1.Role of endoplasmic reticulum stress-mediated DEAD-box helicase 3 X-linked in a mouse model of concanavalin A-induced immune-mediated liver injury
Zhenzhen PAN ; Ling XU ; Xianru ZHU ; Zihao FAN ; Yaling CAO ; Yinkang MO ; Sai YAN ; Feng REN
Journal of Clinical Hepatology 2026;42(1):134-142
ObjectiveTo investigate the role of DEAD-box helicase 3 X-linked (DDX3X) in immune-mediated liver injury (ILI), and to clarify its mechanism by regulating endoplasmic reticulum stress (ERS)-dependent apoptotic pathway and its association with the clinical progression of hepatitis B. MethodsMice were given injection of concanavalin A (ConA) via the caudal vein to establish a model of ILI, PBS (control group) and different concentrations of ConA were injected into the tail vein of hepatocyte-specific DDX3X-knockout mice (DDX3XΔHep and DDX3X-flox mice (DDX3Xfl/fl), respectively.. The log-rank survival analysis, measurement of the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and HE staining of liver tissue were performed to assess liver injury, and qRT-PCR and Western Blot were used to measure the mRNA and protein expression levels of glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), and DDX3X in liver tissue. Intraperitoneal injection of 4-phenylbutyric acid (4-PBA, 100 mg/kg) was performed to inhibit ERS. Serum samples (n=30) and liver tissue samples (n=6) were collected from healthy controls, chronic hepatitis B (CHB) patients, and hepatitis B virus-associated liver failure (HBV-LF) patients; ELISA was used to measure the serum level of DDX3X, and qRT-PCR/Western Blot was used to analyze the expression of targets in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the control group of mice, the expression of DDX3X in the liver of mice induced by ConA was significantly increased after liver injury (P<0.05), and hepatocyte-specific DDX3X knockout increased the 72-hour survival rate of mice by 55% (compared with 20% in the DDX3Xfl/fl group), with significant reductions in the serum levels of ALT and AST (P<0.000 1) and the expression levels of the ERS markers GRP78 and CHOP (P<0.05). After ERS was inhibited by 4-PBA, there was alleviation of liver injury (with reductions in ALT and AST, P <0.001) and a reduction in DDX3X expression (P<0.01). The analysis of clinical samples showed that the mRNA and protein expression levels of liver DDX3X in CHB patients and HBV-LF patients were significantly higher than those in healthy controls (all P<0.01), and there was a significant increase in the serum level of DDX3X in HBV-LF patients (P<0.000 1). ConclusionDDX3X exacerbates ILI by regulating the ERS-dependent apoptotic pathway (GRP78/CHOP), and its expression is associated with the progression of hepatitis B. Therefore, it can be used as a potential therapeutic target.
3.Clinical outcomes and prognostic factors of pemphigus vulgaris and pemphigus foliaceus: A 20-year retrospective study.
Hongda LI ; Wenchao LI ; Zhenzhen WANG ; Shan CAO ; Pengcheng HUAI ; Tongsheng CHU ; Baoqi YANG ; Yonghu SUN ; Peiye XING ; Guizhi ZHOU ; Yongxia LIU ; Shengli CHEN ; Qing YANG ; Mei WU ; Zhongxiang SHI ; Hong LIU ; Furen ZHANG
Chinese Medical Journal 2025;138(10):1239-1241
4.Evaluation of the treatment effect on sinus elevation and implant restoration in cases with odontogenic maxillary sinusitis after tooth extraction
ZHU Yunying ; LIU Yun ; XU Ting ; LIU Zhenzhen ; CAO Shaoping ; WANG Zhangsong ; WU Donghui
Journal of Prevention and Treatment for Stomatological Diseases 2024;32(3):202-208
Objective:
To investigate the clinical effects of sinus elevation surgery and implant restorationdue to insufficient bone massafter tooth extraction in patients with odontogenic maxillary sinusitis (OMS) and to provide a reference for use in clinical practice.
Methods:
This study was reviewed and approved by the Ethics Committee, and informed consent was obtained from the patients. Forty-five teeth were extracted from patients with OMS in the maxillary posterior area (the study group). Sinus elevation and implantation were performed due to insufficient bone height in the implant area 6-8 months after tooth extraction in the study group. Forty-eight teeth were extracted from patients without "OMS" in the maxillary posterior area (the control group), and sinus elevation and implantation were performed due to insufficient bone height in the implant area 6-8 months after tooth extraction inthe control group. In the study group, 13 cases of discontinuous maxillary sinus floor bone and residual alveolar bone height of the maxillary sinus floor less than 4 mm were addressed with lateral wall sinus elevation, and the other 32 cases were addressed with crest-approach sinus elevation. In the control group, 8 cases of residual alveolar bone height less than 4 mm in the maxillary sinus floor were addressed with lateral wall sinus,and the other 40 cases were addressed with crest approach sinus elevation. Restorations were placed 6 to 8 months after surgery. The patients were followed up 21 days, 3 months, and 8 months after implantation and every 6 months after the placement of the restorations. The sinus bone gain (SBG), apical bone height (ABL) and marginal bone loss (MBL) were statistically analyzed 24 months after the restoration.
Results:
The average preoperative mucosal thickness in the 45 patients in the study group was (1.556 ± 0.693) mm, which was significantly larger than that in the control group (1.229 ± 0.425) mm (P<0.001). There were no perforations in either group. Twenty-four months after restoration, there was no significant difference in the SBG, ABH or MBL between the two groups (P>0.05).
Conclusion
After the extraction of teeth from patients with OMS, the inflammation of the maxillary sinus decreased, and the bone height and density in the edentulous area were restored to a certain degree. The effects of sinus floor lifting surgery and implant restoration do not differ between patients with and without OMS.
5.Effects of sodium hydrosulfide on HK2-NLRP3-GSDMD pathway and pyroptosis induced by lung ischemia/reperfusion in rats
Lu SHI ; Xiaoting WANG ; Zhenzhen LUO ; Jun CHENG ; Sian CHEN ; Jun-Peng XU ; Qihao ZHANG ; Wenjie CAO ; Man HUANG ; Yunna TIAN ; Xuguang JIA ; Wantie WANG
Chinese Journal of Pathophysiology 2024;40(6):1105-1113
AIM:To investigate the effects of sodium hydrosulfide(NaHS)on hexokinase 2(HK2)-nucleo-tide-binding oligomerization domain-like receptor protein 3(NLRP3)-gasdermin D(GSDMD)pathway and pyroptosis in-duced by lung ischemia/reperfusion(I/R)in rats.METHODS:Male Sprague-Dawley rats were divided into 6 groups:control group,control+NaHS group,I/R group,low-dose NaHS+I/R(L+I/R)group,medium-dose NaHS+I/R(M+I/R)group,and high-dose NaHS+I/R(H+I/R)group,with 6 rats in each group.The NaHS was administered via intraperi-toneal injection at 1.5 mL,30 min before modeling.The left lung tissues were collected 30 min after ischemia and 1 h af-ter reperfusion,and the wet/dry weight ratio and total lung water content were recorded.Hematoxylin-eosin(HE)staining was used to examine lung tissue morphological changes.The levels of malondialdehyde(MDA),myeloperoxidase(MPO)and lactate in lung tissues were measured with test kits.ELISA was employed to determine the levels of interleukin-1β(IL-1β)and IL-18.The expression of glycolysis-and pyroptosis-related indicators was analyzed by Western blot,qRT-PCR and immunofluorescence staining.RESULTS:Compared with control group,the rats in NaHS group showed no signifi-cant differences in all laboratory tests(P>0.05).The rats in I/R group exhibited significant lung injury,oxidative stress,increased lactate level,and up-regulated glycolysis and pyroptosis(P<0.05 or P<0.01).Compared with I/R group,the indicators in L+I/R group showed a downward trend(P<0.01)or no difference(P>0.05),while those in M+I/R group dis-played a significant reduction(P<0.05 or P<0.01).However,the indexes in H+I/R group exhibited no significant dif-ferences in these tests(all P>0.05).CONCLUSION:A moderate dose(56 μmol·L-1·kg-1)of NaHS mitigated the oc-currence of pyroptosis by inhibiting the HK2-NLRP3-GSDMD pathway,thus contributing to the attenuation of lung I/R in-jury in rats.
6.Prediction of cognitive function in patients with cerebral small vessel disease based on morphological brain network connection model
Cunsheng WEI ; Yuan CHEN ; Zhenzhen HE ; Meng CAO ; Yusheng YU ; Xuemei CHEN
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(11):1320-1324
Objective To construct a morphological brain network in patients with cerebral small vessel disease(CSVD)and predict it application for cognitive function.Methods A total of 64 eld-erly CSVD patients admitted in our hospital from January 2020 to February 2024 were retrospec-tively recruited.Cognitive function was assessed with Mini-Mental State Examination(MMSE)and Montreal Cognitive Assessment(MoCA).Their clinical data,and results of cognitive function and multi-modal MRI scanning were collected and analyzed.3D T1-weighted imaging based on Kullback-Leibler divergence similarity was used to construct individual morphological brain net-work,and the connectome-based predictive model was employed to construct a cognitive predic-tion model.Results The network,which is significantly and positively correlated with the MMSE and MoCA scores,was mainly located in the default mode network,and could effectively predict individual MMSE and MoCA scores(r=0.795,P=4.436×10-15;r=0.794,P=4.974×10-15,P<0.01).The connections,which were significantly negatively correlated with MMSE or MoCA scores,were mainly located between the salience/ventral attention network and other networks,and could also effectively predict individual MMSE and MoCA scores(r=0.766,P=1.679× 10-13;r=0.850,P=6.915×10-19,P<0.01).Combined positive correlation and negative correla-tion networks,the model showed further improved predictive performance(r=0.849,P=7.603 × 10-19;r=0.888,P=1.445 × 10-22,P<0.01).Conclusion Individual morphological brain network can effectively predict cognitive function in elderly CSVD patients,and can be used as a convenient tool for early warning of cognitive impairment related to CSVD.
7.Changes in serum TIMP-1 and PTX3 levels and clinical significance in patients with obstructive sleep apnea-hypopnea syndrome
Hui WANG ; Jinhong ZHANG ; Hong WANG ; Meiyu SUN ; Wenyi ZHAO ; Juan CAO ; Zhenzhen ZHANG ; Guangjie SUN
International Journal of Laboratory Medicine 2024;45(2):141-145
Objective To explore the expression and clinical significance of tissue inhibitor of matrix metal-loproteinases(TIMP)-1 and pentraxin-3(PTX3)in the serum of patients with obstructive sleep apnea-hypop-nea syndrome(OSAHS).Methods A total of 120 patients with OSAHS admitted to the hospital from 2021 to 2022 were selected as the study group,and another 114 healthy people who underwent the physical exami-nation in the same period were selected as the control group.The severity of OSAHS was determined accord-ing to the apnea-hypopnea index(AHI)and the minimum oxygen saturation(LSpO2),and the patients were divided into mild group(66 cases)and the moderate-severe group(54 cases).Serum TIMP-1 and PTX3 levels were measured by enzyme-linked immunosorbent assay.Pearson method was used to analyze the correlation between serum TIMP-1,PTX3 and AHI,LSpO2.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of serum TIMP-1 and PTX3 on the severity of disease in patients with OSAHS.Logistic regression was used to analyze the factors influencing the severity of the disease in OSAHS patients.Results Serum TIMP-1,PTX3 and AHI levels in the study group were higher than those in the control group,and LSpO2 level was lower than that in the control group(P<0.05).The body mass index(BMI),the proportion of hypertension history,the proportion of coronary heart disease history,the levels of total choles-terol,triglycerides,low-density lipoprotein cholesterol,TIMP-1,PTX3 and AHI in the moderate-severe group were significantly higher than those in the mild group,and the high density lipoprotein cholesterol,LSpO2 lev-el was significantly lower than that in the mild group(P<0.05).Pearson method results showed that serum TIMP-1,PTX3 levels were positively correlated with AHI(r=0.428,0.392,P<0.05),and serum TIMP-1,PTX3 levels were negatively correlated with LSpO2(r=-0.645,-5.836,P<0.05).The results of the ROC curve showed that the area under the curve(AUC)of serum TIMP-1 and PTX3 alone predicted the severity of the patients'disease was 0.813 and 0.777,with cut-off values were 2.47 μg/L and 7.23 ng/L,with the sensi-tivity of 70.37%and 77.78%and the specificity of 77.27%and 72.23%,respectively.The AUC for predic-ting the severity of patients'disease by combining the two was 0.866,which was significantly higher than those of serum TIMP-1(Z=2.067,P=0.039)and PTX3 alone(Z=2.331,P=0.020).Logistic regression a-nalysis showed that TIMP-1,PTX3,history of hypertension,and history of coronary artery disease,AHI and LSpO2 were influential factors for severity of disease in patients with OSAHS(P<0.05).Conclusion TIMP-1 and PTX3 are both up-regulated in the serum of OSAHS patients and closely related to the severity of the disease,and they are the influential factors in the severity of OSAHS patients.
8.Application of WHO molecular classification in endometrial cancer(2020)and its clinicopathological significance
Liyu CAO ; Zhuangzhuang TIAN ; Lili ZHU ; Zhenzhen BAI ; Cong ZHANG
Chinese Journal of Clinical and Experimental Pathology 2024;40(3):279-284
Purpose To explore the application and clini-copathological significance of molecular classification in endome-trial cancer(EC)of WHO(2020)tumors of the female repro-ductive system.Methods Sixty-two EC patients were collected and categorized into four subgroups,namely POLE mutation type,mismatch repair deficient(MMRd)type,non-specific molecular spectrum(NMSP)type,and p53 mutation type,based on WHO molecular classification tested by PCR and im-munohistochemistry.The correlation among four molecular sub-groups and their clinicopathological features were analyzed.Re-sults The molecular classification was distributed as follows:3(4.8%)cases were POLE-mutated,15(24.2%)cases MMRd,36(58.1%)cases NSMP and 8(12.9%)cases p53 abnormal expression.There were no significant differences a-mong POLE-mutated and infiltration depth,grade,lymph vascu-lar space invasion and other pathological factors such as lymph node metastasis and FIGO stage(P>0.05).Among 15 patients with MMRd,the proportion of FIGO stage Ⅱ+Ⅲ significantly increased.One case showed abnormal overexpression of p53 pro-tein,while two cases showed complete loss of expression in MMRd subgroup.36 cases of NSMP were associated with low histopathological grade(Grade Ⅰ+Ⅱ)(P<0.05),and no significant differences were observed among NSMP and other clinicopathological factors(P>0.05).The p53 abnormal ex-pression in 8 cases was related to high histopathological grade(Grade Ⅲ)(P<0.05),and the rate of lymph node metastasis and FIGO stage Ⅱ+Ⅲ significantly increased in patients with p53 abnormal expression,and although the difference was not statistically significant(P>0.05).Conclusion The molecu-lar subgroups of EC have certain clinical application value,the cases with MMRd and p53 abnormal expression may have poor prognosis than these with POLE-mutated and NSMP.
9.The effects of combining transcranial magnetic stimulation with biofeedback in retraining the swallowing of stroke survivors with dysphagia
Qian XU ; Zhenzhen HAN ; Dongyan ZHU ; Liang WANG ; Fang CAO ; Jiajia ZHAI ; Hongjian LU
Chinese Journal of Physical Medicine and Rehabilitation 2024;46(1):17-22
Objective:To evaluate the effect of combining contralateral high-frequency transcranial magnetic stimulation (rTMS) with biofeedback-controlled empty swallowing training on dysphagia among stroke survivors.Methods:Eighty dysphagic stroke survivors were divided at random into a control group, a biofeedback group, an rTMS group and a combined treatment group, each of 20. In addition to routine dysphagia rehabilitation, the biofeedback group and the rTMS group received empty swallowing training based on biofeedback or high-frequency rTMS applied to the healthy motor cortex as appropriate. The combined treatment group was given both. The treatment was administered once daily, 5 days a week for 3 consecutive weeks. Before and after the treatment, all of the subjects′ swallowing was evaluated using the penetration aspiration scale (PAS), functional oral intake scale (FOIS) and a standardized swallowing assessment (SSA). The latency and amplitude of the mylohyoid muscle′s motor evoked potentials (MEPs) were also recorded before and after the treatment.Results:After the treatment, significant improvement was observed in the average PAS, FOIS and SSA scores as well as in the latency and amplitude of the MEPs in the four groups. The average results in the combined treatment group were significantly better than in the other 3 groups. The latency of the mylohyoid muscle′s MEP was significantly shorter in the combined group than in the control and biofeedback groups on average, while the amplitude was significantly greater than in the control group.Conclusion:Combining contralateral high frequency rTMS with empty swallowing training based on biofeedback can better improve the swallowing of dysphagic stroke survivors.
10.Consistent analysis of swept-source optical coherence tomography and time-domain optical coherence tomography in measuring the parameters of chamber angle of patients with myopia
Anhai WEI ; Yangcheng ZOU ; Li YANG ; Zhenzhen CAO ; Hehua ZHANG
China Medical Equipment 2024;21(2):28-32
Objective:To investigate the consistency of swept-source optical coherence tomography(SS-OCT)and time-domain optical coherence tomography(TD-OCT)in measuring the parameters of anterior chamber angle.Methods:A total of 46 myopic patients(92 eyes)were retrospectively selected from Department of Ophthalmology of Army Specialty Medical Center from January 2023 to May 2023.Both SS-OCT and TD-OCT were used to measure respectively the parameters of anterior chamber angle of patients.And then,the differences of central anterior chamber depth(ACD),angle opening distance(AOD500,AOD750),scleral spur angle(SSA),trabecular iris area(TISA500,TISA750)between SS-OCT and TD-OCT were compared and analyzed.The Pearson correlation analysis and Bland-Altman test were adopted to analyze and measure the correlation and consistency of the measures.Results:There was significant difference in ACD between the two kinds of scan methods(t=-6.83,P<0.001).Additionally,the differences of the AOD500,AOD750,SSA500,TISA500 and TISA750 of measured data beside of nose were significant(t=-5.16,5.51,-6.51,-4.75,-5.69,P<0.001),respectively.Similarly,the differences of them beside of temple were significant(t=-5.04,-4.8,-6.06,-3.84,-4.02,P<0.001),respectively.There was positive correlation between the two kinds of scan methods(r=0.71-0.92).The Bland-Altman analysis showed that 2.1% to 8.9% of the measured values were outside the consistency limit by 95%.Conclusion:There are differences between SS-OCT and TD-OCT in the measures of the parameters of anterior chamber angle of myopic patients,and the measured results of them appear positive correlation.


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