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.

BACKGROUND: Pulmonary arterial hypertension (PAH) presents a significant health burden in Asia and remains a critical challenge. This study aims to delineate the PAH burden in Asia from 1990 to 2021. METHODS: Using the latest data from the Global Burden of Disease 2021, we evaluated and analyzed the distributions and patterns of PAH disease burden among various age groups, sexes, regions, and countries in Asia. Additionally, we examined the associations between PAH disease burden and key health system indicators, including the socio-demographic index (SDI) and the universal health coverage (UHC) index. RESULTS: In 2021, there were 25,989 new PAH cases, 103,382 existing cases, 13,909 PAH-associated deaths, and 385,755 DALYs attributed to PAH in Asia, which accounted for approximately 60% of global PAH cases. The age-standardized rates (ASRs) for prevalence and deaths were 2.05 (95% uncertainty interval [UI]: 1.66-2.52) per 100,000 population and 0.31 (95% UI: 0.23-0.38) per 100,000 population, respectively. From 1990 to 2021, Asia reported the lowest ASRs for PAH prevalence but the highest ASRs for deaths compared to other continents. While the ASRs for prevalence increased slightly, ASRs for mortality and DALYs decreased over time. This increasing burden of PAH was primarily driven by population growth and aging. The burden was especially pronounced among individuals aged ≥60 years and <9 years, who collectively accounted for the majority of deaths and DALYs. Moreover, higher SDI and UHC levels were linked to reduced incidence, but higher prevalence rates. CONCLUSIONS Although progress has been made in reducing PAH-related mortality and DALYs, the disease continues to impose a substantial burden in Asia, particularly among older adults and young children. Region-specific health policies should focus on improving early diagnosis, expanding access to treatment, and effectively addressing the growing PAH burden in the region.
Humans ; Global Burden of Disease ; Male ; Female ; Middle Aged ; Adult ; Asia/epidemiology* ; Prevalence ; Aged ; Pulmonary Arterial Hypertension/mortality* ; Adolescent ; Young Adult ; Child ; Child, Preschool ; Infant ; Hypertension, Pulmonary/epidemiology*

BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

This study aims to explore the mechanism of Huanglian Jiedu Decoction(HJD) in treating acute liver injury(ALI) in the mouse model of sepsis induced by lipopolysaccharide(LPS). Fifty-four male C57BL/6 mice were randomized into six groups: blank group, model group, low-, medium-, and high-dose group HJD, and dexamethasone group. The mouse model of sepsis was established by intraperitoneal injection of LPS after 7 days of gavage with HJD, and dexamethasone(0.2 mL) was injected intraperitoneally 1.5 h after modeling. The murine sepsis score(MSS) was recorded 12 h after modeling. The levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) in the liver tissue and tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in the serum were measured by ELISA. Hematoxylin-eosin(HE) staining was used to observe the pathological changes of the mouse liver. The content of light chain 3 of microtubule-associated protein 1(LC3) was detected by immunofluorescence, and that of sirtuin 1(SIRT1) was detected by immunohistochemistry. The mRNA levels of adenosine 5'-monophosphate-activated protein kinase(AMPK), LC3, and P62 were detected by RT-PCR. Western blot was employed to determine the protein levels of AMPK, p-AMPK, and SIRT1 in the liver tissue. The results showed that compared with model group, drug interventions decreased the MSS and liver injury indicators, lowered the levels of inflammatory cytokines, improved the liver tissue structure, upregulated the protein levels of of p-AMPK/AMPK and SIRT1 and the mRNA levels of AMPK and LC3, and downregulated the mRNA level of P62. To sum up, HJD can regulate the autophagy level and reduce inflammation to ameliorate acute liver injury in septic mice by activating the AMPK/SIRT1 autophagy pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Sirtuin 1/genetics* ; Male ; Mice ; Sepsis/metabolism* ; Mice, Inbred C57BL ; Autophagy/drug effects* ; AMP-Activated Protein Kinases/genetics* ; Liver/metabolism* ; Humans ; Signal Transduction/drug effects* ; Disease Models, Animal ; Tumor Necrosis Factor-alpha/genetics*

This study aims to comprehensively analyze the material basis of toad visceral oil(hereafter referred to as toad oil), and explore the pharmacological effect of toad oil on atopic dermatitis(AD). Ultra-high performance liquid chromatography-linear ion trap/orbitrap high-resolution mass spectrometry(UHPLC-LTQ-Orbitrap-MS) and gas chromatography-mass spectrometry(GC-MS) were employed to comprehensively identify the chemical components in toad oil. The animal model of AD was prepared by the hapten stimulation method. The modeled animals were respectively administrated with positive drug(0.1% hydrocortisone butyrate cream) and low-and high-doses(1%, 10%) of toad oil by gavage. The effect of toad oil on AD was evaluated with the AD score, ear swelling rate, spleen index, and pathological section results as indicators. A total of 99 components were identified by UHPLC-LTQ-Orbitrap-MS, including 14 bufadienolides, 7 fatty acids, 6 alkaloids, 10 ketones, 18 amides, and other compounds. After methylation of toad oil samples, a total of 20 compounds were identified by GC-MS. Compared with the model group, the low-and high-dose toad oil groups showed declined AD score, ear swelling rate, and spleen index, alleviated skin lesions, and reduced infiltrating mast cells. This study comprehensively analyzes the chemical composition and clarifies the material basis of toad oil. Meanwhile, this study proves that toad oil has a good therapeutic effect on AD and is a reserve resource of traditional Chinese medicine for external use in the treatment of AD.
Animals ; Dermatitis, Atopic/immunology* ; Disease Models, Animal ; Mice ; Male ; Gas Chromatography-Mass Spectrometry ; Humans ; Bufonidae ; Oils/administration & dosage* ; Chromatography, High Pressure Liquid ; Female ; Mice, Inbred BALB C