1.Mechanisms of Qizhujianwei Granules in Blocking Malignant Progression of Gastric Intraepithelial Neoplasia
Yuling YU ; Yanmin WANG ; Siqi WANG ; Yateng SUN ; Yunhe WANG ; Yonghuang YAN ; Xinyu YANG ; Siqi HAN ; Yuhong SONG ; Yuhan WANG ; Cai ZHANG ; Zeqi SU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):143-151
ObjectiveTo investigate the effects of Qizhujianwei granules (QZJW) on abnormal proliferation and malignant transformation of gastric mucosal cells in rats with gastric intraepithelial neoplasia (GIN) and to explore the related mechanisms. MethodsA total of 80 SPF male Wistar rats were used. A GIN rat model was established using a four-factor comprehensive method consisting of methylnitronitrosoguanidine (MNNG), ranitidine, irregular feeding patterns, and sodium salicylate. Except for the normal group, after successful modeling, the rats were randomly divided according to body weight into a model group, a Moluodan group (0.55 g·kg-1), and a QZJW group (7.34 g·kg-1), with 12 rats in each group. All groups were treated for 8 weeks. The general characteristics of the rats and morphological changes of the gastric mucosa were observed. Histopathological changes of the gastric mucosa were examined by hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of pepsinogenⅠ (PGⅠ), pepsinogenⅡ (PGⅡ), and gastrin (G-17), as well as the expression level of transforming growth factor-β1 (TGF-β1) in gastric mucosal tissue, and the PGⅠ/PGⅡ ratio was calculated. Immunohistochemistry (IHC) was used to detect the localization and expression levels of proliferating cell nuclear antigen (Ki-67) and Vimentin in gastric mucosal tissue. Western blot analysis was used to determine the protein expression levels of Wnt family member 3A (Wnt3a), β-catenin, CyclinD1, proto-oncogene Cmyc, transforming growth factor-β receptor Ⅰ (TGFβRⅠ), intracellular signaling transducers Smad2/3, phosphorylated (p)-Smad2/3, twist family transcription factor (Twist1), and Vimentin in gastric mucosal tissue. ResultsCompared with the normal group, the model group showed characteristic changes including dim eyes, pale ears and claws, dark-red tongue, and reduced luster of the tail. The gastric mucosa appeared pale, with surface congestion and erosion. The gastric mucosal glands were disordered, the nuclear-to-cytoplasmic ratio increased, and local tumor cells were observed. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly decreased (P<0.01), while the level of G-17 was significantly increased (P<0.01). The protein expression levels of Ki-67, Wnt3a, β-catenin, CyclinD1, Cmyc, TGF-β1, TGFβRⅠ, Smad2/3, Twist1, and Vimentin in gastric mucosal tissue were significantly increased (P<0.05, P<0.01), whereas the ratio of p-Smad2/3 to Smad2/3 was significantly decreased (P<0.05). Compared with the model group, the general characteristics and gastric mucosal conditions of rats in the Moluodan group and the QZJW group were improved. HE staining showed that QZJW could effectively block the malignant progression of GIN. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly increased (P<0.05, P<0.01), while the level of G-17 was significantly decreased (P<0.01). The protein expression levels of Ki-67, Wnt3a, β-catenin, CyclinD1, Cmyc, TGF-β1, TGFβRⅠ, Smad2/3, Twist1, and Vimentin in gastric mucosal tissue were significantly decreased (P<0.05, P<0.01). ConclusionQZJW have a therapeutic effect on rats with GIN. The mechanism may involve inhibition of the Wnt/β-catenin signaling pathway to regulate the cell cycle and suppress abnormal cell proliferation. Meanwhile, it may inhibit epithelial-mesenchymal transition by suppressing the TGF-β1/Smad/Twist1 signaling pathway, thereby blocking the malignant progression of GIN.
2.Mechanisms of Qizhujianwei Granules in Blocking Malignant Progression of Gastric Intraepithelial Neoplasia
Yuling YU ; Yanmin WANG ; Siqi WANG ; Yateng SUN ; Yunhe WANG ; Yonghuang YAN ; Xinyu YANG ; Siqi HAN ; Yuhong SONG ; Yuhan WANG ; Cai ZHANG ; Zeqi SU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):143-151
ObjectiveTo investigate the effects of Qizhujianwei granules (QZJW) on abnormal proliferation and malignant transformation of gastric mucosal cells in rats with gastric intraepithelial neoplasia (GIN) and to explore the related mechanisms. MethodsA total of 80 SPF male Wistar rats were used. A GIN rat model was established using a four-factor comprehensive method consisting of methylnitronitrosoguanidine (MNNG), ranitidine, irregular feeding patterns, and sodium salicylate. Except for the normal group, after successful modeling, the rats were randomly divided according to body weight into a model group, a Moluodan group (0.55 g·kg-1), and a QZJW group (7.34 g·kg-1), with 12 rats in each group. All groups were treated for 8 weeks. The general characteristics of the rats and morphological changes of the gastric mucosa were observed. Histopathological changes of the gastric mucosa were examined by hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of pepsinogenⅠ (PGⅠ), pepsinogenⅡ (PGⅡ), and gastrin (G-17), as well as the expression level of transforming growth factor-β1 (TGF-β1) in gastric mucosal tissue, and the PGⅠ/PGⅡ ratio was calculated. Immunohistochemistry (IHC) was used to detect the localization and expression levels of proliferating cell nuclear antigen (Ki-67) and Vimentin in gastric mucosal tissue. Western blot analysis was used to determine the protein expression levels of Wnt family member 3A (Wnt3a), β-catenin, CyclinD1, proto-oncogene Cmyc, transforming growth factor-β receptor Ⅰ (TGFβRⅠ), intracellular signaling transducers Smad2/3, phosphorylated (p)-Smad2/3, twist family transcription factor (Twist1), and Vimentin in gastric mucosal tissue. ResultsCompared with the normal group, the model group showed characteristic changes including dim eyes, pale ears and claws, dark-red tongue, and reduced luster of the tail. The gastric mucosa appeared pale, with surface congestion and erosion. The gastric mucosal glands were disordered, the nuclear-to-cytoplasmic ratio increased, and local tumor cells were observed. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly decreased (P<0.01), while the level of G-17 was significantly increased (P<0.01). The protein expression levels of Ki-67, Wnt3a, β-catenin, CyclinD1, Cmyc, TGF-β1, TGFβRⅠ, Smad2/3, Twist1, and Vimentin in gastric mucosal tissue were significantly increased (P<0.05, P<0.01), whereas the ratio of p-Smad2/3 to Smad2/3 was significantly decreased (P<0.05). Compared with the model group, the general characteristics and gastric mucosal conditions of rats in the Moluodan group and the QZJW group were improved. HE staining showed that QZJW could effectively block the malignant progression of GIN. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly increased (P<0.05, P<0.01), while the level of G-17 was significantly decreased (P<0.01). The protein expression levels of Ki-67, Wnt3a, β-catenin, CyclinD1, Cmyc, TGF-β1, TGFβRⅠ, Smad2/3, Twist1, and Vimentin in gastric mucosal tissue were significantly decreased (P<0.05, P<0.01). ConclusionQZJW have a therapeutic effect on rats with GIN. The mechanism may involve inhibition of the Wnt/β-catenin signaling pathway to regulate the cell cycle and suppress abnormal cell proliferation. Meanwhile, it may inhibit epithelial-mesenchymal transition by suppressing the TGF-β1/Smad/Twist1 signaling pathway, thereby blocking the malignant progression of GIN.
3.Asociation between intolerance of uncertainty and severity of obsessive-compulsive symptom: the mediating role of cerebellar ALFF value
Shaoxia WANG ; Xiang ZHANG ; Shihao LU ; Yuhan LI ; Fangqing SONG ; Jianqun FANG
Sichuan Mental Health 2026;39(3):227-233
BackgroundObsessive-compulsive disorder (OCD) carries a considerable disability burden. Intolerance of uncertainty (IU) is associated with the severity of obsessive-compulsive symptoms, yet its neural underpinnings remain unclear. The cerebellum has been implicated in uncertainty processing and demonstrates structural and functional abnormalities in OCD, but direct evidence linking its spontaneous activity to the relationship between IU and obsessive-compulsive symptoms is still lacking. ObjectiveTo explore the pathway through which spontaneous cerebellar neural activity mediates the relationship between IU and obsessive-compulsive symptoms in OCD patients, with the aim of providing a new perspective for understanding the neural mechanisms of OCD. MethodsA total of 51 patients with OCD who visited the Mental Health Center outpatient clinic of the General Hospital of Ningxia Medical University from November 2022 to November 2024 and met the diagnostic criteria for OCD according to the International Classification of Diseases, tenth edition (ICD-10). During the same period, 43 community-based volunteers matched for gender and age were enrolled as the control group. Resting-state functional magnetic resonance imaging data were collected from two groups. Amplitude of low-frequency fluctuation (ALFF) analysis was used to compare whole-brain spontaneous neural activity between two groups. Clinical assessments were conducted using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Intolerance of Uncertainty Scale-12 (IUS-12). Pearson correlation analysis was used to examine correlations between cerebellar ALFF values and scale scores in OCD patients. Using IU as the independent variable, obsessive-compulsive symptoms as the dependent variable, and ALFF values from between-group difference brain regions as the mediator, Process 4.0 for SPSS 24.0 (model 4) was used to examine the mediating role of these ALFF values between IU and obsessive-compulsive symptoms. The Bootstrap method was used to test the mediation effect. ResultsA total of 47 OCD patients and 40 controls completed this study. Compared with the control group, the OCD group showed decreased ALFF values in the right cerebellar Crus Ⅱ (t=-5.254, FWE-corrected P<0.01). Correlation analysis revealed that ALFF value in the right cerebellar Crus Ⅱ was negatively correlated with Y-BOCS total score (r=-0.851), compulsive behavior subscale score (r=-0.647), IUS-12 total scores (r=-0.617), and prospective IU subscale scores (r=-0.717) in OCD group (P<0.01). Prospective IU subscale scores were positively correlated with Y-BOCS total scores (r=0.811) and compulsive behavior subscale score (r=0.535) (P<0.01). Mediation analysis showed that ALFF value in the right cerebellar Crus Ⅱ region partially mediated the effect of prospective IU on obsessive-compulsive behavior, with a mediation effect of 0.064 (95% CI: 0.004–0.136), accounting for 24.57% of the total effect. ConclusionPatients with OCD showed reduced spontaneous neural activity in the right cerebellar Crus Ⅱ region, which was significantly associated with IU and obsessive-compulsive symptoms. This region partially mediated the effect of IU on compulsive behaviors. [Funded by Basic Conditions and Innovation Platform Construction Project of Ningxia Hui Autonomous Region in 2023 (number, 2022YXGCJS001)]
4.Clinical Observation on Ziwu Liuzhu Timing Point Application in Treating Pediatric Pneumonic Cough of Phlegm-Heat Obstructing Lung Syndrome
Lingling ZHUANG ; Zengling WANG ; Yuhan SONG
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(2):403-409
Objective To observe the clinical efficacy of Ziwu Liuzhu(midnight-midday ebb and flow,the movement of qi and blood in the meridians following heavenly-stems and earthly-branches cycle)timing point application in treating pediatric pneumonic cough of phlegm-heat obstructing lung syndrome.Methods A total of 300 cases of children with pediatric pneumonic cough of phlegm-heat obstructing lung syndrome admitted to the First Clinical Hospital of Jilin Academy of Traditional Chinese Medicine from January 2023 to April 2024 were randomly divided into observation group and control group according to random number table method,150 cases in each group,and both groups of children were given the conventional symptomatic treatment with western medicine,while the control group was given Cefuroxime Sodium intravenous drip.The observation group was treated with Ziwu Liuzhu timing point application on the basis of treatment of the control group.After treatment,the clinical efficacy of the two groups was evaluated,and the changes in traditional Chinese medicine(TCM)syndrome scores before and after treatment were observed,and the symptoms such as disappearance time of lung rale,recovery time of body temperature,recovery time of heart rate,and return to normal time of X-ray findings of the two groups were observed.The changes of red blood cell count(RBC),white blood cell count(WBC),platelet count(PLT)and C-reactive protein(CRP)levels before and after treatment were compared between the two groups.The safety and occurrence of adverse reactions in the two groups were also evaluated.Results(1)The total effective rate was 94.67%(142/150)in the observation group and 84.67%(127/150)in the control group.The efficacy of the observation group was superior to that of the control group,the difference being statistically significant(P<0.05).(2)After treatment,the TCM syndrome scores of the children in the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(3)After treatment,the observation group was superior to the control group in the disappearance time of lung rales,recovery time of body temperature,recovery time of heart rate,and return to normal time of X-ray findings,the difference being statistically significant(P<0.05).(4)After treatment,the RBC,WBC,PLT and CRP levels of the children in the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(5)The incidence rate of adverse reactions in the observation group was 10.67%,and that in the control group was 16.00%;the intergroup comparison showed that the difference being not statistically significant(P>0.05).Conclusion Ziwu Liuzhu timing point application in treating pediatric pneumonic cough of phlegm-heat obstructing lung syndrome can effectively improve the children's clinical symptoms,promote their recovery of lung function,alleviate the inflammatory reaction,which is safety,and with less adverse reaction.
5.Effect of Electroacupuncture on Autophagy and Apoptosis of Interstitial Cells of Cajal in Gastric Antrum of Functional Dyspepsia Rats
Mohao ZHU ; Ling QIU ; Wenhua HAN ; Tianya YAN ; Yuhui SONG ; Yuhan HE ; Jianan CAO ; Weiai LIU
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(8):75-81
Objective To observe the effects of electroacupuncture at"Neiguan"and"Gongsun"on autophagy and apoptosis related indexes of interstitial cells of Cajal(ICC)in rats with functional dyspepsia(FD);To explore its possible mechanism on improving gastrointestinal motility of FD.Methods Totally 32 SPF grade SD rats were randomly divided into blank group,model group,electroacupuncture group and Western medicine group,with 8 rats in each group.An FD model was constructed using a composite etiology modeling method.The electroacupuncture group received electroacupuncture at"Neiguan"and"Gongsun",while the Western medicine group received oral administration of mosapride once a day for 7 consecutive days.The general condition,body mass and average daily intake of rats were observed every week,and gastric emptying rate and small intestine propulsion rate were detected,transmission electron microscopy was used to observe the structure of gastric antrum ICC,Western blot was used to observe the expressions of c-kit,Beclin1,LC3Ⅱ/Ⅰ,p62,Caspase-3 protein in gastric antrum tissue,qPCR was used to observe the mRNA expressions of Beclin1,LC3Ⅱ/Ⅰ,p62 and c-kit in gastric antrum tissue,TUNEL staining was used to detect the apoptosis rate of cells in gastric antrum tissue.Results Compared with the blank group,the model group rats were mentally lethargic,clustered and curled up,with reduced activity,rough and dull hair,loose and unformed feces,reduced body mass and daily food intake(P<0.05),and gastric emptying rate and small intestine propulsion rate decreased(P<0.01),ICC mitochondria swelled and dissolved,with varying degrees of vacuolar formation,rough endoplasmic reticulum dilation and destruction,and a large number of autophagosomes,the expressions of Beclin1 and LC3 Ⅱ/Ⅰ protein and mRNA in gastric antrum tissue increased(P<0.01),the expressions of p62,c-kit protein and mRNA decreased(P<0.01),while Caspase-3 protein expression increased(P<0.01),and the apoptosis rate of gastric antral tissue cells increased(P<0.01).Compared with the model group,the condition of rats in electroacupuncture group and the Western medicine group were improved,with increased responsiveness,increased mobility,neat hair,formed feces,increased body mass and daily food intake(P<0.01),and gastric emptying rate and small intestine propulsion rate increase(P<0.01),a normal ICC structure,and a small amount of autophagosomes were still visible,the expressions of Beclin1,LC3Ⅱ/Ⅰ protein and mRNA in gastric antrum tissue decreased(P<0.01),the expressions of p62,c-kit protein and mRNA increased(P<0.01),while Caspase-3 protein expression decreased(P<0.01),and the apoptosis rate of gastric antral tissue cells decreased(P<0.01).There was no statistically significant difference in various indicators between electroacupuncture group and Western medicine group(P>0.05).Conclusion Electroacupuncture at"Neiguan"and"Gongsun"can restore the number and structure of ICC and improve gastrointestinal motility,and its mechanism may be related to the inhibition of autophagy and apoptosis levels.
6.Study on the Quality Evaluation of Online Medical Services in Public Hospitals Based on the Standardized Pa-tient Method and lOM Model
Yuting YANG ; Faying SONG ; Yuhan LI ; Xue GONG ; Yipei WANG ; Rui GUO
Chinese Hospital Management 2025;45(4):6-11
Objective To provide a comprehensive and multi-dimensional objective assessment of the online medi-cal service quality supplied by public hospitals in China,and providing feasible suggestions for further improving.Methods It adopted a standardized patient method and relied on the IOM model to conduct a descriptive analy-sis of the online medical service quality from the perspectives of safety and effectiveness,efficiency,patient-cen-tered care,and accessibility.Results The process quality(adherence to checklist)in public hospital was 17.65%,the diagnostic accuracy was 66.04%,and the treatment correctness was 88.68%.The average consultation fee was 50 yuan.The patients'disease experience was 4.00 points,the social situation was 0,and the agreement between the physician and the patient was 12.00 points.The average time waiting for first response was about 1.60 hours,the average time waiting for each response was about 5.14 hours,and the patient's total time was about 20.32 hours.The time for response was 3,and the total words of providers was 149.50.Conclusion Internet medical ser-vices quality in public hospital are still insufficient in three aspects:the process quality(adherence to checklist),pa-tient-centered care,and accessibility.Improving online medical service quality can be achieved by strengthening"in-process supervision"and improving physicians'comprehensive clinical ability.
7.Applied research and prospect of key assessment method for sonography about trauma in pre-examination triage of emergency for patients with closed thoracic and abdominal trauma
China Medical Equipment 2025;22(11):179-184
It is possible that patients with closed thoracic and abdominal trauma quickly occur death caused by deterioration of the condition in short time if their conditions could not be recognized and intervened timely because their early symptoms are concealed and the processing of their condition is rapid.The pre-examination triage of emergency is the first safety line of defense that patients with closed thoracic and abdominal trauma obtained timely rescue and treatment,and both the accuracy of its judgement and the timeliness of its response are critical.At present,there are many kinds of assessment methods and tools about pre-examination triage of emergency for patients with closed thoracic and abdominal trauma at home and abroad,such as conventional vital sign assessment and various kinds of trauma scoring systems.However,these methods have still limitations in recognizing early concealed injuries of closed thoracic and abdominal trauma.Focused trauma ultrasound(FAST),as a rapidly,non-invasively,and repeatable bedside ultrasound method,can effectively explore whether exists free liquid through conducts systematically scans for key areas such as the pericardium,hepatorenal space,splenorenal space,and pelvis cavity,thus,can provide important basis for early judging internal bleeding and organ damage.Based on this analysis,this article systematically reviewed the current status about the application of standards,assessment methods,and tools in pre-examination triage of emergency for patients with closed thoracic and abdominal trauma,and analyzed the advantages and limitations of FAST that was used in pre-examination triage of emergency,and conducted prospect,which aimed to provide references for pre-examination triage of emergency about closed thoracic and abdominal trauma in looking for the best assessment tools.
8.Mechanism of electroacupuncture-mediated PINK1/Parkin signal pathway in the treatment of functional dyspepsia in rats
Yuhan HE ; Yuhui SONG ; Yi QIU ; Yuhan HUANG ; Mohao ZHU ; Zhen KANG ; Wei'ai LIU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(6):869-876
Objective To investigate the mechanism of electroacupuncture-mediated PTEN-induced kinase 1(PINK 1)/Parkin signal pathway activation in treating functional dyspepsia model rats.Methods Thirty-six SD rats were randomly divided into the blank control(n=8)and the modeling groups(n=28)using the random number table method.The functional dyspepsia model was established using the compound etiology modeling method.After successful modeling,24 rats were divided into the model,electroacupuncture,and mosapride groups using the random number table method,with eight rats per group.The blank group was not intervened.The electroacupuncture,mosapride,and model groups were bound for 30 min,and only the electroacupuncture group was administered"Neiguan"(PC 6)and"Gongsun"(SP 4)while bound.The electroacupuncture and model groups were administered the same amount of normal saline,and the mosapride group was given mosapride citrate solution(1.35 mg/kg).The above intervention method were performed once a day for 7 consecutive days to observe the general condition of rats.Gastric emptying and small intestinal propulsion experiments were used to observe gastric emptying rate and small intestine propulsion rate in each group of rats.The interstitial cells of the Cajal(ICC)ultrastructure of gastric antrum were observed under a transmission electron microscope.The protein and mRNA expressions of C-kit proto-oncogene protein(C-kit),microtubule-associated protein 1 light chain 3(LC3)Ⅱ/Ⅰ,ubiquitin-binding protein p62(p62),Bcl-2 interacting protein 1(Beclin1),PINK1,and Parkin were detected using Western blotting and real-time fluorescence PCR.Results Compared with the blank group,the rats in the model group exhibited lethargy,dull and dry fur,sluggish responses,and substantial decreases in food intake and body weight.Their feces alternated between dry and loose consistency.Furthermore,the gastric emptying and small intestinal propulsion rates were reduced(P<0.01).The ultrastructural morphology of ICC and their mitochondria in the gastric antrum tissue showed apparent damage.The protein and mRNA expressions of C-kit and p62 were decreased(P<0.01),whereas those of PINK1,Parkin,Beclin1,and LC3Ⅱ/Ⅰ were increased(P<0.01).Compared with the model group,the rats in the electroacupuncture and mosapride groups showed notable improvements in their mental state,with neat fur,enhanced activity and responsiveness,gradual increases in food intake and body weight,and well-formed feces.Additionally,the gastric emptying and intestinal propulsion rates increased(P<0.01).The ultrastructural morphology of ICC and their mitochondria in the gastric antrum tissue were notably improved.The protein and mRNA expressions of C-kit and p62 were increased(P<0.01),whereas those of PINK1,Parkin,Beclin1,and LC3Ⅱ/Ⅰwere decreased(P<0.01).Conclusion Electroacupuncture improves the gastrointestinal motility of functional dyspepsia rats,and its mechanism may be related to upregulating C-kit and p62 expression,downregulating PINK1,Parkin,Beclin1,and LC3Ⅱ/Ⅰ expression,inhibiting abnormal PINK1/Parkin signal pathway activation,and blocking the excessive mitophagy of ICC.
9.Interaction between gender and visceral adiposity index-associated risk of type 2 diabetes
Hongzhou LIU ; Xuelian ZHANG ; Song DONG ; Xiaojing LI ; Xiaomin FU ; Yuhan WANG ; Xiaodong HU ; Bing LI ; Zhaohui LYU
Chinese Journal of Internal Medicine 2025;64(8):736-744
Objective:To examine the interaction between gender and the visceral adiposity index (VAI) in relation to the risk of type 2 diabetes mellitus (T2DM).Methods:This retrospective cohort study utilized data from the public Dryad database derived from the NAGALA (NAFLD in the Gifu Area, Longitudinal Analysis) project (1994-2016). Participants were stratified into quartiles based on VAI levels. A multivariate Cox proportional hazards regression model was employed to evaluate whether VAI independently predicts T2DM risk. Kaplan-Meier survival curves and receiver operating characteristic (ROC) curves were constructed for each VAI quartile. Subgroup analyses were conducted to examine associations across age and body mass index categories. Both multiplicative and additive interaction effects between gender and VAI were assessed. Additionally, gender-specific Cox models were fitted to further explore these associations.Results:A total of 15 453 participants [8 419 males and 7 034 females; mean age, (43.7±8.9) years] were included, with a median follow-up duration of 5.39 years. During follow-up, 373 participants (2.4%) developed T2DM. After adjustment for potential confounders, higher VAI levels were independently associated with increased T2DM risk ( HR=1.16; 95% CI 1.11-1.21), consistent with the results across VAI quartiles. Kaplan-Meier analysis revealed a significant trend of increasing T2DM incidence across VAI quartiles ( P<0.001). The area under the ROC curve for VAI in predicting T2DM at 3, 5, and 10 years was 0.755, 0.735, and 0.696, respectively. Sensitivity analyses showed that elevated VAI was associated with increased T2DM risk across all age and body mass index subgroups (all P<0.05). Regarding interaction analysis, the HR (95% CI) for the multiplicative interaction between VAI and gender was 1.22 (1.19-1.26). The relative excess risk of interaction was -1.08 (95% CI -2.96 to -0.06), the attributable proportion of interaction was -0.54 (95% CI -1.35 to -0.01), and the synergy index was 0.48 (95% CI 0.26-0.91), indicating a negative additive interaction. Using low-VAI women as the reference group, the risk of T2DM in high-VAI women was higher ( HR=2.53, 95% CI 1.59-4.02) compared to high-VAI men ( HR=2.01, 95% CI 1.49-2.72). In gender-specific analyses, increasing VAI remained significantly associated with elevated T2DM risk after adjustment in both females ( HR=1.43, 95% CI 1.21-1.68) and males ( HR=1.16; 95% CI 1.11-1.22), with consistent findings across VAI quartiles. Conclusions:VAI and gender demonstrated multiplicative and additive interaction in relation to T2DM risk. The association between increasing VAI and T2DM risk was more pronounced in women than in men.
10.Charcot-Marie-Tooth disease type 2 caused by SORD gene mutation: a case report and literature review
Mingshan SONG ; Yuhan BAI ; Kangqin YANG ; Wenhua DENG ; Gang WU ; Min ZHANG ; Xin ZHAO
Chinese Journal of Neurology 2025;58(6):650-657
Objective:To report a Charcot-Marie-Tooth disease type 2 (CMT2) patient with SORD gene mutations, aiming to enhance the understanding of SORD gene-associated peripheral neuropathy. Methods:A CMT2 patient with SORD gene mutations was identified through whole exome sequencing in the Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology in January 2024, and the patients′ clinical features were elaborated in detail. 31-Phosphorus magnetic resonance spectroscopy ( 31P-MRS) was employed to assess the phosphorus profile of the limbs, and real-time quantitative reverse transcription polymerase chain reaction was utilized to detect peripheral blood SORD gene mRNA expression levels in the patient, the family members, and the normal control. Additionally, the genetic and clinical characteristics of SORD gene mutation-related CMT2 and distal hereditary motor neuropathy (dHMN) were reviewed by searching the CNKI and PubMed databases. Results:The male CMT2 patient was 15 years old, presented with early-onset lower limb muscle weakness and atrophy, hypoesthesia, reduced tendon reflexes, and flat feet. 31P-MRS examination indicated that the pH of the patient′s leg was lower than that of the upper limb. Whole exome sequencing showed the patient carrying complex heterozygous mutations c.757delG (p.Ala253GlnfsTer27) and c.218C>T (P.Ser73Leu) in the SORD gene. The mRNA expression of the SORD gene of the patient′s mother [0.623(0.614, 0.645)] was lower than that of the patient′s father [0.961(0.888,1.020), H=13.330, P=0.007] and normal people [1.001(0.917, 1.092), H=14.830, P=0.002]. Through literature review, it is found that 31 SORD gene mutations have been reported worldwide, among which c.757delG (p.Ala253GlnfsTer27) was found to be a hotspot mutation, and all patients exhibited an autosomal recessive inheritance pattern. Conclusions:A patient with CMT2 caused by a compound heterozygous mutation c.757delG/c.218C>T in the SORD gene, with the main clinical symptoms of bilateral lower limb weakness, atrophy, sensory disturbance and reduced tendon reflexes is reported. Furthermore, 31P-MRS of the extremities is anticipated to both early and sensitively detect muscle lesions in patients with hereditary peripheral neuropathy.

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