Objective To analyze the characteristics of HIV-1 pretreatment drug resistance(PDR)and molecular transmission networks in Yubei District,Chongqing,providing evidence for targeted interventions.Methods Using a cross-sectional design,plasma samples were collected from HIV/AIDS patients receiving antiretroviral therapy(ART)in Yubei District from January 2022 to December 2023.Pol gene fragments were extracted and amplified for HIV-1 genotyping and drug resistance analysis.Molecular transmission networks were constructed based on genetic distance calculations.Results Among 478 HIV-1 pol sequences,eight geno-types were identified:with CRF07_BC(60.4%,289/478),CRF08_BC(15.5%,74/478),CRF01_AE(11.7%,56/478),and CRF85_BC(5.9%,28/478).The overall PDR rate was 6.3%(30/478),with resistance to nucleoside reverse transcriptase inhibitors(NRTIs)and non-nucleoside reverse transcriptase inhibitors(NNRTIs)at 1.7%(8/478)and 5.2%(25/478),respectively.No protease inhibitor(PI)resistance was de-tected.The molecular network included 177 cases(37.0%network entry rate),forming 53 clusters with 198 connections.Cluster sizes ranged from 2 to 17 nodes,and 75.3%(149/198)of connections were associated with five subdistricts/towns:Shuanglonghu Street,Huixing Street,Luoqi Town,Gulu Town,and Baoshenghu Street.Conclusion HIV-1 genotypes in Yubei District exhibit diversity and complexity,with moderate PDR prevalence.Regional clustering of transmission networks suggests the need for enhanced molecular surveil-lance and targeted interventions based on analytical findings.

Objective To investigate the mechanism of action of Guizhi Fuling pill in treating chro-nic prostatitis(CP)using network pharmacology and molecular docking techniques.Methods Compo-nents of Guizhi Fuling pill were collected from the Traditional Chinese Medicines Systems Pharmacolo-gy Platform(TCMSP),and target information was obtained from the SwissTarget database.Targets for chronic prostatitis were screened from the GeneCards,OMIM,CTD,and DisGeNET disease data-bases.A protein-protein interaction(PPI)network was established and analyzed.Gene ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway en-richment analysis were performed using the DAVID database.The Cytoscape software was employed to construct an association network linking the components of Guizhi Fuling Pill,their targets,and the targets of chronic prostatitis.Molecular docking was conducted using AutoDock Vina software to verify the binding stability between the components of Guizhi Fuling pill and their targets.Results After screening and deduplication in the TCMSP database,76 components of Guizhi Fuling Pill were iden-tified,and 655 component targets were retrieved from the SwissTarget database.There were 190 intersecting targets between GuizhiFuling Pill and chronic prostatitis.GO analysis indicated that Guizhi Fuling Pill may treat chronic prostatitis by participating in processes such asapoptosis,ATP binding,and signal transduction.KEGG analysis suggested that Guizhi Fuling Pill can regulate pathways such as phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)and mitogen-acti-vated protein kinase(MAPK)to intervene in chronic prostatitis.Molecular docking data demonstra-ted that the components of Guizhi Fuling pill exhibited stable conformations with their targets.Con-clusion The components of Guizhi Fuling Pill can stably bind to their targets and exert therapeutic effects on chronic prostatitis through multiple targets and pathways.

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens. Pharmacological screening identified romidepsin, YM155, apitolisib, NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models. Notably, romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway. A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models. Collectively, our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer, providing a feasible multidimensional platform for personalized medicine.

Objective The aim of this study is to analyze the prevalence of depression and anxiety symptoms and its relationship with the socio-economic position(SEP)among the elderly people in Dai rural areas of Jinggu County,Yunnan province.Methods A multi-stage stratified random sampling method was used to conduct a questionnaire survey among 1409 people aged 60 and over in Dai rural areas of Jinggu County,Yunnan Province.The individual SEP index was constructed using the principal component analysis.Results The prevalence of anxiety symptoms,depression symptoms,and mixed anxiety-depressive disorder symptoms was 4.8%,52.0%,and 4.2% among them,2.6%,49.4%,and 2.3% among the males,and 6.8%,54.5%,and 6.0% among the females respectively.Females had the higher prevalence of anxiety symptoms and mixed anxiety-depressive disorder symptoms than males(P<0.05).Elderly people with the higher level of education,annual per capita household income and SEP had the lower prevalence of anxiety symptoms and mixed anxiety-depressive disorder symptoms than their counterparts(both P<0.05).The prevalence of depression symptoms increased with age(P<0.01).The difference in the prevelence of depression symptoms among the elderly people with the different numbers of chronic conditions was statistically significant(P<0.01).The results of multivariate logistic regression analysis showed that the elderly people with lower SEP were more likely to suffer from the anxiety symptoms(OR=0.707,95% CI:0.566～0.883),depression symptoms(OR=0.492,95% CI:0.438～0.552),and mixed anxiety-depressive disorder symptoms(OR=0.602,95% CI:0.469～0.773).Conclusion There are significant socio-economic differences in the prevalence of anxiety symptoms and depression symptoms among the elderly people in Dai rural areas of Jinggu County,Yunnan province.Future mental health interventions should more focus on females,elderly people with advanced age,multiple chronic diseases and low SEP,so as to reduce the occurrence of depression symptoms and anxiety symptoms.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective To investigate the clinical effect of lithium disilicate glass ceramic cantilever resin-bonded fixed partial dentures(CRBFPDs)on single anterior tooth loss to provide a reference for the selection of restoration methods for single anterior tooth loss.Methods This study was reviewed and approved by the Ethics Committee,and informed consent was obtained from the patients.Forty-two patients with less than two anterior teeth with monomaxillary loss were included in this study.After 6 months,1 year,2 years,and 3 years,the aesthetic and functional effects of the restorations and the periodontal health status were evaluated,and the visual analog scale(VAS)was used to assess pa-tient satisfaction.Results During the observation period,the connector fractured in one case within 3 months.One case had debonded within 2 years.The aesthetic restoration effect of all lithium disilicate glass ceramic CRBFPDs was categorized as Class A.The periodontal health was good,there was no clinical absorption in the soft and hard tissues of the abutment or subbridge,periodontal status according to the evaluation indices was classified as class A,and the total satisfaction rate of the patient was 100%.Conclusion For single anterior tooth loss patients,lithium disilicate glass ceramic cantilever resin-bonded fixed partial denture can achieve the restoration effect of less invasion,better adhesion,aesthetics,comfort and good biocompatibility.With high patient satisfaction,it can be considered an ideal restoration method for replacing a single anterior tooth.

Objective To investigate the effect of erector spinae plane block on ultrasound-based hemodynamic parameters of the arteries of the four limbs and biochemical stress indicators in patients with thoracoscopic lobectomy. Methods A total of 120 patients with thoracoscopic lobectomy were randomly divided into study group and control group, with 60 cases in each group.The study group received erector spinae plane block during surgery, while the control group received conventional anesthesia measures.Pulmonary function indicators[peak expiratory flow rate (PEFR), forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁)], ultrasound-based hemodynamic parameters of the arteries of the four limbs (maximum systolic velocity, minimum diastolic velocity, mean velocity, arterial pulsatility index, and arterial resistance index), stress indicators[cortisol (Cor), norepinephrine (NE), angiotensin Ⅱ(Ang Ⅱ), and adrenocorticotropic hormone (ACTH)], and analgesic effect were compared between the two groups at different time points[before anesthesia induction (T₀), after extubation (T₁), and after drainage tube removal (T₂)]. Results FEV₁, FVC and PEFR in both groups were significantly lower at T₁ and T₂ than at T₀, and FEV₁, FVC and PEFR in the study group were significantly higher than those in the control group at T₁ and T₂(P < 0.05).The maximum systolic velocity and arterial resistance index in both groups were significantly lower at T₁ and T₂ than at T₀, while the minimum diastolic velocity, mean velocity and arterial pulsatility index were significantly higher at T₁ and T₂ than at T₀(P < 0.05).The maximum systolic velocity and arterial resistance index in the study group were significantly higher than those in the control group at T₁ and T₂, but the minimum diastolic velocity, mean velocity and arterial pulsatility index were significantly lower than those in the control group (P < 0.05).Cor, ACTH, Ang Ⅱ and NE in both groups were significantly higher at T₂ than at T₀, and Cor, ACTH, Ang Ⅱ and NE in the study group were significantly lower than those in the control group at T₂(P < 0.05).The Prince-Henry pain score, effective compression times, and actual compression times in the study group were significantly lower than those in the control group (P < 0.05). Conclusion Application of erector spinae plane block in thoracoscopic lobectomy causes smaller fluctuations in hemodynamic parameters of the arteries of four limbs and biochemical stress indicators, with a better anesthetic effect.

OBJECTIVES: Surgical robot system has broken the limitation of traditional surgery and shown excellent performance in surgery, and has been widely used in minimally invasive treatment in most areas of surgery. This study aims to verify the basic performance of the domestic surgical robot system and the safety and effectiveness of the integrated bipolar electrocoagulation and ultrasonic knife. METHODS: The basic performance of the domestic surgical robot system was evaluated by completing the square knot and surgical knot, vertical and horizontal perforation and right ring perforation and suture, as well as picking up beans. Compared with laparoscopy, the safety and effectiveness of the domestic surgical robot after integrated interconnection bipolar electrocoagulation and ultrasonic scalpel were evaluated by detecting the vascular closure performance and the degree of histopathological damage in animals. RESULTS: Compared with freehand knotting, domestic robot knotting speed and circumference were slightly worse, but better than laparoscopic knotting. There was no statistical significance in the tension difference of the surgical knots among the 3 methods (P>0.05), but the tension of the square knots made by the freehand and the domestic surgical robot was greater than that of the laparoscopy (P<0.05). The space required for both the left and right forceps heads of knots was smaller than that of laparoscopy (P<0.001), which successfully completed the 4 quadrant suture tasks, and the time of picking up beans was significantly less than that of laparoscopy (P<0.05). There was no significant difference in the temperature of the liver tissue after the bipolar electrocoagulation between the interconnected domestic surgical robot and the laparoscopy (P>0.05), and the acute thermal injury was observed under the light microscope. The temperature of the liver tissue treated by the domestic robotic ultrasound knife was higher than that of the laparoscopic ultrasound knife (P<0.05). CONCLUSIONS Domestic surgical robots are obviously superior to laparoscopy in suturing, knotting, and moving objects, and domestic surgical robots' interconnect bipolar electrocoagulation and ultrasonic knife have achieved success in animal experiments, and hemostasis is considered to be safe and effective.
Animals ; Robotics ; Laparoscopy/methods* ; Ultrasonography

OBJECTIVE To mine and analyze adverse drug event （ADE） signals after the marketing of pazopanib and provide references for clinically safe medication. METHODS OpenVigil 2.1 data platform was used to mine ADE signals from the US FDA adverse event reporting system （FAERS） database. ADE reports of pazopanib from October 2009 to June 2022 were collected， and ADE signals were analyzed using proportional reporting ratio （PRR） method and reporting odds ratio （ROR） method in the proportional imbalance method. RESULTS A total of 16 655 ADE reports were identified with pazopanib as the primary suspect drug. Through ROR and PRR analysis， 220 ADE signals involving 19 system organ classes were identified. The top 10 ADE signals by frequency were recorded in the drug instruction. Additionally， 88 new ADE signals were discovered， mainly related to the gastrointestinal system， various investigations， and the renal and urinary system. Decreased basophil count， nail bed hemorrhage， tumor rupture， and vaginal fistula were both new ADE signals and the top 10 ADE signals by strength. CONCLUSIONS The occurrence of common ADEs （diarrhea， hair color changes， hypertension， etc.） during the use of pazopanib after marketing is generally consistent with its drug instruction； the number of reported cases for new suspected risk signals （decreased basophil count， nail bed hemorrhage， tumor rupture， and vaginal fistula， etc.） is limited， and continuous monitoring is required.