobar pneumonia were selected and randomly divided into control group and intervention group u-sing a double-blind method,with 93 cases in each group.The control group received conventional nursing intervention,while the intervention group implemented the dual-track nursing intervention model on the basis of conventional nursing.This model included the establishment and training of nurs-ing teams,personalized nursing plans,health education,and psychological support.Outside the hos-pital,it emphasized family support,regular follow-up guidance,and community-based collaborative ed-ucation.Both groups received a 3-week intervention.The improvement times of clinical symptoms,hos-pital stay,pulmonary function indicators before and after nursing,treatment compliance,and family members' satisfaction with nursing were compared and analyzed between the two groups.Results The fever resolution time[(3.89±0.96)d],cough relief time[(6.21±1.34)d],disappearance time of pulmonary rales[(7.89±1.56)d],and hospital stay duration[(9.45±1.89)d]in the intervention group were all shorter than those in the control group[(5.23±1.14),(7.45±1.67),(9.32±2.01),and(11.28±2.35)d,respectively],with statistically significant differences(P＜0.05).After nursing,the forced expiratory volume in one second(FEV1)[(1.51±0.22)L],forced vital capacity(FVC)[(1.75±0.25)L],and FEV1/FVC[(94.12±5.65)％]in the intervention group were all higher than those in the control group[(1.42±0.15)L,(1.66±0.22)L,and(85.73±8.41)％,respectively],with statistically significant differences(P＜0.05).The scores for exami-nation cooperation[(23.91±3.82)points],nursing cooperation[(24.19±4.03)points],standardized medication use[(24.26±3.94)points],and rational diet[(23.77±3.62)points]in the intervention group were higher than those in the control group[(20.16±3.53),(19.64±3.46),(23.05±3.68),and(18.85±3.41)points,respectively],with statistically significant differences(P＜0.05).The satisfaction rate of family members with nursing work in the intervention group was higher than that in the control group,with a statistically significant difference(98.92％versus 89.25％,P＜0.05).Conclusion The dual-track nursing intervention model has a signifi-cant application effect in children with lobar pneumonia.It can accelerate their recovery process,improve treatment compliance,promote pulmonary function improvement,and enhance family mem-bers' satisfaction.

Objective:To evaluate the efficacy of liposomal bupivacaine transversus abdominis plane block (TAPB) in combination with general anesthesia for elderly patients undergoing laparoscopic radical resection of colorectal cancer.Methods:In this randomized controlled trial, 70 American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ patients, aged 60-80 yr, with body mass index of 18-28 kg/m 2, scheduled for elective laparoscopic radical resection of colorectal cancer at the General Hospital of Ningxia Medical University from September 2023 to June 2024, were divided into 2 groups ( n=35 each) using a table of random numbers: liposomal bupivacaine group (LB group) and hydrochloride bupi-vacaine group (HB group). After anesthesia induction, bilateral TAPB was performed under ultrasound guidance. In LB group, 0.44% liposomal bupivacaine 30 ml was injected on each side. In HB group, 0.25% hydrochloride bupivacaine 30 ml was injected on each side. Total intravenous anesthesia was adopted for both groups. Patient-controlled intravenous analgesia (PCIA) with sufentanil was carried out after surgery. When the visual analogue scale (VAS) score at rest was ≥ 4 within 72 h after surgery, hydromorphone 0.5 mg was intravenously injected for rescue analgesia. The area under the curve of VAS scores at rest and during activity was calculated within 12-72 h after surgery. The first pressing time of patient-controlled analgesia (PCA) and the effective pressing numbers of PCA, requirement for rescue analgesia, and score for satisfaction with analgesia were recorded. The sleep quality on 1 day before surgery and 1, 2 and 3 days after surgery was evaluated using the Richards-Campbell Sleep Questionnaire. The occurrence of adverse reactions, duration of post-anesthesia care unit stay, time to first ambulation, time to first flatus, and time to first oral intake, and postoperative length of hospital stay were recorded within 72 h after surgery. Results:Compared with HB group, the area under the curve of VAS scores at rest and during activity was significantly reduced at 12-72 h after operation, the first pressing time of PCA was prolonged, and the effective pressing numbers of PCA was reduced, the rate of rescue analgesia was decreased, the score for satisfaction with analgesia was increased, the Richards-Campbell Sleep Questionnaire scores were increased on the 2nd and 3rd days after surgery, the duration of post-anesthesia care unit stay and postoperative length of hospital stay were shortened, and the incidence of postoperative nausea was decreased in LB group ( P<0.05). Conclusions:The efficacy of liposomal bupivacaine TAPB combined with general anesthesia is superior to that of hydrochloride bupivacaine TAPB combined with general anesthesia in elderly patients undergoing laparoscopic colorectal cancer radical resection.

Objective To observe the effect of pirfenidone on myocardial fibrosis in rats and inves-tigate its underlying mechanism.Methods Twenty-four SD rats were randomly divided into sham-operation group,model group,low-and high-dose pirfenidone groups,with 6 rats in each group.Rat model of myocardial fibrosis was established by injecting isoprenaline into the tail vein,while normal saline was given to the sham operation group.Pirfenidone of 150 and 300 mg/(kg·d)were infused gastrically to the rats of low-and high-dose pirfenidone groups after modeling.Mas-son staining was used to observe the severity of myocardial fibrosis,immunohistochemical assay was employed to detect the expression of Collagen-1,NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome,cysteinyl aspartate-specific protease-1(Caspase-1),and Western blotting was performed to detect the protein levels of Collogen-1 and atrial desmo-plakin D(gasdermin D,GSDMD).Results The model group showed obvious myocardial fibrosis,and elevated expression of Collogen-1,NLRP3,Caspase-1 and GSDMD when compared with the sham operation group(P＜0.05).Low-and high-dose pirfenidone treatment resulted in signifi-cantly reduced myocardial fibrosis and reduced expression of Collogen-1,NLRP3,Caspase-1 and GSDMD[(8.14±1.40)％,(6.56±0.75)％vs(22.15±2.57)％,P＜0.05;0.14±0.03 vs 0.33±0.05,0.42±0.13,P＜0.05;(10.34±1.40)％,(10.33±3.40)％vs(23.22±1.99)％,P＜0.05;(15.67±0.56)％,(17.33±0.78)％vs(22.87±1.92)％,P＜0.05;0.43±0.06,0.46±0.11 vs 0.65±0.03,P＜0.05].Conclusion Pirfenidone inhibits cardiomyocyte pyroptosis and attenuates myocar-dial fibrosis through the NLRP3/Caspase-1/GSDMD signaling axis.

Objective: To assess the impact of long-term antiretroviral therapy (ART) on human immunodeficiency virus (HIV) blood screening outcomes in post-exposure prophylaxis (PEP) failure cases through a longitudinal analysis of blood screening results over a 7-year period in a patient with HIV PEP failure. Methods: This study conducted 13 follow-up assessments for a high-risk individual who initiated ART shortly after exposure. The effectiveness of various blood screening methods, including immunological assays and nucleic acid testing (NAT), was analyzed. Blood samples were also tested with HIV RNA quantification testing, Western blot (WB) confirmation testing, chemiluminescence immunoassay (CLIA), and HIV rapid tests utilizing gold and selenium labels. A comprehensive analysis was performed to evaluate the changes in diagnostic capabilities of different testing methods for HIV biomarkers over an extended period following PEP failure. Results: The patient had two high-risk exposures: one day before ART initiation (BA1) and seven days preceding treatment (BA7). On the first day after the ART treatment (AA1), the HIV RNA concentration (viral load) was 9.07×10 copies/mL; by day five (AA5), the viral load decreased to 1.04×10 copies/mL. At day eleven (AA11), NAT and ELISA tests were both positive, with the WB result remaining indeterminate (gp160+). At day 48 (AA48), the S/CO value of the fourth generation ELISA reagent was 1.07, while results from a 6-sample pool and quantitative NAT were negative. However, a single sample NAT returned a positive result and WB tests indicated positivity for p17, p24, and gp160. At AA74, the quantitative NAT rebounded to 2.83×10 copies/mL, with positive NAT results for single and 6-sample pool NAT tests. The S/CO values of the imported and domestic ELISA reagents were 3.39 and 23.44, respectively. At AA201, 6-sample pool and quantitative NAT were negative again, while single sample NAT remained positive. From AA319 to AA2221, all NAT results have remained consistently below the minimum detection limit. At AA2221, S/CO values of the imported and domestic ELISA reagents were 3.47 and 23.44, respectively. Conclusion: The findings indicate that patients experiencing PEP failure after high-risk HIV exposure are at a higher risk of being missed by mixed-sample NAT pools and individual serological tests. Nonetheless, anti-HIV antibody levels are sustained at elevated values for an extended duration, underscoring antibody testing as an effective measure for blood screening.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To evaluate the efficacy of liposomal bupivacaine transversus abdominis plane block (TAPB) in combination with general anesthesia for elderly patients undergoing laparoscopic radical resection of colorectal cancer.Methods:In this randomized controlled trial, 70 American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ patients, aged 60-80 yr, with body mass index of 18-28 kg/m 2, scheduled for elective laparoscopic radical resection of colorectal cancer at the General Hospital of Ningxia Medical University from September 2023 to June 2024, were divided into 2 groups ( n=35 each) using a table of random numbers: liposomal bupivacaine group (LB group) and hydrochloride bupi-vacaine group (HB group). After anesthesia induction, bilateral TAPB was performed under ultrasound guidance. In LB group, 0.44% liposomal bupivacaine 30 ml was injected on each side. In HB group, 0.25% hydrochloride bupivacaine 30 ml was injected on each side. Total intravenous anesthesia was adopted for both groups. Patient-controlled intravenous analgesia (PCIA) with sufentanil was carried out after surgery. When the visual analogue scale (VAS) score at rest was ≥ 4 within 72 h after surgery, hydromorphone 0.5 mg was intravenously injected for rescue analgesia. The area under the curve of VAS scores at rest and during activity was calculated within 12-72 h after surgery. The first pressing time of patient-controlled analgesia (PCA) and the effective pressing numbers of PCA, requirement for rescue analgesia, and score for satisfaction with analgesia were recorded. The sleep quality on 1 day before surgery and 1, 2 and 3 days after surgery was evaluated using the Richards-Campbell Sleep Questionnaire. The occurrence of adverse reactions, duration of post-anesthesia care unit stay, time to first ambulation, time to first flatus, and time to first oral intake, and postoperative length of hospital stay were recorded within 72 h after surgery. Results:Compared with HB group, the area under the curve of VAS scores at rest and during activity was significantly reduced at 12-72 h after operation, the first pressing time of PCA was prolonged, and the effective pressing numbers of PCA was reduced, the rate of rescue analgesia was decreased, the score for satisfaction with analgesia was increased, the Richards-Campbell Sleep Questionnaire scores were increased on the 2nd and 3rd days after surgery, the duration of post-anesthesia care unit stay and postoperative length of hospital stay were shortened, and the incidence of postoperative nausea was decreased in LB group ( P<0.05). Conclusions:The efficacy of liposomal bupivacaine TAPB combined with general anesthesia is superior to that of hydrochloride bupivacaine TAPB combined with general anesthesia in elderly patients undergoing laparoscopic colorectal cancer radical resection.

Otitis media is an infection of the middle ear mainly caused by bacteria, and current treatments rely heavily on antibiotics. However, the emergence of antibiotic-resistant bacterial strains seriously affects their efficacy. In our study, we found that extracellular vesicles (EVs) derived from human natural killer cells (NKs) inhibit the proliferation of both standard and levofloxacin (LVX)-resistant strains of Staphylococcus aureus in a dose-dependent manner. Moreover, compared to LVX, EVs were more effective at reducing effusion and rescuing hearing thresholds in animal models. For LVX-sensitive strains, EVs were significantly more effective in terms of curative time but not curative rate. For LVX-resistant strains, EVs were significantly more effective in terms of both curative rate and curative time when applied alone or applied jointly with LVX. In summary, we found that NK EVs are highly effective in treating otitis media, providing an alternative approach for treating this common disease.
Killer Cells, Natural/metabolism* ; Exosomes/metabolism* ; Animals ; Humans ; Otitis Media/therapy* ; Staphylococcus aureus/drug effects* ; Disease Models, Animal ; Anti-Bacterial Agents/pharmacology* ; Levofloxacin/pharmacology*