OBJECTIVE To investigate the effects of baicalin （BC） on insulin resistance in rats with gestational diabetes mellitus （GDM） and its underlying mechanism based on the adenosine monophosphate-activated protein kinase （AMPK）/suppressor of variegation 3-9 homolog 1 （SUV39H1）/histone H3 lysine 9 trimethylation （H3K9me3） axis. METHODS A GDM rat model was established by a combination of a high-fat diet and streptozotocin injection. The successfully modeled rats were divided into the GDM group， BC low-dose group， BC high-dose group， and high-dose of BC+AMPK inhibitor （Compound C） group， with 10 rats in each group. Another 10 pregnant rats fed a normal diet served as the control group. Rats in each group were given corresponding drugs/normal saline intragastrically and/or intraperitoneally， once daily for 2 consecutive weeks. After the last administration， the levels of fasting blood glucose （FBG）， pancreatic function indexes [fasting insulin （FINS）， homeostasis model assessment of insulin resistance （HOMA-IR）， insulin sensitivity index （ISI）]， blood lipid indexes （total cholesterol， triglyceride， low-density lipoprotein cholesterol）， liver function indexes （alanine transferase， aspartate transferase， alkaline phosphatase）， inflammatory indicators （C-reactive protein， interleukin-1β， interleukin-6）， metabolic regulatory protein [complement-C1q/tumor necrosis factor-related protein 3 （CTRP3）]， insulin sensitivity related factors [glucose transporter 4 （GLUT4）， adiponectin]， and oxidative stress indicators [superoxide dismutase （SOD）， catalase （CAT）， malondialdehyde （MDA）] were measured. Pathological changes in liver tissue were observed， and the expressions of proteins related to the AMPK/SUV39H1/H3K9me3 axis in liver tissue were detected. RESULTS Compared with the GDM group， rats in the BC low- and high-dose groups showed varying degrees of improvement in pathological changes such as disordered cell arrangement， vacuolar degeneration， lipid deposition， and inflammatory cell infiltration in liver tissue. Their FBG and FINS levels， HOMA-IR， the levels of blood lipid indexes， liver function indexes， inflammatory indicators and MDA， and the expressions of SUV39H1 and H3K9me3 were significantly decreased or down-regulated， while metabolic regulatory protein， insulin sensitivity-related factors and AMPK protein phosphorylation levels were significantly increased （ P ＜0.05）. The improvement was more significant in the BC high-dose group （ P ＜0.05）. Compound C could significantly reverse the ameliorative effects of high-dose BC on the above quantitative indicators （ P ＜0.05）. CONCLUSIONS BC can significantly reduce oxidative stress and inflammatory responses， increase serum levels of CTRP3， GLUT4 and adiponectin， thereby improving insulin resistance in GDM rats. These effects may be related to the activation of AMPK and inhibition of SUV39H1-mediated H3K9me3 modification.

[摘 要] 目的：开发新型溶瘤呼肠孤病毒（Reo）递送系统，以克服中和抗体对Reo的中和作用并提升其肿瘤靶向性。方法：通过切向流过滤联合超高速离心法制备自然杀伤细胞外泌体（NKexo），叶酸（FA）修饰后采用挤压法包载Reo，构建FA-NKexo-Reo递送系统；通过透射电镜（TEM）、纳米粒径分析、蛋白质印迹（WB）法、核磁共振氢谱及流式细胞术等技术表征其理化性质；采用CCK-8、流式细胞术、Transwell实验及激光共聚焦显微镜评估FA-NKexo-Reo递送系统体外细胞毒性及细胞摄取能力；通过人卵巢癌裸鼠皮下移植瘤模型评价FA-NKexo-Reo的肿瘤靶向性、疗效及安全性。结果：FA-NKexo-Reo粒径为（94.0 ± 28.5）nm，Zeta电位为（-21.26 ± 1.57）mV，包封率达（49.7 ± 15.6）%；在中和抗体的存在下，FA-NKexo-Reo对卵巢癌细胞SKOV3和A2780仍可表现出显著的细胞毒性（P < 0.01）；荷瘤鼠活体成像显示FA-NKexo-Reo肿瘤靶向性显著优于NKexo组，肿瘤抑制率提升60%（P < 0.001）。结论：成功制备FA-NKexo-Reo递送系统，在中和抗体的存在下，FA-NKexo-Reo可保护并靶向递送Reo到高表达叶酸受体的卵巢癌细胞，从而增强Reo的抗肿瘤作用。

Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

OBJECTIVE To investigate the current career development status and existing bottlenecks among graduates of clinical pharmacist training bases， and to provide evidence for optimizing the training system， enhancing trainees’ job competency， and promoting the sound development of the clinical pharmacy discipline. METHODS Graduates from a clinical pharmacist training base in a tertiary class A hospital were selected as survey subjects. A six-dimensional questionnaire was designed using “Wenjuanxing” platform， distributed and collected via a mobile APP and E-mail. The survey analyzed participants’ basic characteristics， the impact of training on their professional roles， as well as their satisfaction regarding professional sentiment， competence， career status， professional recognition， the current state of the clinical pharmacist workforce， and the teaching model of the training base. The reliability of the questionnaire responses was assessed using Cronbach’s α coefficient. RESULTS A total of 164 questionnaires were distributed， and 147 valid responses were recovered， yielding a valid response rate of 89.63%. The Cronbach’s α coefficient for the questionnaire content was 0.943. The surveyed trainees were primarily employed at general hospitals （81.63%） and tertiary class A hospitals （72.11%）， with women constituting the majority （79.59%）. Their ages were concentrated between 26 and 35 years old （63.27%）， and most of them were supervising pharmacists（59.86%）. After training， 96.60% of graduates returned to their original institutions， and the proportion working in clinical pharmacist positions increased from 52.38% to 84.35%. Trainees’ overall satisfaction rate with the training model was 84.35%. However， their satisfaction with innovation and research capacity in clinical pharmacy was only 42 .18%， the satisfaction with salary and benefits was 35.37%， and the satisfaction with both occupational recognition and rationality of staffing was less than 50%. CONCLUSIONS Clinical pharmacist training bases can effectively promote trainees’ career transition， enhance job competency， and stabilize the talent pool among trainees. Nonetheless， the profession still faces bottlenecks such as relatively weak research capacity， low compensation， insufficient professional recognition， and unreasonable staffing. These issues require a multi-pronged， collaborative approach involving the optimization of training systems， the enhancement of career support， and the improvement of industry policies.

Objective To explore the epidemiological characteristics of gouty arthritis in Northwest China from 2023 to 2025, and to formulate preventive intervention measures. Methods By retrospectively analyzing the case data of medical institutions in Northwest China from January 2023 to June 2025 (a total of 8 139 cases), the incidence trend and population distribution characteristics of gouty arthritis in this area were analyzed. Multivariate logistic regression analysis was performed to identify risk factors. Results From 2023 to 2025, the prevalence rate of gouty arthritis in adult residents in Northwest China was 3.74% (304/8 139). Among the sites affected by gouty arthritis, the metatarsophalangeal joint accounted for the highest proportion (P<0.05). From the perspective of age distribution, the prevalence rate was the highest in 40-59 years old group (5.90%), followed by 66-80 years old group (4.21%) and >80 years old group (2.75%). The incidence rate in 40-65 years old group was higher than that in the other age groups (P<0.05). High blood uric acid and creatinine, alcohol drinking, obesity, high purine diet, concurrent chronic kidney disease and metabolic syndrome were risk factors affecting gouty arthritis in Northwest China (P<0.05). Conclusion High blood uric acid level, high creatinine level, alcohol drinking, obesity, high purine diet, concurrent chronic kidney disease and metabolic syndrome are risk factors influencing gouty arthritis in Northwest China. Based on the above factors, this study proposes comprehensive prevention strategies from the individual, community and public health levels to provide a scientific basis for reducing the incidence rate of gouty arthritis.

ObjectiveTranscranial focused ultrasound (tFUS) has emerged as a promising noninvasive neuromodulation technique capable of modulating neural activity with high spatial specificity. However, whether tFUS stimulation of the primary somatosensory cortex (S1) can reliably evoke conscious tactile perception without external peripheral sensory input remains unclear. Therefore, this study examined the feasibility of inducing hand-related tactile perception through targeted S1 stimulation and further investigated how sonication duration (SD), a key temporal parameter, influences the consistency of this perceptual response. The findings may provide empirical evidence for optimizing tFUS parameters in human somatosensory modulation. MethodsForty-eight healthy adults participated in the study and were assigned to two experiments. Experiment 1 included 24 participants and was designed to preliminarily examine whether S1-targeted tFUS could evoke hand-related tactile sensations. This experiment comprised two sub-experiments, Experiment 1a and Experiment 1b, with 12 participants in each. Specifically, Experiment 1a used a randomized active stimulation protocol targeting the bilateral S1 to assess the initial feasibility of inducing contralateral tactile perception, whereas Experiment 1b employed an alternating hemispheric design incorporating both active and sham stimulation to verify the specificity of the tFUS-induced sensations. Experiment 2 enrolled another 24 participants and used a real-sham dual-probe design to control for spatial tactile cues that might arise from probe-scalp contact. Five SD levels, including 200, 400, 600, 800, and 1 000 ms, were systematically tested to evaluate how stimulation duration influenced the behavioral response. The primary behavioral outcome was the perceptual consistency rate, quantified according to the accuracy of contralateral tactile localization. ResultsIn Experiment 1, 91.7% of participants reported reliable hand-related tactile sensations during active tFUS stimulation, including numbness, tingling, or similar sensory experiences. Contralateral localization accuracy under active stimulation was significantly higher than the0.50 chance level (P<0.05). In contrast, localization performance under sham stimulation did not differ from chance, suggesting that the observed tactile responses were mainly induced by active S1-targeted tFUS stimulation rather than nonspecific stimulation cues. In Experiment 2, perceptual consistency rates significantly exceeded the chance level under the 400 and 1 000 ms SD conditions(P<0.05), whereas no significant effect was observed at 200, 600, or 800 ms. Pairwise comparisons further showed that the 400 and 1 000 ms conditions produced significantly higher perceptual consistency rates than the 200 ms condition (P<0.05). ConclusiontFUS stimulation of S1 can elicit distinct hand-related tactile sensations without peripheral sensory input, demonstrating the feasibility of using targeted cortical ultrasound stimulation to induce conscious somatosensory perception. The reliability of this perceptual effect was modulated by sonication duration, indicating that temporal stimulation parameters play an important role in shaping both the occurrence and consistency of behavioral responses. Among the tested conditions, 400 ms appeared to provide a favorable temporal window for generating stable tactile perception, whereas excessively short stimulation may be insufficient to produce consistent responses. These findings highlight the sensitivity of somatosensory networks to ultrasonic modulation and provide useful parameter guidance for the application of tFUS in noninvasive sensory enhancement and cortical functional mapping.

Multiple system atrophy (MSA) is a rare neurodegenerative disease with complex clinical manifestations, presenting substantial challenges in clinical diagnosis and treatment. Its symptoms and the eight extraordinary meridians are potentially correlated; therefore, this article explores the association between MSA symptom clusters and the eight extraordinary meridians based on their circulation and physiological functions, as well as their treatment strategies. The progression from deficiency to damage in the eight extraordinary meridians aligns with the core pathogenesis of MSA, which is characterized by "the continuous accumulation of impacts from the vital qi deficiency leading to eventual damage". Liver and kidney deficiency and the emptiness of the eight extraordinary meridians are required for the onset of MSA; the stagnation of qi deficiency and the gradual damage to the eight extraordinary meridians are the key stages in the prolonged progression of MSA. The disease often begins with the involvement of the yin and yang qiao mai, governor vessel, thoroughfare vessel, and conception vessel before progressing to multiple meridian involvements, ultimately affecting all eight extraordinary meridians simultaneously. The treatment approach emphasizes that "the direct method may be used for joining battle, but indirect method will be needed in order to secure victory" and focuses on "eliminate pathogenic factors and reinforce healthy qi". Distinguishing the extraordinary meridians and focusing on the primary symptoms are pivotal to improving efficacy. Clinical treatment is aimed at the target, and tailored treatment based on careful clinical observation ensures precision in targeting the disease using the eight extraordinary meridians as the framework and core symptoms as the specific focus. Additionally, combining acupuncture, daoyin therapy, and other method may help prolong survival. This article classifies clinical manifestations based on the theory of the eight extraordinary meridians and explores treatment.

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

In recent years, there has been a growing interest in the research on NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome inhibitors in the treatment of inflammatory diseases. The NLRP3 inflammasome is integral to the innate immune response, and its abnormal activation can lead to the release of pro-inflammatory cytokine, consequently facilitating the progression of various pathological conditions. Therefore, investigating the pharmacological inhibition pathway of the NLRP3 inflammasome represents a promising strategy for the treatment of inflammation-related diseases. Currently, the Food and Drug Administration(FDA) has not approved drugs targeting the NLRP3 inflammasome for clinical use due to concerns regarding liver toxicity and gastrointestinal side effects associated with chemical small molecule inhibitors in clinical trials. Natural small molecule compounds such as polyphenols, flavonoids, and alkaloids are ubiquitously found in animals, plants, and other natural substances exhibiting pharmacological activities. Their abundant sources, intricate and diverse structures, high biocompatibility, minimal adverse reactions, and superior biochemical potency in comparison to synthetic compounds have attracted the attention of extensive scholars. Currently, certain natural small molecule compounds have been demonstrated to impede the activation of the NLRP3 inflammasome via various action mechanisms, so they are viewed as the innovative, feasible, and minimally toxic therapeutic agents for inhibiting NLRP3 inflammasome activation in the treatment of both acute and chronic inflammatory diseases. Hence, this study systematically examined the effects and potential mechanisms of natural small molecule compounds derived from traditional Chinese medicine on the activation of NLRP3 inflammasomes at their initiation, assembly, and activation stages. The objection is to furnish theoretical support and practical guidance for the effective clinical application of these natural small molecule inhibitors.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/metabolism* ; Inflammation/drug therapy* ; Anti-Inflammatory Agents/therapeutic use* ; Humans ; Animals ; Disease Models, Animal ; Biological Products/therapeutic use* ; Drug Discovery ; Medicine, Chinese Traditional/methods*

OBJECTIVE: To compare the short-term clinical efficacy and safety of closed reduction with Kirschner wire fixation versus open reduction with plate fixation for treating osteoporotic Colles' fractures in middle-aged and elderly patients. METHODS: Between January 2018 and January 2023, 119 patients with Colles fractures were retrospectively analyzed, including 39 males and 80 females, aged from 48 to 74 years old with an average of(60.58±6.71) years old. The time from injury to operation ranged 1 to 13 days with an average of (5.29±2.52) days. According to the surgical method, they were divided into Kirschner wire fixation group (Kirschner wire group) and plate internal fixation group (plate group). In Kirschner wire group, there were a total of 68 patients, comprising 21 males and 47 females. The average age was (61.15±6.24) years old, ranged from 49 to 74 years old. Among them, 41 cases involved the left side while 27 cases involved the right side. In the plate group, there were a total of 51 patients, including 18 males and 33 females. The average age was (59.78±5.71) years old ranged from 48 to 72 years old. Among them, there were 31 cases on the left side and 20 cases on the right side. The following parameters were recorded before and after the operation:operation time, intraoperative blood loss, hospitalization days, hospitalization expenses, postoperative complications, and radiographic parameters of distal radius (distal radius height, ulnar deviation angle, palmar tilt angle). The clinical efficacy was evaluated at 3 and 12 months after the operation using Gartland-Werley and disabilites of the arm shoulder and hand (DASH) scores. RESULTS: The patients in both groups were followed up for a duration from 12 to 19 months with an average of(13.32±2.02) months. The Kirschner wire group exhibited significantly shorter operation time compared to the plate group 27.91(13.00, 42.00) min vs 67.52(29.72, 105.32) min, Z=-8.74, P=0.00. Intraoperative blood loss was also significantly lower in the Kirschner wire group than in the plate group 3.24(1.08, 5.40) ml vs 21.91(17.38, 26.44) ml, Z=-9.31, P=0.00. Furthermore, patients in the Kirschner wire group had a shorter length of hospital stay compared to those in the plate group (8.38±2.63) days vs (11.40±2.78) days, t=-3.12, P=0.00. Additionally, hospitalization cost was significantly lower in the Kirschner wire group than in the plate group 10 111.29(6 738.98, 13 483.60) yuan vs 15 871.11(11 690.40, 20 051.82) yuan, Z=-5.62, P=0.00. The incidence of complications was 2 cases in the Kirschner wire group and 1 case in the plate group, with no statistically significant difference(P>0.05). At 3 months postoprative, the radial height of the Kirschner wire group was found to be significantly smaller than that of the plate group, with measurements of (11.45±1.69) mm and (12.11±1.78) mm respectively (t=-2.06, P=0.04). However, there were no statistically significant differences observed in ulnar deviation angle and palmar tilt angle between the two groups (P>0.05). The DASH score and Gartland-Werley score in the Kirschner group were significantly higher than those in the plate group at 3 months post-operation (19.10±9.89) vs (13.47±3.51), t=4.34, P=0.00;(11.15±3.61) vs (6.41±2.75), t=8.13, P=0.00). However, there was no significant difference between the two groups at 12 months post-operation (P>0.05). CONCLUSION Compared to plate internal fixation, closed reduction with Kirschner wire support fixation yields a slightly inferior recovery of radial height;however, there is no significant disparity in the functional score of the affected limb at 12 months post-operation. Nonetheless, this technique offers advantages such as shorter operation time, reduced intraoperative blood loss, decreased hospitalization duration, and lower cost.
Humans ; Female ; Male ; Middle Aged ; Aged ; Fracture Fixation, Internal/instrumentation* ; Bone Wires ; Bone Plates ; Retrospective Studies ; Colles' Fracture/surgery* ; Minimally Invasive Surgical Procedures/methods* ; Open Fracture Reduction/methods* ; Osteoporotic Fractures/surgery*