Objective:To observe the effects of acupuncture on the motor function of Parkinson disease(PD)model mice and to investigate the neuroprotective effects of acupuncture on PD from the perspective of cellular senescence.Methods:C57BL/6J mice were randomly divided into a normal control(NC)group,a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)group,an acupuncture(ACU)group,and a rasagiline(RAS)group,with 6 mice in each group.Except for the mice in the NC group,all mice were injected intraperitoneally with MPTP[30 mg/(kg·bw)]to establish a PD mouse model.After the models were successfully established,mice in the ACU group received acupuncture at Baihui(GV20)and bilateral Yanglingquan(GB34)for 15 min,once a day for 14 consecutive days.Mice in the RAS group were treated with gavage of rasagiline mesylate[0.5 mg/(kg·bw)],once daily for 14 d.Mouse balance and motor functions were detected using the mouse fatigue rotating rod apparatus.Immunohistochemistry staining was used to detect the number of tyrosine hydroxylase(TH)-positive neurons and the protein expression levels of special AT-rich sequence-binding protein 1(SATB1),p21,and p53 in the substantia nigra(SN)region of the mouse brain in each group.The glutathione peroxidase(GSH-Px)activity of mouse brain SN tissue was detected by enzyme-linked immunosorbent assay.The protein expression levels of interleukin(IL)-6 and senescence-associated β-galactosidase(SA-β-gal)in the SN tissue of mice in each group were detected by Western blotting.The relative expression of SATB1,p21,and p53 mRNA in the SN of each group was detected by real-time quantitative polymerase chain reaction.Results:Compared to the NC group,the overall rod performance(ORP)score,the number of TH-positive neurons,and GSH-Px activity in the SN region were significantly lower in the mice in the MPTP group(P<0.01);compared to the MPTP group,the ORP score,the number of TH-positive neurons,and GSH-Px activity were significantly increased in the ACU group and the RAS group(P<0.01 or P<0.05).Compared to the NC group,the protein levels of IL-6 and SA-β-gal in the SN tissue,the protein and mRNA expression levels of p21 and p53 were significantly increased(P<0.01);compared to the MPTP group,the protein levels of IL-6 and SA-β-gal in the SN tissue,the protein and mRNA expression levels of p21 and p53 were significantly decreased in the ACU group and the RAS group(P<0.01 or P<0.05).Compared to the NC group,the relative expression of SATB1 protein and mRNA in the SN of mice in the MPTP group was significantly decreased(P<0.01);compared to mice in the MPTP group,mice in the ACU group and the RAS group showed significant increases in the relative expression of SATB1 protein and mRNA(P<0.01 or P<0.05).Conclusion:Acupuncture can improve motor function and increase the number of TH-positive neurons in the SN of PD model mice.Its neuroprotective effect may relate to the regulation of the SATB1/p21 signaling pathway and the inhibition of cellular senescence-related biomarker expression in the SN.

In this work,near infrared carbon quantum dots(NIR-CDs)were synthesized by hydrothermal method using biomass material Clausena lansium leaves.The synthesized NIR-CDs emitted maximum fluorescence signal at 677 nm,which was independent of excitation wavelength.The characterization results showed that there were abundant groups on the surface of NIR-CDs.Pd2+could form non-fluorescent compounds with the surface groups of NIR-CDs,resulting in fluorescence quenching(Fluorescence signal was denoted as F0).Because chlorpromazine hydrochloride(CPZ)parent nucleus contained unoxidized S atom,CPZ could form stable colored complex with Pd2+under acidic conditions.In the presence of CPZ,Pd2+dissociated from the surface of NIR-CDs and bonded with CPZ,so that the fluorescence signal could be restored(Fluorescence signal was denoted as F).An"on-off-on"fluorescence sensor was thus constructed.The fluorescence signal recovery value of NIR-CDs(△F=F-F0)showed a good linear relationship with the concentration of CPZ in the range of 5.68-28.43 μg/mL,and the detection limit(3σ)was 0.078 μg/mL.The sensor was applied to determination of CPZ in pharmaceutical preparations,and the recoveries were 94％-106％.The developed fluorescence sensor was expected to be used in quality control of actual pharmaceutical preparations.

Objective To evaluate the clinical efficacy of Dangui Siwei Yin cell-wall broken powder in the treatment of degenerative lumbar spinal stenosis(DLSS)with qi deficiency and blood stasis syndrome.Methods A randomized controlled trial was conducted on 72 patients with qi deficiency and blood stasis-typed DLSS admitted to Guangdong Second Traditional Chinese Medicine Hospital(Huangpu Hospital)from November 2023 to January 2025.Patients were randomly divided into a cell-wall broken powder group and a traditional midicinal slice group(36 cases each)using a random number table method.Both groups received conventional western treatment(oral administration of Etoricoxib Tablets and Mecobalamin Tablets).Additionally,the cell-wall broken powder group was treated with Dangui Siwei Yin cell-wall broken powder,while the traditional midicinal slice group received traditional decoction of Dangui Siwei Yin.Both groups underwent a 1-week treatment course.Changes in Visual Analogue Scale(VAS)of pain scores,Oswestry Disability Index(ODI)scores,and Japanese Orthopaedic Association(JOA)lumbar function scores were observed before and after treatment.Clinical efficacy and medication safety were evaluated.Results(1)After one week of treatment,the total effective rate was 88.89％(32/36)in the cell-wall broken powder group and 75.00％(27/36)in the traditional midicinal slice group.The intergroup comparison(by chi-square test)showed that the efficacy in the cell-wall broken powder group was superior to the traditional midicinal slice group(P＜0.05).(2)After treatment,VAS and ODI scores were significantly decreased in both groups(P＜0.05),while JOA scores significantly increased(P＜0.05).The cell-wall broken powder group demonstrated superior improvements in VAS and ODI reduction and JOA elevation compared to the traditional midicinal slice group(P＜0.05).(3)The adverse reaction rate was 8.33％(3/36)in the cell-wall broken powder group and 11.11％(4/36)in the traditional midicinal slice group,with no statistically significant difference(P＞0.05).Conclusion Compared with traditional midicinal slice,Dangui Siwei Yin cell-wall broken powder exhibit better efficacy in alleviating low back and leg pain and improving lumbar function in qi deficiency and blood stasis-typed DLSS patients.This study provides evidence-based medical support for the clinical application and further development of cell-wall broken powder formulations in traditional Chinese medicine.

Objective:To summarize the clinical characteristics of focal cerebral arteriopathy (FCA) in children, and to analyze its influencing factor of prognosis.Methods:A retrospective cohort study was conducted. Clinical data from 40 children with FCA who were hospitalized at the Department of Neurology, Beijing Children′s Hospital, Capital Medical University, from September 2015 to August 2024 were collected. A centralized follow-up was conducted in October 2024 via outpatient clinics or the internet. The pediatric stroke outcome measure (PSOM) was used to evaluate their outcomes. Based on the PSOM, the children were further divided into a group with normal neurological function and another group with abnormal neurological function. Differences between groups were analyzed using the Mann-Whitney U test and Fisher exact test. Univariate Logistic regression analysis was performed to identify the influencing factors for neurological outcomes in children with FCA. Results:A total of 40 children were included, with 20 males and 20 females, and the onset age of 9.2 (6.8, 12.5) years. Among them, 12 cases (30%) had a history of varicella within 1 year before onset. There were 23 cases (58%) presenting with transient ischemic attack (TIA) or recurrent fluctuating symptoms of onset, while 3 cases (8%) developed progressive stroke within the first month of onset. The M1 segment of the middle cerebral artery was the most commonly affected vascular site, with a total of 16 cases (40%). Arterial occlusion occurred in 8 cases (20%). Lumbar puncture was completed in 36 children, and white blood cell counts in cerebrospinal fluid was increased in 6 cases. All 23 patients who completed magnetic resonance vessel wall imaging (VWI) showed circular enhancement of the arterial wall. A total of 28 patients (70%) received antiplatelet or anticoagulation therapy, and 16 patients (40%) received hormone therapy. At admission, the pediatric National Institute of Health Stroke Scale (PedNIHSS) score was 6.0 (2.0, 8.8) points, which decreased to 0.5 (0, 3.0) points at discharge. The follow-up duration was 1.6 (0.8, 4.9) years, with 1 case lost to follow-up. There was 1 case presenting with recurrence course manifesting as TIA. Among the 39 cases who completed the follow-up, 23 cases (59%) were assessed as neurologically normal by PSOM, while 16 cases (41%) were assessed as neurologically abnormal. Among the 29 cases who completed the imaging review, magnetic resonance angiography (MRA) review in 23 cases indicated stability or improvement in the original arterial stenosis, with 6 cases experiencing transient worsening of arterial stenosis early in the disease course (within 2 months), which later improved. Arterial stenosis progression occurred in 6 cases at the final review of 29 cases who completed the imaging review, with 1 case developing progressive cerebral arteriopathy. The proportion of patients with headache, altered consciousness, and aphasia in the abnormal neurological function group, as well as the PedNISS scores at admission and discharge, were all higher than those in the normal neurological function group (all P<0.05). Univariate Logistic regression analysis revealed that only a PedNISS score>6 points at onset was an influencing factor for abnormal neurological function ( OR=20.58, 95% CI 3.93-107.70, P<0.001). Conclusions:Childhood FCA often presents with fluctuating onset, and the proximal segment of the middle cerebral artery is frequently affected. Progression of arterial stenosis is common within 2 months of the disease course, but clinical progression and new ischemic lesions are uncommon. Most patients have a favorable long-term prognosis. PedNIHSS score>6 points at admission is related to abnormal neurological function outcomes.

Objective:To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and 24-h urinary calcium excretion (24-h UCaE) and hypercalciuria in Chinese adults.Methods:This cross-sectional study was conducted from March 2022 to March 2023 in nine cities in China and included 1 239 residents. Demographic characteristics were collected through questionnaires and physical examinations, fasting blood samples were assessed for bone metabolism indicators, and 24-h urine samples were used to determine the 24-h UCaE. Multiple linear regression analysis was used to explore the relationship between serum 25(OH)D and 24-h UCaE and bone metabolism indexes. The relationship between serum 25(OH)D and hypercalciuria was analyzed using a multiple logistic regression model combined with restricted cubic spline modeling.Results:The mean participant age was (47.9±18.1) years, of which 453 (36.6%) were male. The percentages of vitamin D sufficiency, insufficiency, and deficiency were 7.6% (94/1 239), 29.0% (359/1 239), and 63.4% (786/1 239), respectively. The multiple linear regression model showed that after adjusting for the covariates the 24-h UCaE gradually increased with higher levels of 25(OH)D ( P overall <0.001, P nonlinear <0.001). The logistic regression analysis revealed that compared with the vitamin D deficient group, the OR for the prevalence of hypercalciuria in the vitamin D sufficient and vitamin D insufficient groups were 3.290 (95% CI 1.745 to 6.202) and 3.742 (95% CI 2.458 to 5.697), respectively. The results of the restricted cubic spline modeling showed a positive nonlinear relationship between 25(OH)D and the prevalence of hypercalciuria ( P overall <0.001, P nonlinear <0.001). The prevalence of hypercalciuria increased when 25(OH)D was >17.00 μg/L and peaked at 26.71 μg/L, after which there was a decreasing trend in the prevalence of hypercalciuria with increasing 25(OH)D. Conclusion:Associations between serum 25(OH)D levels and urinary calcium excretion and the prevalence of hypercalciuria were observed in the Chinese adult population.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50％).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P＜0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P＜0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P＜0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P＜0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by impaired motility of cilia and flagella. Mutations in cilia- and flagella-associated protein 300 ( CFAP300 ) are associated with human PCD and male infertility; however, the underlying pathogenic mechanisms remain poorly understood. In a consanguineous Chinese family, we identified a homozygous CFAP300 loss-of-function variant (c.304delC) in a proband presenting with classical PCD symptoms and severe sperm abnormalities, including dynein arm deficiency and acrosomal malformation, as confirmed by transmission electron microscopy (TEM). Histological analysis revealed multiple morphological abnormalities of the sperm flagella in CFAP300 -mutant individual, whereas immunofluorescence demonstrated markedly reduced CFAP300 expression in the spermatozoa of the proband. Furthermore, tandem mass tag (TMT)-based quantitative proteomics showed that the CFAP300 mutation reduced key spermatogenesis proteins (e.g., sperm flagellar 2 [SPEF2], solute carrier family 25 member 31 [SLC25A31], and A-kinase anchoring protein 3 [AKAP3]) and mitochondrial ATP synthesis factors (e.g., SLC25A31, cation channel sperm-associated 3 [CATSPER3]). It also triggered abnormal increases in autophagy-related proteins and signaling mediator phosphorylation. These molecular alterations are likely to contribute to progressive deterioration of sperm ultrastructure and function. Notably, successful pregnancy was achieved via intracytoplasmic sperm injection (ICSI) using the proband's sperm. Overall, this study expands the known CFAP300 mutational spectrum and offers novel mechanistic insights into its role in spermatogenesis.
Humans ; Male ; Infertility, Male/pathology* ; Acrosome/pathology* ; Sperm Tail/pathology* ; Pedigree ; Spermatozoa ; Adult ; Loss of Function Mutation ; Ciliary Motility Disorders/genetics* ; Spermatogenesis/genetics* ; Female