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.
2.Effectiveness of group skills training intervention on social ability of high functional autism spectrum disorder children
HU Shasha, ZHAO Xiao, ZHU Zhenzhen, LIU Xiaoli, WANG Rong, HU Zhenyu, ZHANG Wenwu
Chinese Journal of School Health 2025;46(2):167-171
Objective:
To evaluate the intervention efficacy of integrated group social skills training on social ability in school age patients with high functioning ASD, so as to provide a reference for improving social skills in children with high functioning ASD.
Methods:
From January 2021 to December 2023, 62 children aged 7-12 with high functioning ASD who visited the Children s Psychiatry Outpatient Department of the Affiliated Kangning Hospital of Ningbo University were recruited, and were randomly divided into a training ( n =31) and a control group ( n =31) by a random number table method. The training group received a 20 week structured group social training program (mental interpretation courses and social courses), while the control group received only conventional treatment. Chinese version of Griffith Empathy Measure Parent Ratings (GEM-PR) and Social Response Scale (SRS) were used to assess the symptoms of social deficits before and after treatment. Emotional face recognition tasks and eye movement trajectories were used to test the characteristics of social visual attention in children with ASD. Group comparison was conducted using t-test and Mann-Whitney U test.
Results:
At baseline, there were no significant differences in GEM-PR score ( t = -1.20 to -0.81), SRS score ( t =-0.36-1.75), emotional face recognition accuracy and reaction time ( t =-0.58-1.85), and eye movement trajectory ( U/t =-1.63-0.29) between the two group ( P >0.05). After intervention, the total GEM-PR score and empathic cognitive factor score of training group [18.00(10.00,24.00),9.00(8.00,13.00)] were significantly higher than those of the control group [12.00(-1.00,18.00),2.00(-2.00,7.00)], and the total SRS score and social cognition, social perception, social communication, social motivation (73.23±14.20, 16.16±2.72, 6.58±2.50, 24.29±5.61, 9.52±3.73) were significantly lower than those of the control group (95.26±15.29, 19.90±2.84, 12.58±2.49,31.94±6.38, 13.74±4.81) ( U/t =-2.38, -4.59; -5.88, -5.29, -9.47, -5.01, -3.87, P <0.05). The overall correct rate of emotional face recognition and the correct rate of angry, fearful and neutral faces recognition in the training group [(81.55±6.62)%,(76.86±12.06)%,(79.61±12.42)%,(94.27±6.26)%] were significantly higher than the control group [(70.55±13.82)%,(62.82±18.77)%,(67.18±18.85)%,(79.60±20.05)%], and the average reaction time [(2 226.70±274.43)ms] was lower than the control group [(2 417.27±324.10)ms] (t=4.00, 3.50, 3.07, 3.89, -2.42, P<0.05). The time to first eye gaze [764.74 (748.64, 793.73) ms] in the training group was significantly lower than that in the control group [810.92 (782.86, 877.42) ms], and the proportion of moderatetohigh intensity attention area in the face [(37.37±1.27)%] was significantly higher than that in the control group [(30.34±1.23)%] (U/t=3.44, 8.89, P<0.05).
Conclusion
Integrated group social training can significantly improve the social communication and empathy ability of high functioning ASD children, increase active attention and recognition ability of faces, and improve mental development of children with ASD.
3.Effect of Scutellariae Radix Combined with EGFR-TKIs on Non-small Cell Lung Cancer
Yaya YU ; Chenjing LEI ; Zhenzhen XIAO ; Qi MO ; Changju MA ; Lina DING ; Yadong CHEN ; Yanjuan ZHU ; Haibo ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):106-115
ObjectiveTo investigate the effects of Scutellariae Radix combined with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) on cell proliferation, apoptosis, cancer stem cell (CSC) marker expression, and metabolism in non-small cell lung cancer (NSCLC) cells. MethodsThe anti-tumor effects of Scutellariae Radix and EGFR-TKIs (gefitinib or osimertinib) in NSCLC cells were evaluated using the cell counting kit-8 (CCK-8) and Annexin V-FITC/propidium iodide (PI) double staining apoptosis assay. The activity of Scutellariae Radix and EGFR-TKIs in three-dimensional (3D) cultures of NSCLC cells was assessed using the CellTiter-Glo® 3D cell viability assay. The mRNA and protein expression levels of CSC markers, sex determining region y box protein 2 (SOX2) and aldehyde dehydrogenase 1 family member A1 (ALDH1A1), were detected by quantitative real-time polymerase chain reaction (Real-time PCR) and Western blot, respectively. Changes in intracellular reactive oxygen species (ROS) levels were detected by ROS staining, and the redox ratio was detected by femtosecond laser labeling free imaging (FLI). ResultsUnder both two-dimensional (2D) and 3D culture conditions, compared with the blank group and EGFR-TKI group, the combination group showed significantly reduced cell viability and increased apoptosis rate (P<0.05). Compared with the EGFR-TKI group, the mRNA and protein levels of CSC markers were significantly downregulated in the combination group (P<0.05). Additionally, the redox ratio was significantly elevated (P<0.05), and ROS levels were also increased in the combination group compared with the EGFR-TKI group. ConclusionIn NSCLC cells, Scutellariae Radix enhances the redox ratio and increases ROS levels, thereby inhibiting the expression of CSC markers and strengthening the anti-tumor effects of EGFR-TKIs. This provides a novel molecular mechanism by which Scutellariae Radix may enhance the sensitivity of targeted therapies.
4.B1 corrected T1 mapping for distinguishing pathological types and differentiation degrees of lung cancers
Zhenzhen LI ; Gaofeng XU ; Yigang FU ; Yong XIAO ; Mingming ZHU ; Xiao ZHOU ; Xun SHI ; Jianqin JIANG
Chinese Journal of Medical Imaging Technology 2024;40(2):231-234
Objective To observe the value of B1 corrected T1 mapping for distinguishing pathological types and differentiation degrees of lung cancers.Methods A total of 74 lesions in 65 patients with lung cancers were prospectively enrolled,including 49 poorly differentiated lesions and 25 moderately or well differentiated ones,i.e.42 adenocarcinomas,14 squamous cell carcinomas and 18 small cell lung cancers(all poorly differentiated).B1 corrected T1 mapping was performed,ROI(ROI1 and ROI2)were delineated using 2 methods,and T1 values of different pathological types and differentiation degrees lung cancers were compared.The receiver operating characteristic(ROC)curves were drawn,and the areas under the curve(AUC)were calculated.Results Significant differences of T1 values were found among different pathological types of lung cancer(all P<0.05),as well as between small cell lung cancer and the rest 2 types of lung cancer(both P<0.05).There were significant differences of T1 values between poorly differentiated and moderately well differentiated lung cancer(squamous cell carcinoma+adenocarcinoma)(both P<0.05).Taken ROI1 T1 value=1 524.21 ms as the cut-off value,the AUC of T1 value for distinguishing poorly differentiated and moderately well differentiated lung cancer(squamous cell carcinoma+adenocarcinoma)was 0.698,with sensitivity of 64.50%and specificity of 76.00%.Taken ROI2 T1 value=1 630.68 ms as the cut-off value,the AUC of T1 value was 0.676,with sensitivity of 54.80%and specificity of 80.00%.Conclusion B1 corrected T1 mapping was helpful for distinguishing pathological types and differentiation degrees of lung cancers.
5.Analysis on the Registration of Clinical Trials of Headache Treated by TCM
Yanhua JIANG ; Zhenzhen QIAN ; Sha ZHOU ; Yonglie ZHAO ; Jian ZHU ; Guang WU ; Hongli WU ; Zhiwei JING
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(4):79-85
Objective To analyze the registered clinical trials of headache treated by TCM;To discuss the current research status;To provide reference for the optimization of subsequent clinical trial research plans.Methods All clinical trials of headache treated by TCM were retrieved from the ChiCTR and the ClinicalTrials.The retrieval time was from the database establishment to May 22,2023.The general characteristics,study types,intervention measures and outcome indicators of the trials were analyzed respectively.Results A total of 104 registered studies were included,with the number of registered studies increasing since 2004 and reaching a peak in 2020,involving 25 provincial administrative regions or countries and 69 clinical trial institutions;the funding sources were mainly scientific research funds of universities,national finance and local finance.The research type was mainly intervention research;the designing scheme was mainly randomized parallel control study;the high frequency random method was simple random method;45 registered studies used blind methods.Exploratory studies/pre-trials were the most commonly used in the phases of clinical researches.Most of the registered studies were single-center clinical trials with a total sample size of 9 648 patients.The main interventions were acupuncture and oral Chinese medicines.The high frequency outcome indicators included life quality of score,headache attack frequency,headache attack days and headache severity,etc.There were some problems in outcome indicators,such as non-standard,lack of TCM characteristic advantages,and insufficient patient participation.Conclusion The number of registered studies of headache treated by TCM has increased by year,but there are some problems in design elements,such as random method,blind method,number of research centers,sample size and the setting of outcome indicator.
6.Characterizing immune microenvironment cell composition of chronic rhinosinusitis with nasal polyps based on mass cytometry technology
Lei WANG ; Weiqing WANG ; Surita AODENG ; Yuzhuo LIU ; Zhenzhen ZHU ; Jingjing LI ; Wei LYU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(6):532-542
Objective:To analyze the cellular composition characteristics of the nasal tissue immune microenvironment in patients with control, chronic rhinosinusitis without nasal polyps (CRSsNP), non-eosinophilic chronic rhinosinusitis with nasal polyps (neCRSwNP), and eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) using mass cytometry flow technology.Methods:Thirteen CRS patients who underwent endoscopic nasal surgery at the Department of Otorhinolaryngology Head and Neck Surgery of Peking Union Medical College Hospital from March to December 2022 were recruited, including 8 males and 5 females, aged 22.3 to 58.3 years. Three control mucosae were obtained from normal ethmoid or sphenoid sinuses of patients with benign tumors of the temporal fossa or non-functional pituitary adenomas who underwent endoscopic surgery, excluding allergic rhinitis and sinusitis. Sixteen clinical tissue samples (3 of control, 3 of CRSsNP, 4 of neCRSwNP, and 6 of eCRSwNP) were prepared into single-cell suspensions. Mass cytometry flow detection was performed using a combination of 42 molecular markers to analyze the differences in cell subpopulations among the groups. Data were analyzed using GraphPad Prism 9.Results:Based on the mass cytometry flow results, cells from control, CRSsNP, neCRSwNP, and eCRSwNP were divided into seven main cell subgroups, with detailed subgrouping of T/NK cells and myeloid cells. In T/NK cells, compared with the control group, the number of NK CD56bright cells increased in the CRSsNP group, while NK CD56dim cells decreased; compared with the CRSsNP group, the eCRSwNP group showed a decrease in NKT cells and CD4 +Tem cells; compared with the CRSsNP group, the eCRSwNP group showed a significant increase in CD25 expression within Treg cells; compared with the CRSsNP group, the eCRSwNP group showed a significant decrease in Tbet expression in CD8 +Teff cells and CD8 +TRM cells; in eCRSwNP, the expression of CD103 in CD8 +TRM cells was significantly lower than in CRSsNP. In myeloid cells, compared with the other three groups, the eCRSwNP group showed a significant increase in macrophages and a significant decrease in cDC1 and monocytes; compared with the control group and CRSsNP, the eCRSwNP group also showed a significant decrease in resting state macrophages; compared with the CRSsNP group, the eCRSwNP group showed a significant decrease in the level of CX3CR1 within cDC2 and monocytes; the expression levels of NLRP3 in cDC2 and macrophages in the eCRSwNP group were significantly higher than in the other three groups; compared with the control group, the expression levels of Gata3 in cDC2 and macrophages in the eCRSwNP group were also significantly increased; additionally, the expression of CCR2 within monocytes in the eCRSwNP group was lower than in the CRSsNP group. In ILC, compared with the control group, the expression of CCR6 decreased in the eCRSwNP group. Conclusions:Compared with the control group, CRSsNP, and neCRSwNP, eCRSwNP shows an increase in macrophage number, a decrease in cDC1 and resting state macrophages, and depletion of protective cells CD103 +CD8 +TRM. Additionally, the expression levels of CCR2 and CX3CR1 in monocytes of eCRSwNP are decreased.
7.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.
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.Evaluation of the treatment effect on sinus elevation and implant restoration in cases with odontogenic maxil-lary sinusitis after tooth extraction
Yunying ZHU ; Yun LIU ; Ting XU ; Zhenzhen LIU ; Shaoping CAO ; Zhangsong WANG ; Donghui WU
Journal of Prevention and Treatment for Stomatological Diseases 2024;(3):202-208
Objective To investigate the clinical effects of sinus elevation surgery and implant restorationdue to in-sufficient bone massafter tooth extraction in patients with odontogenic maxillary sinusitis(OMS)and to provide a refer-ence for use in clinical practice.Methods This study was reviewed and approved by the Ethics Committee,and in-formed 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.Restora-tions were placed 6 to 8 months after surgery.The patients were followed up 21 days,3 months,and 8 months after im-plantation 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 de-creased,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.
10.Study on the Influence of Medical Record First Page Quality on DRG Payment and its Countermeasures
Linlin LI ; Yangyang LI ; Yingxue ZHU ; Enyou WANG ; Meizi YUAN ; Zhenzhen LIANG ; Jibing QIAO
Chinese Hospital Management 2024;44(9):75-78
DRG has been applied in most hospitals.The quality management of the first page of medical records,which is directly related to DRG grouping,has become an important part of hospital management.To some extent,the quality of the first page of medical records affects the inclusion of DRG,the payment of medical treatment,and the performance assessment and evaluation of hospital.Through examples,it focuses on the quality problems of the first page of medical records and its impact on DRG payment,analyzes the reasons leading to the cases of DRG not entered in the group or in the wrong group,and puts forward countermeasures to strengthen the quality manage-ment of the first page of medical records,in order to provide theoretical support and practical reference for hospital management and DRG payment management.


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