Children， as a special group， frequently experience of off-label drug use worldwide. Common reasons for off-label drug use in children include the lack of data on pediatric patients during the clinical trial stage of drug development， delayed updates to drug instructions， and the non-standard professional behavior of some doctors. Off-label drug use in children is a double-edged sword. It could save lives and provide a way to explore additional functions of drugs， while it may also lead to the phenomenon of hyper-indication abuse， increasing the risk of adverse drug events. Regulating off-label drug use in children can safeguard the best treatment rights and interests of children. It is recommended to encourage pharmaceutical enterprises to conduct research and development of pediatric new drugs， simplify the approval process for drug instructions amendments， accumulate evidence-based medical evidence for off-label drug use in children， standardize the process of off-label drug use in children in medical institutions， continuously improve the standardized diagnosis and treatment capabilities of pediatricians， and actively cooperate with the families of pediatric patients in diagnosis and treatment， so as to comprehensively safeguard the rights and interests of both doctors and patients.

Objective: To investigate the efficacy of implantable neuromuscular electrical stimulation system on stress urinary incontinence (SUI) model in female rats. Methods: A total of 21 female infertile SD rats were randomly divided into the control，sham stimulation，and stimulation groups，with 7 rats in each group.All rats received vaginal dilation (VD) to simulate postpartum SUI.One week after VD，the control group was given normal feeding，stimulators were implanted in the pelvic floor muscles of the sham stimulation and stimulation groups.The sham stimulation group received normal feeding for 2 weeks，and the stimulation group received pelvic floor electrical stimulation (PFES) for 2 consecutive weeks.The leak point pressure (LPP) of each rat was measured with cystometry before VD (baseline value)，1 week after VD，and 2 weeks after PFES. Results: In the control group and sham stimulation group，LPP increased after 2 weeks of treatment compared with that after 1 week of VD，but it still did not return to the baseline level (P<0.001).In the stimulation group，after 2 consecutive weeks of PFES，LPP increased significantly compared with that 1 week after VD，and returned to the baseline value (P>0.05).There was no significant difference in the LPP baseline values and levels after 1 week of VD among the 3 groups (P>0.05).The LPP in the stimulation group after 2 weeks of PFES was significantly higher than that in the sham stimulation group and stimulation group (P<0.001). Conclusion: The implantable neuromuscular electrical stimulation system is effective in short-term intervention of SUI in female rats，the further studies are needed to confirm the long-term efficacy and safety of the system，the optimal stimulation sites，optimal stimulation parameters，and potential mechanisms of action.

Mitochondria, ubiquitous energy-producing organelles in eukaryotic cells, can have their normal functions disrupted by bacterial infections, leading to mitochondrial dysfunction. This dysfunction is closely associated with inflammatory diseases. Periodontitis, a chronic inflammatory disorder of periodontal tissues caused by pathogenic microorganisms, has been increasingly linked to mitochondrial dysfunction in its pathogenesis and progression. Compared to healthy periodontal tissues, inflammatory lesions exhibit more pronounced mitochondrial dysfunction—a pathological process that is strongly correlated with periodontal pathogen infection. Studies reveal that these pathogens disrupt mitochondrial homeostasis in host cells (e.g., gingival epithelial cells and fibroblasts) through multiple mechanisms, including disrupting mitochondrial biogenesis, altering mitochondrial dynamics (promoting excessive fission), inhibiting mitophagy, impairing mitochondrial dysfunction-associated apoptosis, and inducing endogenous oxidative stress, which upregulates pro-inflammatory cytokines. Collectively, these processes drive the establishment and persistence of an inflammatory microenvironment. This review explores how periodontal pathogens affect mitochondrial function and their mechanistic contributions to periodontitis progression, with the goal of providing novel insights for developing mitochondria-targeted therapeutic strategies.

Objective: To investigate the predictive value of EZH2 expression for malignant transformation in oral leukoplakia (OLK) and to provide a reference for clinical practice. Methods: This study was approved by the institutional ethics committee, and informed consent was obtained from all participants. A total of 114 patients diagnosed with OLK by pathological examination and treated at our hospital between November 2020 and July 2022 were initially enrolled. After excluding those with incomplete data or follow-up, 105 participants were included in the final analysis, comprising 14 in the high EZH2 expression group and 91 in the low EZH2 expression group. Histopathological examination of oral mucosa and immunohistochemical detection of EZH2 protein expression were performed. The follow-up period was 30 months; participants were followed until malignant transformation occurred or until the end of follow-up, at which point they were withdrawn from the study. The exposure factor was the level of EZH2 protein expression, and the outcome was the malignant transformation rate of OLK. Differences in EZH2 expression levels and transformation outcomes were analyzed. Results: There were no statistically significant differences between the high and low EZH2 expression groups in terms of age, sex, history of systemic disease, lifestyle habits, psychological status, diet, and sleep conditions (P > 0.05). Lesions in the high EZH2 expression group were mainly located on the ventral tongue, while in the low EZH2 expression group, they were more commonly found on the dorsal tongue and buccal mucosa. The malignant transformation rate was 28.6% (4/14) in the high expression group and 8.8% (8/91) in the low expression group; these differences were not statistically significant (P=0.053). In univariate Cox regression analysis, the risk of malignant transformation in the high EZH2 expression group was 3.647 times that of the low EZH2 expression group (HR = 3.647, 95% CI: 1.097-12.120, P<0.05). Kaplan-Meier survival analysis showed that over the 30-month follow-up period, the cancer-free survival rate in the high EZH2 expression group was 19.8% lower than in the low expression group, and the difference was statistically significant (P<0.05). In multivariate Cox regression analysis, only moderate and severe epithelial dysplasia were identified as independent risk factors for malignant transformation. The risk of malignant transformation in the moderate and severe dysplasia groups was 10.695 and 13.623 times higher, respectively, than in the mild dysplasia group (HR = 10.695, 95% CI: 2.270-50.396, P<0.05; HR=13.623, 95% CI: 1.918-96.774, P<0.05). EZH2 high expression was not an independent risk factor in the multivariate model (HR= 2.528, 95% CI: 0.752-8.500, P = 0.134). Conclusion High EZH2 protein expression is a risk factor for the malignant transformation of OLK but does not have independent predictive value.

OBJECTIVE To explore the practice pathway and evaluate the effectiveness of the resident pharmacists stationed in the Drug Clinical Trial Institution Office （hereinafter referred to as the “GCP resident pharmacist”） in the management of dermatological drug clinical trials. METHODS The practical approach of GCP resident pharmacists participating in dermatological drug clinical trials at our hospital was introduced. A retrospective analysis was conducted on the data of dermatological drug clinical trials from 2021 to 2024， comparing efficiency and quality indicators between dermatological clinical trials and those of other specialties. RESULTS With the involvement of our hospital’s GCP resident pharmacists throughout, the process for dermatology drug clinical trials was constructed and optimized， a dedicated quality control system was established， and the acceleration strategy for subject enrollment was optimized. The number of dermatological drug clinical trials at our hospital showed a compound annual growth rate of 69.56% from 2021 to 2023. In terms of efficiency indicators， the approval waiting time for dermatological drug clinical trials was （12.31±4.99） days， which was significantly shorter than that of other specialties （[ 19.68±6.09） days， P＜0.05]. Regarding quality indicators， the enrollment rate for dermatological drug clinical trials was 75.71%（50.00%，114.48%）， which was significantly higher than that of other specialties [51.00%（25.00%，174.17%）， P＜0.05]. The numbers of first quality control issues （[ 8.31±3.25）items vs.（ 11.68±4.49）items] and protocol deviations [5.5（2.0，11.0）times vs. 11.0（5.5，17.5）times] were significantly lower than those of other specialties （P＜0.05）. CONCLUSIONS GCP resident pharmacists significantly enhance the overall efficiency of dermatological drug clinical trials， playing a crucial role in ensuring the reliability and authenticity of drug clinical trials， as well as safeguarding the rights and safety of trial subjects.

Objective　To analyze the clinical characteristics and prognostic factors for clinical cure in chronic hepatitis B virus (HBV) infected patients with pegylated interferon-α-2b (PEG-IFN-α-2b) based therapy. Methods　This is a retrospective study. Chronic HBV infected patients receiving PEG-IFN-α-2b therapy were enrolled in Yuncheng Central Hospital affiliated to Shanxi Medical University between August 2020 and November 2023. Treatment-naïve patients received PEG-IFN-α-2b monotherapy, while nucleoside (acid) analogs (NAs)-experienced patients received PEG-IFN-α-2b add-on therapy. The study endpoint was hepatitis B surface antigen (HBsAg) negative in accompany with HBV DNA below the detection limit (course of treatment < 48 weeks) or treatment for 48 weeks. The general characteristics, virological variables, blood routine test, and liver function of patients were collected at baseline and study endpoint. Student’s t test or Mann-Whitney U test was used for comparison. The prognostic factors of clinical cure were examined using univariate and multivariate stepwise logistic regression models. Results　A total of 61 chronic HBV infected patients were enrolled, including 39 males and 22 females. The age were (39.13±7.53) years. Twenty-one cases were treatment-naïve, while 40 patients were NAs-experienced. Nineteen cases were positive for HBV DNA at baseline. The baseline HBsAg levels were 211.30(50.93, 2 110.00) IU/mL. Thirty-four patients achieved clinical cure at the study endpoint with 25.50 weeks of median course of PEG-IFN-α-2b treatment. Twenty-seven patients did not achieve clinical cure at the study endpoint, and the course of treatment was 48 weeks. Clinical cure group had significant lower baseline HBsAg level when compared with non-clinical cure group [78.66(19.54, 204.60) IU/mL vs 2 078.00(442.20, 4 237.00) IU/mL, P<0.001]. At the study endpoint, the white blood cell, platelet, red blood cell, hemoglobin levels were lower than those in baseline (P<0.05), while alanine aminotransferase and asparatate aminotransferase levels were higher than those in baseline (P<0.05). There were no remarkable differences in blood routine tests or liver function between clinical cure and non-clinical cure group at either baseline or study endpoint (P>0.05). Baseline low HBsAg level was a predictor for clinical cure in patients receiving PEG-IFN-α-2b therapy (OR=0.998, 95%CI: 0.998-0.999). No severe adverse events were happened during therapy. Conclusion　PEG-IFN-α-2b-based therapy was well-tolerant, and could achieve high rate of clinical cure in chronic HBV-infected patients who had low baseline HBsAg level.

Background Existing studies have confirmed that fine particulate matter (PM_2.5)is one of the important factors inducing pulmonary fibrosis. Pulmonary fibrosis is the terminal stage of a major category of lung diseases characterized by the destruction of tissue structure, and eventually leading lung ventilation and ventilation dysfunction. No effective pulmonary fibrosis treatment is available yet. Objective To investigate the protective effect of salidroside on pulmonary fibrosis induced by the exposure of PM_2.5 and its molecular mechanism. Methods Seventy 7-week-old male C57BL/6 mice were randomly divided into four groups: control group (intratracheal instillation of normal saline + saline by gavage, n=25), Sal group (intratracheal instillation of normal saline + Sal 60 mg·kg⁻¹ by gavage, n=10), PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ + saline by gavage, n=10), and Sal + PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ +Sal 60 mg·kg⁻¹ by gavage, n=10). The mice were administered by gavage once daily, intratracheal instillation once every 3 d, and every 3 d constituted an experimental cycle. At the end of the 26-30th cycles, 3 mice in the control group and 3 mice in the PM_2.5 group were randomly sacrificed, and the lung tissues were collected for Masson staining to verify whether the pulmonary fibrosis model was successfully established. After 30 cycles, the model was successfully constructed. After 1 week of continuous observation, the mice were sacrificed, and the blood and lung tissues of the mice were collected to make lung tissue sections. Assay kits were correspondingly employed to detect oxidative stress indicators such as serum malondialdehyde (MDA) and superoxide dismutase (SOD). Western blotting was used to detect the expression of fibrosis-related proteins (Collagen-III, α-SMA), mitochondrial dynamics-related proteins (MFN1, Drp1), and mitophagy-related proteins (PINK1, Parkin, and LC3). Results Compared with the control group, the weight gain rate of the PM_2.5 group was slowed down (P<0.05), which was alleviated by the Sal intervention (P<0.05). The lung coefficient increased after the PM_2.5 exposure (P<0.05), which was alleviated by Sal intervention. Compared with the control group, the PM_2.5 group showed severe alveolar structure damage, inflammatory cell infiltration, and blue collagen deposition, and significantly increased the lung injury score, collagen volume fraction (CVF), Szapiel score, and Ashcroft score (P<0.05), as well as serum oxidative stress levels (P<0.05). The protein expression levels of Collagen-III, α-SMA, Drp1, PINK1, Parkin, and LC3 II/I were increased (P<0.05), and the expression of MFN1 was decreased (P<0.05). Compared with the PM_2.5 group, the Sal intervention alleviated lung injury, reduced inflammatory cell infiltration and collagen deposition, showing decreased lung injury score, CVF, Szapiel score, and Ashcroft score (P<0.05), and decreased serum oxidative stress levels (P<0.05); the protein expression levels of Collagen-III, α-SMA, PINK1, Parkin, and LC3 II/I were decreased (P<0.05), the expression level of Drp1 was decreased, and the expression level of MFN1 was increased. Conclusion In the process of pulmonary fibrosis induced by PM_2.5 exposure in mice, Sal may affect mitochondrial autophagy through PINK1/Parkin pathway and play a protective role. The specific mechanism needs to be further verified.

Objective To investigate the genetic causes of auditory neuropathy with optic atrophy in a family.Methods The proband's medical history and family history were inquired in detail,and relevant clinical examina-tions were performed to confirm the diagnosis of auditory neuropathy with optic atrophy,and the genetic pedigree of the family was drawn.Peripheral blood of proband(Ⅲ-7)was collected for whole exome sequencing,and the patho-genicity of the detected mutations were interpreted.Blood samples of proband's wife(Ⅲ-8),eldest daughter(Ⅳ-7),second daughter(Ⅳ-9)and son(Ⅳ-10)were tested for mutation sites by Sanger sequencing.Combined with clinical manifestations and examination results,the family was studied.Results The genetic pattern of this family was autosomal dominant.The proband showed decreased visual acuity at the age of 19,bilateral sensorineural deaf-ness at the age of 30,and decreased speech recognition rate.Among 20 members of the family of 5 generations,10(2 deceased)showed similar symptoms of hearing and visual impairment.Proband(Ⅲ-7),eldest daughter(Ⅳ-7)and son(Ⅳ-10)underwent relevant examination.Pure tone audiometry showed bilateral sensorineural deafness.ABR showed no response bilaterally.The 40 Hz AERP showed no response in both ears.OAE showed responses in some or all of the frequencies.No stapedial reflex was detected.The eye movement of Ⅲ-7 and Ⅳ-10 were reasona-ble in all directions,and color vision was normal.Ocular papilla atrophy was observed in different degrees in fundus examination.OCT showed thinning of optic disc nerve fibers in both eyes,and visual evoked potential showed pro-longed P100 wave peak.They were diagnosed as hereditary auditory neuropathy with optic atrophy.A mutation of the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)at a pathogenic locus on chromosome 3 was detected by whole exon detection in Ⅲ-7.The results of generation sequencing analysis showed that the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)mutation of chromosome 3 was also found in Ⅳ-7 and Ⅳ-10.Meanwhile,the gen-otypes of Ⅲ-8 and Ⅳ-9 were wild homozygous,that is,no mutation occurred.Conclusion The OPA1 c.1334G＞A(p.Arg445His,NM_015560.2)mutation site might be the pathogenic mutation in this family.

ObjectiveTo understand the epidemiological characteristics of syphilis in Ruian City, so as to provide a scientific basis for developing syphilis prevention and control strategies. MethodsDescriptive epidemiological methods were used to investigate the infection status of syphilis cases reported among the permanent resident population in Ruian City from 2014 to 2023, and its epidemiological characteristics were analyzed. ResultsA total of 5 482 syphilis cases were reported in Ruian from 2014 to 2023, with a male-female ratio of 1∶1.47. The average annual incidence rate from 2014 to 2023 was 37.51/100 000, with a declining trend in the incidence rate among females (APC=-4.78%, P<0.05). The incidence of primary and secondary syphilis decreased, while the proportion of latent syphilis cases increased. No cases of congenital syphilis were reported from 2017 to 2023. The majority of cases (60.29%) were reported among individuals aged 20‒<50 years. In terms of occupation, the highest proportion was found among housekeepers and the unemployed, constituting 42.70% the total cases. Dermatology departments reported the most cases in medical institutions, accounting for 33.38% of the total cases. The most likely route of infection was heterosexual transmission, accounting for 85.84%. ConclusionThe incidence of syphilis among females in Ruian City shows a declining trend, but the overall situation remains concerning. Prevention and control efforts should be intensified among key groups and high-risk populations, along with an enhancement on health education to curb the spread of syphilis.

Background Salidroside (SAL) has a protective effect on multiple organ systems. Exposure to fine particulate matter (PM_2.5) in the atmosphere may lead to disruptions in gut microbiota and impact intestinal health. The regulatory effect of SAL on the gut microbiota of mice exposed to PM_2.5 requires further investigation. Objective To evaluate gut microbiota disruption in mice after being exposed to PM_2.5 and the potential effect of SAL. Methods Forty male C57BL/6 mice, aged 6 to 8 weeks, were randomly divided into four groups: a control group, an SAL group, a PM_2.5 group, and an SAL+PM_2.5 group, each containing 10 mice. In the SAL group and the SAL+PM_2.5 group, the mice were administered SAL (60 mg·kg⁻¹) by gavage, while in the control group and the PM_2.5 group, sterile saline (10 mL·kg⁻¹) was administered by gavage. In the PM_2.5 group and the SAL+PM_2.5 group, PM_2.5 suspension (8 mg·kg⁻¹) was intratracheally instilled, and in the control group and SAL group, sterile saline (1.5 mL·kg⁻¹) was intratracheally administered. Each experiment cycle spanned 2 d, with a total of 10 cycles conducted over 20 d. Histopathological changes in the ileum tissue of the mice were observed after HE staining. Colon contents were collected for gut microbiota sequencing and short-chain fatty acids (SCFAs) measurements. Results The PM_2.5 group showed infiltration of inflammatory cells in the ileum tissue, while the SAL+PM_2.5 group exhibited only a small amount of inflammatory cell infiltration. Compared to the control group, the PM_2.5 group showed decreased Shannon index (P<0.05) and increased Simpson index (P<0.05), indicating that the diversity of gut microbiota in this group was decreased; the SAL+PM_2.5 group showed increased Shannon index compared to the PM_2.5 group (P<0.05) and decreased Simpson index (P<0.05), indicating that the diversity of gut microbiota in mice intervened with SAL was increased. The principal coordinates analysis (PCoA) revealed a significant separation between the PM_2.5 group and the control group, while the separation trend was less evident among the control group, the SAL group, and the SAL+PM_2.5 group. The unweighted pair-group method with arithmetic means (UPGMA) clustering tree results showed that the control group and the SAL group clustered together first, followed by clustering with the SAL+PM_2.5 group, and finally, the three groups clustered with the PM_2.5 group. The PCoA and UPGMA clustering results indicated that the uniformity and similarity of the microbiota in the PM_2.5 group were significantly decreased. Compared to the control group, the PM_2.5 group showed decreased abundance of phylum Bacteroidetes and Candidatus_Saccharimonas (P<0.05) and increased abundance of phylum Proteobacteria, genus Escherichia, genus Bacteroides, genus Prevotella, genus Enterococcus, and genus Proteus (P<0.05). Compared to the PM_2.5 group, the SAL+PM_2.5 group showed decreased abundance of phylum Proteobacteria, phylum Actinobacteria, genus Prevotella, and genus Proteus (P<0.05), and increased abundance of Candidatus_Saccharimonas (P<0.05). The PM_2.5 group showed reduced levels of propionic acid, valeric acid, and hexanoic acid compared to the control group (P<0.05), while the SAL+PM_2.5 group showed increased levels of propionic acid, isobutyric acid, butyric acid, valeric acid, and hexanoic acid compared to the PM_2.5 group (P<0.05). Conclusion Exposure to PM_2.5 can cause pathological alterations, microbial dysbiosis, and disturbing production of SCFAs in intestinal tissue in mice. However, SAL can provide a certain degree of protective effect against these changes.