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.

Objective:To summarize the clinicopathological features, evolving trends in treatment and surgical approaches, and survival outcomes of patients who underwent D2 radical gastrectomy for gastric cancer in Shanxi Provincial Cancer Hospital over the past 11 years with the goal of providing a reference for the clinical practice of gastric cancer in this region.Methods:A retrospective observational study was conducted to analyze the clinicopathological data of patients who underwent D2 radical gastrectomy for pathologically confirmed gastric malignancy at the Department of Gastrointestinal Surgery, Shanxi Provincial Cancer Hospital from January, 2013 to December, 2023. Exclusion criteria consisted of: (1) residual gastric cancer or recurrent gastric cancer after surgery; (2) emergency gastric cancer resection due to bleeding, perforation, obstruction, or other causes; (3) comorbidity with other primary malignant tumors; (4) severe preoperative cardiopulmonary insufficiency or hepatic and renal insufficiency who cannot tolerate radical surgery; and (5) inconsistent main diagnosis information across the medical record system, pathological system, and gastric cancer-specific database. Patients were divided into three groups based on treatment methods: the surgery-only group, the perioperative chemotherapy group, and the adjuvant chemotherapy group. Endpoints included: (1) baseline patient characteristics; (2) trends in tumor location and pathological features; (3) evolution of treatment modalities; and (4) survival outcomes.Results:A total of 15,644 patients were included in the analysis, with 12,591 males and 3,053 females, the male-to-female gender ration was approximately 4∶1; the mean age was (61.2±9.5) years. The tumor sites were mainly concentrated in the esophagogastric junction (EGJ) (57.4%), followed by the antrum (25.9%). The incidence of EGJ cancer initially rose and then declined. However, gastric antrum tumors remained stable, and gastric body tumors showed a slow upward trend after 2020, accounting for 16.7%. In terms of pathological types, poorly differentiated carcinoma was the most prevalent, accounting for 55.9%, followed by moderately differentiated carcinoma (24.2%), mucinous adenocarcinoma (or signet ring cell carcinoma,14.1%), neuroendocrine carcinoma (4.8%), and well-differentiated carcinoma (0.9%). The proportion of poorly differentiated adenocarcinoma showed a significant upward trend overall as well, peaking at 65.6% in 2022 and decreasing to 57.5% in 2023. Mucinous adenocarcinoma (or signet ring cell carcinoma) exhibited fluctuations with a first increase followed by a decrease: it peaked at 17.3% in 2018, dropped sharply to 8.4% in 2022, and rose back to 13.8% in 2023. The proportions of well-differentiated adenocarcinoma, moderately differentiated adenocarcinoma, and neuroendocrine tumors remained stable year by year. In terms of pathological staging, the overall proportions of gastric cancer at Stage 0, Stage I, Stage II, Stage III, and Stage IVa were 0.5%, 17.3%, 25.1%, 54.9%, and 2.3%, respectively. For Stage III, its proportion was 74.6% in 2013, which decreased to 46.4% by 2023. Stages I and II gastric cancer showed an upward trend, with their proportions rising from 10.2% and 12.1% in 2013 to nearly 21.0% and 29.6% in 2023, respectively. Between 2013 and 2023, the proportion of patients who received surgery alone continued to decrease, with this proportion dropping to 34.7% in 2023. In contrast, the number of patients who received adjuvant chemotherapy increased year by year, reaching 54.2% in 2023. Since 2017, the application of perioperative chemotherapy has gradually increased, rising to 11.1% in 2023. Immunotherapy showed an almost synchronous growth trend with perioperative chemotherapy. However, targeted therapy exhibited a downward trend after a period of growth. There were 10,704 cases of open surgery (68.4%), 4,744 cases of laparoscopic surgery (30.3%), and 193 cases of transthoracic surgery (1.2%). Pathological margin positivity was observed in 443 cases (2.8%), and the volume of gastric cancer surgeries gradually increased, peaked in 2021 before subsequently decreasing gradually. However, the volume of laparoscopic surgeries did not decrease; instead, it showed an upward trend. The main resection method for EGJ tumors was total gastrectomy, accounting for 78.5% of the total, followed by proximal gastrectomy, which accounted for 21.5%. After total gastrectomy, esophagojejunal Roux-en-Y anastomosis was the primary anastomotic method, and for proximal gastrectomy, the main anastomotic method was esophagogastric anastomosis, which accounted for 68.0% of the total. For distal gastrectomy, Billroth II anastomosis was the most common anastomotic technique, accounting for 92.7% of these procedures. The overall incidence of postoperative complications was 14.5% (2,264/15,644), among which the incidence of severe complications (grades III-IV) was 4.5% (706/15,644). The entire cohort was followed up with for (47.1±36.8) months, and the 1-year, 3-year, and 5-year overall survival rates were 86.4%, 65.9%, and 58.1%, respectively. For patients with stage 0, I, II, III, and IV gastric adenocarcinoma, the 1-year overall survival rates were 95.7%, 98.0%, 89.4%, 81.0%, and 49.1%, respectively; the 3-year overall survival rates were 92.1%, 94.6%, 81.9%, 51.4%, and 14.7%, respectively; and the 5-year overall survival rates were 89.4%, 91.7%, 75.1%, 41.5%, and 10.0%, respectively. For patients with stage I, II, III, and IV gastric neuroendocrine carcinoma, the 1-year overall survival rates were 96.7%, 91.1%, 73.8%, and 52.6%, respectively; the 3-year overall survival rates were 87.2%, 69.6%, 46.1%, and 32.1%, respectively; and the 5-year overall survival rates were 87.2%, 62.2%, 36.7%, and 32.1%, respectively.Conclusions:Gastric cancer in Shanxi Province is characterized by a male predominance, a high prevalence of tumors at the esophagogastric junction, a large proportion of poorly differentiated adenocarcinoma, and presentation at advanced stages (predominantly Stage III). The detection rate of early gastric cancer has been increasing year by year, the volume of laparoscopic surgeries has been on the rise annually, and the treatment model has shifted from single surgery to comprehensive treatment.

Objective To design a VR-based air evacuation training system for simulating the on-board medical treatment process during air evacuation.Methods A VR-based air evacuation training system was developed which used 3D modeling technology to construct models of the medical aircraft cabin,medical devices and virtual characters to achieve scene interaction.The hardware part of the system included server computers,training terminal computers,VR equipment,3D fusion projection equipment,motion capture equipment,etc.The software of the system was developed using C++,UE4 Blueprint and C# programming languages,including two modules for medical treatment unit and medical treatment training process evaluation.The efficacy of the system was verified by the trials in air evacuation.Results The system developed successfully simulated the scenarios of tracheal tube dislodgement and increased intracranial pressure in the scenario model of open severe craniocerebral injury.The expert evaluation showed that the system gained advantages in training efficiency,low cost,safety,sense of immersion and recorded the operation data in real time to optimize the follow-up training.Conclusion The system developed delivers a virtual training environment with high-fidelity replication of real-mission conditions,enabling whole-course and immersive air evacuation drills.[Chinese Medical Equipment Journal,2025,46(3):15-20]

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 understand the changing composition and antibiotic resistance of bacterial species in the clinical isolates from outpatient and emergency department(hereinafter referred to as outpatients)and inpatient children over time in various hospitals,and to provide laboratory evidence for rational antibiotic use.Methods The data on clinically isolated pathogenic bacteria and antimicrobial susceptibility of isolates from outpatients and inpatient children in the CHINET program from 2015 to 2021 were collected and analyzed.Results A total of 278 471 isolates were isolated from pediatric patients in the CHINET program from 2015 to 2021.About 17.1％of the strains were isolated from outpatients,primarily group A β-hemolytic Streptococcus,Escherichia coli,and Staphylococcus aureus.Most of the strains(82.9％)were isolated from inpatients,mainly SS.aureus,E.coli,and H.influenzae.The prevalence of methicillin-resistant S.aureus(MRSA)in outpatients(24.5％)was lower than that in inpatient children(31.5％).The MRSA isolates from outpatients showed lower resistance rates to the antibiotics tested than the strains isolated from inpatient children.The prevalence of vancomycin-resistant Enterococcus faecalis or E.faecium and penicillin-resistant S.pneumoniae was low in either outpatients or inpatient children.S.pneumoniae,β-hemolytic Streptococcus and S.viridans showed high resistance rates to erythromycin.The prevalence of erythromycin-resistant group A β-hemolytic Streptococcus was higher in outpatients than that in inpatient children.The prevalence of β-lactamase-producing H.influenzae showed an overall upward trend in children,but lower in outpatients(45.1％)than in inpatient children(59.4％).The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn),carbapenem-resistant Pseudomonas aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 14％,11.7％,47.8％in outpatients,but 24.2％,20.6％,and 52.8％in inpatient children,respectively.The prevalence of multidrug-resistant E.coli,K.pneumoniae,Proteus mirabilis,P.aeruginosa and A.baumannii strains was lower in outpatients than in inpatient children.The prevalence of fluoroquinolone-resistant E.coli,ESBLs-producing K.pneumoniae,ESBLs-producing P.mirabilis,carbapenem-resistant E.coli(CREco),CRKpn,and CRPae was lower in children in outpatients than in inpatient children,but the prevalence of CRAba in 2021 was higher than in inpatient children.Conclusions The distribution of clinical isolates from children is different between outpatients and inpatients.The prevalence of MRSA,ESBL,and CRO was higher in inpatient children than in outpatients.Antibiotics should be used rationally in clinical practice based on etiological diagnosis and antimicrobial susceptibility test results.Ongoing antimicrobial resistance surveillance and prevention and control of hospital infections are crucial to curbing bacterial resistance.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

OBJECTIVE: To investigate the predictive value of the prognostic nutritional index (PNI) and systemic inflammatory response index (SIRI) for short-term efficacy and prognosis in newly treated patients with peripheral T-cell lymphoma (PTCL). METHODS: The general data, laboratory indicators, disease stage and other clinical data of 91 newly treated PTCL patients admitted to the Affiliated Hospital of Xuzhou Medical University from January 2015 to December 2023 were retrospectively analyzed. The optimal cutoff values for PNI and SIRI were determined using receiver operating characteristic (ROC) curves, and the patients were stratified into groups based on these cutoffs to compare clinical features and short-term efficacy between the different groups. Kaplan-Meier method was used to plot survival curves, and univariate and multivariate analyses were performed to identify the factors affecting overall survival (OS). RESULTS: The optimal cutoff values for PNI and SIRI were 45.30 and 1.74×10⁹/L, respectively. Patients in different PNI groups showed statistically significant differences in age, Ann Arbor stage, lactate dehydrogenase (LDH) level, international prognostic index (IPI), prognostic index for PTCL-not otherwise specified (PIT), pathological subtypes, and complete response (CR) rate (P < 0.05). PTCL patients in different SIRI groups exhibited significant differences in Ann Arbor stage, LDH level, IPI score, PIT score, and CR rate (P < 0.05). Logistic regression analysis showed that age ≥60 years old (OR =2.750), Ann Arbor stage Ⅲ-Ⅳ (OR =5.200), IPI score ≥2 (OR =7.650), low PNI (OR =3.296), and high SIRI (OR =3.130) were independent risk factors affecting treatment efficacy in PTCL patients (P < 0.05). Cox proportional hazards regression model analysis showed that low PNI and elevated β₂-microglobulin (β₂-MG) levels were independent risk factors affecting OS (P < 0.05). CONCLUSION PNI and SIRI have certain application value in evaluating short-term efficacy and prognosis in patients with PTCL. Compared with SIRI, PNI demonstrates greater predictive value for patient prognosis.
Humans ; Prognosis ; Lymphoma, T-Cell, Peripheral/therapy* ; Retrospective Studies ; Nutrition Assessment ; Male ; Female ; Middle Aged ; ROC Curve ; Inflammation

Salvia miltiorrhiza (S. miltiorrhiza) represents a crucial component of traditional Chinese medicine, demonstrating effects on blood circulation activation and stasis removal, and has been widely utilized in asthma treatment. This study isolated a novel phenolic acid (S1) from S. miltiorrhiza and investigated its anti-asthmatic activity and underlying mechanisms for the first time. An allergic asthma (AA) model was established using ovalbumin (OVA). The mechanism of S1's effects on AA was investigated using multi-factor joint analysis, flow cytometry, and co-culture systems to facilitate clinical asthma treatment. S1 (10 or 20 mg·kg^-1) was administered daily to mice with OVA-induced AA (OVA-AA) during days 21-25. The study examined airway responsiveness, lung damage, inflammation, and levels of immunoglobulin E (IgE), PGD2, interleukins (IL-4, 5, 10, 13, 17A), tumor necrosis factor α (TNF-α), GM-CSF, CXCL1, CCL11, and mMCP-1. Additionally, mast cell (MC) activation and degranulation were explored, along with T helper type 17 (Th17)/Treg immune cells and TLR4 pathway biomarkers. The antagonistic activity of that specific antagonist of TLR4 (TAK-242) (1 µmol·L^-1), a specific TLR4 blocker, against S1 (10 µmol·L^-1) was examined in co-cultured 16HBE cells and bone marrow-derived cells (BMDCs) or splenic lymphocytes (SLs) induced with LPS (1 µg·mL^-1) to elucidate the TLR4 pathway's mediating role. S1 demonstrated reduced airway responsiveness, lung damage, and inflammation, with downregulation of IgE, PGD2, interleukins, TNF-α, GM-CSF, CXCL1, CCL11, and mMCP-1. It also impeded MC activation and degranulation, upregulated IL-10, and influenced Th17/Treg immune cell transformation following OVA challenge. Furthermore, S1 inhibited the TLR4 pathway in OVA-AA mice, and TLR4 antagonism enhanced S1's positive effects. Analysis using an OVA-AA mouse model demonstrated that S1 alleviates AA clinical symptoms, restores lung function, and inhibits airway response. S1's therapeutic effects occur through regulation of Th17/Treg immune cells and inflammation, attributable at least partially to the TLR4 pathway. This study provides molecular justification for S1 in AA treatment.

IL-33 and its receptor ST2 play crucial roles in tissue repair and homeostasis. However, their involvement in optic neuropathy due to trauma and glaucoma remains unclear. Here, we report that IL-33 and ST2 were highly expressed in the mouse optic nerve and retina. Deletion of IL-33 or ST2 exacerbated retinal ganglion cell (RGC) loss, retinal thinning, and nerve fiber degeneration following optic nerve (ON) injury. This heightened retinal neurodegeneration correlated with increased neurotoxic astrocytes in Il33^-/- mice. In vitro, rIL-33 mitigated the neurotoxic astrocyte phenotype and reduced the expression of pro-inflammatory factors, thereby alleviating the RGC death induced by neurotoxic astrocyte-conditioned medium in retinal explants. Exogenous IL-33 treatment improved RGC survival in Il33^-/- and WT mice after ON injury, but not in ST2^-/- mice. Our findings highlight the role of the IL-33/ST2 axis in modulating reactive astrocyte function and providing neuroprotection for RGCs following ON injury.
Animals ; Interleukin-33/genetics* ; Interleukin-1 Receptor-Like 1 Protein/genetics* ; Optic Nerve Injuries/pathology* ; Retinal Ganglion Cells/pathology* ; Astrocytes/pathology* ; Mice ; Mice, Knockout ; Mice, Inbred C57BL ; Neuroprotection/physiology*

Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) cause a severe neurodevelopmental disorder, yet the impact of truncating mutations remains unclear. Here, we introduce the Cdkl5^492stop mouse model, mimicking C-terminal truncating mutations in patients. 492stop/Y mice exhibit altered dendritic spine morphology and spontaneous seizure-like behaviors, alongside other behavioral deficits. After creating cell lines with various Cdkl5 truncating mutations, we found that these mutations are regulated by the nonsense-mediated RNA decay pathway. Most truncating mutations result in CDKL5 protein loss, leading to multiple disease phenotypes, and offering new insights into the pathogenesis of CDKL5 disorder.
Animals ; Disease Models, Animal ; Mice ; Protein Serine-Threonine Kinases/deficiency* ; Mutation/genetics* ; Epileptic Syndromes/genetics* ; Humans ; Dendritic Spines/pathology* ; Spasms, Infantile/genetics* ; Male ; Seizures/genetics* ; Mice, Inbred C57BL