Objective: To investigate the urban and rural differences in adverse outcomes of pulmonary tuberculosis (PTB) in patients with pulmonary tuberculosis-diabetes mellitus comorbidity (PTB-DM), so as to provide insights into improving the prevention and treatment measures for PTB-DM. Methods: Patients with PTB-DM who were admitted and discharged from 14 designated tuberculosis hospitals in Hangzhou City from 2018 to 2022 were selected. Basic information, and history of diagnosis and treatment were collected through hospital information systems. The adverse outcomes of PTB were defined as endpoints, and the proportions of adverse outcomes of PTB in urban and rural patients with PTB-DM were analyzed. Factors affecting the adverse outcomes of PTB were identified using a multivariable Cox proportional hazards regression model. Results: A total of 823 patients with PTB-DM were enrolled, including 354 (43.01%) urban and 469 (56.99%) rural patients. There were 112 (13.61%) patients with adverse outcomes of PTB. The proportions of adverse outcomes of PTB in urban and rural patients were 14.41% and 13.01%, respectively, with no statistically significant difference (P>0.05). Multivariable Cox proportional hazards regression analysis identified first diagnosed in county-level hospitals or above (HR=2.107, 95%CI: 1.181-3.758) and drug resistance (HR=3.303, 95%CI: 1.653-6.600) as the risk factors for adverse outcomes of PTB in urban patients with PTB-DM, while the treatment/observed management throughout the process (HR=0.470, 95%CI: 0.274-0.803) and fixed-dose combinations throughout the process (HR=0.331, 95%CI: 0.151-0.729) as the protective factors for adverse outcomes in rural patients with PTB-DM. Conclusions There are differences in influencing factors for adverse outcomes of PTB in urban and rural patients with PTB-DM. The adverse outcomes of PTB are associated with first diagnosed hospitals and drug resistance in urban patients, and are associated with the treatment/observed management and fixed-dose combinations throughout the process in rural patients.

BACKGROUND:Flap transplantation technique is a commonly used surgical procedure for the treatment of severe tissue defects,but postoperative flap necrosis is easily triggered by ischemia-reperfusion injury.Therefore,it is still an important research topic to improve the survival rate of transplanted flaps. OBJECTIVE:To review the pathogenesis and latest treatment progress of flap ischemia-reperfusion injury. METHODS:CNKI,WanFang Database and PubMed database were searched for relevant literature published from 2014 to 2024.The search terms used were"flap,ischemia-reperfusion injury,inflammatory response,oxidative stress,Ca2+overload,apoptosis,mesenchymal stem cells,platelet-rich plasma,signaling pathways,shock wave,pretreatment"in Chinese and English.After elimination of irrelevant literature,poor quality and obsolete literature,77 documents were finally included for review. RESULTS AND CONCLUSION:Flap ischemia/reperfusion injury may be related to pathological factors such as inflammatory response,oxidative stress response,Ca2+overload,and apoptosis,which can cause apoptosis of vascular endothelial cells,vascular damage and microcirculation disorders in the flap,and eventually lead to flap necrosis.Studies have found that mesenchymal stem cell transplantation,platelet-rich plasma,signaling pathway modulators,shock waves,and pretreatment can alleviate flap ischemia/reperfusion injuries from different aspects and to varying degrees,and reduce the necrosis rate and necrosis area of the grafted flap.Although there are many therapeutic methods for skin flap ischemia/reperfusion injury,a unified and effective therapeutic method has not yet been developed in the clinic,and the advantages and disadvantages of various therapeutic methods have not yet been compared.Most of the studies remain in the stage of animal experiments,rarely involving clinical observations.Therefore,a lot of research is required in the future to gradually move from animal experiments to the clinic in order to better serve the clinic.

Purpose: The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs). Materials and Methods: Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. Results: A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. Conclusion USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

Purpose: The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs). Materials and Methods: Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. Results: A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. Conclusion USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

Purpose: The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs). Materials and Methods: Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. Results: A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. Conclusion USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

ObjectiveTo investigate the protective effects and mechanisms of Bushen Zhuyun prescription （BSZY） on abortion rats with kidney deficiency-corpus luteum inhibition syndrome. MethodsAn abortion rat model with kidney deficiency-corpus luteum inhibition syndrome was constructed. Pregnant mice aged 8-10 weeks were randomly divided into a control group （Control）， a model group （Model）， low-dose BSZY （BSZY-L）， medium-dose BSZY （BSZY-M）， and high-dose BSZY （BSZY-H） groups （2.57， 5.14， 10.28 g·kg^-¹）， and a Zishen Yutai Pill （ZSYT） group （1.575 g·kg^-¹）. Hematoxylin-eosin （HE） staining was used to evaluate histopathological changes in ovarian and decidual tissue of rats in each group. Enzyme-linked immunosorbent assay （ELISA） was employed to measure levels of estrogen （E₂）， progesterone （P）， luteinizing hormone （LH）， prolactin （PRL）， and follicle-stimulating hormone （FSH） in serum. The candidate targets of BSZY were obtained from the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP） v2.0 databases， while disease targets for recurrent spontaneous abortion （RSA） were retrieved from GeneCards， DrugBank， Online Mendelian Inheritance in Man （OMIM）， and Therapeutic Target Database （TTD）. The intersection targets were identified by the Venny 2.1.0 platform. Pathway enrichment analysis was conducted based on the Metascape database to predict the potential mechanisms of BSZY. Additionally. Western blot was used to verify the effects of BSZY on the expression of estrogen receptor （ERα）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） and explore its protective mechanism on RSA rats. ResultsCompared with the control group， the model group exhibited significantly decreased uterine， ovarian， and embryonic wet weights （P<0.05， P<0.01）， with an abortion rate of 57.18%. The ovarian tissue showed varying degrees of reduction in primordial follicles， primary follicles， mature follicles， and corpora lutea， along with a large number of atretic follicles. The endometrium was thinner， and decidual tissue exhibited cellular edema and disorganized arrangement. In contrast， compared with the model group， the BSZY groups at all doses and the ZSYT group demonstrated increased uterine， ovarian， and embryonic wet weights， along with a reduced abortion rate. The number of primordial follicles， primary follicles， mature follicles， and corpora lutea increased， while atretic follicles decreased. The endometrium thickened， and decidual tissue displayed normal cellular structure with tight arrangement. Additionally， the model group showed significantly decreased levels of E₂， P， PRL， and FSH in serum （P<0.05， P<0.01）， along with a decreasing trend in LH level. In contrast， the BSZY groups at all doses exhibited significantly elevated levels of E₂， P， LH， PRL， and FSH in serum （P<0.05， P<0.01）. Network pharmacology predictions suggested that BSZY may exert protective effects against abortion in rats by activating the ERα/PI3K/Akt signaling pathway. Western blot results confirmed that BSZY significantly upregulated the expression of ERα， PI3K， and p-Akt proteins （P<0.05， P<0.01）. ConclusionBSZY has a protective effect on the abortion rats with kidney deficiency-corpus luteum inhibition syndrome， possibly by activating the ERα/PI3K/Akt signaling pathway to reduce ovarian apoptosis and regulate endocrine function， thereby lowering the abortion rate.

OBJECTIVE: To evaluate the clinical efficacy of ultrasound-guided needle knife release with different pathways for carpal tunnel syndrome (CTS). METHODS: Sixty CTS patients were randomly divided into a transverse group and a longitudinal group, with 30 patients in each group. The transverse group received the needle knife release under ultrasound above and below the median nerve along the short axis, while the longitudinal group received the needle knife release under ultrasound above the median nerve along the long axis. The patients' visual analogue scale (VAS) scores, Levine scores, and median nerve cross-section area (CSA) were assessed before treatment, on the 7th, 14th, and 30th days after treatment. The median nerve conduction indexes (motor conduction: latency [Lat], amplitude[Amp], motor conduction velocity [MCV]; sensory conduction: Lat, Amp, sensory conduction velocity [SCV]) were evaluated before treatment and on the 30th day after treatment. RESULTS: Compared before treatment, the VAS scores, Levine scores, and median nerve CSA were reduced in both groups on the 7th, 14th, and 30th days after treatment (P<0.05); the transverse group showed lower VAS and Levine scores and smaller CSA than those in the longitudinal group (P<0.05). On the 30th day after treatment, motor and sensory Lat was reduced (P<0.05), motor and sensory Amp was increased (P<0.05), and MCV and SCV were faster (P<0.05) in both groups. The transverse group had shorter Lat, higher Amp, and faster MCV and SCV than those in the longitudinal group (P<0.05). CONCLUSION The ultrasound-guided needle knife release with transverse and longitudinal pathways could both effectively alleviate pain and improve median nerve conduction in CTS patients, with the transverse pathway showing superior efficacy to longitudinal pathway.
Humans ; Carpal Tunnel Syndrome/therapy* ; Female ; Middle Aged ; Male ; Adult ; Median Nerve/physiopathology* ; Acupuncture Therapy/instrumentation* ; Treatment Outcome ; Neural Conduction ; Aged ; Ultrasonography

BACKGROUND: Approximately 40% of individuals with diabetes worldwide are at risk of developing diabetic kidney disease (DKD), which is not only the leading cause of kidney failure, but also significantly increases the risk of cardiovascular disease, causing significant societal health and financial burdens. This study aimed to describe the burden of DKD and explore its cross-country epidemiological status, predict development trends, and assess its risk factors and sociodemographic transitions. METHODS: Based on the Global Burden of Diseases (GBD) Study 2021, data on DKD due to type 1 diabetes (DKD-T1DM) and type 2 diabetes (DKD-T2DM) were analyzed by sex, age, year, and location. Numbers and age-standardized rates were used to compare the disease burden between DKD-T1DM and DKD-T2DM among locations. Decomposition analysis was used to assess the potential drivers. Locally weighted scatter plot smoothing and Frontier analysis were used to estimate sociodemographic transitions of DKD disability-adjusted life years (DALYs). RESULTS: The DALYs due to DKD increased markedly from 1990 to 2021, with a 74.0% (from 2,227,518 to 3,875,628) and 173.6% (from 4,122,919 to 11,278,935) increase for DKD-T1DM and DKD-T2DM, respectively. In 2030, the estimated DALYs for DKD-T1DM surpassed 4.4 million, with that of DKD-T2DM exceeding 14.6 million. Notably, middle-sociodemographic index (SDI) quintile was responsible for the most significant DALYs. Decomposition analysis revealed that population growth and aging were major drivers for the increased DKD DALYs in most regions. Interestingly, the most pronounced effect of positive DALYs change from 1990 to 2021 was presented in high-SDI quintile, while in low-SDI quintile, DALYs for DKD-T1DM and DKD-T2DM presented a decreasing trend over the past years. Frontiers analysis revealed that there was a negative association between SDI quintiles and age-standardized DALY rates (ASDRs) in DKD-T1DM and DKD-T2DM. Countries with middle-SDI shouldered disproportionately high DKD burden. Kidney dysfunction (nearly 100.0% for DKD-T1DM and DKD-T2DM), high fasting plasma glucose (70.8% for DKD-T1DM and 87.4% for DKD-T2DM), and non-optimal temperatures (low and high, 5.0% for DKD-T1DM and 5.1% for DKD-T2DM) were common risk factors for age-standardized DALYs in T1DM-DKD and T2DM-DKD. There were other specific risk factors for DKD-T2DM such as high body mass index (38.2%), high systolic blood pressure (10.2%), dietary risks (17.8%), low physical activity (6.2%), lead exposure (1.2%), and other environmental risks. CONCLUSIONS DKD markedly increased and varied significantly across regions, contributing to a substantial disease burden, especially in middle-SDI countries. The rise in DKD is primarily driven by population growth, aging, and key risk factors such as high fasting plasma glucose and kidney dysfunction, with projections suggesting continued escalation of the burden by 2030.
Humans ; Global Burden of Disease ; Risk Factors ; Male ; Female ; Disability-Adjusted Life Years ; Diabetic Nephropathies/epidemiology* ; Middle Aged ; Diabetes Mellitus, Type 2/epidemiology* ; Adult ; Diabetes Mellitus, Type 1/complications* ; Aged ; Adolescent ; Young Adult ; Quality-Adjusted Life Years

OBJECTIVE: To evaluate the effect of biodegradable magnesium alloy materials in promoting tendon-bone healing during rotator cuff tear repair and to investigate their potential underlying biological mechanisms. METHODS: Forty-eight 8-week-old Sprague Dawley rats were taken and randomly divided into groups A, B, and C. Rotator cuff tear models were created and repaired using magnesium alloy sutures in group A and Vicryl Plus 4-0 absorbable sutures in group B, while only subcutaneous incisions and sutures were performed in group C. Organ samples of groups A and B were taken for HE staining at 1 and 2 weeks after operation to evaluate the safety of magnesium alloy, and specimens from the supraspinatus tendon and proximal humerus were harvested at 2, 4, 8, and 12 weeks after operation. The specimens were observed macroscopically at 4 and 12 weeks after operation. Biomechanical tests were performed at 4, 8, and 12 weeks to test the ultimate load and stiffness of the healing sites in groups A and B. At 2, 4, and 12 weeks, the specimens were subjected to the following tests: Micro-CT to evaluate the formation of bone tunnels in groups A and B, HE staining and Masson staining to observe the regeneration of fibrocartilage at the tendon-bone interface after decalcification and sectioning, and Goldner trichrome staining to evaluate the calcification. Immunohistochemical staining was performed to detect the expressions of angiogenic factors, including vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2), as well as osteogenic factors at the tendon-bone interface. Additionally, immunofluorescence staining was used to examine the expressions of Arginase 1 and Integrin beta-2 to assess M1 and M2 macrophage polarization at the tendon-bone interface. The role of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway in tendon-bone healing was further analyzed using real-time fluorescence quantitative PCR. RESULTS: Analysis of visceral sections revealed that magnesium ions released during the degradation of magnesium alloys did not cause significant toxic effects on organs such as the heart, liver, spleen, lungs, and kidneys, indicating good biosafety. Histological analysis further demonstrated that fibrocartilage regeneration at the tendon-bone interface in group A occurred earlier, and the amount of fibrocartilage was significantly greater compared to group B, suggesting a positive effect of magnesium alloy material on tendon-bone interface repair. Additionally, Micro-CT analysis results revealed that bone tunnel formation occurred more rapidly in group A compared to group B, further supporting the beneficial effect of magnesium alloy on bone healing. Biomechanical testing showed that the ultimate load in group A was consistently higher than in group B, and the stiffness of group A was also greater than that of group B at 4 weeks, indicating stronger tissue-carrying capacity following tendon-bone interface repair and highlighting the potential of magnesium alloy in enhancing tendon-bone healing. Immunohistochemical staining results indicated that the expressions of VEGF and BMP-2 were significantly upregulated during the early stages of healing, suggesting that magnesium alloy effectively promoted angiogenesis and bone formation, thereby accelerating the tendon-bone healing process. Immunofluorescence staining further revealed that magnesium ions exerted significant anti-inflammatory effects by regulating macrophage polarization, promoting their shift toward the M2 phenotype. Real-time fluorescence quantitative PCR results demonstrated that magnesium ions could facilitate tendon-bone healing by modulating the PI3K/AKT signaling pathway. CONCLUSION Biodegradable magnesium alloy material accelerated fibrocartilage regeneration and calcification at the tendon-bone interface in rat rotator cuff tear repair by regulating the PI3K/AKT signaling pathway, thereby significantly enhancing tendon-bone healing.
Animals ; Rotator Cuff Injuries/metabolism* ; Rats, Sprague-Dawley ; Signal Transduction ; Wound Healing/drug effects* ; Alloys/pharmacology* ; Rats ; Proto-Oncogene Proteins c-akt/metabolism* ; Rotator Cuff/metabolism* ; Macrophages/metabolism* ; Magnesium/pharmacology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Male ; Biocompatible Materials ; Bone Morphogenetic Protein 2/metabolism*