Objective:To investigate the effectiveness and safety of secondary cytoreductive surgery (SCS) in patients with platinum-sensitive recurrent epithelial ovarian cancer who progressed after first-line maintenance therapy with poly adenosine diphosphate ribose polymerase inhibitor (PARPi).Methods:Clinical pathological data and prognostic information were retrospectively collected from 30 ovarian cancer patients who underwent SCS between January 2018 and June 2024. The Kaplan-Meier method was used to analyze the second progression-free survival (PFS2) time and 3-year overall survival (OS) rate.Results:(1) Primary treatment: the median age at diagnosis was 51.3 years. A total of 40% (12/30) patients underwent primary debulking surgery with an expectation of achieving no gross residual disease (R0), while 60% (18/30) received neoadjuvant chemotherapy and interval debulking surgery. Optimal cytoreduction was achieved in 93% (28/30) of patients. BRCA1/2 gene testing was performed in 29 patients (testing rate 97%, 29/30), identifying 11 BRCA-mutated (37%, 11/30) and 18 BRCA wild-type (60%, 18/30) patients. The median duration of PARPi maintenance therapy among the 30 patients was 11.9 months; patients with BRCA gene mutations had a median duration of 19.2 months, while those with BRCA wild-type had a median duration of 10.1 months. (2) Secondary surgery: pathologically confirmed recurrence patterns, single lesion in 9 patients (30%, 9/30), oligo-lesion (2 lesions) in 3 patients (10%, 3/30), and multi-lesion (≥3 lesions) in 18 patients (60%, 18/30). Among the 30 patients, optimal cytoreduction was achieved in 97% (29/30) of SCS patients, with suboptimal cytoreduction in 1 patient (3%, 1/30). Adjuvant chemotherapy included platinum+paclitaxel in 24 (80%, 24/30) patients and platinum+liposomal doxorubicin in 6 (20%, 6/30) patients. PARPi re-treatment was administered to 17 patients (57%, 17/30) after chemotherapy. (3) Efficacy and safety: as of the follow-up cutoff in June 2024, the median follow-up time was 28.0 months. A total of 19 (63%, 19/30) patients experienced the next recurrence. The median PFS2 time after SCS was 18.5 months. Recurrence occurred in 7 BRCA-mutated and 12 BRCA gene wild-type patients. Median PFS2 time was significantly longer in BRCA-mutated patients compared to BRCA wild-type patients (25.7 vs 14.1 months; P=0.028). Three deaths occurred during follow-up, resulting in a 3-year OS rate of 90%. Among the 30 patients, postoperative complications occurred in 4 patients (13%, 4/30). One patient developed a ureteral fistula on 7 days post-SCS requiring ureteral stenting, and one patient was transferred to the intensive care unit on 1 day post-SCS due to hypovolemic shock. No deaths occurred within 30 days after SCS. Conclusion:For platinum-sensitive recurrent ovarian cancer patients progressed after first-line PARPi maintenance therapy who are anticipated to achieve R0 resection, SCS represents a safe and effective second-line treatment option.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

Objective:To compare the clinical outcomes of APTT-HTO and Biplanar-high tibial osteotomy (Biplanar-HTO) in treating medial compartment knee osteoarthritis.Methods:A non-randomized controlled trial was conducted. Twenty-eight patients with medial compartment knee osteoarthritis who underwent HTO at the Affiliated Hospital of Guizhou Medical University from August 2021 to January 2022 were enrolled. Based on the patients' surgical preference, they were assigned to either the APTT-HTO group ( n=15) or the Biplanar-HTO group ( n=13), followed up for 12 months postoperatively. Postoperative pain Visual Analog Scale (VAS) scores, Knee Society Score (KSS), changes in patellar height (Caton-Deschamps Index, CDI), and posterior tibial slope (PTS) were compared between the two groups. Results:The APTT-HTO group demonstrated a significantly shorter operative time (64.13±4.85 min) compared to the Biplanar-HTO group (81.54±6.09 min) ( P<0.05). No significant differences were observed in intraoperative correction (APTT-HTO: 12.19°±4.85°; Biplanar-HTO: 11.23°±3.02°) or postoperative drainage volume (APTT-HTO: 47.00±13.79 ml; Biplanar-HTO: 47.00±11.17 ml) ( P>0.05). At 12-month follow-up (APTT-HTO: 13.93±2.05 months; Biplanar-HTO: 14.08±2.14 months; no dropouts), the APTT-HTO group showed no significant changes in PTS (9.32°±2.04° vs. preoperative 8.82°±1.89°) or CDI (0.95±0.11 vs. 0.98±0.11) ( P>0.05), while the Biplanar-HTO group exhibited increased PTS (13.27°±1.99° vs. 8.86°±1.99°) and decreased CDI (0.64±0.10 vs. 0.97±0.16) ( P<0.05). The differences in PTS and CDI between the APTT HTO group and the Biplanar HTO group at 12 months after surgery were statistically significant ( P<0.05). Both groups achieved significant clinical improvements: in APTT-HTO, VAS decreased (preopreation 4.80±1.01 to postopreation 1.06±0.88), KSS knee scores increased (47.67±12.03 to 87.93±4.38), and KSS function scores improved (48.00±4.93 to 67.00±5.91); in Biplanar-HTO, VAS reduced (5.08±1.12 to 1.85±1.14), KSS knee scores rose (46.85±11.48 to 85.85±5.11), and KSS function scores enhanced (46.92±5.60 to 66.92±5.22) ( P<0.05 for all). Complications included soft tissue irritation (2 cases per group), with Biplanar-HTO additionally reporting deep vein thrombosis (1 case), hinge fracture (1 case), and patella baja (3 cases). Conclusions:Both APTT-HTO and Biplanar-HTO effectively treat medial compartment knee osteoarthritis. However, APTT-HTO outperforms Biplanar-HTO in preventing postoperative patella infera and minimizing alterations in PTS.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Insulin is an important protein hormone that participates in multiple metabolic pathways.Biosynthetic insulin has been widely used in the treatment of type 1 and type 2 diabetes.Currently,the number of reported cases of insulin overdose both at home and abroad is gradually increasing,and insulin homicide is no longer a means of"committing murder without leaving a trace".At present,there are no systematic protocols for the identification of insulin overdose in the field of forensic medi-cine in China.This article introduces the causes,toxicological characteristics,forensic examination,labo-ratory testing methods and indicator reference of insulin overdose.Based on the identification practice and research results and referring to relevant studies on insulin overdose at home and abroad,this pa-per aims to provide recommendations and references for the formulation of forensic identification guide-lines for insulin overdose cases.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*

OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

Objective:To compare the clinical outcomes of APTT-HTO and Biplanar-high tibial osteotomy (Biplanar-HTO) in treating medial compartment knee osteoarthritis.Methods:A non-randomized controlled trial was conducted. Twenty-eight patients with medial compartment knee osteoarthritis who underwent HTO at the Affiliated Hospital of Guizhou Medical University from August 2021 to January 2022 were enrolled. Based on the patients' surgical preference, they were assigned to either the APTT-HTO group ( n=15) or the Biplanar-HTO group ( n=13), followed up for 12 months postoperatively. Postoperative pain Visual Analog Scale (VAS) scores, Knee Society Score (KSS), changes in patellar height (Caton-Deschamps Index, CDI), and posterior tibial slope (PTS) were compared between the two groups. Results:The APTT-HTO group demonstrated a significantly shorter operative time (64.13±4.85 min) compared to the Biplanar-HTO group (81.54±6.09 min) ( P<0.05). No significant differences were observed in intraoperative correction (APTT-HTO: 12.19°±4.85°; Biplanar-HTO: 11.23°±3.02°) or postoperative drainage volume (APTT-HTO: 47.00±13.79 ml; Biplanar-HTO: 47.00±11.17 ml) ( P>0.05). At 12-month follow-up (APTT-HTO: 13.93±2.05 months; Biplanar-HTO: 14.08±2.14 months; no dropouts), the APTT-HTO group showed no significant changes in PTS (9.32°±2.04° vs. preoperative 8.82°±1.89°) or CDI (0.95±0.11 vs. 0.98±0.11) ( P>0.05), while the Biplanar-HTO group exhibited increased PTS (13.27°±1.99° vs. 8.86°±1.99°) and decreased CDI (0.64±0.10 vs. 0.97±0.16) ( P<0.05). The differences in PTS and CDI between the APTT HTO group and the Biplanar HTO group at 12 months after surgery were statistically significant ( P<0.05). Both groups achieved significant clinical improvements: in APTT-HTO, VAS decreased (preopreation 4.80±1.01 to postopreation 1.06±0.88), KSS knee scores increased (47.67±12.03 to 87.93±4.38), and KSS function scores improved (48.00±4.93 to 67.00±5.91); in Biplanar-HTO, VAS reduced (5.08±1.12 to 1.85±1.14), KSS knee scores rose (46.85±11.48 to 85.85±5.11), and KSS function scores enhanced (46.92±5.60 to 66.92±5.22) ( P<0.05 for all). Complications included soft tissue irritation (2 cases per group), with Biplanar-HTO additionally reporting deep vein thrombosis (1 case), hinge fracture (1 case), and patella baja (3 cases). Conclusions:Both APTT-HTO and Biplanar-HTO effectively treat medial compartment knee osteoarthritis. However, APTT-HTO outperforms Biplanar-HTO in preventing postoperative patella infera and minimizing alterations in PTS.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.