BACKGROUND:Fibromyalgia syndrome,as a common rheumatic disease,is related to central sensitization and immune abnormalities.However,the specific mechanism has not been elucidated,and there is a lack of specific diagnostic markers.Exploring the possible pathogenesis of this disease has important clinical significance. OBJECTIVE:To screen the potential diagnostic marker genes of fibromyalgia syndrome and analyze the possible immune infiltration characteristics based on bioinformatics methods,such as weighted gene co-expression network analysis(WGCNA),and machine learning. METHODS:Gene expression profiles in peripheral serum of fibromyalgia syndrome patients and healthy controls were obtained from the gene expression omnibus(GEO)database.The differentially co-expressed genes were screened in the expression profile by differential analysis and WGCNA analysis.Least absolute shrinkage and selection operator(LASSO)and support vector machine-recursive feature elimination(SVM-RFE)machine learning algorithm were further used to identify hub biomarkers,and draw receiver operating characteristic curve(ROC)to evaluate the accuracy of diagnosing fibromyalgia syndrome.Finally,single sample gene set enrichment analysis(ssGSEA)and gene set enrichment analysis(GSEA)were used to evaluate the immune cell infiltration and pathway enrichment in patients with fibromyalgia syndrome. RESULTS AND CONCLUSION:Eight down-regulated differentially expressed genes(DEGs)were obtained after differential analysis of the GSE67311 dataset according to the conditions of log2|(FC)|>0 and P<0.05.After WGCNA analysis,497 genes were included in the module(MEdarkviolet)with the highest positive correlation(r=0.22,P=0.04),and 19 genes were included in the module(MEsalmon2)with the highest negative correlation(r=-0.41,P=6×10-5).After intersecting DEGs and the module genes of WGCNA,seven genes were obtained.Four genes were screened out by LASSO regression algorithm and five genes were screened out by SVM-RFE machine learning algorithm.After the intersection of the two,three core genes were identified,which were germinal center associated signaling and motility like,integrin beta-8,and carboxypeptidase A3.The areas under the ROC curve of the three core genes were 0.744,0.739,and 0.734,respectively,indicating that they have good diagnostic value and can be used as biomarkers for fibromyalgia syndrome.The results of immune infiltration analysis showed that memory B cells,CD56 bright NK cells,and mast cells were significantly down-regulated in patients with fibromyalgia syndrome compared with the control group(P<0.05),and were significantly positively correlated with the above three biomarkers(P<0.05).The enrichment analysis suggested that there were nine fibromyalgia syndrome enrichment pathways,mainly related to olfactory transduction pathway,neuroactive ligand-receptor interaction,and infection pathway.The above results showed that the occurrence and development of fibromyalgia syndrome are related to the involvement of multiple genes,abnormal immune regulation,and multiple pathways imbalance.However,the interactions between these genes and immune cells,as well as their relationships with various pathways need to be further investigated.

ObjectiveTo investigate the prevalence of gynecological and breast diseases among retired or economically disadvantaged women in part of Pudong New Area of Shanghai under the policy support of screening gynecological diseases and breast diseases for retired and women with economic difficulties in life in Shanghai, to analyze the characteristics of these diseases, so as to provide a scientific basis for the improvement of relevant prevention and treatment strategies. MethodsBased on the gynecological census data of 13 031 cases in five towns, including Xinchang Town, Xuanqiao Town, Laogang Town, Wanxiang Town and Shuyuan Town, conducted by Shanghai Pudong Hospital in 2023, descriptive analysis methods were used to explore the prevalence and age characteristics of common gynecological and breast diseases. ResultsThe total detection rate of gynecological and breast diseases among women in the screening area in this study was 68.29%, with uterine fibroid (22.35%), sarcoidosis of the breast (17.06%), cervicitis (15.37%), vaginitis (8.39%) and ovarian cyst (2.61%) ranking the top 5 in the detection rate among the screening population. The differences of the detection rates in the four major diseases [uterine fibroid (χ²=233.217, P<0.001), breast nodules(χ²=169.896, P<0.001), cervicitis (χ²=388.683, P<0.001), and ovarian cysts (χ²=72.298, P<0.001)] by different age groups were statistically significant (P<0.05) . Moreover, the results of pairwise comparison of different age groups showed that the detection rates in the age group under 45 years old and 45‒55 years old were higher than that in the age group of 55‒65 years old and over 65 years old. ConclusionThe detection rate of gynecological and breast diseases in the younger age group was higher, indicating a certain trend of younger onset of diseases. Uterine fibroid, sarcoidosis of the breast , and reproductive tract diseases such as cervicitis, vaginitis, and ovarian cyst are the main diseases affecting the research subjects. Therefore, medical institutions can combine routine work in screening diseases and carry out corresponding health education and health promotion activities for these key diseases to improve women’s health.

Central retinal vein occlusion(CRVO)is a retinal vascular disorder that significantly impairs vision, with its underlying mechanisms involving complex interactions across multiple biological systems. This article provides a systematic review of the pathological mechanisms associated with CRVO, emphasizing critical factors such as endothelial dysfunction, arteriosclerosis, thrombophilia, inflammation, and oxidative stress. The pathological mechanisms of CRVO are characterized by arteriosclerosis, which obstructs venous return through a dual mechanism involving mechanical compression and endothelin-1-mediated contraction; endothelial dysfunction, which exacerbates disturbances in blood flow; genetic and acquired coagulation abnormalities that disrupt hemostatic balance and promote thrombosis; and the synergistic effects of inflammation and oxidative stress that activate cytokines, thereby aggravating ischemia and vascular leakage. Innovatively, this review explores emerging mechanisms such as miRNA-mediated vascular regulation via exosomes, gut microbiota-retina crosstalk through the “gut-eye axis,” and systemic metabolic interactions that link local retinal lesions to broader dysregulation of CRVO. These insights underscore the importance of integrated eye-system interventions and provide a theoretical foundation for advancing early biomarker discovery, multitarget therapeutics, and personalized treatment paradigms. By bridging localized pathology and systemic mechanisms, this work promotes a transformative shift toward an integrative medicine model in the diagnosis and management of CRVO.

Central nervous system（CNS） disorders are characterized by complex pathological mechanisms and the presence of the blood-brain barrier（BBB）， which significantly limits the effectiveness of drug therapy. Traditional drug delivery modes include oral administration， intravenous injection and transdermal delivery， which have certain advantages， but it is difficult for the drugs to effectively cross the BBB. Therefore， it is crucial to find drug delivery modes that can efficiently traverse the BBB. Nasal drug delivery， as a non-invasive method， can realize the targeted delivery of drugs to the CNS via three pathways， including olfactory neurons， trigeminal neurons and blood circulation， and shows a broad application prospect in the treatment of CNS diseases. Numerous studies have further confirmed that nasal drug delivery combined with novel drug delivery systems such as lipid nanocarriers， nanoparticles， nanoemulsions and composite in situ gels can effectively load the active components of traditional Chinese medicine（TCM）， and significantly increase drug concentration in the brain， which provides new strategies for the treatment of CNS diseases. In this paper， the current status of drug delivery for CNS diseases was systematically sorted out， the characteristics of nasal drug delivery were discussed in depth， and the research progress of passive targeting， active targeting， and "guiding the meridian" drug delivery strategies for the nasal-to-brain transport of TCM active components was summarized and analyzed， which was aimed to provide references and insights for the development of drugs for CNS diseases and the application of TCM in nasal-to-brain delivery.

Central nervous system（CNS） disorders are characterized by complex pathological mechanisms and the presence of the blood-brain barrier（BBB）， which significantly limits the effectiveness of drug therapy. Traditional drug delivery modes include oral administration， intravenous injection and transdermal delivery， which have certain advantages， but it is difficult for the drugs to effectively cross the BBB. Therefore， it is crucial to find drug delivery modes that can efficiently traverse the BBB. Nasal drug delivery， as a non-invasive method， can realize the targeted delivery of drugs to the CNS via three pathways， including olfactory neurons， trigeminal neurons and blood circulation， and shows a broad application prospect in the treatment of CNS diseases. Numerous studies have further confirmed that nasal drug delivery combined with novel drug delivery systems such as lipid nanocarriers， nanoparticles， nanoemulsions and composite in situ gels can effectively load the active components of traditional Chinese medicine（TCM）， and significantly increase drug concentration in the brain， which provides new strategies for the treatment of CNS diseases. In this paper， the current status of drug delivery for CNS diseases was systematically sorted out， the characteristics of nasal drug delivery were discussed in depth， and the research progress of passive targeting， active targeting， and "guiding the meridian" drug delivery strategies for the nasal-to-brain transport of TCM active components was summarized and analyzed， which was aimed to provide references and insights for the development of drugs for CNS diseases and the application of TCM in nasal-to-brain delivery.

ObjectiveTo investigate the current status of latent tuberculosis infection (LTBI) among the elderly population in rural areas of Changxing County, Zhejiang Province, and to provide an evidence for the development of LTBI prevention and control measures. MethodsBetween January and May 2024, elderly individuals participating in urban and rural residents’ health checkups were screened for Mycobacterium tuberculosis infection using a domestically produced interferon-γ release assay (IGRA) kit. Individuals tested positive by IGRA but without active tuberculosis were classified as LTBI cases. The prevalence of LTBI among the participants was subsequently analyzed. ResultsAmong the 6 765 subjects, 637 tested positive by IGRA, including one identified active tuberculosis patient, resulting in a LTBI prevalence rate of 9.40%. There was a statistically significant difference in positivity rates across different IGRA methodologies (χ²=35.530, P<0.001). Higher LTBI rate was observed in males, individuals with a history of diabetes mellitus, and those with a history of pulmonary tuberculosis, exhibiting statistically significant differences (χ²=32.401, P<0.001; χ²=5.789, P=0.020; χ²=39.248, P<0.001, respectively.) No statistically significant difference in LTBI rate was found across different age groups (χ²=0.238, P=0.971). ConclusionThe prevalence of LTBI among the elderly rural residents in Changxing County is relatively low. Male, individuals with a history of diabetes mellitus, and those with a history of pulmonary tuberculosis have an increased risk of LTBI, warranting targeted risk monitoring and timely interventions.

OBJECTIVES: To explore the therapeutic effect of LuoFuShan Rheumatism Plaster (LFS) on neuropathic pain (NP) and its molecular mechanism. METHODS: Mouse models of sciatic nerve chronic constriction injury (CCI) were treated with low, medium, and high doses (2.2, 4.4, and 8.8 cm², respectively) of LFS by topical application for 14 consecutive days. The therapeutic effects were assessed by evaluating the mechanical withdrawal threshold (MWT), paw withdrawal latency (PWL), plasma IL-6 and TNF-α levels, and histopathology of the sciatic nerve. Network pharmacology and molecular docking were used to identify the key targets and signaling pathways. The key targets were verified by RT-qPCR and immunohistochemistry. The biosafety of LFS was evaluated by measuring the organ indices and damage indicators of the heart, liver, and kidneys. RESULTS: Compared with the CCI group, LFS dose-dependently increased MWT and PWL, reduced plasma IL-6 and TNF-α levels, and alleviated sciatic nerve inflammation in the mouse models. Network pharmacology identified 378 bioactive compounds targeting 279 NP-associated genes enriched in TLR and TNF signaling. Molecular docking showed that quercetin and ursolic acid in LFS could stably bind to TLR4 and TNF‑α. In the mouse models of sciatic nerve CCI, LFS significantly downregulated the mRNA expression levels of Tlr4 and Tnf-α in the spinal cord in a dose-dependent manner and lowered the protein expressions of TLR4 and TNF-α in the sciatic nerve. LFS treatment did not cause significant changes in the organ indices or damage indicators of the heart, liver and kidneys as compared with those in the CCI model group and sham-operated group. CONCLUSIONS LFS alleviates NP in mice by suppression of TLR4/TNF-α-mediated neuroinflammation with a good safety profile.
Animals ; Toll-Like Receptor 4/metabolism* ; Neuralgia/metabolism* ; Mice ; Signal Transduction/drug effects* ; Tumor Necrosis Factor-alpha/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Sciatic Nerve/injuries* ; Male ; Molecular Docking Simulation ; Disease Models, Animal ; Interleukin-6

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective To investigate the anesthetic effects and adverse effects of cypropofol and propofol combined with alfentanil,respectively,for gastroenteroscopy.Methods A total of 162 patients who underwent elective gastroenteroscopy at the Gastrointestinal Endoscopy Center of the First Hospital of Lanzhou University from January to February 2024 were enrolled,including 86 males and 76 females,at an age of 18～65 years old,with a BMI value of 18～30 kg/m2,and ASA grade ≤ Ⅱ.They were randomly divided into propofol group(Group P)and cypropofol group(Group C),with 81 cases in each group.All patients were sedated with 0.7 μg/kg alfentanil,and in 30 s later,2 mg/kg propofol and 0.4 mg/kg cypropofol was intravenously dripped into Group P and Group C,respectively.When the modified alertness/sedation score(MOAA/S)≤1,a gastroscope was started to insert.The related indicators,including total procedure time,successful cases of sedation,induction time and awakening time,heart rate,blood pressure,and pulse oximetry saturation were recorded,occurrence of adverse reactions such as hypotension,respiratory depression,injection pain,intraoperative body movement,nausea and vomiting were observed,and the satisfaction of endoscopists and of patients to anesthesia were recorded and compared between the 2 groups.Results There were no statistical differences in the success rate of sedation,induction time and awakening time between the 2 groups.The patients of the Group C had more stable intraoperative vital signs,statistically lower incidences of injection pain,respiratory depression and hypotension(P＜0.05),and increased satisfaction for anesthesia(P＜0.05)when compared with those in Group P.No obvious difference were observed in the satisfaction of endoscopist to anesthesia between the 2 groups.Conclusion In combination with small-dose alfentanil,0.4 mg/kg cypropofol shows similar sedation effect as 2 mg/kg propofol in gastroenteroscopy,with comparable induction and awakening time.Cypropofol has more advantages in stable intraoperative vital signs,less adverse effects such as low blood pressure,respiratory depression and injection pain,higher the patient satisfaction,which is worthy of clinical promotion.

Objective To systematically evaluate the efficacy and safety of ciprofol for sedation and anesthesia outside the operating room.Methods Databases such as PubMed,Embase,Cochrane Library,Web of Science,CNKI,Wanfang Data,CBM,and VIP were searched for randomized controlled trials(RCTs)related to the efficacy and safety of ciprofol for sedation and anesthesia outside the operating room.The search covered all publications up to June 2023.Statistical analysis was performed using RevMan 5.4 software and Stata 15.0.Results Twelve RCTs were included,involving 2 192 patients,of which 1 154 were in the ciprofol group and 1 038 in the propofol group.Compared with the propofol group,the anesthesia induction time(MD=0.28 min,95％CI 0.08-0.47 min,P=0.006)and recovery time(MD=1.16 min,95％CI 0.44-1.87 min,P=0.001)were significantly longer in the ciprofol group,and the inci-dences of injection pain(OR=0.04,95％CI 0.02-0.06,P＜0.001),hypotension(OR=0.64,95％CI 0.49-0.83,P=0.0008),hypoxemia(OR=0.44,95％CI 0.21-0.91,P=0.03),and respirato-ry depression(OR=0.19,95％CI 0.11-0.32,P＜0.001)were significantly lower.There were no sta-tistically significant differences between the two groups in terms of sedation success rate,physician satisfac-tion,the difference in heart rate before and after anesthesia induction,incidence of body movement,brady-cardia,nausea and vomiting,and dizziness.Conclusion The anesthetic effect of cyclopofol and propofol is similar when used for anesthesia outside the operating room.Compared to propofol,ciprofol offers comparable anesthetic effects for sedation and anesthesia outside the operating room,with a lesser impact on respiratory function and more stable hemodynamics.Ciprofol also significantly lowers the incidence of adverse reactions such as injection pain,hypotension,hypoxemia,and respiratory depression.