OBJECTIVE To optimize the management model of drugs used in investigator-initiated trial （IIT）. METHODS With benchmarking analysis， based on the practical work experience of a tertiary specialized hospital in the field of IIT drug management in Shanghai， a thorough review was conducted， involving relevant laws， regulations， and academic literature to establish benchmark criteria and the evaluation standards. Starting from the initiation of IIT projects， a detailed comparative analysis of key processes was carried out， such as the receipt， storage， distribution， use and recycling of drugs for trial. The deficiencies in the current management of IIT drugs were reviewed in detail and a series of optimization suggestions were put forward. RESULTS It was found that the authorized records of drug management were missing， the training before project implementation was insufficient， and the records of receipt and acceptance of IIT drugs were incomplete. In light of these existing problems， improvement measures were put forward， including strengthening the training of drug administrators and stipulating that only drug administrators with pharmacist qualifications be eligible to inspect and accept drugs， etc. The related systems were improved， and 17 key points of quality control for the management of IIT drugs were developed. CONCLUSIONS A preliminary IIT drug management system for medical institutions has been established， which helps to improve the institutional X2023076） framework of medical institutions in this field.

ObjectiveTo explore the application value of modified Wendantang in the treatment of perimenopausal insomnia of phlegm heat type and observe its effects on neurotransmitters and body fat. MethodsA total of 162 patients with perimenopausal insomnia of phlegm heat type who were treated in the Traditional Chinese Medicine Department of The First Affiliated Hospital with Nanjing Medical University from May 2021 to November 2023 were randomly divided into two groups before inclusion in the study. The control group of 81 cases received conventional Western medicine treatment， while the observation group of 81 cases received combined treatment with modified Wendantang， and the treatment lasted for 4 weeks. ResultsInterleukin-β （IL-1β）， and tumor necrosis factor alpha （TNF-α） decreased， while serum dopamine （DA）， melatonin （MT） and serotonin （5-HT） increased in both groups after treatment compared with before treatment （P<0.05）. After treatment， compared with the control group， the observation group showed better improvement in the above indicators （P<0.05）. The levels of follicle stimulating hormone （FSH） and luteinizing hormone （LH） decreased， while the level of estradiol （E₂） increased in both groups after treatment compared with before treatment （P<0.05）. Compared with the control group， the observation group showed better improvement in the above sex hormone indicators after treatment （P<0.05）. The rapid eye movement sleep period （REM） and total sleep time （TST） were prolonged， and the sleep latency （SL） was shortened in the two groups after treatment compared with before treatment （P<0.05）. Compared with the control group， the observation group showed better improvement in sleep conditions after treatment （P<0.05）. The Pittsburgh sleep quality index （PSQI） and Traditional Chinese Medicine （TCM） total symptom score decreased significantly in both groups after treatment compared with before treatment （P<0.05）. Compared with the control group， the observation group showed better improvement in PSQI and TCM total symptom score after treatment （P<0.05）. The total effective rate of the observation group was 93.83% （76/81）， while that of the control group was 82.72% （67/81）， and the two had a statistically significant difference （χ²=9.135， P<0.05）. ConclusionFor patients with perimenopausal insomnia of phlegm heat type， the application of modified Wendantang can help regulate neurotransmitters and inflammatory factor levels， improve sex hormone levels， enhance sleep quality， and improve therapeutic effects.

Ultrasound-guided local ablation therapy for liver tumors has extensive clinical application because of its minimal invasiveness, proven effectiveness, low complication rates, and suitability for repeat treatments. Ultrasound-guided interventional therapy has continuously evolved in terms of the following: technological advancements, from the initial utilization of percutaneous ethanol injection to thermal ablation therapies exemplified by radiofrequency ablation and microwave ablation and presently advancing toward emerging techniques such as irreversible electroporation; imaging methods, from conventional ultrasound guidance to contrast-enhanced ultrasound and fusion imaging for precise guidance and assessment; supplementary strategies, from monotherapy to auxiliary method and synergistic therapy; and innovative treatment concepts, from early-stage small hepatocellular carcinoma to intermediate and even large liver cancers. The development of ultrasound-guided local ablation of liver cancers has progressed from an initial phase of rapid advancement to a mature stage characterized by further enhancements. This article provides a comprehensive overview of the status of technical equipment, treatment processes, efficacy, complications, and challenges encountered in ultrasound-guided local ablation for liver tumors, with the objective of offering valuable insights for interventional ultrasound physicians.

Objective To analyze the prevalence status of cardiometabolic risk factor (CMRF) and its aggregation among workers engaged in new forms of employment. Methods A total of 5 429 new employment workers (including couriers, online food delivery workers, and ride hailing drivers) who underwent health medical examinations at a tertiary hospital in Beijing City were selected as the research subjects using the judgment sampling method. Data on waist circumference, blood pressure, blood glucose, and blood lipid levels were collected to analyze their CMRF [central obesity, elevated blood pressure, elevated blood glucose, elevated triglycerides, and reduced high-density lipoprotein cholesterol (HDL-C)] and their aggregation (with ≥ 2 of the above 5 risk factors) status. Results The detection rates of central obesity, elevated blood pressure, elevated blood glucose, elevated triglycerides, and reduced HDL-C were 61.2%, 38.2%, 29.5%, 40.9% and 22.6%, respectively. The detection rates of CMRF aggregation was 57.8%. The result of multivariable logistic regression analysis showed that male, age ≥45 years, smoking, overweight, and obesity were risk factors for CMRF aggregation (all P<0.05). Conclusion The detection rate of CMRF and its aggregation among workers with new forms of employment in Beijing City is relatively high. Targeted prevention and control efforts should be strengthened for high-risk populations, especially males, workers aged ≥45 years, smokers, and those who are overweight or obese.

Objective To explore the efficiency improvement in segmenting neural network with the application of Transformer + U-Net artificial intelligence (AI) and modeling with the application of Python scripts in three-dimensional (3D) printing brachytherapy. Methods A Transformer + U-Net AI neural network model was constructed, and Adam optimizer was used to ensure rapid gradient descent. Computed tomography or magnetic resonance imaging data of patients were standardized and processed as self-made data sets. The training set was used to train AI and the optimal result weight parameters were saved. The test set was used to evaluate the AI ability. Python programming language was used to write an automated script to obtain the output segmentation image and convert it to the STL file for import. The source applicator and needle could be automatically modeled. The time of automatic segmentation and modeling and the time of manual segmentation and modeling were entered by two people, and the difference was verified by paired t-test. Results Dice similarity coefficient (DSC), mean intersection over union (MIOU), and Hausdorff distance (HD95) were used for evaluation. DSC was 0.9341, MIOU was 0.8762, and mean HD95 was 2.516. The mean time of manual segmentation was 1187 s, and the mean time of AI segmentation was 145 s (P < 0.01). The mean time of manual modeling was 321 s, and the mean time of modeling with Python automated scripts was 18 s (P < 0.01). Conclusion The application of Transformer + U-Net automatic segmentation and Python automated scripts can effectively improve work efficiency in the 3D printing brachytherapy for cervical cancer.

Objective: To investigate the epidemic situation of notifiable infectious diseases in Zhejiang Province in 2024, so as to summarize the epidemic characteristics. Methods: Data of notifiable infectious diseases cases in Zhejiang Province from January 1 to December 31, 2024 were collected from the Infectious Disease Surveillance System of Chinese Disease Prevention and Control Information System. The epidemiological characteristics were analyzed according to the classification and transmission routes using the descriptive epidemiological method. Results: A total of 32 types of notifiable infectious diseases with 1 858 695 cases and 392 deaths were reported in Zhejiang Province in 2024, with a reported incidence of 2 804.73/105 and a reported mortality of 0.591 5/100 000. A total of 238 infectious disease public health emergencies were reported, of which 218 (91.60%) occurred in schools and kindergartens. There were 22 types of class A and B notifiable infectious diseases reported, with incidence of 470.62/100 000 and mortality of 0.591 5/100 000. Totally 10 types of class C notifiable infectious diseases, with a reported incidence of 2 334.11/105, and no deaths were reported. Classified by transmission route, respiratory infectious diseases had the highest reported incidence of 2 423.87/100 000, among which influenza exhibited the highest reported incidence of 2 024.22/100 000. The reported incidence of intestinal infectious diseases was 312.94/105, among which the incidence of other infectious diarrhea and hand-foot-mouth disease (HFMD) were high, with reported incidences of 169.52/100 000 and 136.18/100 000, respectively. Blood-borne and sexually transmitted infectious diseases accounted for the largest number of reported deaths, among which AIDS had the highest mortality of 0.424 0/100 000. Natural and insect-borne infectious diseases exhibited a low reported incidence of 1.37/105. The reported incidence of dengue fever was 0.40/100 000, and 95.08% of the cases were imported. Conclusions The reported incidence of respiratory and intestinal infectious diseases and the reported mortality of AIDS were high in Zhejiang Province in 2024. It is recommended to strengthen the prevention and control of infectious diseases such as influenza, other infectious diarrhea, and HMFD in schools and kindergartens.

Objective To investigate the effect of nobiletin(Nb)on lipopolysaccharide(LPS)-induced inflammatory injury of mesangium cells(HBZY-1)by regulating AMP-activated protein kinase(AMPK)/NOD-like receptor protein 3(NLRP3)signaling pathway.Methods HBZY-1 cells were separated into 5 groups:normal control(NC)group,LPS group(100 ng·mL-1 LPS),and Nb group(100 ng·mL-1 LPS+40 μmol·L-1 Nb),Rapamycin(Rap,AMPK/NLRP3 signaling pathway inhibitor)group[100 ng·mL-1 LPS+0.5 μmol·L-1 Rap],and Nb+Rap group(100 ng·mL-1 LPS+40 μmol·L-1 Nb+0.5 μmol·L-1 Rap).MTT was applied to detect the cytotoxicity and proliferation of HBZY-1 cells.ELISA was applied to detect the contents of interleukin(IL)-1β,IL-6,tumor necrosis factor-α(TNF-α),catalase(CAT),superoxide dismutase(SOD),and glutathione(GSH)in HBZY-1 cells.Flow cytometry was used to detect cell apoptosis.Western Blot was applied to detect the protein levels of AMPK/NLRP3 signaling pathway.Results Compared with the NC group,the levels of CAT,SOD,GSH,cell OD value,and the level of AMPK protein in the LPS group were significantly reduced(P＜0.05).The apoptosis rate,contents of IL-1β,IL-6,TNF-α,and the level of NLRP3 protein were significantly increased(P＜0.05).Compared with the LPS group,the levels of CAT,SOD,GSH,OD value,and the level of AMPK protein in the Nb group were significantly increased(P＜0.05).The apoptosis rate,contents of IL-1β,IL-6,TNF-α,and the level of NLRP3 protein were significantly decreased(P＜0.05),while the above indicators in the Rap group showed an opposite trend to the Nb group(P＜0.05).Compared with the Nb group,the above indicators in the Nb+Rap group also showed an opposite trend to the Nb group(P＜0.05).Conclusion Nb may alleviate LPS-induced inflammatory injury to MC cells by up-regulating the AMPK/NLRP3 signaling pathway.But down-regulation of the AMPK/NLRP3 signaling pathway may eliminate the improvement effect of Nb on LPS-induced inflammatory injury in MC cells.

Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses. Orthodontic tooth movement (OTM) is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament (PDL) progenitor cells. However, whether and how force induces PDL progenitor cell pyroptosis, thereby influencing OTM and alveolar bone remodeling remains unknown. In this study, we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process. Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively. Using Caspase-1^-/- mice, we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1. Moreover, mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro, which influenced osteoclastogenesis. Mechanistically, transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells. Overall, this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli, indicating a promising approach to accelerate OTM by targeting Caspase-1.
Animals ; Humans ; Mice ; Rats ; Bone Remodeling/physiology* ; Caspase 1 ; Periodontal Ligament ; Pyroptosis ; Tooth Movement Techniques

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Objective:To investigate the effect of dexmedetomidine combined with chloroprocaine on epidural anesthesia for cesarean section.Methods:A total of 133 women who underwent epidural anesthesia for cesarean section at the Department of Anesthesiology, Jinhua People's Hospital between January 2020 and December 2022 were included in this prospective case-control study. These women were divided into a ropivacaine group ( n = 66) and a chloroprocaine group ( n = 67) using a random number table method. The ropivacaine group received epidural anesthesia with dexmedetomidine combined with ropivacaine, while the chloroprocaine group received epidural anesthesia with dexmedetomidine combined with chloroprocaine. The anesthesia effect (anesthesia onset time, anesthesia duration, peak effect time), changes in blood pressure (systolic blood pressure, diastolic blood pressure), adverse reactions (shivering, nausea and vomiting, urinary retention, skin itching, numbness of lower limbs), and satisfaction with muscle relaxation were observed in the two groups. Results:The anesthesia onset time, anesthesia duration, and peak effect time in the chloroprocaine group were (6.91 ± 1.54) minutes, (61.54 ± 5.31) minutes, and (11.79 ± 4.12) minutes, respectively, which were significantly shorter than those in the ropivacaine group [(9.65 ± 1.92) minutes, (83.57 ± 6.69) minutes, (18.32 ± 4.81) minutes, t = 9.08, 21.05, 8.41, all P < 0.001). The systolic and diastolic blood pressure increased in both groups after 10 minutes of anesthesia and at the end of the procedure; however, the increments observed in the chloroprocaine group were relatively smaller. There were significant differences in systolic and diastolic blood pressure, measured at 10 minutes of anesthesia and at the end of the procedure, between the two groups ( F = 7.36, P < 0.001; F = 5.12, P = 0.001). There were significant differences in systolic and diastolic blood pressure between different time points ( F = 10.03, P < 0.001; F = 6.72, P < 0.001). The group-by-time interaction effect on systolic and diastolic blood pressure was also highly significant ( F = 9.83, P < 0.001; F = 8.01, P < 0.001). The chloroprocaine group exhibited a significantly lower incidence of adverse reactions compared with the ropivacaine group [4.48% (3/67) vs. 15.15% (10/66), χ2 = 4.29, P < 0.05). Additionally, the chloroprocaine group had a significantly higher satisfaction rate with muscle relaxation compared with the ropivacaine group [94.03% (63/66) vs. 81.82% (54/66), Z = 5.73, P < 0.05]. Conclusion:The combination of dexmedetomidine and chloroprocaine offers remarkable benefits in epidural anesthesia for cesarean sections. This combined approach not only enhances epidural anesthesia but also stabilizes the blood pressure of puerperants, reduces adverse reactions, and provides exceptional muscle relaxation. It deserves consideration for clinical application.