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.

Ischemic stroke(IS) is a complex pathological process involving multiple cellular and molecular mechanisms and it is characterized by high mortality, high disability, and high recurrence. In recent years, the incidence of IS in China has been increasing year by year, and it has a trend of occurring in increasingly young individuals. Herb pairs are the smallest unit of traditional Chinese medicine(TCM) compatibility and an important part of TCM compounding, and the research on them is of great significance in guiding the clinical medication. Pharmacological studies have confirmed that certain herb pairs can exert anti-ischemic effects through various pathways such as reducing inflammation, alleviating oxidative stress, protecting the nervous system, and promoting neovascularization. By reviewing the relevant articles in the past decade, this paper probes into the combination rules, modern experimental studies, and combination ratios of the commonly used herb pairs from the etiology and pathogenesis of IS and summarizes 18 commonly used and deeply studied herb pairs, with a view to providing reference for the application, research, and development of clinical medicines.
Humans ; Drugs, Chinese Herbal/chemistry* ; Animals ; Ischemic Stroke/metabolism* ; Medicine, Chinese Traditional

OBJECTIVE: To investigate the clinical effect of minimally invasive technique in the treatment of moderate and severe gluteal muscle contracture. METHODS: A retrospective study was conducted on 85 patients (170 sides) with bilateral gluteal muscle contracture admitted from January 2016 to December 2019. All patients were treated with minimally invasive release of tendon knife. There were 32 males and 53 females, ranging in age from 15 to 37 years old, with an average age of (22.3±6.3) years old. Operation time, intraoperative blood loss, incision length, first postoperative ambulation time, complication rate, recurrence rate, and Harris hip score (HHS) were analyzed and evaluated. RESULTS: The average follow-up time was (16.2±4.6) months, ranging from 12 to 30 months. The operation time ranged from 7 to 15 min, with an average of (10.2±3.1) min. Intraoperative blood loss ranged from 2 to 20 ml, with an average of (8.4±2.2) ml. The incision length ranged from 0.6 to 2.0 cm, with an average of (0.8±0.3) cm. The time to postoperative ambulation ranged from 12 to 28 h, with an average of (20.0±3.2) h. All patients achieved primary wound healing without sciatic nerve injury or recurrence. HHS hip function scores ranged from 90 to 98, with an average score of (96.2±1.4). Complications included intraoperative tendon blade tip fracture in two cases (removed under fluoroscopic guidance) and subcutaneous hematoma in three cases-two resolved with compression and one with open evacuation.. Twenty-nine patients exhibited transient swaying gait postoperatively, of which 24 patients returned to normal after 4 weeks and 5 patients returned to normal after 6 weeks. CONCLUSION Minimally invasive tendon blade release is a safe and effective technique for treating gluteal muscle contracture, offering minimal trauma, rapid recovery, and excellent cosmetic and functional outcomes. However, it exhibits a low risk of blade tip fracture and sciatic nerve injury, warranting experienced surgical handling.
Humans ; Male ; Female ; Adult ; Minimally Invasive Surgical Procedures/methods* ; Adolescent ; Retrospective Studies ; Buttocks/surgery* ; Young Adult ; Contracture/surgery* ; Tendons/surgery* ; Muscle, Skeletal/surgery*

OBJECTIVES: To explore the relationship between white matter injury (WMI) and cerebral perfusion in preterm infants using arterial spin labeling (ASL). METHODS: A total of 293 preterm infants (gestational age <34 weeks) hospitalized at the Third Affiliated Hospital of Zhengzhou University between June 2022 and June 2024 were included. After achieving clinical stability, the infants underwent brain magnetic resonance imaging (MRI) and ASL. Based on MRI findings, infants were classified into WMI (n=66) and non-WMI (n=227) groups. Cerebral perfusion parameters were compared between groups, and the association between WMI and perfusion alterations was evaluated. RESULTS: The WMI group showed a higher incidence of mild intraventricular hemorrhage (IVH) than the non-WMI group (P<0.05). Significantly lower cerebral perfusion was observed in the WMI group across bilateral frontal, temporal, parietal, and occipital lobes, as well as the basal ganglia and thalamus (P<0.05). After adjusting for gestational age, corrected gestational age at ASL scan, and mild IVH, WMI remained significantly associated with reduced regional perfusion (P<0.05). CONCLUSIONS WMI in preterm infants correlates with localized cerebral hypoperfusion. ASL-detected perfusion abnormalities may provide novel insights into WMI pathogenesis.
Humans ; White Matter/blood supply* ; Infant, Newborn ; Spin Labels ; Infant, Premature ; Female ; Male ; Cerebrovascular Circulation ; Magnetic Resonance Imaging

OBJECTIVES: To explore the status and risk factors of neuropsychological development in small for gestational age (SGA) infants at corrected 12-24 months of age. METHODS: Clinical data were retrospectively collected for 754 SGA infants at corrected ages 12-24 months in Shenzhen Bao'an Women and Children's Hospital between April 2018 and December 2023. Developmental quotient (DQ) levels were analyzed. According to the presence of global developmental delay (GDD), participants were divided into a GDD group (71 cases) and a control group (683 cases), and the incidence and influencing factors of GDD were investigated. RESULTS: In the high-risk preterm SGA group, the total DQ and DQ in all domains were lower than in the full-term SGA group (P<0.017). The overall incidence of GDD was 9.4% (71/754) and increased with decreasing gestational age (P<0.017). Compared with the control group, the GDD group had higher proportions of males; low-risk and high-risk preterm birth; mothers with less than a bachelor's degree; multiple birth; neonatal hypoglycemia; neonatal pneumonia; neonatal respiratory distress syndrome; bronchopulmonary dysplasia; and, at corrected 12-24 months, low body weight, growth retardation, and microcephaly. The length of neonatal hospital stay was longer in the GDD group than in the control group (P<0.05). The weight-for-age Z score, length-for-age Z score, and head circumference-for-age Z score at birth and at corrected 12-24 months were lower in the GDD group than in the control group (P<0.05). Multivariable logistic regression showed that male sex and maternal education below a bachelor's degree were independent risk factors for GDD in SGA infants (P<0.05). CONCLUSIONS Neuropsychological development in preterm SGA infants is comparatively delayed; male SGA infants born to mothers with less than a bachelor's degree should receive priority attention.
Humans ; Female ; Male ; Infant, Small for Gestational Age/psychology* ; Risk Factors ; Infant ; Retrospective Studies ; Child Development ; Developmental Disabilities/epidemiology* ; Infant, Newborn ; Child, Preschool

OBJECTIVE: To investigate the effects of Bushen Huoxue Granule on the ubiquitin-proteasome system (UPS) in an in vitro model of Parkinson's disease. METHODS: After treated with 1-methyl-4-phenylpyridinium (MPP⁺, 1 mmol/L) for 24 h, the cells were incubated with drug-free serum, Madopar-containing serum or Bushen Huoxue Granule-containing serum (BCS, 5%, 10%, and 20%) for another 24 h. The levels of α-synuclein (α-syn), tyrosine hydroxylase (TH) and UPS-related proteins were detected by Western blot. The expression levels of α-syn in PC12 cells were also analyzed by Western blot after treated with proteasome inhibitor MG132 and WT-α-syn plasmid transfection, respectively, as well as the alterations induced by subsequent BCS intervention. Immunocytochemistry was performed to determine the changes in α-syn phosphorylation at serine 129 (pSer129-α-syn) expression. The 20S proteasome levels were measured by enzyme-linked immunosorbnent assay. RESULTS: BCS (volume fraction ⩽20%) intervention could alleviate the MMP⁺-induced cell viability decrease (P<0.05). In the MPP⁺ treated cells, α-syn was up-regulated, while TH and proteins of UPS such as ubiquitin (Ub), Ub binding with Ub-activating enzyme (UBE1), Parkin and Ub C-terminal hydrolase-1 (UCHL-1) were down-regulated (P<0.05). BCS intervention could attenuate the above changes (P<0.05). The activity of BCS on blocking α-syn accumulation was weakened by MG132 (P<0.05). While α-syn level was significantly increased in cells transfected with plasmid, and reduced by BCS intervention (P<0.05). pSer129-α-syn was increased in MPP⁺-induced PC12 cells, whereas decreased by later BCS intervention (P<0.05). The 20S proteasome activity of MPP⁺-induced PC12 cells was decreased, but increased after BCS intervention (P<0.05). CONCLUSION BCS intervention protected UPS function, increased 20S proteasome activity, promoted pathological α-syn clearance, restored cell viability, and reversed the damage caused by MPP⁺ in the in vitro model of Parkinson's disease.
PC12 Cells ; alpha-Synuclein/metabolism* ; Rats ; Animals ; 1-Methyl-4-phenylpyridinium/toxicity* ; Proteasome Endopeptidase Complex/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Ubiquitin/metabolism* ; Cell Survival/drug effects* ; Phosphorylation/drug effects* ; Tyrosine 3-Monooxygenase/metabolism*

Peptide-drug conjugates (PDCs) have emerged as a promising modality in precision oncology, enabling targeted delivery of cytotoxic payloads while minimizing off-target toxicity. The integration of covalent warheads, such as those based on sulfur(VI) fluoride exchange (SuFEx) chemistry, enhances drug-target residence time and tumor accumulation. However, existing screening methods for covalent peptide (CP) libraries require post-translational warhead conjugation, limiting throughput. Here, we present an integrated mRNA display platform that incorporates covalent warheads during ribosomal synthesis, enabling efficient screening of ultra-diverse covalent macrocyclic peptide libraries (>10¹³ variants). This approach, using site-specific incorporation of N-chloroacetyl-d-phenylalanine and fluorosulfate-l-tyrosine, accelerated the discovery of irreversibly binding (K _i = 3.58 μmol/L) Nectin-4-targeting peptide CP-N1-N₃ via proximity-triggered SuFEx. The peptide was further conjugated to cytotoxic payloads, yielding the covalent PDC CP-N1-MMAE with potent cytotoxicity (IC₅₀ ≈ 43 nmol/L) against MDA-MB-468 cells. This platform establishes a new paradigm for precision covalent drug discovery.

Objective To evaluate the test-retest reliability of the ballistic push-up(BPU)test and establish predictive models for upper-limb strength and explosive power in young males.Methods A total of 71 male college students performed assessments of upper-limb bench press 1 repetition maximum(1RM)strength,bench press explosive power,and two BPU tests with a 48-hour interval.BPU test data were recorded using a three-dimensional(3D)force platform and motion capture system to calculate concentric metrics such as peak force(PF)and mean velocity(MV).The intraclass correlation coefficient(ICC)was used to examine the retest reliability of the BPU test.The Pearson correlation coefficient was used to evaluate the correlation of the BPU metrics with upper-limb strength and explosive power.Predictive models for upper-limb strength and explosive power were created using stepwise regression analysis.Results BPU metrics showed a good test-retest reliability(ICC=0.764-0.935).PF and MV,along with body weight(BW),were effective predictors of bench press 1RM in young males:bench press 1RM=0.129PF-16.772[R2=0.790,standard error of the estimate(SEE)=8.17 kg];bench press 1RM=1.511BW+87.15 MV-110.136(R2=0.767,SEE=8.60 kg).PF and BW were also predictors of bench press explosive power:bench press explosive power=2.755BW+0.287PF-17.351(R2=0.620,SEE=46.1 W).Conclusions The BPU test demonstrates a good test-retest reliability,and PF and MV from the BPU test can be used to predict upper-limb strength and explosive power in young males.

OBJECTIVE To investigate the analgesic effects and potential mechanisms of the partial agonist of the 5-hydroxytryptamine 1A(5-HT1A)receptor and the selective 5-HT reuptake inhibitor,viladazone(Vil),in various animal models of pain.METHODS ① Mouse acetic acid writhing test:KM mice were divided into the model group,model+morphine 10 mg·kg-1 group,and model+Vil 2,4,8 mg·kg-1 groups.Thirty minutes after ig administration of saline(model group)or corresponding drugs,each group was ip injected with a 2%acetic acid aqueous solution(0.01 mL·g-1),and the writhing frequency of the mice was observed and recorded from 5 to 20 min.② Mouse formalin pain test:KM mice were divided into the model group and model+Vil 2,4 and 8 mg·kg-1 groups.Thirty minutes after ig adminis-tration of saline(model group)or drugs,20 μL of 5%formalin solution was sc injected into the right plantar region of the mice.The licking time(the sum of the duration of licking and biting the paw)of the mice was observed and recorded during two periods:the acute phase(0-5 min after sc formalin injec-tion)and the delayed phase(15-35 min after sc formalin injection).③ Rat chronic constriction injury(CCI)of the sciatic nerve experiment:SD rats successfully examined with a paw withdrawal threshold(PWT)<5 g were randomly divided into a CCI model group and a CCI model+Vil 2,4 and 8 mg·kg-1 group.Solvent(model group)or corresponding drugs were ig administered,and the PWT of the modeled side was measured at 30,60,120 and 240 min after the first administration to evaluate the acute anal-gesic effect of Vil on mechanical pain.Then,Vil was continuously ig administered for 14 d,and the PWT was measured 1 h after Vil administration on the 7th and 14th d to evaluate the long-term analgesic effect of Vil.Immunofluorescence staining was employed to analyze the expression levels of inflamma-tion-related proteins,ionized calcium binding adapter molecule 1(IBA-1),tumor necrosis factor α(TNF-α),and interleukin 1β(IL-1β),in brain tissues.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of IBA-1,TNF-α and IL-1β in the dorsal root ganglion of the spinal cord in the CCI model.RESULTS ① In the mouse model of acetic acid writhing,single ig administration of morphine 10 mg·kg-1 and Vil at varied doses significantly reduced the number of writhings induced by acetic acid compared to the model group.② In the formalin-induced pain model,the average licking time of the model group was 50.5 s during the acute phase of inflammatory pain(0-5 min after intraplantar injec-tion of 5%formalin),and 347.9 s during the delayed phase of inflammatory pain(25-35 min after formalin injection).Compared to the model group,single ig administration of Vil 2-8 mg·kg-1 reduced chronic pain induced by formalin in mice,and each dose of Vil significantly decreased the licking time of mice,but had no notable impact on the licking duration exhibited by mice during acute phase.③ In the CCI model,the PWT values of CCI model rats significantly decreased compared with the control group.Pathological damage to varying extents was observed in brain slices,manifested as enlarged intercellular spaces and the appearance of vacuoles.The expression of IBA-1 in brain tissue significantly increased,while TNF-α and IL-1β hardly changed.The levels of IBA-1,TNF-α and IL-1β in the spinal dorsal root ganglion significantly increased.Compared with the CCI model,after single administration of Vil 2-8 mg·kg-1 for 60,120 and 240 min,Vil significantly reduced the PWT values.After two-week continuous administration,the PWT values in Vil 4 and 8 mg·kg-1 were significantly reduced,and Vil 2-8 mg·kg-1 could alleviate the neuropathic pain to some extent.Vil 8 mg·kg-1 significantly reduced the elevated levels of inflammatory factors compared to CCI rats.CONCLUSION The antidepressant Vil exhibits analgesic effects in mouse models of acetic acid writhing,formalin-induced inflammation,and neuropathic pain induced by CCI in rats,with a more pronounced effect on neuropathic pain.The mechanism of action may be related to the inhibition of inflammatory pathways of IBA-1.