Objective:To investigate the mechanism of transient receptor potential vanilloid subfamily 1(TRPV1)-mediated microglia autophagy in postherpetic neuralgia.Methods:Forty mice were randomly divided into control group,postherpetic neuralgia(PHN)group,PHN-sh-NC group,and PHN-sh-TRPV1 group,with 10 mice in each group.We tested the mice's mechanical withdrawal threshold(MWT)and thermal withdrawal latency(TWL);measured serum levels of tumor necrosis factor-alpha(TNF-α),interleukin(IL)-1β,IL-6,and brain-derived neurotrophic factor(BDNF)by enzyme-linked immunosorbent assay;assessed the formation of au-tophagosomes in the spinal cord tissues by transmission electron microscopy;measured the expression of microtubule-associated pro-tein 1 light chain 3(LC3)and ionized calcium binding adaptor molecule 1(Iba-1)in the spinal cord tissues by immunofluorescence assay;and determined the protein expression of Beclin-1,microtubule-associated protein 1 light chain 3B(LC3B),and p62 in the spinal cord tissues by Western blot.Results:Compared with the control group,the PHN group and PHN-sh-NC group had sig-nificant decreases in MWT,serum BNDF level(t=10.49,P<0.001),and p62(P=0.004)protein expression in the spinal cord tissues and significant increases in TWL,serum TNF-α(t=26.27,P<0.001),IL-1β(t=17.0,P<0.001),and IL-6 levels(t=25.48,P<0.001),and the expression of Iba-1(P=0.002),LC3(P<0.001),LC3B(P=0.001),and Beclin-1 proteins(P=0.001)in the spinal cord tissues.Compared with the PHN group,the PHN-sh-TRPV1 group had a significantly higher MWT,a significantly higher serum BNDF level(t=5.174,P<0.001,a significantly higher p62 protein expression level(P<0.001)in the spinal cord tissues,a significantly lower TWL,significantly lower serum TNF-α(t=20.57,P<0.001),IL-1β(t=8.260,P<0.001),and IL-6 levels(t=19.81,P<0.001),and signifi-cantly lower expression levels of Iba-1(P<0.001),LC3(P<0.001),LC3B(P=0.001),and Beclin-1(P<0.001)in the spinal cord tis-sues.Conclusion:Microglia autophagy is activated in the spinal cord of PHN mice,and suppressing the expression of TRPV1 can in-hibit microglia autophagy to relieve pain in PHN mice.

Objective:By analyzing the genetic risk of triglyceride-glucose index(Tyg)and insulin resistance(IR)for cardiovascular disease(CVD), to elucidate the extent to which the contribution of Tyg to the risk of CVD development is influenced by IR genetic risk.Methods:In this study, we selected data from a cohort of elderly people in the Kunshan community, screened 7, 385 individuals with both clinical and genomic data, and calculated the polygenic risk score of insulin resistance(IRPRS)for each participant based on publicly available IR genome-wide association data, and assessed the effect of genetic risk and Tyg level on the risk of developing CVD using a multivariate Cox proportional risk model.Calculating interactions to assess the effects of genetic risk and Tyg levels on the risk of developing CVD, the effects of Tyg tertile grouping and IRPRS on the risk of developing CVD were assessed using a multivariate Cox proportional risk model, and subgroup analyses were performed for gender to assess the effects of Tyg tertile grouping and IRPRS on the risk of developing CVD by gender.Results:In the univariate Cox model, Q3 and IRPRS with the highest TYG levels were significantly associated with the risk of CVD, respectively( HR=1.59, 95% CI: 1.33-1.89; P<0.001; HR=1.61, 95% CI: 1.18-2.20; P=0.003).After adjusting for multiple confounders, the Q3 Group with the highest TYG level was still significantly associated with the risk of CVD( HR=1.28, 95% CI: 1.05-1.57; P=0.014), the Association of TYG with the risk of CVD did not change significantly( HR=1.29, 95% CI: 1.05-1.57; P=0.014).We conducted a subgroup analysis by sex and found that among older men, 13, the highest levels of TYG and IRPRS were significantly associated with CVD risk, respectively( HR=1.70, 95% CI: 1.31.2.20; P<0.001; HR=1.98, 95% CI: 1.24-3.15; P=0.004).After adding IRPRS to the model, the Association of TYG with the risk of CVD remained unchanged( HR=1.69, 95% CI: 1.31-2.19; P<0.001).After adjusting for various confounders, Tyg remained significantly associated with the risk of CVD( HR=1.39, 95% CI: 1.04-1.88; P=0.028), the results showed that TYG remained significantly associated with the risk of CVD( HR=1.41, 95% CI: 1.05-1.90; P=0.023), and the association did not decrease.No Association of IRPRS with CVD risk was found in older women. Conclusions:IRPRS and TYG are the risk factors of CVD, and diet, exercise, drugs and other external factors on TYG are the main risk factors of CVD.For individuals with high genetic factors, the risk of CVD can still be reduced by lifestyle adjustments such as diet, exercise and drug intervention.

This review delves into the pivotal role of necrotic apoptosis in Alzheimer's disease(AD),with a focus on treatment strategies,drug development,prospects,and challenges,highlighting its significance in the progression of the disease.Firstly,necrotic apoptosis plays a crucial role in the pathogenesis of AD,particularly in association with the abnormal metabolism of β-amyloid(Aβ)and Tau proteins.The primary focus of drug design is to regulate the metabolism pathways of these two proteins to slow down or inhibit the progression of necrotic apoptosis.Secondly,the progress in drug development further emphasizes the importance of necrotic apoptosis in treating AD.Current research mainly focuses on drugs that affect the metabolism of Aβ and Tau proteins,such as lecanemab.Still,inconsistent result underscore the necessity for a more comprehensive understanding of the molecular mechanisms of necrotic apoptosis.Finally,the prospects and challenges of necrotic apoptosis research in AD are thoroughly discussed.A deeper understanding of necrotic apoptosis contributes to a better comprehension of the pathological mechanisms of AD but also may reveal new therapeutic targets.However,challenges such as multifactorial influences and the selection of treatment timing necessitate further in-depth research in the future.In conclusion,this review advocates for future research to deepen the understanding of the molecular mechanisms of necrotic apoptosis,enhance research on treatment strategies,gain a deeper understanding of its cross-regulation with other cell death pathways,and promote collaboration between basic research and clinical practice to advance the comprehensive understanding and treatment of Alzheimer's disease and necrotic apoptosis.

Objective To analyze the correlation of cholecystectomy and changes in intestinal microbiota composition and function by observing functional characteristics of differential microbial communities.Methods A cross-sectional study was conducted on the patients(PC group,n=73)undergoing cholecystectomy in our hospital from 2020 to 2021.Another 56 healthy age-and gender-matched individuals(HC group)without a history of cholecystectomy were subjected and served as the control group.Fecal specimens were collected from the 2 groups.16S rRNA sequencing analysis was performed to examine the changes in composition and function of intestinal microbiota.Results There were no statistical differences between the 2 groups in baseline indicators,such as gender,age,BMI,smoking and drinking history,blood pressure,heart rate,and comorbidities,but significant difference was observed in total bilirubin(TBIL)between them(P<0.01).Alpha diversity analysis showed no significant difference in Chao1,Shannon,and Simpson indices between the 2 groups.Beta diversity analysis using the Bray-Curtis distance algorithm revealed a significant difference between the 2 groups at the class and genus levels(P<0.05).The analysis of microbiota relative abundance using LEFSE showed that Enterobacteriaceae,Lactobacillales,Citrobacter,Megasphaera,Lactobacillus,Enterococcus,Akkermansia,Streptococcus,Klebsiella,and Ruminococcus_gnavus were up-regulated in the PC group,and Lachnospiraceae,Sutterellaceae,Lachnospirales,Lachnospira,and Sutterella were down-regulated.Kyoto Encyclopedia of Genes and Genomes(KEGG)functional prediction analysis indicated that significant differences were seen between the 2 groups in metabolic pathways,including ascorbic acid(vitamin C)metabolism and aldonic acid metabolism(P<0.05),tricarboxylic acid cycle(TCA cycle)(P<0.05),glutathione metabolism(P<0.05),glutamic acid metabolism(P<0.05),secondary bile acid metabolism(P<0.05),and pentose phosphate pathway(P<0.01).Conclusion Cholecystectomy is closely associated with the structural alterations in the composition of intestinal microbiota.Variations in microbiota composition and function may induce perturbations in TCA cycle and glutathione metabolism,glutamate metabolism,secondary bile acid metabolism,and pentose phosphate pathways.

Nitrogen oxides(NOx=NO+NO2)are important precursors of ozone(O3),and NOx and its oxides together constitute reactive nitrogen oxides(NOy)in the atmosphere.A comprehensive understanding of the total NOy level in the atmosphere is of great significance for a deeper understanding of the atmospheric nitrogen cycle and oxidation,as well as for formulating strategies for air pollution prevention and control.In this work,a thermal decomposition-broadband cavity enhanced absorption spectroscopy(TD-BBCEAS)technique for online measurement of total NOy in the atmosphere was developed.With this method,the NOy was efficiently converted into NO2,and the total NOy concentration in the atmosphere was indirectly obtained by measuring NO2.Focusing on the key factors affecting the measurement of total NOy,the influence of NO titration efficiency and other NOy component TD efficiency on measurement accuracy was emphasized.By changing the oxygen(O2)flow rate through the mercury lamp to alter the O3 concentration for titrating NO,the conversion efficiency of NO was evaluated.At O2 flow rate of 6 mL/min,the conversion efficiency of NO was greater than 99%.TD efficiency testing and analysis on NO2,peroxyacetyl nitrate(PAN),nitric acid(HNO3),and nitrous acid(HONO),which account for a large proportion of atmospheric NOy components,was carried out using 680℃as the optimal TD temperature for efficient conversion of NOy.With NO and HONO sample gases as typical verification gases,the conversion efficiency of NOy and the accuracy of NOy measurement by TD-BBCEAS system were verified by switching the on and off modes of mercury lamp and TD device.At integration time of 60 s,the detection limit of the system for NOy was 2.83×1010 molecules/cm3(60 s,2σ).A comparative measurement of actual atmospheric NOy was conducted between the TD-BBCEAS system and the NOy analyzer.The observation results showed a correlation coefficient(R2)of 0.98 and a slope of 0.93,further verifying the feasibility and accuracy of applying the TD-BBCEAS system to measurement of total NOy.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

OBJECTIVES: To summarize the clinical manifestations and genetic characteristics of creatine deficiency syndrome (CDS) caused by GAMT gene mutations. METHODS: A retrospective analysis was conducted on the clinical and genetic data of two children diagnosed with GAMT deficiency-type CDS at the Children's Medical Center of Xiangya Hospital, Central South University, from December 2020 to December 2024. RESULTS: The two patients presented with symptoms in infancy, and both had compound heterozygous mutations in the GAMT gene. Case 1 exhibited seizures and intellectual disability, while Case 2 had intellectual disability and attention-deficit hyperactivity disorder. Magnetic resonance spectroscopy of cranial MRI in both patients indicated reduced creatine peaks. After creatine treatment, seizures in Case 1 were controlled, but both patients continued to experience intellectual disabilities and behavioral issues. As of December 2024, a total of 21 cases have been reported in China (including this study), and 115 cases have been reported abroad. All patients exhibited developmental delay or intellectual disabilities, with 66.9% (91/136) experiencing seizures, 33.8% (46/136) presenting with motor disorders, and 36.8% (50/136) having behavioral problems. Seventy-five percent (102/136) of patients received creatine treatment, leading to significant improvements in seizures and motor disorders, although cognitive improvement was not substantial. CONCLUSIONS GAMT deficiency-type CDS is rare and presents with nonspecific clinical features. Timely diagnosis facilitates targeted treatment, which can partially improve prognosis.
Child ; Female ; Humans ; Male ; Creatine/deficiency* ; Guanidinoacetate N-Methyltransferase/deficiency* ; Intellectual Disability/genetics* ; Mutation ; Retrospective Studies ; Rhabdomyolysis/genetics* ; Language Development Disorders ; Movement Disorders/congenital*

Alzheimer's disease (AD), a prototypical neurodegenerative disorder, encompasses multifaceted pathological processes. As pivotal cellular structures within the central nervous system, ion channels play critical roles in regulating neuronal excitability, synaptic transmission, and neurotransmitter release. Extensive research has revealed significant alterations in the expression and function of ion channels in AD, implicating an important role of ion channels in the pathogenesis of abnormal Aβ deposition, neuroinflammation, oxidative stress, and disruptions in calcium homeostasis and neural network functionality. This review systematically summarizes the crucial roles and underlying mechanisms of ion channels in the onset and progression of AD, highlighting how these channel abnormalities contribute to AD pathophysiology. We also discuss the therapeutic potential of ion channel modulation in AD treatment, emphasizing the importance of addressing multifactorial nature and heterogeneity of AD. The development of multi-target drugs and precision therapies is proposed as a future direction of scientific research.
Alzheimer Disease/therapy* ; Humans ; Ion Channels/physiology* ; Oxidative Stress ; Animals ; Amyloid beta-Peptides/metabolism* ; Synaptic Transmission ; Calcium/metabolism*

OBJECTIVE: To explore clinical effect of reverse shoulder replacement in treating giant irreparable rotator cuff tear complicated with glenohumeral arthritis. METHODS: A retrospective analysis was performed on 18 patients (18 shoulders) with glenohumeral arthritis combined with large irreparable rotator cuff tear admitted from April 2020 to April 2022, including 10 males and 8 females, aged from 60 to 78 years old;7 patients on the left side, 11 patients on the right side;the course of disease ranged from 6 to 21 months;7 patients with grade 3 and 11 patients with grade 4 according to Goutallier grading;8 patients with grade 4b and 10 patients with grade 5 according to Hamada grading. Shoulder joint motion, visual analogue scale (VAS), University of California at Los Angeles (UCLA) score and Constant-Murley shoulder joint function score and complications were compared at the latest follow-up. RESULTS: Eighteen patients were followed up for 24 to 48 months. At the latest follow-up, shoulder joint flexion ranged from 120° to 145°, abduction ranged from 100° to 130°, and rotation ranged from 45° to 60°. VAS ranged from 1 to 3;Constant-Murley score ranged from 80 to 95;and UCLA scores ranged from 27 to 35, and 6 patients obtained excellent result, 11 good and 1 average. Dislocation of shoulder joint occurred in 1 patient at 3 months after operation, but no dislocation occurred after manual reduction. The incision surface infection occurred in 1 patient at 1 week after operation, and the incision healed after anti-infection and cleaning. The other patients did not have complications such as dislocation, infection, prosthesis loosening and peripheral fracture. CONCLUSION Reverse shoulder replacement for the treatment of huge irreparable rotator cuff injury combined with glenohumeral arthritis disease, the clinical effect is good, could significantly improve shoulder joint function and improve quality of life, but still need to strengthen the prevention and treatment of postoperative complications such as dislocation and infection.
Humans ; Male ; Female ; Middle Aged ; Rotator Cuff Injuries/physiopathology* ; Aged ; Retrospective Studies ; Arthroplasty, Replacement, Shoulder/methods* ; Range of Motion, Articular ; Shoulder Joint/physiopathology*

Objective:By analyzing the genetic risk of triglyceride-glucose index(Tyg)and insulin resistance(IR)for cardiovascular disease(CVD), to elucidate the extent to which the contribution of Tyg to the risk of CVD development is influenced by IR genetic risk.Methods:In this study, we selected data from a cohort of elderly people in the Kunshan community, screened 7, 385 individuals with both clinical and genomic data, and calculated the polygenic risk score of insulin resistance(IRPRS)for each participant based on publicly available IR genome-wide association data, and assessed the effect of genetic risk and Tyg level on the risk of developing CVD using a multivariate Cox proportional risk model.Calculating interactions to assess the effects of genetic risk and Tyg levels on the risk of developing CVD, the effects of Tyg tertile grouping and IRPRS on the risk of developing CVD were assessed using a multivariate Cox proportional risk model, and subgroup analyses were performed for gender to assess the effects of Tyg tertile grouping and IRPRS on the risk of developing CVD by gender.Results:In the univariate Cox model, Q3 and IRPRS with the highest TYG levels were significantly associated with the risk of CVD, respectively( HR=1.59, 95% CI: 1.33-1.89; P<0.001; HR=1.61, 95% CI: 1.18-2.20; P=0.003).After adjusting for multiple confounders, the Q3 Group with the highest TYG level was still significantly associated with the risk of CVD( HR=1.28, 95% CI: 1.05-1.57; P=0.014), the Association of TYG with the risk of CVD did not change significantly( HR=1.29, 95% CI: 1.05-1.57; P=0.014).We conducted a subgroup analysis by sex and found that among older men, 13, the highest levels of TYG and IRPRS were significantly associated with CVD risk, respectively( HR=1.70, 95% CI: 1.31.2.20; P<0.001; HR=1.98, 95% CI: 1.24-3.15; P=0.004).After adding IRPRS to the model, the Association of TYG with the risk of CVD remained unchanged( HR=1.69, 95% CI: 1.31-2.19; P<0.001).After adjusting for various confounders, Tyg remained significantly associated with the risk of CVD( HR=1.39, 95% CI: 1.04-1.88; P=0.028), the results showed that TYG remained significantly associated with the risk of CVD( HR=1.41, 95% CI: 1.05-1.90; P=0.023), and the association did not decrease.No Association of IRPRS with CVD risk was found in older women. Conclusions:IRPRS and TYG are the risk factors of CVD, and diet, exercise, drugs and other external factors on TYG are the main risk factors of CVD.For individuals with high genetic factors, the risk of CVD can still be reduced by lifestyle adjustments such as diet, exercise and drug intervention.