Prostate cancer is the most prevalent malignant tumor among men, ranking first in incidence and second in mortality globally. Novel hormone therapies (NHT) targeting the androgen receptor (AR) pathway have become the standard of care for metastatic prostate cancer. This review offers a comprehensive overview of NHT, including abiraterone, enzalutamide, apalutamide, darolutamide, and rezvilutamide, which have demonstrated efficacy in delaying disease progression and improving patient survival and quality of life. Nevertheless, resistance to NHT remains a critical challenge. The mechanisms underlying resistance are complex, involving AR gene amplification, mutations, splice variants, increased intratumoral androgens, and AR-independent pathways such as the glucocorticoid receptor, neuroendocrine differentiation, DNA repair defects, autophagy, immune evasion, and activation of alternative signaling pathways. This review discusses these resistance mechanisms and examines strategies to counteract them, including sequential treatment with novel AR-targeted drugs, chemotherapy, poly ADP-ribose polymerase inhibitors, radionuclide therapy, bipolar androgen therapy, and approaches targeting specific resistance pathways. Future research should prioritize elucidating the molecular basis of NHT resistance, optimizing existing therapeutic strategies, and developing more effective combination regimens. Additionally, advanced sequencing technologies and resistance research models should be leveraged to identify novel therapeutic targets and improve drug delivery efficiencies. These advancements hold the potential to overcome NHT resistance and significantly enhance the management and prognosis of patients with advanced prostate cancer.

Guided by molecular networking, nine novel curvularin derivatives (1-9) and 16 known analogs (10-25) were isolated from the hydrothermal vent sediment fungus Penicillium sp. HL-50. Notably, compounds 5-7 represented a hybrid of curvularin and purine. The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance (NMR) spectroscopy, X-ray diffraction, electronic circular dichroism (ECD) calculations, ¹³C NMR calculation, modified Mosher's method, and chemical derivatization. Investigation of anti-inflammatory activities revealed that compounds 7-9, 11, 12, 14, 15, and 18 exhibited significant suppressive effects against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in murine macrophage RAW264.7 cells, with IC₅₀ values ranging from 0.44 to 4.40 μmol·L^-1. Furthermore, these bioactive compounds were found to suppress the expression of inflammation-related proteins, including inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), NLR family pyrin domain-containing protein 3 (NLRP3), and nuclear factor kappa-B (NF-κB). Additional studies demonstrated that the novel compound 7 possessed potent anti-inflammatory activity by inhibiting the transcription of inflammation-related genes, downregulating the expression of inflammation-related proteins, and inhibiting the release of inflammatory cytokines, indicating its potential application in the treatment of inflammatory diseases.
Penicillium/chemistry* ; Mice ; Animals ; Anti-Inflammatory Agents/isolation & purification* ; RAW 264.7 Cells ; Nitric Oxide/metabolism* ; Hydrothermal Vents/microbiology* ; Macrophages/immunology* ; Molecular Structure ; Nitric Oxide Synthase Type II/immunology* ; Cyclooxygenase 2/immunology* ; Geologic Sediments/microbiology* ; NF-kappa B/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology*

Hepatic encephalopathy is a difficult and critical disease with rapid progression and limited treatment methods in the field of liver disease， and it is urgently needed to make breakthroughs in its pathogenesis. Selection of appropriate prevention and treatment strategies is of great importance in delaying disease progression and reducing the incidence and mortality rates. This article reviews the theory of “turbid toxin pathogenesis” and related prevention and treatment strategies for hepatic encephalopathy in traditional Chinese medicine/Zhuang medicine， proposes a new theory of “turbid toxin pathogenesis”， analyzes the scientific connotations of “turbid”， “toxin”， and the theory of “turbid toxin pathogenesis”， and constructs the “four-step” prevention and treatment strategies for hepatic encephalopathy， thereby establishing the new clinical prevention and treatment regimen for hepatic encephalopathy represented by “four prescriptions and two techniques” and clarifying the effect mechanism and biological basis of core prescriptions and techniques in the prevention and treatment of hepatic encephalopathy， in order to provide a reference for the prevention and treatment of hepatic encephalopathy.

OBJECTIVE: To investigate the application of three-dimensional (3D) reconstruction technology in preoperative planning for anterolateral thigh flap transplantation. METHODS: A retrospective analysis was performed on the clinical data of 11 patients with skin and soft tissue defects treated with free anterolateral thigh flap transplantation between January 2022 and January 2024, who met the selection criteria. There were 8 males and 3 females, aged 34-70 years (mean, 50.8 years). Causes of injury included traffic accidents (4 cases), machine trauma (3 cases), heavy object crush injury (3 cases), and tumor (1 case). The time from injury to flap repair ranged from 7 to 35 days (mean, 23 days). Preoperatively, the patients' CT angiography images were imported into Mimics21.0 software. Through the software's segmentation, editing, and reconstruction functions, 3D visualization and measurement of the vascular pedicle, perforators, wound size, and morphology were performed to plan the flap harvest area, contour, vascular pedicle length, and anastomosis site, guiding the implementation of flap transplantation. RESULTS: The length of the vascular pedicle needed by the recipient site was (9.1±0.9) cm, and the maximum length of vascular pedicle in the donor area was (10.6±0.6) cm, with a significant difference ( t=4.230, P<0.001). The operation time ranged from 220 to 600 minutes (mean, 361.9 minutes). One patient had poor wound healing at the recipient site, which healed after dressing changes. All 11 flaps survived well without necrosis. All patients were followed up 6-19 months (mean, 11 months). Four flaps showed bulkiness and underwent secondary debulking; the remaining flaps had good contour and soft texture. The donor sites healed well, with no sensory disturbance around the incision or complications such as walking impairment. CONCLUSION Preoperative planning using CT angiography data and 3D reconstruction software can effectively determine the flap area, contour, required vascular pedicle length, anastomosis site, and whether vascular grafting is needed, thereby guiding the successful execution of anterolateral thigh flap transplantation.
Humans ; Middle Aged ; Male ; Female ; Adult ; Thigh/diagnostic imaging* ; Aged ; Plastic Surgery Procedures/methods* ; Retrospective Studies ; Imaging, Three-Dimensional/methods* ; Soft Tissue Injuries/surgery* ; Surgical Flaps ; Computed Tomography Angiography ; Free Tissue Flaps/blood supply* ; Preoperative Care

Objective:To compare the efficacy of pars plana vitrectomy (PPV) combined with subretinal or intravitreal injection of Conbercept for the treatment of refractory diabetic macular edema (DME).Methods:A retrospective case control study. From June 2022 to March 2024, 32 eyes of 32 patients with refractory DME diagnosed at The Affiliated Eye Hospital of Nanchang University were included in the study. There were 17 male cases with 17 eyes and 15 female cases with 15 eyes. Age was (57.44±8.99) years old; The duration of diabetes was (12.72±6.11) years. All patients had received regular treatment with anti-vascular endothelial growth factor (VEGF) drugs or corticosteroid drugs for at least 5 times, and had undergone focal retinal laser photocoagulation or panretinal laser photocoagulation, the central macular thickness (CMT) persisted or decreased by less than 50 μm. All affected eyes underwent best-corrected visual acuity (BCVA), intraocular pressure, optical coherence tomography (OCT), microperimetry, and laboratory glycated hemoglobin (HbA1c) testing. BCVA was measured using a standard logarithmic visual acuity chart, and converted to the logarithm of the minimum angle of resolution (logMAR) for statistical analysis. CMT was measured using an OCT device. Microperimetry was performed using an MP-3 microperimeter, recording the mean sensitivity (MS) of the retina within a 12° range of the fovea. The affected eyes were treated with 23G PPV combined with internal limiting membrane peeling and either macular subretinal or intravitreal injection of Conbercept, and were divided into subretinal injection group and the intravitreal injection group, each consisting of 16 cases and 16 eyes. The same equipment and methods as before surgery were used for related examinations at 1, 3, and 6 months post-surgery. Changes in BCVA, CMT, and MS were observed and compared, as well as the number of additional anti-VEGF treatments required within 6 months after surgery. Intergroup comparisons were made using independent samples t tests, and repeated measures data were analyzed using repeated measures analysis of variance. Results:The age ( t=-0.271), gender composition ( χ2=0.001), duration of diabetes ( Z=-0.868), HbA1c ( t=-0.789), intraocular pressure ( t=1.689), logMAR BCVA ( t=1.393), CMT ( t=-0.613), MS ( Z=-0.132), and the number of anti-VEGF injections ( t=-0.752) between the subretinal injection group and the intravitreal injection group showed no statistically significant differences ( P>0.05). The within-subject effects comparison of BCVA, CMT, and MS at 1, 3, and 6 months post-surgery compared to pre-surgery for all affected eyes showed statistically significant differences ( F=8.060, 125.722, 39.054; P<0.05). The overall comparison of logMAR BCVA between the subretinal and intravitreal injection groups post-surgery showed no statistically significant difference ( F=0.662, P=0.422), however, comparisons of CMT ( F=4.540) and MS ( F=6.066) showed statistically significant differences ( P<0.05). At 1, 3, and 6 months post-surgery, comparisons of logMAR BCVA between the two groups showed no statistically significant differences ( t=-0.123, 0.239, 1.087; P>0.05), comparisons of CMT showed statistically significant differences ( t=-3.474, -4.832, -2.482; P<0.05), comparisons of MS showed statistically significant differences at 1 and 3 months ( t=-2.940, -2.545; P<0.05), but not at 6 months ( t=-1.527, P>0.05). At 6 months post-surgery, the number of additional intravitreal anti-VEGF injections required in the subretinal and intravitreal injection groups showed a statistically significant difference ( Z=-2.033, P=0.042). During the follow-up period and at the final follow-up, no complications such as injection site bleeding, retinal detachment, vitreous hemorrhage, macular hole, or retinal pigment epithelial tear or atrophy occurred in all affected eyes. Conclusion:Compared with intravitreal injection, subretinal injection of Conbercept for the treatment of refractory DME has more advantages in reducing macular edema and improving visual function in the macular area, and also reduces the number of postoperative anti-VEGF drug treatments.

Objective:To compare and observe the efficacy and safety of pars plana vitrectomy (PPV) combined with 41G ultrafine needle injection of balanced salt solution (BSS) and internal limiting membrane inversion and coverage in the treatment of large-diameter macular hole (MH).Methods:A prospective study. From April 2023 to April 2024, 42 patients (42 eyes) diagnosed with large-diameter MH at The Affiliated Eye Hospital of Nanchang University were included in the study. The substrate diameters (BD) of MH are all greater than 1 000 μm. All affected eyes underwent best corrected visual acuity (BCVA), microvisual field, optical coherence tomography (OCT), and OCT angiography (OCTA) examinations before surgery. BCVA examination was conducted using the international standard logarithmic visual acuity chart, and the statistics were converted to the logarithm of the minimum angle of resolution (logMAR) visual acuity. Microfield-of-view examination records the mean retinal sensitivity (MS) within a 12° range of the fovea. The minimum diameter (MD) and BD of the hole were measured by OCT and the MH index (MHI) was calculated. OCTA measures the area and perimeter (PERIM) of the foveal avascular zone (FAZ) in the fovea centralis, as well as the retinal vessel length density (VLD) and vessel perfusion density (VPD) in the central area. The affected eyes were divided into the observation group (22 eyes, treated with PPV combined with 41G ultra-micro needle subretinal injection of BSS and the control group (20 eyes, treated with PPV combined with internal limiting membrane inversion and coverage) according to the random number table method. The patients were followed up for 6 months after the operation, and the above indicators were reexamined at 1, 3 and 6 months. The changes of BCVA, MS, FAZ parameters, VLD, VPD before and after the operation, as well as the closure of the hole and the occurrence of complications were compared between the two groups. The independent sample t test was used for comparison between groups. The correlation between postoperative indicators and preoperative structural parameters was analyzed using Pearson analysis. Results:In the 22 eyes of the observation group, the hole closure rate was 100.0% (22/22) 6 months after the operation, and the complete closure rate was 90.9% (20/22). In the control group of 20 eyes, the closure rate was 95.0% (19/20), and the complete closure rate was 90.0% (18/20). The hole closure rate of the affected eyes in the observation group was better than that in the control group, but the difference was not statistically significant ( χ2=1.736, P=0.420). The logMAR BCVA, MS, FAZ area, PERIM, VLD and VPD at each time point after the operation in both groups were significantly improved compared with those before the operation, and the differences were statistically significant ( P<0.05). The results of Pearson correlation analysis showed that in the observation group, logMAR BCVA at 6 months after surgery was positively correlated with BD before surgery ( r=0.340, P=0.029), and negatively correlated with MHI before surgery ( r=?0.350, P=0.023). Six months after the operation, MS was positively correlated with the preoperative hole height and MHI ( r=0.330, P=0.034). In the control group, 6 months after the operation, MS was negatively correlated with BD before the operation ( r=?0.480, P=0.032), and positively correlated with MHI before the operation ( r=0.510, P=0.027). Six months after the operation, the FAZ area of the affected eyes in the observation group [(0.17±0.09) mm 2] was larger than that in the control group [(0.12±0.07) mm 2], and the difference was statistically significant ( t=?0.340, P=0.025). No complications such as abnormal intraocular pressure, retinal pigment epithelium injury or retinal detachment occurred in all the affected eyes after the surgery. Conclusions:PPV combined with 41G ultra-micro needle subretinal injection of BSS for the treatment of large-diameter MH has a high rate of hole closure and good safety. Larger BD and MD, lower MHI and hole height before surgery may affect the recovery of visual function after surgery.

Primary liver cancer,particularly hepatocellular carcinoma,is one of the most common malignancies in China,and hepatectomy remains the primary curative treatment.However,the efficacy of hepatectomy is significantly limited due to the heterogeneity of liver cancer,its high recurrence rate,and the fact that most patients are diagnosed at advanced stages.In recent years,the development of precision medicine has brought new hope to liver cancer treatment,especially with notable advancements in preoperative assessment,systemic therapy,minimally invasive surgery,and personalized treatment strategies.Preoperative assessment,including imaging technologies such as three-dimensional visualization and molecular imaging,helps physicians accurately evaluate tumor characteristics and liver function,guiding the choice of treatment plan.The combined application of immunotherapy and targeted therapy has significantly improved survival rates for patients with advanced liver cancer.The strategy of combining systemic therapy with local treatment has provided new pathways for translational therapy,expanding the indications for hepatectomy.The optimal selection of patients based on tumor biological characteristics,especially molecular subtyping and liver function status,to maximize patient benefit still requires further exploration.The"seven-step"modular laparoscopic hepatectomy,by achieving scientific hepatectomy,demonstrates the clinical practice of maximizing patient benefit,further elucidating a multidisciplinary,personalized treatment model centered on surgical therapy.

Objective To investigate the prevalence and risk factors of work-related musculoskeletal disorders (WMSDs) among construction workers. Methods A total of 5 783 workers were selected as participants from 12 construction companies in Guangdong Province, Guangxi Zhuang Autonomous Region and Zhejiang Province using a convenient sampling method. The revised Musculoskeletal Disorders Questionnaire was used to investigate the prevalence and influencing factors of WMSDs. Results The prevalence of WMSDs was 27.4% among the construction workers. The prevalence of WMSDs in shoulder, neck, waist/lower back and hand/wrist was 10.6%, 9.5%, 9.5% and 9.4% respectively, which was higher than that in other body parts. Bianry logistic regression analysis showed that the risk of WMSDs in construction workers with junior high school education and below was higher than that of high school/ college and above (P<0.05). The risk of WMSDs was higher in drinkers than that in non-drinkers (P<0.01). The worse the health status of construction workers, the higher the risk of WMSDs (P<0.01). The risk of WMSDs in those who exercised once or twice a month was lower than that in those who did not exercise (P<0.05). The risk of WMSDs was higher in construction workers with longer working hours in uncomfortable postures and greater back bending amplitude at work (all P<0.01). The risk of WMSDs in construction workers with hands holding above the shoulder was higher than that with hands below the shoulder (P<0.05). Construction workers who repeated the same work daily, involved in high-temperature work, often worked overtime, had insufficient rest time, and had a shortage of department personnel had a relatively high risk of WMSDs (all P<0.01). Conclusion The prevalence of WMSDs among the construction workers was relatively high, and the most common WMSDs occurred in shoulder, neck, waist/lower back and hand/wrist. Individual characteristic, work type, work posture and work organization are the influencing factors of WMSDs. Comprehensive measures, especially ergonomic measures based on personal and occupational characteristics should be taken to reduce the risk of WMSDs among construction workers.

Objective To analyze the current status and influencing factors of occupational stress, job burnout and sleep quality among workers in the secondary industry in Jinshan District, Shanghai City. Methods A total of 1 418 workers from six key industries in Jinshan District, Shanghai City were selected as the study subjects by the stratified cluster sampling method. The Occupational Stress Core Scale, Maslash Burnout Inventory General Survey and Pittsburgh Sleep Quality Index were used to investigate occupational stress, job burnout and sleep quality of the workers. Results The detection rates of occupational stress, job burnout and sleep disturbance among the study subjects were 33.6%, 65.4% and 23.3%, respectively. Multivariate logistic regression analysis showed that the workers with a monthly income <5 000 yuan had a higher risk of occupational stress than those with a monthly income ≥5 000 yuan (P<0.01). The workers with ≥5.0 years of service had a higher risk than those with <1.0 year (P<0.05). Lack of physical exercise, employment in medium- and large-sized enterprises, and shift work were risk factors of occupational stress in the workers (all P<0.01). The workers aged 18-<30 years had a higher risk of job burnout than those aged 45-<60 years (P<0.05). The workers monthly income <5 000 yuan was associated with a higher risk of job burnout than those with ≥9 000 yuan (P<0.05). The workers with 1.0-<10.0 years or ≥15.0 years of service had higher job burnout risks than those with <1.0 year (all P<0.05). Being unmarried, lack of physical exercise, and employment in medium- and large-sized enterprises were risk factor of job burnout in the workers (all P<0.05). The workers with an educational level of high school or above had a higher risk of sleep disturbance than those with junior school or below (P<0.05). The workers who work >56 hours per week had a higher risk than those working ≤40 hours per week (P<0.01). Conclusion There is a high detection rate of occupational stress, job burnout, and sleep disturbance in the secondary industry workers in Jinshan District, Shanghai City. Special attention should be given to workers with low income, lack of physical exercise, employment in medium- and large-sized enterprises, shift work, long service duration, and long weekly working hours to protect their physical and mental health.

Objective To investigate clinical efficacy of endoscopic transforaminal lumbar interbody fusion(Endo-TLIF)combined with huge-large cage insertion technique in the treatment of lumbar instability.Methods A retrospective analysis was made on 18 cases of lumbar instability from May 2022 to August 2022.Endo-TLIF was performed to complete neural decompression,Kambin's triangle exposure,and endplate preparation.A huge-large cage was inserted in the intervertebral space through the Kambin's triangle with full-visualization endoscopy.Results The operation time was(180.3±24.4)min,and the intraoperative blood loss was(72.2±25.6)ml.Symptoms of numbness and weakness in the front thigh were gradually relieved after symptomatic treatment in 1 case.The hospital stay was(7.9±1.8)d.The 18 cases were followed up for 19-22 months(mean,19.9±1.1 months).As compared to pre-operation,Visual Analogue Scale[(2.3±1.4)points vs.(7.7±1.0)points,P=0.000;(1.1±0.4)points vs.(7.7±1.0)points,P=0.000]and Oswestry Disability Index[(18.61±4.79)％ vs.(52.78±8.08)％,P=0.000;(9.28±4.03)％ vs.(52.78±8.08)％,P=0.000]were significantly improved at 3 months after surgery and at final follow-up.As compared to pre-operation,the intervertebral height[(12.56±1.62)mm vs.(8.28±1.27)mm,P=0.000;(12.11±1.45)mm vs.(8.28±1.27)mm,P=0.000]and intervertebral foramen heigh[(22.89±2.00)mm vs.(17.17±1.69)mm,P=0.000;(22.61±1.86)mm vs.(17.17±1.69)mm,P=0.000]were significantly improved at 3 months after surgery and at the final follow-up.All the patients had a good bone fusion,and the excellent and good rate of the modified Macnab criteria was 94.4％(17/18).Conclusion Endo-TLIF combined with huge-large cage insertion can acquire a significantly good clinical outcomes in patients with lumbar instability,with advantages of safe and simple performance,good recovery of intervertebral height,and minimal damage to paraspinal soft tissue.