Parkinson’s disease (PD) is a common neurodegenerative disorder that significantly impacts patients’ independence and quality of life, imposing a substantial burden on both individuals and society. Although dopaminergic replacement therapies provide temporary relief from various symptoms, their long-term use often leads to motor complications, limiting overall effectiveness. In recent years, non-invasive deep brain stimulation (DBS) techniques have emerged as promising therapeutic alternatives for PD, offering a means to modulate deep brain regions with high precision without invasive procedures. These techniques include temporal interference stimulation (TIs), low-intensity transcranial focused ultrasound stimulation (LITFUS), transcranial magneto-acoustic stimulation (TMAS), non-invasive optogenetic modulation, and non-invasive magnetoelectric stimulation. They have demonstrated significant potential in alleviating various PD symptoms by modulating neural activity within specific deep brain structures affected by the disease. Among these approaches, TIs and LITFUS have received considerable attention. TIs generate low-frequency interference by applying two slightly different high-frequency electric fields, targeting specific brain areas to alleviate symptoms such as tremors and bradykinesia. LITFUS, on the other hand, uses low-intensity focused ultrasound to non-invasively stimulate deep brain structures, showing promise in improving both motor function and cognition in PD patients. The other three techniques, while still in early research stages, also hold significant promise for deep brain modulation and broader clinical applications, potentially complementing existing treatment strategies. Despite these promising findings, significant challenges remain in translating these techniques into clinical practice. The heterogeneous nature of PD, characterized by variable disease progression and individualized treatment responses, necessitates flexible protocols tailored to each patient’s unique needs. Additionally, a comprehensive understanding of the mechanisms underlying these treatments is crucial for refining protocols and maximizing their therapeutic potential. Personalized medicine approaches, such as the integration of neuroimaging and biomarkers, will be pivotal in customizing stimulation parameters to optimize efficacy. Furthermore, while early-stage clinical trials have reported improvements in certain symptoms, long-term efficacy and safety data are limited. To validate these techniques, large-scale, multi-center, randomized controlled trials are essential. Parallel advancements in device design, including the development of portable and cost-effective systems, will improve patient access and adherence to treatment protocols. Combining non-invasive DBS with other interventions, such as pharmacological treatments and physical therapy, could also provide a more comprehensive and synergistic approach to managing PD. In conclusion, non-invasive deep brain stimulation techniques represent a promising frontier in the treatment of Parkinson’s disease. While they have demonstrated considerable potential in improving symptoms and restoring neural function, further research is needed to refine protocols, validate long-term outcomes, and optimize clinical applications. With ongoing technological and scientific advancements, these methods could offer PD patients safer, more effective, and personalized treatment options, ultimately improving their quality of life and reducing the societal burden of the disease.

Aim To investigate the effects of puerarin on the proliferation,migration,and apoptosis of glio-blastoma cells and the underlying mechanisms.Meth-ods Differentially expressed genes associated with gli-oma and mitochondrial disease were analyzed using the GEO database.Cytotoxicity was detected by CCK-8 as-say.Cell migration was detected by the scratch wound healing assay and Transwell assay.Cell proliferation was assessed by EdU assay.Apoptosis level was meas-ured by TUNEL assay.Mitochondrial membrane poten-tial was detected by Mito-Tracker assay.ATP contents were detected using the ATP kit.The protein expres-sion levels were detected by Western blot.Antitumor efficacy of puerarin was analyzed using subcutaneous xenograft.Results There were 178 genes co-related differentially expressed genes in glioma and mitochon-drial disease.Core genes of co-related differentially ex-pressed genes were screened by GO and KEGG enrich-ment analyses,and the interaction networks.Among them,ubiquitin C(UBC)level was highly expressed in tissues of glioma patients.Puerarin could bind to UBC and reduce UBC expression at the animal and cell levels.Puerarin treatment inhibited the growth of glio-ma and decreased cell proliferation,migration and pro-moted cell apoptosis signals.Meantime,puerarin treat-ment also reduced mitochondrial membrane potentials and ATP contents,and down-regulated the levels of UBC related proteins.Conclusion Puerarin inhibits the proliferation,migration and promotes apoptosis of glioma cells.The mechanism of induction of mitochon-drial dysfunction is involved.

Aim To investigate the effect of paeonol(PAE)on cardiac hypertrophy induced by Angio-tensinogen Ⅱ(Ang Ⅱ)in rats and its mechanism.Methods Forty Sprague-Dawley rats were divided in-to five groups:control group,Ang Ⅱ model group,low concentration paeonol group,middle concentration pae-onol group,high concentration paeonol group.PAE was administered intragastrically(25,50 and 100 mg·kg-1·d-1)for 28 days.The hypertrophic model was established by adding 1 μmol·L-1 Ang Ⅱ to H9c2 cells for 48 hours.Results In Ang Ⅱ-induced rats,PAE improved echocardiography parameters,the cardi-ac hypertrophy index,the mRNA and protein expres-sion levels of ANP and BNP were decreased,and the cardiac fibrosis was alleviated.In vitro,PAE reduced cardiomyocyte hypertrophy and decreased the mRNA and protein expression levels of ANP and BNP in H9c2 cells induced by Ang Ⅱ,at the same time,the expres-sion of endoplasmic reticulum stress marker proteins p-PERK,GRP78,ATF4 and CHOP were decreased and reversed after treatment with the endoplasmic reticulum stress agonist tunicamycin(TN).Conclusion This study suggests that PAE can improve cardiac hypertro-phy by inhibiting endoplasmic reticulum stress,which may be a new drug to delay the development of cardiac hypertrophy.

Objective To investigate the effect of Polyetheretherketone(PEEK)rod semi-rigid pedicle screw fixation sys-tem in lumbar spine non-fusion surgery.Methods A total of 74 patients with tow-level lumbar degenerative diseases who un-derwent surgery from March 2017 to December 2019 were divided into PEEK rod group and titanium rod group.In the PEEK rod group,there were 34 patients,including 13 males and 21 females,aged from 51 to 79 years old with an average of(62.4±6.8)years old;There were 1 patient of L1-L3 segments,7 patients of L2-L4 segments,20 patients of L3-L5 segments and 6 pa-tients of L4-S1 segments.In the titanium rod group,there were 40 patients,including 17 males and 23 females,aged from 52 to 81 years old with an average of(65.2±7.3)years old;There were 3 patient of L1-L3 segments,11 patients of L2-L4 segments,19 patients of L3-L5 segments and 7 patients of L4-S1 segments.The general conditions of operation,such as operation time,intraoperative blood loss,postoperative drainage was recorded.The visual analogue scale(VAS)for low back pain and Os-westry disability index(ODI)were compared in preoperatively and postoperatively(3 months,12 months and last follow-up)between two groups.The change of range of motion(ROM)was observed by flexion and extension x-ray of lumbar Results All patients successfully completed the operation.The follow-up time ranged from 22 to 34 months with an average of(26.8±5.6)months.The operative time(142.2±44.7)min and intraoperative blood loss(166.5±67.4)ml in PEEK group were lower than those in titanium group[(160.7±57.3)min、(212.8±85.4)ml](P＜0.05).There was no significant differences in postoperative drainage between the two groups(P＞0.05).At the final follow-up visit,in PEEK group and titanium group VAS of low back pain[(0.8±0.4)points vs(1.0±0.5)points],VAS for leg pain[(0.7±0.4)points vs(0.8±0.5)points]and ODI[(9.8±1.6)％vs(12.1±1.5)％]were compared with preoperative[(5.8±1.1)points vs(6.0±1.1)points],[(7.2±1.7)points vs(7.0±1.6)points],[(68.5±8.9)％vs(66.3±8.2)％]were significantly different(P＜0.05).There was no significant difference in VAS scores between the two groups at each postoperative time point(P＞0.05).At 3 months after surgery,there was no difference in ODI between the two groups(P＞0.05).There were significant differences in ODI between PEEK group and titanium rod group at 12 months[(15.5±2.1)％vs(18.4±2.4)％]and at the last follow-up[(9.8±1.6)％vs(12.1±1.5)％](P＜0.05).The total range of motion(ROM)of lumbar decreased in both groups after surgery.At 12 months after surgery and the last follow-up,the PEEK group compared with the titanium rod group,the total range of motion of lumbar was statistically significant(P＜0.05).The range of motion(ROM)of the fixed segments decreased in both groups after surgery.The ROM of the fixed segments in PEEK group decreased from(9.5±4.6)° to(4.1±1.9)° at the last follow-up(P＜0.05),which in the titanium rod group was de-creased from(9.8±4.3)°to(0.9±0.5)° at the last follow-up(P＜0.05).The range of motion(ROM)of upper adjacent segment increased in both groups,there was statistical significance in the ROM of upper adjacent segment between the two groups at 12 months after surgery and the last follow-up,(P＜0.05).There was no screw loosening and broken rods in both groups during the follow-up period.Conclusion The PEEK rod semi-rigid pedicle screw internal fixation system used in lumbar non-fusion surgery can retain part of the mobility of the fixed segment,showing comparable short-term clinical efficacy to titanium rod fu-sion.PEEK rod semi-rigid pedicle screw internal fixation system is a feasible choice for the treatment of lumbar spine degener-ative diseases,and its long-term efficacy needs further follow-up observation.

This study was aimed at understanding the genomic characteristics of the Vibrio cholerae O1 group isolated from humans in Fujian Province,to provide essential data for the molecular epidemiological study of cholera.From 2008 to 2022,16 strains of the V.cholerae O1 group from patients and carriers were collected,and antibiotic sensitivity was determined accord-ing to the minimum inhibitory concentration(MIC).The whole genome sequences obtained through second generation sequen-cing were analyzed in open source software,including snippy,Roary,and Prokka,as well as online analysis websites,inclu-ding NCBI and BacWGSTdb,for core-genome multilocus sequence typing(cgMLST),core-genome single nucleotide polymor-phism analysis(cgSNP),virulence gene analysis,drug resistance gene prediction,and pan-genomic diversity analysis.The whole genome sequences of V.cholerae were divided into five sequence types(STs),among which the newly discovered ST182 and ST1480 were the evolutionary branches of the current dominant clonal group ST75 in China,and were highly related to two strains isolated from Taiwan in 2010 and 2013,respectively.Both toxigenic strains and non-toxigenic strains carried a variety of virulence factors and showed gene variation to varying degrees.Thirteen drug resistance genes in seven categories were predicted,among which the distribution of colistin and tetracycline resistance genes was consistent with the drug resistance phenotype.Pan-ge-nomic analysis indicated that V.cholerae had an open pan-genome,and Roary cluster analysis showed higher resolution than cgMLST.In summary,V.cholerae O1 group isolates from humans in Fujian Province have polymorphisms in genome structure and function,and the newly discovered ST1480 clone group has epidemic potential.Therefore,the monitoring of such strains must be strengthened.

In industrial production,the expression level of drug proteins in Chinese hamster ovary cells(CHO)is influenced by many factors:the regulatory elements on transcription and translation,the ge-nomic integration sites,and the expression system.Transcription,as the first step of gene expression,largely affects protein expression,and the promoter plays a crucial role in the initiation of transcription.Most of the promoters were screened through transient transfection or random integration,but the presence of unclear copy number or random integration sites makes it difficult to accurately evaluate the promoter activity.To some extent,site-specific integration can reduce the impact of positional effects on exogenous genes and may potentially increase the expression level of exogenous genes.In the early stage of our re-search,multiple sites that can stably express exogenous proteins were identified and verified in the CHO cell genome.In this study,one of these sites(2c6)was selected for the evaluation of promoter activity.The CRISPR/Cas9 gene editing technique was used to site-specifically integrate the reporter gene(EG-FP)regulated by the simian virus early promoter(SV40),mouse elongation factor-1α(mEF-1α),chicken β-actin(cACTB)promoter,and human phosphoglycerate kinase promoter(hPGK)into the 2c6 site,respectively.The mean fluorescence intensity of the cells was analyzed by flow cytometry,and the mRNA level of EGFP was detected by qPCR to comprehensively evaluate the activity of the promoter.The results showed that the activities of the mEF-1α and mACTB promoters were better than those of SV40 and hPGK.The results of the secondary flow cytometry sorting showed that site-specific integration can more accurately evaluate the activity of the promoter in the CHO cell expression system.

Objective To explore the changes in gut microbiota and levels of short-chain fatty acids(SCFA)in infants with cow's milk protein allergy(CMPA),and to clarify their role in CMPA.Methods A total of 25 infants diagnosed with CMPA at Children's Hospital Affiliated to Zhengzhou University from August 2019 to August 2020 were enrolled as the CMPA group,and 25 healthy infants were selected as the control group.Fecal samples(200 mg)were collected from both groups and subjected to 16S rDNA high-throughput sequencing technology and liquid chromatography-mass spectrometry to analyze the changes in gut microbial composition and metabolites.Microbial diversity was analyzed in conjunction with metabolites.Results Compared to the control group,the CMPA group showed altered gut microbial structure and significantly increased α-diversity(P＜0.001).The abundance of Firmicutes,Clostridiales and Bacteroidetes was significantly decreased,while the abundance of Sphingomonadaceae,Clostridiaceae_l and Mycoplasmataceae was significantly increased in the CMPA group compared to the control group(P＜0.001).Metabolomic analysis revealed reduced levels of acetic acid,butyric acid,and isovaleric acid in the CMPA group compared to the control group,and the levels of the metabolites were positively correlated with the abundance of SCFA-producing bacteria such as Faecalibacterium and Roseburia(P＜0.05).Conclusions CMPA infants have alterations in gut microbial structure,increased microbial diversity,and decreased levels of SCFA,which may contribute to increased intestinal inflammation.[Chinese Journal of Contemporary Pediatrics,2024,26(3):236-243]

OBJECTIVE: To explore the mechanism of electroacupuncture (EA) in promoting recovery of the facial function with the involvement of autophagy, glial cell line-derived neurotrophic factor (GDNF), and phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway. METHODS: Seventy-two male Sprague-Dawley rats were randomly allocated into the control, sham-operated, facial nerve injury (FNI), EA, EA+3-methyladenine (3-MA), and EA+GDNF antagonist groups using a random number table, with 12 rats in each group. An FNI rat model was established with facial nerve crushing method. EA intervention was conducted at Dicang (ST 4), Jiache (ST 6), Yifeng (SJ 17), and Hegu (LI 4) acupoints for 2 weeks. The Simone's 10-Point Scale was utilized to monitor the recovery of facial function. The histopathological evaluation of facial nerves was performed using hematoxylin-eosin (HE) staining. The levels of Beclin-1, light chain 3 (LC3), and P62 were detected by immunohistochemistry (IHC), immunofluorescence, and reverse transcription-polymerase chain reaction, respectively. Additionally, IHC was also used to detect the levels of GDNF, Rai, PI3K, and mTOR. RESULTS: The facial functional scores were significantly increased in the EA group than the FNI group (P<0.05 or P<0.01). HE staining showed nerve axons and myelin sheaths, which were destroyed immediately after the injury, were recovered with EA treatment. The expressions of Beclin-1 and LC3 were significantly elevated and the expression of P62 was markedly reduced in FNI rats (P<0.01); however, EA treatment reversed these abnormal changes (P<0.01). Meanwhile, EA stimulation significantly increased the levels of GDNF, Rai, PI3K, and mTOR (P<0.01). After exogenous administration with autophagy inhibitor 3-MA or GDNF antagonist, the repair effect of EA on facial function was attenuated (P<0.05 or P<0.01). CONCLUSIONS EA could promote the recovery of facial function and repair the facial nerve damages in a rat model of FNI. EA may exert this neuroreparative effect through mediating the release of GDNF, activating the PI3K/mTOR signaling pathway, and further regulating the autophagy of facial nerves.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Electroacupuncture ; Phosphatidylinositol 3-Kinase/metabolism* ; Facial Nerve Injuries/therapy* ; Phosphatidylinositol 3-Kinases/metabolism* ; Beclin-1 ; Glial Cell Line-Derived Neurotrophic Factor ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism* ; Autophagy ; Mammals/metabolism*

Objective To establish a stable and reliable method for the determination of ethylene oxide residue,and to analyze ethylene oxide residue in multi components made of different materials involved in some medical devices,so as to provide references for sample selection and ethylene oxide residue detection of multi-component medical device kits.Methods A method for the determination of ethylene oxide residue of multi-component medical devices was developed using headspace-gas chromatography and DB-WAX column under the conditions of headspace extraction with equilibration at 80℃ for 20 min,and the weighing mass,linearity,limit of detection,limit of quantification,precision and recovery of the method were determined.Trials of the method were carried out on the items undergoing ethylene oxide sterilization,including disposable perineal care kit,disposable gynecological examination kit,disposable suture dressing kit,disposable debridement kit and the components contacting human body in the disposable dialysis kit,and the abilities of different materials of the components were analyzed in absorbing,retaining and releasing ethylene oxide.Results The method showed high linearity(r=0.999 8)in the range of ethylene oxide mass concentration from 0.4 to 16.0 μg/mL with a weighing mass of 1.00 g,which had the limit of detection being 0.11 μg/mL,the limit of quantification being 0.37 μg/mL and the relative standard deviations(RSDs)for the precision from 0.35％to 1.52％.The average recoveries of different spiked amounts of ethylene oxide in the three blank matrices ranged from 92.68％to 101.42％with the relative standard deviations(RSDs)from 2.46％to 7.59％,which all satisfied the detection requirements.The components made of rubber and acrylonitrile-butadiene-styrene copolymer(ABS)in multi-component medical device kits had the highest ethylene oxide residues,followed by the components made of wood,degreased cotton,polypropylene and polystyrene.Conclusion The method proposed gains advantages in easy operation and high specificity,quantification and reproducibility,which can be used for the determination of ethylene oxide residue in the multi-component medical device kit undergoing ethylene oxide sterilization.References are provided for sample selection of multi-component medical devices.[Chinese Medical Equipment Journal,2024,45(1):56-61]

Humans ; Vascular Stiffness ; Coal Mining ; Occupational Diseases/epidemiology* ; Risk Factors ; Coal ; Miners