Objective: To explore the clinical features, treatment and prognosis of emphysematous pyelonephritis (EPN), so as to enhance the clinical awareness of this disease. Methods: A retrospective analysis was conducted on the clinical data of one EPN patient at The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, and a literature review was performed on articles published in the China National Knowledge Infrastructure and PubMed databases from Jan.1, 2015 to Dec.31, 2024. Results: The patient, a 62-year-old male with a 5 years' history of type 2 diabetes, was admitted due to left flank pain for 4 days, with a temperature of 39.4 ℃.Laboratory tests indicated significantly elevated inflammatory markers, decreased platelet count, and abnormal coagulation function.Preoperative blood and urine cultures showed positivity for Escherichia coli.Computed tomography (CT) revealed complete erosion of the left kidney, with gas in the left ureter and surrounding effusion, as well as multiple free gas in the abdominal cavity, bilateral ureteral stones, right renal lower calyx stones.After a multidisciplinary consultation, he underwent emergency phase Ⅰ left pyeloplasty and perirenal drainage with ureteral stenting.After discharge, the patient received maintenance hemodialysis once every two days in the outpatient clinic.One week after-discharge, the patient was readmitted due to polypnea.Following symptomatic management, vital signs stabilized.Approximately 2 months after the first-stage surgery, ureteroscopic stone extraction was successfully performed.One month after the stone extraction procedure, a follow-up CT showed normalization of the left kidney, renal pelvis and calyces, leading to phase Ⅱ laparoscopic left nephrectomy via the abdominal approach, with postoperative pathology indicating renal necrosis.Among 89 EPN patients reported in 35 articles, the median age was 58(24-92) years old；there were 59（66.3%） females and 30（33.7%） males；fever was the most common clinical symptom (60.7%)；73(82.0%) had diabetes, 12 (13.5%) had urinary tract obstruction；55 (61.8%) were infected with Escherichia coli, and 7 (7.9%) were infected with Klebsiella pneumoniae; 13 died due to ineffective treatmen. Conclusion: EPN presents acutely and progresses rapidly, often leading to misdiagnosis due to the lack of specific early symptoms.Abdominal CT is the preferred imaging modality for rapid diagnosis, and proactive interdisciplinary intervention can improve survival rates, reduce the need for nephrectomy, and enhance prognosis.

The influenza A virus (IAV), renowned for its high contagiousness and potential to catalyze global pandemics, poses significant challenges due to the emergence of drug-resistant strains. Given the critical role of RNA polymerase in IAV replication, it stands out as a promising target for anti-IAV therapies. In this study, we identified a novel C-3-substituted oleanolic acid benzyl amide derivative, A5, as a potent inhibitor of the PA_C-PB1_N polymerase subunit interaction, with an IC₅₀ value of 0.96 ± 0.21 μmol/L. A5 specifically targets the highly conserved PA_C domain and demonstrates remarkable efficacy against both laboratory-adapted and clinically isolated IAV strains, including multidrug-resistant strains, with EC₅₀ values ranging from 0.60 to 1.83 μmol/L. Notably, when combined with oseltamivir, A5 exhibits synergistic effects both in vitro and in vivo. In a murine model, dose-dependent administration of A5 leads to a significant reduction in IAV titers, resulting in a high survival rate among treated mice. Additionally, A5 treatment inhibits virus-induced Toll-like receptor 4 activation, attenuates cytokine responses, and protects against IAV-induced inflammatory responses in macrophages. In summary, A5 emerges as a novel inhibitor with high efficiency and broad-spectrum anti-influenza activity.

ObjectiveTo understand the usage of antibiotics in outpatients in a county of Zhejiang Province from 2015 to 2020， so as to provide a basis for further standardizing the clinical application of antibiotics in this region. MethodsOutpatient records and prescription records of 146 public medical institutions from 2015 to 2020 were extracted from the electronic medical record data sharing platform system of medical institutions in a county of Zhejiang Province. The utilization rates and the number of types of antibiotics used in outpatient patients were described. According to the drug anatomy， therapeutic and chemical classification system （ATC）， clinical application classification and dosage form， the use status of different types of antibiotics was observed. The annual percentage change （APC） was used to analyze the time trend of antibiotic use. Among the antibiotic prescriptions in each year， the proportions of prescriptions aimed for different use reasons and patients were compared to analyze the changes in the structures of antibiotic prescriptions. ResultsDuring 2015‒2020， a total of 2 861 438 prescriptions were issued in146 primary public medical institutions in this county， including 314 642 prescriptions for antibiotics， and the overall utilization rate of antibiotics was 11%. The utilization rate of antibiotics showed a decreased trend across the years （from 14.23% in 2015 to 7.59% in 2020，APC=-11.51%， 95%CI=-0.01%‒-21.7%， t=-12.05， P<0.001） and an obvious seasonal variation character （higher in winter and spring， lower in summer and autumn）. Cefoxitin sodium for injection was the most used antibiotic in 2015， and cefuroxime was the most used antibiotic from 2015 to 2020， respectively. The utilization rates of cephalosporins （APC=-11.06%， 95%CI=0‒-20.89%， t=-22.233， P<0.001）， quinolones （APC=-9.74%， 95%CI=0‒-18.53%， t=-7.652， P=0.002）， macrolides （APC=-17.52%， 95%CI=0‒-17.52%， t=-3.626， P=0.022） and lincoamides （APC=-49.01%， 95%CI=0‒-74%， t=-3.35， P=0.029） showed a decreasing trend across the years. There were differences in the distribution of drug use reasons （χ²=9 458.427， P<0.001）， as well as the age （χ²=5 421.709， P<0.001） and sex （χ²=245.322， P<0.001） of patients. During the observation period， 50.69% of antibiotic prescriptions were used to treat respiratory diseases， with the highest proportion of 57.67% in 2015 and the lowest proportion of 34.93% in 2020. 58.37% of patients were aged 50‒70 years， with a decreasing proportion of patients under 50 years （17.83% in 2015， 6.64% in 2020） and an increasing proportion of patients over 70 years （24.1% in 2015， 38.41% in 2020）. ConclusionThe utilization rate of antibiotics used in outpatients from primary public medical institutions in a county of Zhejiang Province shows a decreasing trend across the years， but higher than that of secondary and above hospitals in China， and also higher than that of primary medical institutions in economically-developed areas. The management and monitoring of the clinical use of antibiotics in the county should be actively strengthened.

Self-assembly refers to the spontaneous process where basic units such as molecules and nanostructured materials form a stable and compact structure. Peptides can self-assemble by non-covalent driving forces to form various morphologies such as nanofibers, nano layered structures, and micelles. Peptide self-assembly technology has become a hot research topic in recent years due to the advantages of definite amino acid sequences, easy synthesis and design of peptides. It has been shown that the self-assembly design of certain peptide drugs or the use of self-assembled peptide materials as carriers for drug delivery can solve the problems such as short half-life, poor water solubility and poor penetration due to physiological barrier. This review summarizes the formation mechanism of self-assembled peptides, self-assembly morphology, influencing factors, self-assembly design methods and major applications in biomedical field, providing a reference for the efficient use of peptides.
Pharmaceutical Preparations ; Peptides/chemistry* ; Amino Acid Sequence ; Nanostructures/chemistry* ; Drug Delivery Systems

Objective:To analyze the syndrome differentiation medication law of TCM in treating overactive bladder (OAB) based on data mining techniques.Methods:The articles about the treatment of OAB with TCM were collected from China National Knowledge Infrastructure (CNKI), Wanfang database, Chongqing VIP database and SinoMed. A prescription database for OAB was established. Methods such as frequency statistics, association rule analysis, clustering analysis, and factor analysis were used to analyze the medication law of the prescriptions.Results:The results showed that a total of 91 prescriptions were included, involving 134 kinds of Chinese materia medica. Five drugs were with a usage frequency of >30%. The top 4 categories with medication frequency were herbs for tonifying deficiency, herbs for inducing diuresis and draining dampness, herbs for relieving exterior syndrome and herbs for regulating qi. The properties of the included herbs were characterized by mild and warm, and the tastes were mainly sweet, pungent and bitter. The majority of meridian tropism was kidney meridian, supplemented by spleen, liver and lung meridians. The association rule analysis showed eight high-relevance medicine pairs, and four new candidate prescriptions were summarized after the clustering analysis, and six common factors were extracted by factor analysis.Conclusions:The location of the lesion of overactive bladder is mainly about the kidney, related to the spleen, liver and lung. And the pathogenesis is based on the kidney deficiency, which also due to the adverse qi transformation in triple energizer. Clinical medication is mainly about the herbs for tonifying deficiency and the herbs for inducing diuresis and draining dampness; at the same time those herbs for regulating qi and relieving exterior syndrome should be paid attention to, which are able to smooth and regulate the qi of the whole body.

Objective To observe the impacts of Xingnao Kaiqiao acupuncture(AC)method on synaptic plasticity and intestinal flora in stroke rats.Methods The middle cerebral artery occlusion method was applied to establish a rat model of ischemic stroke,and the rats with Zea Longa score of 1-3 were randomly grouped into model(M)group and AC group,and rats without middle cerebral artery occlusion were regarded as the sham(S)group,with 15 animals per group.After modeling,groups S and M were not intervened,and group AC was intervened with AC,once a day,for 7 consecutive days.The Zea Longa method was applied to assess neurological function;transmission electron microscopy(TEM)and Golgi staining were applied to visualize synaptic structures in the ischemic penumbra(IP);Western blot was applied to detect the protein expression of BDNF,SYN and GAP-43 in the IP cortex tissue;ELISA was applied to detect the content of IL-1β,TNF-α,IL-17 in the IP cortex tissue;16S rDNA amplification and sequencing method was applied to analyze the structure of rat intestinal flora.Results Compared with the S group,the M group had irregular synaptic morphology,blurred boundaries,thinned postsynaptic zona densities,higher neurological function scores,protein levels of BDNF,SYN,GAP-43 and content of IL-1β,TNF-α,IL-17(P<0.05),and lower density of spines(P<0.05).Compared with the M group,AC intervention could improve the synaptic morphology,reduce the neurological function score and content of IL-1β,TNF-α,IL-17(P<0.05),and increase the density of dendritic spines,BDNF,SYN,and GAP-43 protein levels(P<0.05).The intestinal flora analysis showed that compared with the S group,the M group had a reduced diversity and number of bacterial flora,at the phylum level,the M group had a lower relative abundance of Bacteroidetes,and higher F/B ratio(P<0.05);at the genus level,the group M had a higher relative abundances of Bacteroides and Rikenbacteria(P<0.05),and lower relative abundances of Lactobacillus and Lachnospiraceae_UCG-006(P<0.05).Compared with the M group,AC intervention could increase the diversity and quantity of the flora,increase the relative abundance of Bacteroidetes and reduce the F/B ratio at the phylum level(P<0.05),increase the relative abundances of Faecalibacterium and Lactobacillus and reduce the relative abundances of Riken,Escherichia-Shigella,etc.at the genus level(P<0.05).Conclusion Xingnao Kaiqiao acupuncture can restore the relative abundance of beneficial bacteria,reduce the relative abundance of harmful bacteria,attenuate brain inflammation,improve synaptic plasticity,and reduce neurological damage in stroke rats.

Objective:To investigate the application value of 3D printed model in hemostasis training for laparoscopic sleeve gastrectomy.Methods:The retrospective and descriptive study was conducted. Data were collected from six surgeons who participated in hemostasis training for laparoscopic sleeve gastrectomy using 3D printed model at Zhejiang Provincial People′s Hospital in July 2023. All participants were male, aged (33.5±9.9)years. A 3D printed model simulating bleeding during laparoscopic sleeve gastrectomy was created using hydrogel. Videos were recorded to document the surgeons′ hemostasis techniques and outcomes during laparoscopic sleeve gastrectomy. Two external expert reviewers blindly assessed the training videos using the objective structured assess-ment of technical skills (OSATS) scoring system to evaluate mesentery mobilization, vessel exposure, vessel clipping and bleeding after vessel clipping. Observation indicators: (1) face validity and content validity of the 3D printed model; (2) validity verification of the 3D printed model. Measurement data with normal distribution were represented as Mean± SD. Comparison between groups was conducted using the t test. Results:(1) Face validity and content validity of the 3D printed model. The surgeons′ scores for overall impression, fidelity, texture, appearance, workspace and tactile similarity of the 3D printed model were 4.5±0.6, 4.0±0.6, 3.7±0.5, 4.2±0.8, 3.8±0.8 and 4.2±0.4, respectively. The surgeons′ scores for similarity to real scenarios, operation convenience, learning curve shortening and operation skills improving, patient risk reduction, trainee′s interest enhancing, confidence increasing and recommendation for promotion were 4.0±0.6, 4.2±0.8, 4.3±0.8, 4.3±0.5, 4.3±0.5, 4.0±0.6 and 4.8±0.4, respectively. (2) Validity verification of the 3D printed model. The OSATS scores and operation time to treat bleeding during laparoscopic sleeve gastrectomy for expert surgeons were 18.7±0.6 and (125±12)seconds, respectively, versus 13.7±1.5 and (212±51)seconds for junior doctors, showing significant differences between the two groups ( t=5.30, -2.89, P<0.05). Conclusion:The 3D printed model effectively simulates bleeding scenarios during laparoscopic sleeve gastrectomy and distinguishes between different technical levels of expertise.

Objective To evaluate the analgesic effect of tetrodotoxin (TTX) in four types of acute pain models and provide experimental support for its rational application. Methods Mice or rats were intramuscularly pretreated with morphine (1 mg/kg) or TTX (0, 0.5, 1, 2, 4 and 8 μg/kg) 40 min before acetic acid writhing test, formalin stimulation test, hot plate test or tail flick test. Pain response or pain threshold were recorded, and inhibition rate was calculated during the tests. The arachidonic acid of serum was determined by Elisa. Results Significant analgesic effects were observed with morphine in all four acute pain models. TTX dose-dependently reduced the number of writhing induced by acetic acid and inhibited the pain response induced by formalin during phase I and phase II, with the highest inhibition rate of more than 80.00% in two pain models. TTX showed analgesic effect in tail flick test and hot plate test, with the highest inhibition rate of 25.00% and 19.79%, respectively. Both acetic acid and formalin increased arachidonic acid in animal serum, but TTX had no significant inhibitory effect on the releasing of arachidonic acid. Conclusion TTX showed significant analgesic effect in the chemical stimulation pain models induced by acetic acid and formalin, but limited analgesic effect was observed on the physical stimulation pain model induced by heat (hot plate and hot water). TTX may produce analgesic effect by blocking the inflammatory mediators mediating pain response.

Objective:To evaluate the laparoscopic sleeve gastrectomy combined with hiatal hernia repair surgery for weight loss and antireflux.Methods:This study included 21 obese patients with gastroesophageal reflux who underwent laparoscopic sleeve gastrectomy at the Weight Loss Metabolism Center of the Department of Hepatobiliary and Pancreatic Surgery of Zhejiang Provincial People's Hospital from Dec 2019 to Dec 2020. Patients were divided into simple bariatric surgery group (9 cases) and simultaneous combined surgery group (12 cases).Results:In the combined surgery group, 1 case had postoperative gastric leakage. The postoperative body weight, waist circumference, and BMI indexes of the two groups showed a downward trend ( F=5.154, P=0.013; F=14.319, P<0.001; F=6.725, P=0.004). There was a statistically significant difference in the excess weight loss in both the two groups at 6 months after the operation compared to 1 month after the operation ( t=8.927, P<0.001; t=8.926, P<0.001). There was no statistically significant difference in postoperative lower esophageal sphincter resting pressure and Gerd symptom score in the bariatric surgery group compared with preoperative ( t=-0.891, P=0.507; t=0.629, P=0.298). The postoperative Gerd symptom score of the patients in the combined surgery group was significantly lower than that before the operation, and the resting pressure of the lower esophageal sphincter was significantly higher than that before the operation, ( t=-10.539, P<0.001; t=5.066, P=0.038). Conclusion:Combined surgery have the same weight loss effect as in simple bariatric surgery in obese patients with gastroesophageal reflux, in addition to stronger anti-reflux effect.