ObjectiveTo investigate the therapeutic effect and mechanism of Xueshisanjia San against liver fibrosis by regulating PTEN-induced putative kinase （PINK1）/Parkin signaling pathway-mediated mitophagy. MethodsForty specific pathogen free （SPF）-grade male C57BL/6 mice were randomized into the control， model， silibinin （100 mg·kg^-1）， high-dose （15.16 g·kg^-1） Xueshisanjia San， and low-dose （7.58 g·kg^-1） Xueshisanjia San groups. The mouse model of liver fibrosis was constructed by intraperitoneal injection of 20% carbon tetrachloride solution. The treatment lasted for 6 weeks. Blood was collected from the abdominal aorta after intraperitoneal anesthesia， and the liver was separated. Liver pathology was examined by hematoxylin-eosin （HE） staining， Masson staining， and Sirius Red staining. Transmission electron microscopy （TEM） was employed to observe the mitochondrial morphology in the liver tissue. The levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， C-reactive protein （CRP）， total bilirubin （TBil）， transforming growth factor-β₁ （TGF-β₁）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） in the serum of mice were measured by enzyme-linked immunosorbent assay. Immunohistochemistry， immunofluorescence assay， and Western blot were employed to determine the protein levels of liver fibrosis markers α-smooth muscle actin （α-SMA） and collagen Ⅰ， as well as mitophagy markers microtubule-associated protein 1 light chain 3 （LC3）， p62， Beclin-1， PINK1， Parkin， and translocase of outer mitochondrial membrane 20 （TOM20）. ResultsCompared with the control group， the model group exhibited elevated levels of ALT， AST， CRP， TBil， IL-6， TGF-β₁， and TNF-α in the serum （P<0.05）， pathological changes such destroyed structure of hepatic lobules， disarrangement of hepatic cells， and collagen accumulation， swollen， vacuolated， and fragment mitochondria， down-regulated expression of p62 and TOM20， and up-regulated expression of LC3， Beclin-1， PINK1， and Parkin （P<0.05）. Compared with the model group， all the treatment groups exhibited declined levels of ALT， AST， CRP， TBil， IL-6， TGF-β₁， and TNF-α in the serum （P<0.05）， alleviated pathological damage of liver tissue and mitochondrial damage， up-regulated expression of p62 and TOM20， and down-regulated expression of α-SMA， COL1A1， LC3， Beclin1， PINK1， and Parkin （P<0.05）. ConclusionXueshisanjia San may prevent excessive mitophagy and improve mitochondrial quality by inhibiting PINK1/Parkin signaling pathway， thereby alleviating liver fibrosis.

Objective:To investigate the molecular characteristics and clinical heterogeneity of Usher syndrome（USH） -related gene variants in patients with hereditary hearing loss in southwest China, providing a basis for early diagnosis and clinical management. Methods:Thirteen patients from twelve families with hearing loss who attended the Affiliated Children's Hospital of Kunming Medical University between January 2017 and March 2021 were enrolled. All patients were identified as carrying USH-related gene variants through next-generation sequencing. Sanger sequencing was performed for all patients and their parents to validate the pathogenic variants. Comprehensive clinical evaluations, including medical history collection, otologic and ophthalmologic examinations, and vestibular function assessments, were conducted. Results:Among the 13 patients, 4 were diagnosed with USH type 1 and 2 with USH type 2. A total of 19 pathogenic or likely pathogenic variants were detected in USH-related genes, including MYO7A,CDH23,USH1C, and USH2A. The causative gene was MYO7A in 3 probands, CDH23 in 5, USH1C in 3, and USH2Ain 2. All patients exhibited an autosomal recessive inheritance pattern. Vestibular dysfunction was observed in 4 patients, and retinitis pigmentosa（RP） in 3 patients. Based on the genotype-phenotype correlation, 6 patients were initially diagnosed with USH, while 7 were classified as having non-syndromic hearing loss（NSHL）. Conclusion:This study revealed the clinical heterogeneity of USH-related gene variants in patients with hereditary deafness in southwest China. Although the clinical manifestations of USH are complex and there are overlapping characteristics between different subtypes, genetic testing provides an important basis for early diagnosis and precise clinical management. Especially for those with typical hearing loss, early genetic diagnosis can provide a window of time for early detection and intervention of retinitis pigmentosa.
Humans ; Usher Syndromes/genetics* ; Myosin VIIa ; Phenotype ; Male ; Female ; Myosins/genetics* ; Mutation ; Cadherins/genetics* ; Child ; Extracellular Matrix Proteins/genetics* ; Adolescent ; Pedigree ; High-Throughput Nucleotide Sequencing ; Cadherin Related Proteins ; Cytoskeletal Proteins ; Cell Cycle Proteins

Objective To explore the predictive value of combined serum soluble hemoglobin scavenger receptor 163(sCD163),hypersensitive C-reactive protein(hs-CRP),and procalcitonin(PCT)for stroke-associated pneumonia(SAP).Methods A total of 100 patients with acute ische-mic stroke admitted to the First Hospital of Zhangjiakou from October 2021 to January 2023 were se-lected as the study subjects.According to whether they developed SPA within 7 days of admission,they were divided into SAP group(n=64)and non-SAP group(n=36).Based on pneumonia se-verity index(PSI),patients in the SAP group were further divided into mild SAP group and severe SAP group.Enzyme-linked immunosorbent assay(ELISA)was used to detect the serum levels of sCD163,hs-CRP,and PCT.The clinical data of the patients were collected and compared.Pearson's method was used to analyze the correlation between the PSI score and the serum levels of sCD163,hs-CRP,and PCT in SAP patients.Multivariate Logistic regression analysis was employed to screen for factors influencing the occurrence of SAP.Receiver operating characteristic(ROC)curve analy-sis was used to evaluate the predictive efficacy of serum sCD163,hs-CRP,and PCT for the occur-rence of SAP.Results The proportion of patients with dysphagia and the National Institutes of Health Stroke Scale(NIHSS)score in the SAP group were significantly higher than those in the non-SAP group(P＜0.05).The serum levels of sCD163,hs-CRP,and PCT in the SAP group were significantly higher than those in the non-SAP group(P＜0.05).The serum levels of sCD163,hs-CRP,and PCT in the severe SAP group were significantly higher than those in the mild SAP group(P＜0.05).Pearson's correlation analysis showed that the PSI score was positively correlated with the serum levels of sCD163,hs-CRP and PCT in SAP patients(r=0.356,0.413,0.391,P＜0.001).Logistic regression analysis revealed that serum sCD163,hs-CRP,PCT,NIHSS score,and dysphagia were all influencing factors for the occurrence of SAP(P＜0.05).The areas under the curve(AUC)for predicting SAP using serum sCD163,hs-CRP,PCT and their combina-tion were 0.842,0.924,0.866 and 0.973,respectively,with sensitivities of 73.44％,84.37％,67.19％and 90.62％,and specificities of 88.89％,83.33％,97.22％and 94.44％,respectively.The predictive value of the combined detection was superior to that of the individual detection of ser-um sCD163,hs-CRP and PCT(P＜0.05).Conclusion The serum levels of sCD163,hs-CRP,and PCT are elevated in SAP patients,and their changes are closely related to the severity of the disease.The combined detection of these three indicators has a high value in predicting the occur-rence of SAP and may serve as auxiliary markers for predicting early SAP.

Objective:To explore the associations of temperature, relative humidity, and their interaction effect with fall risk.Methods:Data on fall cases were collected using the national injury surveillance system from May to September, in 2006-2022 in Hubei Province. Combined with the meteorological and air pollution data, we conducted a time-stratified case-crossover design and used conditional logistic regression models and distributed lag nonlinear models to examine the exposure-response relationships between temperature, humidity, and fall risk. We further divided the low and the high temperature groups and the low and the high relative humidity groups and analyzed the excess risk ( ER) of falls attributed to dry-hot or wet-hot events. Finally, we calculated the additive interactions of temperature and humidity on fall risk. Results:A total of 55 401 fall cases were included. With the increase in temperature and relative humidity decrease, the exposure-response curves of fall showed nonlinear upward trends among all populations. Gender and age differences were found in temperature-fall and relative humidity-fall risk relationships. Compared with wet-non-hot (normal temperature and high relative humidity) events, the ER of fall in dry-hot (high temperature and low relative humidity) events was 14.80% (95% CI: 9.69%- 20.15%), and the ER of wet-hot (high temperature and high relative humidity) events was 9.59% (95% CI: 2.52%-17.13%). However, there was no statistically significant difference between dry-hot and wet-hot events in the fall, and no statistically significant difference between different genders, ages, occupations, and fall occurred place (all P>0.05). No significant synergistic additive interaction was found between temperature and relative humidity on fall risk (relative excess risk due to interaction=-0.08, 95% CI: -0.19-0.02). Conclusions:Higher temperatures and lower relative humidity were associated with increased fall risk. Both dry-hot and wet-hot events had a higher risk of fall, while high temperature and low humidity have no synergistic effect on fall risk.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective To explore the challenges faced by online appointment nurses during nasogastric intubation and to provide a reference for improvement of the quality and safety of the services provided by online appointment nursing.Methods A purposive sampling was employed to select 13 online appointment nurses from our hospital who had previously provided home nasogastric intubation services for patients.Semi-structured interviews were conducted with the online appointment nurses.The results acquired from the interviews were analysed using Colaizzi's method.Results Two themes were identified.Theme 1 covered the increased risks of nasogastric intubation due to the patients themselves and home environment,which included 4 sub-themes of difficulties in identification and response due to complex conditions of patient,high risk of a sudden asphyxia with poor resuscitation facility,psychological stress from unfamiliar home environment,and more challenges in risk identification due to limited conditions for performing home-based intubation procedures;Theme 2 covered the coping strategies of online-scheduled nurses,which included the improvement of knowledge and skills in emergency nursing to improve comfidence and judge ability of intubation,the strengthening of nurse-patient communication to build a trust and cooperation,the conduct of thorough assessment to ensure procedural safety,and the use of alternative tools and collaboration with family members.Conclusion Online appointment nurses face challenges and risks from both of the procedures and patients themselves during home based nasogastric intubation.Hospitals and relevant management should actively implement corresponding strategies,provide training and guidance for online appointment nurses,develop relevant regulations,and improve the management mechanisms of the internet platform to ensure the safety of home based nasogastric intubation for online appointment nurses and improve the quality of the"Internet Plus Nursing Services."

Objective:To detect the expression of sialylated CD15 (CD15s) in the tumor cells of classical Hodgkin lymphoma using a modified immunohistochemical approach.Methods:From 2009 to 2024, 53 cases of classical Hodgkin lymphoma were collected in the Department of Pathology, Peking University Cancer Hospital, in which 21 cases that were CD15-negative or showed only focal weak positivity were selected. Immunohistochemical staining for CD15 was performed on a Leica automated stainer using three different antibody clones (MMA, Carb3, and IHC527). Tissue sections were digested with sialidase at varying concentrations and incubation times, followed by immunohistochemical staining with the MMA clone. Multiplex immunofluorescence was applied for co-staining of CD15 (MMA) and CD30 (JCM182), and analysis was conducted using APTIME and HALO software.Results:There were 30 male patients and 23 female patients, with an age range of 14 to 73 years and a median age of 32(26,46) years. None of the three CD15 antibody clones significantly improved the CD15 positive rate in the 14 completely negative and 7 weakly positive cases, with no notable differences observed among the clones( P>0.05). After sialidase digestion, tissue morphology remained well-preserved. Optimal CD15 staining was achieved with a 1∶1 diluted sialidase incubated at 37 ℃ for one hour. This treatment significantly enhanced the detection rate of CD15 antigen in Hodgkin Reed-Sternberg cells ( P<0.001). Conclusion:Sialidase digestion effectively unveils sialylated CD15 expression in classical Hodgkin lymphoma, markedly improving its detection in HRS cells.

Objective To investigate the protective effect of Ghrelin on traumatic brain injury(TBI)in rats based on the HO-1/PGC-1αsignaling pathway.Methods Thirty SPF male rats were randomly divided into sham,TBI,and Ghrelin groups,with 10 rats in each group.A TBI rat model was established using the Feeney free-fall impingement method.The Ghrelin group was injected by caudal vein at a dose of 20 μg/kg 30 min after modeling,while the sham group was not impinged.After 72 h of modeling,the brain tissues of the rats were col-lected,and the brain water content was measured in order to analyze the severity of brain edema.HE staining was used to observe patho-logical changes in brain tissue.The levels of the oxidative stress factors MDA,SOD,and GSH-Px were determined using ELISA.TUNEL staining was used to detect the apoptosis of the brain cells,and the expression levels of Bcl-2,Bax,caspase-3 and caspase-9 in the brain tissues were detected by Western blotting.Mitochondrial reactive oxygen species(mtROS)in the brain tissues were detected by immuno-fluorescence.Mitochondrial function indicators,including mitochondrial mitogen Mfn 1/2,nuclear respiration factor 1(NRF1),and mito-chondrial transcription factor A(TFAM)were detected by Western blotting.The expression levels of HO-1 and PGC-1α in the brain tis-sues of rats in each group were detected by Western blotting.Twenty TBI model rats treated with Ghrelin were divided into Ghrelin+sh-NC and Ghrelin+sh-HMOX1 group with 10 rats in each group.Rats were treated with Ghrelin and injected with knock-down control(adenovirus 2.5 × 109 pfu)or knock-down HMOX1 adenovirus(2.5 × 109 pfu)via tail vein.Western blotting was used to detect the expressions of HO-1,PGC-1 α,Bcl-2,Bax,caspase-3 and caspase-9 in the brain tissues of the two groups.The levels of MDA,SOD and GSH-Px in brain tissue of two groups were detected by ELISA.Results Compared with the sham group,the pathological injury and brain edema in TBI group were aggravated,the number of brain cell apoptosis increased,the levels of oxidative stress factors SOD and GSH-Px decreased,the level of MDA increased,the level of mtROS in brain tissue decreased,the expressions of Bax,caspase-3 and caspase-9 increased,and the expressions of Mfn1/2,NRF1,TFAM,HO-1 and PGC-1α decreased(P＜0.05).Compared with TBI group,the pathological damage of brain tissue in Ghrelin group was improved,the brain edema was alleviated,the number of brain cell apoptosis was reduced,the levels of oxidative stress factors SOD and GSH-Px were increased,the level of MDA was decreased,the mtROS in brain tissue was decreased,the expression of Bcl-2 protein was increased,the expressions of Bax,caspase-3 and caspase-9 protein were decreased,and the expressions of Mfn1/2,NRF1,TFAM,HO-1 and PGC-1α were decreased(P＜0.05).Compared with Ghrelin+sh-NC group,the expressions of Bax,caspase-3 and caspase-9,MDA in brain tissue of Ghrelin+sh-HMOX1 group increased,while the levels of SOD and GSH-Px decreased(P＜0.05).Conclusion Chrelin has protective effect on TBI in rats,and can inhibit brain tissue injury and apoptosis in rats.Its mechanism may be achieved by regulating mitochondrial oxidative stress through HO-1/PGC-1α signaling pathway.

Objective:To explore the effect of loneliness on self-perceived aging among elderly patients after gastric cancer surgery, and to examine the mediating role of emotion regulation strategies, in order to provide a basis for clinical interventions.Methods:A convenience sample of 220 elderly postoperative gastric cancer patients hospitalized in Shanxi Provincial Cancer Hospital between August and November 2024 was selected. Data were collected using a general demographic questionnaire, the Emotion Regulation Questionnaire (ERQ), the Cancer Loneliness Scale (CLS), and the Brief Aging Perceptions Questionnaire (B-APQ). A structural equation model was constructed using AMOS 26.0, and the significance of the mediating effect was tested using the bootstrap method with 5 000 resamples.Results:A total of 220 questionnaires were distributed in this study, and 203 valid questionnaires were recovered, with a response rate of 92.27%. The total B-APQ score was (47.45±11.43). For the ERQ, the score for cognitive reappraisal was (22.80±8.17), and for expressive suppression was (18.37±5.10). The CLS score was (18.19±6.11). Mediation analysis showed that loneliness had a direct effect of 0.353 on self-perceived aging. Emotion regulation strategy—cognitive reappraisal—partially mediated the relationship between loneliness and self-perceived aging, with a mediation effect value of 0.178, accounting for 33.52% of the total effect (0.178/0.531) .Conclusions:Clinical practitioners should implement interventions to reduce loneliness in elderly patients after gastric cancer surgery and guide them in adopting cognitive reappraisal as an emotion regulation strategy. These approaches may help promote positive aging in this patient population.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.