Objective:To analyze the clinical characteristics, RAN-binding protein 2 ( RANBP2) gene variations, and prognosis in Chinese acute necrotizing encephalopathy (ANE) patients. Methods:A retrospective analysis of ANE cases registered in the Peking Union Medical College Hospital Encephalitis Registry System from 2022 to 2024, involving patients from Peking Union Medical College Hospital and other hospitals, was conducted. A descriptive study was performed on the clinical characteristics, treatments and prognosis, cerebrospinal fluid examination results, and imaging findings of these patients based on adjusted ANE diagnostic criteria. Whole-exome sequencing technology was used to detect gene mutations in these patients.Results:A total of 18 ANE cases were included, ranged in age from 2 to 72 [20(5, 43)] years. The male-to-female ratio was 4∶5. All patients were found with precipitating infections including COVID-19, influenza A virus and Mycoplasma pneumoniae infections. All patients presented with fever, with varying degrees of consciousness disturbance observed in 16 cases, and seizures in 10 cases. All patients underwent lumbar puncture, with normal or mildly elevated white cell counts [3(2, 13)×10 6/L] and mildly to moderately elevated protein levels [1.90(0.92, 4.65) g/L]. A total of 6 patients were found with extremely elevated interleukin-6 level [950(164, 2 000) pg/ml] in cerebrospinal fluid. Bilateral symmetric thalamic lesions were typical imaging features of ANE, while involvement of other areas such as cortical and subcortical white matter, brainstem, and cerebellum was also observed. A total of 14 patients performed genetic tests while 4 patients were identified with RANBP2 gene mutations (c.1754C>T in 3 cases, c.1966A>G in 1 case). All patients received immunotherapy, and 7 patients died at discharge while other patients presented with neurological sequelae of varying degrees. Conclusions:ANE is a rare and severe parainfectious encephalopathy that can occur in both children and adults. Clinically, it is characterized by rapidly progressing encephalopathy following systematic infection, with bilateral symmetric thalamic lesions. The detection of RANBP2 gene mutations could help make the diagnosis.

OBJECTIVE To explore the effect and mechanism of Buyang huanwu decoction （BYHWD） on mitochondrial dynamics in rats with cerebral ischemia-reperfusion injury （CIRI）. METHODS CIRI rats were randomly divided into CIRI group， low-dose BYHWD （L-BYHWD， intragastric administration of 3.15 mg/kg BYHWD） group， high-dose BYHWD （H-BYHWD， intragastric administration of 12.60 mg/kg BYHWD） group， positive control （intraperitoneal administration of 150 mg/kg Extract of Ginkgo biloba leaves injection） group， H-BYHWD+solvent control （intragastric administration of 12.60 mg/kg BYHWD+ intraperitoneal injection of 20 mg/kg DMSO） group and H-BYHWD+Compound C （intragastric administration of 12.60 mg/kg BYHWD+intraperitoneal injection of 20 mg/kg Compound C） group， with 15 rats in each group. Additionally， 15 rats were assigned to the sham operation group. All rats received the corresponding medications or saline solution via intragastric administration or intraperitoneal injection once daily for 4 consecutive weeks. After the last administration， the cerebral infarct volume of rats was measured； the ultrastructure of mitochondria in endothelial cells in the ischemic penumbra （IP） region was observed； the mitochondrial membrane potential was evaluated； the fluorescence colocalization area ratio of optic atrophy 1 （OPA1） to cluster of differentiation 31 （CD31） in the IP region was detected； the expressions of mitofusin 2 （MFN2）， OPA1， mitochondrial fission 1 protein （Fis1）， and proteins related to the AMP-activated protein kinase （AMPK）/dynamin-related protein 1 （Drp1） pathway in the IP region were determined. RESULTS Compared with the sham operation group， mitochondria in endothelial cells of the IP region in brain tissue of rats in the CIRI group were swollen， mostly spherical， with fractured cristae and severe vacuolation； the percentage of cerebral infarct volume， Fis1 expression level and phosphorylation level of Drp1 were increased significantly （P＜0.05）， while mitochondrial membrane potential in the IP region， fluorescence colocalization area ratio of OPA1 to CD31， the expressions levels of MFN2 and OPA1， and phosphorylation level of AMPK were significantly decreased （P＜0.05）. These indicators were improved in the L-BYHWD group， H-BYHWD group， and positive control group， M025） compared with the CIRI group （P＜0.05）. Compared with the H-BYHWD group and H-BYHWD+solvent control group， the above indicators of rats in the H-BYHWD+Compound C group showed significant reversal（P＜0.05）. There was no statistically significant difference in the above indicators between the H-BYHWD+solvent control group and the H-BYHWD group （P＞0.05）. CONCLUSIONS BYHWD may improve CIRI by activating the AMPK/Drp1 pathway and ameliorating mitochondrial dynamic disorders.

Objective:To analyze the clinical characteristics, RAN-binding protein 2 ( RANBP2) gene variations, and prognosis in Chinese acute necrotizing encephalopathy (ANE) patients. Methods:A retrospective analysis of ANE cases registered in the Peking Union Medical College Hospital Encephalitis Registry System from 2022 to 2024, involving patients from Peking Union Medical College Hospital and other hospitals, was conducted. A descriptive study was performed on the clinical characteristics, treatments and prognosis, cerebrospinal fluid examination results, and imaging findings of these patients based on adjusted ANE diagnostic criteria. Whole-exome sequencing technology was used to detect gene mutations in these patients.Results:A total of 18 ANE cases were included, ranged in age from 2 to 72 [20(5, 43)] years. The male-to-female ratio was 4∶5. All patients were found with precipitating infections including COVID-19, influenza A virus and Mycoplasma pneumoniae infections. All patients presented with fever, with varying degrees of consciousness disturbance observed in 16 cases, and seizures in 10 cases. All patients underwent lumbar puncture, with normal or mildly elevated white cell counts [3(2, 13)×10 6/L] and mildly to moderately elevated protein levels [1.90(0.92, 4.65) g/L]. A total of 6 patients were found with extremely elevated interleukin-6 level [950(164, 2 000) pg/ml] in cerebrospinal fluid. Bilateral symmetric thalamic lesions were typical imaging features of ANE, while involvement of other areas such as cortical and subcortical white matter, brainstem, and cerebellum was also observed. A total of 14 patients performed genetic tests while 4 patients were identified with RANBP2 gene mutations (c.1754C>T in 3 cases, c.1966A>G in 1 case). All patients received immunotherapy, and 7 patients died at discharge while other patients presented with neurological sequelae of varying degrees. Conclusions:ANE is a rare and severe parainfectious encephalopathy that can occur in both children and adults. Clinically, it is characterized by rapidly progressing encephalopathy following systematic infection, with bilateral symmetric thalamic lesions. The detection of RANBP2 gene mutations could help make the diagnosis.

Objective:To investigate the preventive and therapeutic effects of epigallocatechin gallate (EGCG) on tetracycline-induced acute drug-induced liver injury (DILI) in mice.Methods:Thirty-two BALB/C mice were divided into four groups, with eight mice in each group. The normal group was raised under conventional condition. Tetracycline-induced acute DILI models were established by intraperitoneal injection of tetracycline in the model group, the blank control group was intraperitoneally injected with equivalent 0.9% NaCl soluation, and EGCG prevention/treatment group was treated with EGCG on the basis of modeling. Blood samples, feces, liver and intestinal tissues of mice were obtained and analyzed by flow cytometry, biochemical test, pathological examination, and 16S rRNA sequencing. The effects of EGCG on gut microbiota, serum lipopolysaccharides (LPS) and transaminase, CD64 expression in intestinal mucosa, hepatic macrophage typing, and hepatic steatosis were evaluated. One-way analysis of variance was performed for analysis of significant difference among groups, and independent sample t test was used for further pairwise comparison. Results:Intraperitoneal injection of tetracycline-caused disorder of gut microbiota in the model group with hepatocytes showing steatosis grade 3 in 7 mice and grade 4 in 1 mouse. The serum level of LPS in model group was significantly higher than that of normal group ( (5.50±0.20) EU/L vs. (3.96±0.19) EU/L) and by the gut-liver axis which caused M1-type macrophages in liver tissues more than that of normal group ((40.00±2.91)% vs. (36.12±2.53)%), and the differences were statistically significant( t=15.83, 2.46; P<0.001, =0.034), and CD64 expression in intestinal mucosa also increased. EGCG intervention altered the gut microbiota in mice with tetracycline-induced acute DILI. The Shannon index and Simpson index of the model group were lower than those of the normal group (4.98±0.56 vs. 5.62±0.47, 0.91±0.03 vs. 0.95±0.02), while the Shannon index (4.08±0.62) and Simpson index (0.83±0.07) of the EGCG prevention/treatment group were lower than those of the model group. The differences were statistically significant ( t=-2.30, -2.85, -2.85, 2.82; P=0.038, 0.013, 0.013, 0.014). Compared with those of the model group, liver pathological changes of EGCG prevention/treatment group improved significantly (grade 2 in 8 mice), the serum level of LPS((4.22±0.17) EU/L) decreased, and the difference was statistically significant( t=-13.63, P<0.001), but had no significant effects on the CD64 expression in intestinal mucosa. Hepatic macrophage typing was compared between EGCG prevention/treatment group and model group, M2-type macrophages promoting repair were predominant in EGCG prevention/treatment group (M2-type macrophoges ratio: (6.20±0.17)% vs. (4.74±0.48)%, t=2.84, P=0.017; M1/M2-type macrophages ratio: 6.20±1.25 vs. 8.48±0.66, t=-4.95, P=0.001). Conclusion:EGCG alleviates tetracycline-induced acute DILI by altering gut microbiota to modulate liver innate immune system.

Metabotropic glutamate receptor 5 (mGluR5) encephalitis is a rare type of anti-cell surface antigen antibody encephalitis mediated by autoimmune mechanisms. This article reported a case of anti-mGluR5 encephalitis. The patient was a 25-year-old young man with a history of Hodgkin′s lymphoma. Due to tumor recurrence, he developed encephalitis symptoms including fever, headache, mental and behavioral abnormalities, memory loss, consciousness disturbance, and seizures after checkpoint immunosuppressive therapy. He was finally diagnosed as anti-mGluR5 encephalitis by positive serum anti-mGluR5 antibodies. Finally, the symptoms alleviated after treatment with hormones and gamma globulin.

Objective:To investigate the preventive and therapeutic effects of epigallocatechin gallate (EGCG) on tetracycline-induced acute drug-induced liver injury (DILI) in mice.Methods:Thirty-two BALB/C mice were divided into four groups, with eight mice in each group. The normal group was raised under conventional condition. Tetracycline-induced acute DILI models were established by intraperitoneal injection of tetracycline in the model group, the blank control group was intraperitoneally injected with equivalent 0.9% NaCl soluation, and EGCG prevention/treatment group was treated with EGCG on the basis of modeling. Blood samples, feces, liver and intestinal tissues of mice were obtained and analyzed by flow cytometry, biochemical test, pathological examination, and 16S rRNA sequencing. The effects of EGCG on gut microbiota, serum lipopolysaccharides (LPS) and transaminase, CD64 expression in intestinal mucosa, hepatic macrophage typing, and hepatic steatosis were evaluated. One-way analysis of variance was performed for analysis of significant difference among groups, and independent sample t test was used for further pairwise comparison. Results:Intraperitoneal injection of tetracycline-caused disorder of gut microbiota in the model group with hepatocytes showing steatosis grade 3 in 7 mice and grade 4 in 1 mouse. The serum level of LPS in model group was significantly higher than that of normal group ( (5.50±0.20) EU/L vs. (3.96±0.19) EU/L) and by the gut-liver axis which caused M1-type macrophages in liver tissues more than that of normal group ((40.00±2.91)% vs. (36.12±2.53)%), and the differences were statistically significant( t=15.83, 2.46; P<0.001, =0.034), and CD64 expression in intestinal mucosa also increased. EGCG intervention altered the gut microbiota in mice with tetracycline-induced acute DILI. The Shannon index and Simpson index of the model group were lower than those of the normal group (4.98±0.56 vs. 5.62±0.47, 0.91±0.03 vs. 0.95±0.02), while the Shannon index (4.08±0.62) and Simpson index (0.83±0.07) of the EGCG prevention/treatment group were lower than those of the model group. The differences were statistically significant ( t=-2.30, -2.85, -2.85, 2.82; P=0.038, 0.013, 0.013, 0.014). Compared with those of the model group, liver pathological changes of EGCG prevention/treatment group improved significantly (grade 2 in 8 mice), the serum level of LPS((4.22±0.17) EU/L) decreased, and the difference was statistically significant( t=-13.63, P<0.001), but had no significant effects on the CD64 expression in intestinal mucosa. Hepatic macrophage typing was compared between EGCG prevention/treatment group and model group, M2-type macrophages promoting repair were predominant in EGCG prevention/treatment group (M2-type macrophoges ratio: (6.20±0.17)% vs. (4.74±0.48)%, t=2.84, P=0.017; M1/M2-type macrophages ratio: 6.20±1.25 vs. 8.48±0.66, t=-4.95, P=0.001). Conclusion:EGCG alleviates tetracycline-induced acute DILI by altering gut microbiota to modulate liver innate immune system.

Objective:To explore the methods of fertility preservation in prepubertal patients with thalassemia major (TM), and to provide further data support for the fertility preservation in prepubertal patients with hematologic diseases.Methods:A case of a prepubertal patient with TM who required urgent hematopoietic stem cell transplantation (HSCT) receiving ovarian tissue cryopreservation (OTC) and in vitro maturation (IVM) to preserve fertility was reported, and the timing, the indications and strategies of fertility preservation in prepubertal girls with thalassemia were discussed in combination with related literature. Results:After ovarian tissue extraction, a total of 24 cumulus-oocyte complexes (COCs) and 11 ovarian cortex pieces were obtained through puncture and aspiration. After IVM for 48 h, a total of 9 M Ⅱ oocytes were frozen by vitrification. Conclusion:For the prepubertal girls facing HSCT urgently, cryopreserving ovarian tissue in combination with retrieving immature oocytes followed by IVM can preserve the fertility of patients to the greatest extent in a short period of time, as well as improve the therapeutic effect of fertility preservation in patients.

Objective:To explore the methods of fertility preservation in prepubertal patients with thalassemia major (TM), and to provide further data support for the fertility preservation in prepubertal patients with hematologic diseases.Methods:A case of a prepubertal patient with TM who required urgent hematopoietic stem cell transplantation (HSCT) receiving ovarian tissue cryopreservation (OTC) and in vitro maturation (IVM) to preserve fertility was reported, and the timing, the indications and strategies of fertility preservation in prepubertal girls with thalassemia were discussed in combination with related literature. Results:After ovarian tissue extraction, a total of 24 cumulus-oocyte complexes (COCs) and 11 ovarian cortex pieces were obtained through puncture and aspiration. After IVM for 48 h, a total of 9 M Ⅱ oocytes were frozen by vitrification. Conclusion:For the prepubertal girls facing HSCT urgently, cryopreserving ovarian tissue in combination with retrieving immature oocytes followed by IVM can preserve the fertility of patients to the greatest extent in a short period of time, as well as improve the therapeutic effect of fertility preservation in patients.

Objective:To investigate the value of jugulo-omohyoid lymph nodes(JOHLN) for the prediction of lateral cervical lymph nodes metastasis behind internal jugular vein in patients with papillary thyroid carcinoma(PTC) and its clinical significance.Methods:The clinical data of 220 patients who underwent lateral neck dissection in our center were retrospectively analyzed, and the early warning effect and clinical significance of JOHLN on lymph node metastasis of the posterior internal jugular vein were analyzed.Results:In this study, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of JOHLN for predicting lymph node metastasis in the posterior group of internal jugular vein were 83.5%, 46.4%, 82.0%, 49.1%, and 74.1%, respectively. The accuracy rate for JOHLN prediction of upper tumor was 84.3%; In this study, side neck skip metastasis was found in 11 cases, all of which were JOHLN metastasis, upper tumors were found in 9 cases and 2 were located in the middle. Among the skip metastases, 6 cases had lymph node metastasis in the posterior group of internal jugular vein, and they were all upper tumors.Conclusions:JOHLN can effectively predict the risk of lateral neck metastasis. Especially for the upper PTC, preoperative evaluation of JOHLN can help decision-making of lateral neck lymph node dissection.

Microsatellite instability (MSI) is caused by the deficiency of DNA mismatch repair (MMR) protein, which is closely related to the occurrence, development, prognosis and efficacy prediction of various tumors. MSI-high (MSI-H) and mismatch repair protein deficiency (dMMR) might be a predictor factor for the good prognosis of patients with gastric cancer, and a negative predictor factor for the chemotherapy efficacy of resectable gastric cancer. MSI-H/dMMR can be used as a marker for predicting the effective treatment outcome of immune checkpoint inhibitors in advanced gastric cancer, however, the predictive role in palliative chemotherapy of advanced gastric cancer is still unclear. This paper reviews the progress of the association of MSI/MMR with prognosis and efficacy prediction in gastric cancer.