Objective To elucidate the molecular mechanism of sirtuin-3 (SIRT3) in regulating mitochondrial biogenesis in human renal tubular epithelial cells. Methods Cells were stimulated with different concentrations of H₂O₂ and divided into four groups: control (NC), 50 μmol/L H₂O₂, 110 μmol/L H₂O₂ and 150 μmol/L H₂O₂. SIRT3 protein expression was then measured. SIRT3 was knocked down with siRNA, and cells were further assigned to five groups: control (NC), negative-control siRNA (NCsi), SIRT3-siRNA (siSIRT3), NCsi+H₂O₂, and siSIRT3+H₂O₂. After 24 h, cellular adenosine triphosphate (ATP) and mitochondrial superoxide anion (O₂•⁻) levels were determined, together with mitochondrial expression of SIRT3, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), superoxide dismutase 2 (SOD2), acetylated-SOD2 and adenosine monophosphate activated protein kinase α1 (AMPKα1). Results The 110 and 150 μmol/L H₂O₂ decreased SIRT3 protein (both P<0.05). ATP and mitochondrial O₂•⁻ did not differ between NC and NCsi groups (both P>0.05). Compared to the NCsi group, the siSIRT3 group exhibited elevated O₂•⁻ level, decreased SIRT3 protein and increased expression levels of SOD2 and acetylated SOD2 protein (all P<0.05). Compared to the NCsi group, the NCsi+H₂O₂ group exhibited decreased cellular ATP levels, elevated mitochondrial O₂•⁻ levels, and reduced protein expression levels of SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 (all P<0.05). Compared with the siSIRT3 group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 protein expression levels and a decrease in acetylated SOD2 protein expression levels (all P<0.05). Compared with the NCsi+H₂O₂ group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, AMPKα1, PGC-1α and NRF1, TFAM protein expression levels, and an increase in SOD2 and acetylated SOD2 protein expression levels (all P<0.05). Conclusions SIRT3 promotes mitochondrial biogenesis in tubular epithelial cells via the AMPK/PGC-1α/NRF1/TFAM axis, representing a key mechanism through which SIRT3 ameliorates oxidative stress-induced mitochondrial dysfunction.

ObjectiveTo evaluate the pregnancy outcomes of assisted reproductive technology （ART） in women with a history of thyroid cancer who retained fertility intentions after completing cancer treatment. MethodsA retrospective analysis was performed on 61 patients with a history of thyroid cancer who underwent in vitro fertilization/intracytoplasmic sperm microinjection and embryo transfer （IVF/ICSI-ET）. These patients were included as the case group. A total of 122 non-cancer patients who received ART during the same period were selected as the control group using 1∶2 matching based on age and oocyte retrieval time. Baseline characteristics， outcomes of the first ART cycle， and cumulative pregnancy outcomes were compared between the two groups. ResultsThere was no significant difference in the basic data， the total amount of gonadotropin （Gn） and the days of use between the case group and the control group （P>0.05）. However， the case group had significantly fewer retrieved oocytes， mature oocytes （MII）， lower fertilization and cleavage rates， and fewer transferable and high-quality embryos， as well as fewer embryos transferred during the first cycle （P < 0.05）. However， there was no significant difference in the rate of first embryo implantation and first clinical pregnancy between the two groups （P>0.05）. In the analysis of cumulative outcomes， the two groups did not show statistically significant differences in the cumulative pregnancy rate， clinical pregnancy rate per transfer cycle， the number of oocyte retrieval cycles required per live birth， the number of embryo transfer cycles required per live birth， and the number of embryos used for each live birth （P>0.05）. However， the cumulative live birth rate was significantly lower in the case group compared to the control group （P=0.005）. ConclusionAfter treatment for thyroid cancer， when ART is used to help pregnant women， the pregnancy outcome is comparable to that of women without tumors. Individualized reproductive management and timely fertility preservation strategies are recommended to optimize reproductive outcomes in this population.

OBJECTIVE To formulate Guidelines for the standardized implementation of pharmacist-managed clinics （ 2026 edition ） in response to the challenges faced by such clinics in China， including uneven development， large discrepancies in service specifications， insufficient patient awareness， and limited medical insurance coverage. METHODS Led by the Pharmaceutical Affairs Professional Committee of the Chinese Hospital Association， the Evidence-based Pharmacy Professional Committee of the Chinese Pharmaceutical Association， and the Hospital Pharmacy Professional Committee of the Cross-strait Medical and Health Exchange Association， a total of 19 domestic hospital pharmacy experts were organized. Through a systematic review of national policies and literature research， current practical experience was summarized. Consensus on the contents of the guidelines was reached after in-depth discussions. RESULTS &CONCLUSIONS The guidelines covered five sections： definition and connotation of pharmacist-managed clinics， establishment requirements， implementation and management， post competency， and practical research. Firstly， the definition and connotation included three operational forms of pharmacist-managed clinics （independent mode， physician-pharmacist joint mode， and online pharmacist-managed clinic mode） and classified service modes （specialty-specific， drug-specific， and disease-specific pharmacist-managed clinics）. The establishment requirements were further refined， covering system construction （pharmaceutical service management system， quality control and assessment mechanism）， personnel qualifications （professional credentials， continuing education and professional training， etc）， service recipients， as well as service venues and facilities. Subsequently， the implementation and management of pharmacist-managed clinics were proposed， involving service procedures， intervention measures， documentation and records， patient education and follow-up， humanistic care， as well as risk management and quality control. Finally， post competency encompassed the competency requirements for pharmacists providing services in pharmacist-managed clinics， as well as the suggestions on teaching methods； practical research encouraged the conduct of high-quality pharmaceutical practice in the setting of pharmacist-managed clinics. The guidelines provide valuable guidance for the standardized implementation of pharmacist-managed clinics in China in terms of establishment， management， teaching， and research， fill the guideline gap in this field， and can promote the high-quality development of pharmacist-managed clinics.

Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

Objective:To investigate the role of cyclooxygenase-2 (COX-2) in glycochenodeoxycholic acid (GCDC)-induced apoptosis of mouse extrahepatic biliary epithelial cells (EBECs) and clarify its possible mechanism.Methods:EBECs were cultured in vitro and infected with RNAi-COX-2 lentivirus (GCDC+ shCOX-2 group). EBECs were then treated with different concentrations (0, 25, 50, 100, 200, 400, 800 μmol/L) of GCDC (GCDC group). Cell proliferation activity was detected by cell counting kit-8 (CCK-8) assay; lactate dehydrogenase (LDH) release rate was measured by colorimetry; apoptosis was analyzed by flow cytometry; caspase-3 activity was detected by fluorescent probe method; COX-2 mRNA expression was determined by real-time quantitative polymerase chain reaction (qRT-PCR); protein levels of COX-2, autophagy-related proteins LC3, p62, Beclin-1, and apoptosis-related proteins Bax, Bcl-2, cleaved caspase-3 were evaluated by Western blot.Results:Compared with the 0 μmol/L GCDC group, the apoptosis level, LDH release rate, and caspase-3 activity in the 50, 100, and 200 μmol/L GCDC groups gradually increased (all P<0.05) in a concentration-dependent manner. After RNAi-COX-2 lentivirus infection, COX-2 mRNA and protein expression levels in EBECs significantly decreased (all P<0.05). Compared with the GCDC group, the apoptosis rate of EBECs in the GCDC+ shCOX-2 group significantly decreased ( P<0.05). The GCDC+ shCOX-2 group showed increased cell proliferation activity, downregulated protein expressions of Bax, cleaved caspase-3, and p62, and upregulated protein expressions of Bcl-2, LC3 II/I, and Beclin-1 (all P<0.05). Conclusions:Inhibition of COX-2 improves GCDC-induced apoptosis of EBECs, and the mechanism may be related to the activation of the autophagy pathway.

The molecular mechanisms underlying the develop-ment and metastasis of prostate cancer remain elusive.This comprehensive review delves into the intricate role of cofilin,an actin-binding protein,in the pathogenesis and progression of prostate cancer.Cofilin is a significant protein in cytoskeletal dynamics,and any dysregulation may result in the morphological changes in normal cells and the invasion and metastasis of tumor cells.Research has revealed that the activity of cofilin is regula-ted by various mechanisms,including phosphorylation/dephos-phorylation and interactions with other molecules.Moreover,this review discusses promising therapeutic interventions,such as co-filin inhibitors and gene therapy,which have demonstrated effica-cy in preclinical models.The challenge of clinically preventing the transition to castration-resistant prostate cancer and tumor metastasis is widely recognized,necessitating the development of precise drug treatments and biomarker identification.As a key regulatory protein,cofilin provides a more comprehensive refer-ence for the prevention and treatment of prostate diseases.

Immune checkpoint inhibitor-related pneumonitis(CIP)is a relatively common immune-related adverse event.The current treatment for CIP mainly relies on glucocorticoids,with 70％～80％of patients being controlled by conventional glucocorticoid therapy.However,steroid-unresponsive CIP is often se-vere and can be life-threatening.There is no standard treatment protocol for steroid-unresponsive CIP,highlighting a significant unmet clinical need.This paper reviews the diagnosis,treatment progress,and exploratory research of steroid-unresponsive CIP to provide evidence-based guidelines and directions for clinical and translational research.

There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

The incidence and mortality rates of hepatocellular carcinoma(HCC)remain high in China,and the application of surgical resection is often limited due to the fact that most patients are in the advanced stage at the time of confirmed diagnosis.This article reviews commonly used advanced locoregional therapies for HCC and the advances in mainstream techniques such as local ablation(radiofrequency ablation,microwave ablation,irreversible electroporation,and cryoablation),intravascular intervention(transcatheter arterial chemoembolization,hepatic arterial infusion chemotherapy,and Y90 hepatic arterial infusion chemotherapy),and radiotherapy(CyberKnife,proton therapy,and heavy-ion therapy),and a multidimensional decision-making framework is constructed for HCC locoregional therapy by comparing treatment principles,indications,limitations,and clinical data of these techniques.This article aims to provide evidence-based support for persistent dilemmas in clinical decision-making,promote the role of locoregional therapies in clinical practice,and propose the directions for future research and clinical application.This article also establishes a comprehensive clinical roadmap for HCC locoregional therapy,which helps to address current challenges regarding technique selection and delineate future directions for innovation,in order to reshape the treatment of HCC through technological integration and paradigm innovation.

Objective:To investigate the role of cyclooxygenase-2 (COX-2) in glycochenodeoxycholic acid (GCDC)-induced apoptosis of mouse extrahepatic biliary epithelial cells (EBECs) and clarify its possible mechanism.Methods:EBECs were cultured in vitro and infected with RNAi-COX-2 lentivirus (GCDC+ shCOX-2 group). EBECs were then treated with different concentrations (0, 25, 50, 100, 200, 400, 800 μmol/L) of GCDC (GCDC group). Cell proliferation activity was detected by cell counting kit-8 (CCK-8) assay; lactate dehydrogenase (LDH) release rate was measured by colorimetry; apoptosis was analyzed by flow cytometry; caspase-3 activity was detected by fluorescent probe method; COX-2 mRNA expression was determined by real-time quantitative polymerase chain reaction (qRT-PCR); protein levels of COX-2, autophagy-related proteins LC3, p62, Beclin-1, and apoptosis-related proteins Bax, Bcl-2, cleaved caspase-3 were evaluated by Western blot.Results:Compared with the 0 μmol/L GCDC group, the apoptosis level, LDH release rate, and caspase-3 activity in the 50, 100, and 200 μmol/L GCDC groups gradually increased (all P<0.05) in a concentration-dependent manner. After RNAi-COX-2 lentivirus infection, COX-2 mRNA and protein expression levels in EBECs significantly decreased (all P<0.05). Compared with the GCDC group, the apoptosis rate of EBECs in the GCDC+ shCOX-2 group significantly decreased ( P<0.05). The GCDC+ shCOX-2 group showed increased cell proliferation activity, downregulated protein expressions of Bax, cleaved caspase-3, and p62, and upregulated protein expressions of Bcl-2, LC3 II/I, and Beclin-1 (all P<0.05). Conclusions:Inhibition of COX-2 improves GCDC-induced apoptosis of EBECs, and the mechanism may be related to the activation of the autophagy pathway.