Objective To investigate the effect of diammonium glycyrrhizinate(DG)on pulmonary injury of rats with pulmonary tuberculosis.Methods The rat models of pulmonary tuberculosis were constructed and then the an-imals were randomly divided into model group,diammonium glycyrrhizinate treatment groups(low-dose,medium-dose and high-dose)groups,high dose of diammonium glycyrrhizinate plus peroxisome proliferator-activated receptor γ(PPARγ)inhibitor group(H-DG+GW9662 group),and another 18 rats were selected as control group.The colony count of Mycobacterium tuberculosis(Mtb)in lung tissue was detected.HE staining microscopy was ap-plied to detect lung histopathology.TUNEL was applied to detect apoptosis of lung tissue cells.ELISA was applied to detect serum level of inflammatory factors.Western blot was applied to measure PPARγ,phosphorylated p38 mi-togen-activated protein kinase(p-p38MAPK)and p38 mitogen-activated protein kinase(p38MAPK)in lung tissue.Results Compared with the control group,the lung tissue structure in model group was severely damaged with a large number of proliferative tuberculosis nodules,changes of alveolar morphology,inflammatory cell infiltration and even caseous necrosis were found,and the number of tuberculosis colonies,apoptosis rate,TNF-α,IL-6,IFN-γ,COX-2 levels,and p-p38MAPK/p38MAPK expression were all increased,while PPARγ expression was decreased(P＜0.05).In L-DG,M-DG,H-DG groups improvement of lung tissue structure,alveolar morphology,inflammatory cell infiltration,and caseous necrosis were found as compared to the model group,while the counting number of tuberculosis colonies decreased and rate of cell apoptosis decreased.The level of TNF-α,IL-6,IFN-γ,COX-2 and expression of p-p38MAPK/p38MAPK reduced,the expression of PPARγ all increased.The H-DG group showed the most significant changes(P＜0.05).GW9662 treatment significantly reversed the improvement of DG on pulmonary injury in rats with pulmonary tuberculosis.Conclusions DG improves lung injury in rats with pul-monary tuberculosis and its mechanism is potentially related to the activation of PPARγ pathway and inhibition of p38MAPK pathway.

Objective:To test the feasibility, efficacy and safety of percutaneous patent foramen ovale(PFO) closure utilizing the Pansy biodegradable occluder(PBO) at 1-, 3-, 6-, 12-, 24-, and 36-month follow-up.Methods:In this single-center prospective clinical study, we enrolled 15 patients with PFO eligible for closure, all treated with the PBO, with device sizes ranging 24-34 mm. All clinical data were recorded in a 36-month follow-up period. Patients were summoned to the hospital in the 1, 3, 6, 12, 24, and 36 months after closure for transthoracic echocardiography(TTE), or transesophageal echocardiography(TEE), contrast transcranial doppler(cTCD) or contrast transthoracic echocardiography(cTTE), and a routine fasting blood sample.Results:The mean age was 27-68(44.0±16.4) years old. Indications for closure were cryptogenic stroke in 6 patients and migraine in 9 patients. Procedures were technically successful in 100%(15/15), in which course TTE showed that the position and shape of occluders were satisfactory. Small residual shunt was found by TTE in 2 patients with ASA in 1 month and 6 months after closure, respectively. 1 patient with cryptogenic stroke had another recurrent stroke 8 months after closure. At 12-month follow-up, 11 cases were closure. At 36-month follow-up, 13 cases were closure. 12 patients without atrial septal aneurysm(ASA) were closure. 1 patients with ASA was complete closure. No device-related complications occurred during the follow-up.Conclusion:PBO has good biocompatibility and suitable degradation time. A high technical success rate and closure rate can be achieved in those patients without ASA. Percutaneous closure of PFO using PBO is feasible, effective, and safe.

Objective:To investigate the clinical and gene variant characteristics of PCDH19 gene related epilepsy, and improve the ability of clinicians in early disease identification. Methods:The clinical data of 3 PCDH19 gene related epilepsy patients admitted to Children′s Hospital Affiliated to Zhengzhou University from October 2018 to August 2023 diagnosed by gene detection were reviewed and analyzed. Results:All the patients are female, and the onset age of seizure ranged in their infancy. Seizures in clusters and fever sensitivity were observed in all patients, and were very hard to control by single-drug treatment. Proband 1 was seizure-free after 2 kinds of anti-epileptic drug treatment, but with mild degree of intellectual disability. Proband 2 had refractory epilepsy with severe degree of intellectual disability. Proband 3 was seizure-free after 2 kinds of anti-epileptic drug treatment and without intellectual disability. In the first family, the proband carried heterozygous c.369C>G variant in the PCDH19 gene which was identified as de novo after parental validation. In the second family, the proband carried c.1652T>A variant inherited from her mother. In the third family, the proband carried c.278G>A variant inherited from her father. The 3 mutations had not been reported in the Human Gene Mutation Database. Conclusions:PCDH19 gene related epilepsy is one special kind of X-linked inherited epilepsy syndrome characterized by seizures in clusters and sensitivity to fever. And gene detection can help with early diagnosis and make rational clinical strategies in time. The variants c.369C>G, c.1652T>A and c.278G>A have enriched the gene variant spectrum of PCDH19.

Brain development requires a delicate balance between self-renewal and differentiation in neural stem cells (NSC), which rely on the precise regulation of gene expression. Ten-eleven translocation 2 (TET2) modulates gene expression by the hydroxymethylation of 5-methylcytosine in DNA as an important epigenetic factor and participates in the neuronal differentiation. Yet, the regulation of TET2 in the process of neuronal differentiation remains unknown. Here, the protein level of TET2 was reduced by the ubiquitin-proteasome pathway during NSC differentiation, in contrast to mRNA level. We identified that TET2 physically interacts with the core subunits of the glucose-induced degradation-deficient (GID) ubiquitin ligase complex, an evolutionarily conserved ubiquitin ligase complex and is ubiquitinated by itself. The protein levels of GID complex subunits increased reciprocally with TET2 level upon NSC differentiation. The silencing of the core subunits of the GID complex, including WDR26 and ARMC8, attenuated the ubiquitination and degradation of TET2, increased the global 5-hydroxymethylcytosine levels, and promoted the differentiation of the NSC. TET2 level increased in the brain of the Wdr26^+/- mice. Our results illustrated that the GID complex negatively regulates TET2 protein stability, further modulates NSC differentiation, and represents a novel regulatory mechanism involved in brain development.
Animals ; Mice ; DNA-Binding Proteins/genetics* ; Cell Differentiation ; Neural Stem Cells ; Translocation, Genetic ; Ubiquitins/genetics* ; Ligases/genetics*

ObjectiveTo observe the architectural parameter changes of the muscles around the knee in middle-aged and elderly women with early knee osteoarthritis (KOA) by musculoskeletal ultrasound, and to clarify the indicators of muscles that affect early KOA. MethodsFrom January to August, 2022, 20 healthy middle-aged and elderly healthy women (controls) and 20 middle-aged and elderly women with unilateral early KOA (KOA group) were recruited through Beijing Bo'ai Hospital, to measure muscle thickness of the popliteus muscle, the muscle thickness and the pennation angle of the quadriceps, as rectus femoris, vastus intermedius, vastus lateralis, vastus medialis longus and vastus medialis oblique. ResultsCompared with the healthy limb of KOA group, and the controls, the muscle thickness of vastus medialis longus, vastus medialis oblique and popliteus muscle of the affected limb of KOA group became thinner (t > 2.133, P < 0.05); the proportion of thickness of vastus medialis oblique to thickness of vastus lateralis became smaller (t > 3.660, P < 0.05). The pennation angle was smaller in the affected limb of KOA group than in the matched dominant side of the controls (t = 3.101, P < 0.05). Logistic regression analysis showed that the muscle thickness of vastus medialis oblique (OR = 0.235, 95%CI 0.068 to 0.805, P = 0.021) and popliteus muscle (OR = 0.387, 95%CI 0.152 to 0.980, P = 0.045) were related to the onset of early KOA. ConclusionThe thickness of vastus medialis longus, vastus medialis oblique and popliteus muscle decrease, and the balance of the strength of vastus medialis oblique and vastus lateralis weakens in the affected limbs of the middle-aged and elderly women with early KOA. The thickness of vastus medialis oblique and popliteus muscle are protective factors for onset of KOA.

Objective:Through TTC staining, immunohistochemical analysis, RT-PCR and hind limb motor function evaluation and other experimental methods, to explore the regulatory mechanism of metformin on anti-apoptosis in rats with spinal cord injury (SCI).Methods:Establish a rat spinal cord injury model. Through Basso-Beattie -Bresnahan locomotor rating scale (BBB) and cant test to evaluate the recovery of hindlimb motor function in rats. The changes of necrotic area of spinal cord tissue were compared by TTC staining. Extraction of rat spinal cord tissue, by Dot blot analysis and immunohistochemical detection of the hydroxyl of DNA methylation level. By qPCR, Western Blot detection TET2mRNA and protein expression level, and the changes in the scope of spinal cord injury were detected by inhibiting the expression of TET2. The interaction between TET2 and Foxo3a was detected by immunoblotting and immunoprecipitation. Through RT-PCR assay Foxo3a downstream related changes in the level of gene expression.Results:Compared with the SCI+NS group, the necrotic area of the spinal cord tissue was reduced after metformin treatment, and the BBB score and the incline test score were higher ( P<0.05). At the same time, we found that the levels of TET2mRNA and protein increased significantly after SCI at 24 h, and the 5-hmC level of DNA increased. The levels of TET2mRNA and protein and 5-hmC increased further after the use of metformin. After using SC-1, compared with the SCI+MET group, the level of 5-hmC decreased and the area of infarction increased. After SCI, the mRNA levels of downstream genes Bim, P27kip, Bax increased significantly. After metformin treatment, the mRNA levels of Bim and Bax were lower than those in the SCI+NS group ( P<0.05). After SCI, the 5-hmC levels of downstream genes Bim, P27kip, Bax increased significantly. After metformin treatment, the 5-hmC levels of Bim and Bax were lower than those in the SCI+NS group ( P<0.05). Conclusion:Metformin can promote the interaction between TET2 and Foxo3a, increase the 5-hmC level of the overall DNA, and inhibit the activation of related apoptosis genes, thereby improving tissue damage and nerve function recovery after spinal cord injury.

Objective:To evaluate the efficacy and safety of recombinant human tumor necrosis factor-α receptorⅡ: IgG Fc fusion protein (rhTNFR:Fc) in the treatment of drug-induced toxic epidermal necrolysis (TEN) .Methods:From 2009 to 2018, 22 patients with TEN were enrolled from 8 centers such as the Second Affiliated Hospital of Soochow University, including 10 males and 12 females, whose age ranged from 22 to 75 years. These patients were subcutaneously injected with rhTNFR:Fc at a dose of 25 mg once every 3 days for 6 - 8 consecutive sessions, and the initial dose was doubled. The drug eruption area and severity index (DASI) score and DASI improvement indices (DASI50, DASI75 and DASI90) were assessed before treatment and on days 4, 7, 10, 13, 16, 19, 22 and 25 after treatment; cytometric bead array (CBA) technology was used to detect the level of tumor necrosis factor (TNF) -α in peripheral blood and blister fluid samples. During the treatment, body temperature, rash changes, liver and kidney function of patients were monitored, and adverse reactions were recorded. Statistical analysis was carried out by using repeated measures analysis of variance, paired t test and Pearson correlation analysis. Results:Of the 22 patients, the temperature stopped rising in 20 patients without infections 24 - 72 hours after the first treatment, and returned to normal after 48 - 120 hours. Among the 22 patients, new blisters stopped appearing 24 - 48 hours after the first treatment, the skin color changed from bright red to dark purple after 48 - 96 hours, and most skin lesions subsided after 2 weeks. After 2 - 4 weeks of treatment, levels of alanine aminotransferase and aspartate aminotransferase returned to normal in 19 patients with abnormal liver function. After 4 - 13 days of treatment, levels of creatinine and urea nitrogen stopped rising in 7 patients with abnormal renal function. During the treatment, the DASI score of the 22 patients gradually decreased ( F = 532.81, P < 0.01) , from 53.64 ± 8.67 before treatment to 2.05 ± 1.21 on day 25 after treatment ( t = 26.60, P < 0.001) . On day 10 after treatment, 22 patients (100%) achieved DASI50; on day 19, 22 (100%) achieved DASI75; on day 25, 20 (90.90%) achieved DASI90. The level of TNF-α in peripheral blood of the 22 patients gradually decreased along with the extension of treatment duration, from 33.95 ± 27.90 ng/L before treatment to 2.38 ± 0.79 ng/L on day 25. Before treatment, the level of TNF-α in blister fluid of 15 patients was 111.99 ± 99.41 ng/L, and the ratio of blister-fluid TNF-α level to peripheral blood TNF-α level was 1.83 - 28.21. Before treatment, no correlation was observed between the serum level of TNF-α and DASI score in the 22 patients ( P = 0.10) , while the blister-fluid TNF-α level was positively correlated with DASI score in the 15 patients ( r = 0.59, P = 0.02) . No acute adverse reactions were observed during the treatment. All the 22 patients completed the treatment and were discharged with complete recovery. During 6 months of follow-up after discharge, no recurrence or any complication was observed. Conclusion:rhTNFR:Fc is effective and safe for the treatment of drug-induced TEN.

OBJECTIVE: To analyze the current status of diagnosis and management of acute appendicitis (AA) in China. METHODS: Questionnaire survey was used to retrospectively collect data of hospitalized patients with AA from 43 medical centers nationwide in 2017 (Sort by number of cases provided: Jinling Hospital of Medical School of Nanjing University, The First Affiliated Hospital of Xinjiang Medical University, Lu'an People's Hospital, Tengzhou Central People's Hospital, Dalian Central Hospital, The Affiliated Hospital of Xuzhou Medical University, Dongying People's Hospital, Jinjiang Hospital of Traditional Chinese Medicine, Huangshan Shoukang Hospital, Xuyi People's Hospital, Nanjing Jiangbei People's Hospital, Lanzhou 940th Hospital of PLA, Heze Municipal Hospital, The First College of Clinical Medical Science of China Three Gorges University, Affiliated Jiujiang Hospital of Nanchang University, The Second People's Hospital of Hefei, Affiliated Central Hospital of Shandong Zaozhuang Mining Group, The Third People's Hospital of Kunshan City, Xuzhou First People's Hospital, The 81st Group Army Hospital of PLA, Linyi Central Hospital, The General Hospital of Huainan Eastern Hospital Group, The 908th Hospital of PLA, Liyang People's Hospital, The 901th Hospital of Joint Logistic Support Force, The Third Affiliated Hospital of Chongqing Medical University, The Fourth Hospital of Jilin University, Harbin Acheng District People's Hospital, The First Affiliated Hospital of Zhengzhou University, Nanjing Luhe People's Hospital, Taixing Municipal People's Hospital, Baotou Central Hospital, The Affiliated Hospital of Nantong University, Linyi People's Hospital, The 72st Group Army Hospital of PLA, Zaozhuang Municipal Hospital, People's Hospital of Dayu County, Taixing City Hospital of Traditional Chinese Medicine, Suzhou Municipal Hospital, Beijing Guang'anmen Hospital, Langxi County Hospital of Traditional Chinese Medicine, Nanyang Central Hospital, The Affiliated People's Hospital of Inner Mongolia Medical University).The diagnosis and management of AA were analyzed through unified summary. Different centers collected and summarized their data in 2017 and sent back the questionnaires for summary. RESULTS: A total of 8 766 AA patients were enrolled from 43 medical centers, including 4 711 males (53.7%) with median age of 39 years and 958 (10.9%) patients over 65 years old. Of 8 776 patients, 5 677 cases (64.6%) received one or more imaging examinations, and the other 3 099 (35.4%) did not receive any imaging examination. A total of 1 858 (21.2%) cases received medical treatment, mainly a combination of nitroimidazoles (1 107 cases, 59.8%) doublet regimen, followed by a single-agent regimen of non-nitroimidazoles (451 cases, 24.4%), a nitroimidazole-free doublet regimen (134 cases, 7.2%), a triple regimen of combined nitroimidazoles (116 cases, 6.3%), nitroimidazole alone (39 cases, 2.1%) and nitroimidazole-free triple regimen (3 cases, 0.2%). Of the 6 908 patients (78.8%) who underwent surgery, 4 319 (62.5%) underwent laparoscopic appendectomy and 2589 (37.5%) underwent open surgery. Ratio of laparotomy was higher in those patients under 16 years old (392 cases) or over 65 years old (258 cases) [15.1%(392/2 589) and 10.0%(258/2 589), respectively, compared with 8.5%(367/4 316) and 8.0%(347/4 316) in the same age group for laparoscopic surgery, χ²=91.415, P<0.001; χ²=15.915,P<0.001]. Patients with complicated appendicitis had higher ratio of undergoing open surgery as compared to those undergoing laparoscopic surgery [26.7%(692/2 589) vs. 15.6%(672/4 316), χ²=125.726, P<0.001].The cure rates of laparoscopic and open surgery were 100.0% and 99.8%(2 585/2 589) respectively without significant difference (P=0.206). Postoperative complication rates were 4.5%(121/2 589) and 4.7%(196/4 316) respectively, and the difference was not statistically significant (χ²=0.065, P=0.799). The incidence of surgical site infection was lower (0.6% vs. 1.7%, χ²=17.315, P<0.001), and hospital stay was shorter [6(4-7) days vs. 6(5-8) days, U=4 384 348.0, P<0.001] in the laparoscopic surgery group, while hospitalization cost was higher (median 12 527 yuan vs. 9 342 yuan, U=2 586 809.0, P<0.001). CONCLUSIONS The diagnosis of acute appendicitis is still clinically based, supplemented by imaging examination. Appendectomy is still the most effective treatment at present. Laparoscopic appendectomy has become the main treatment strategy, but anti-infective drugs are also very effective.
Acute Disease ; Adolescent ; Adult ; Aged ; Anti-Bacterial Agents ; therapeutic use ; Appendectomy ; Appendicitis ; diagnosis ; therapy ; China ; Female ; Health Care Surveys ; Humans ; Laparoscopy ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult

Objective To evaluate the effect of short-term training of objective structured clinical examination (OSCE) examiner in general practice residency training final examination.Methods Sixty examiners from Xinjiang Uygur Autonomous Region participated in half-day workshop of OSCE.The participants were interviewed with questionnaire before and after the training program and the effect of training was evaluated.Results The study showed that 78.3％ (47/60) examiners knew OSCE and understood the concept and implementation steps before the training;21.7％ (13/60)had used it before;95.0％ (57/60) examiners intended to learn the performance of OSCE.After training most participants completely or basically understood the 6 test stands and implementation methods of OSCE;the participants were highly satisfied with the training duration,contents and methods,and the satisfaction rates were all over 70％.Conclusion The examiners recognize the advantages of OSCE in assessment of clinical skills and have strong intention of application.Short-term training has a certain effect and feasibility.

Objective To analysis the implementation of the objective structured clinical examination (OSCE) for completion of general practice residency training in Xinjiang Uygur autonomous region.Methods Ninety eight general practice residents took training-completion examination applying OSCE in Xinjiang Uygur Autonomous Region.The examiners (including SP examiners) and examinees were interviewed with questionnaire after the OSCE.Results All 60 examiners and 98 examinees were generally in favor of using OSCE in general practice residency training completion examination;100.0％ (60/60) examiners and 86.7％ (85/98) examinees thought that it was necessary;98.3％ (59/60) examiners and 89.8％ (88/98) examinees thought that the OSCE was able to evaluate the clinical competence of general practice;95.0％ (57/60) examiners and 78.6％ (77/98) examinees thought the OSCE examination stations reasonable;40.8 ％ (40/98) examinees thought that the difficulty degree of the exam was moderate,35.7％ (35/98) and 20.4％ (20/98) examinees thought that it was difficult or very difficult,particularly for history writing and case analysis.Conclusions The examiners and examinees recognize the advantages of OSCE in assessment of clinical competence.This study provides useful information for application of OSCE in general practice residency training completion assessment.