ObjectiveTo reveal the mechanism of Zuogui Jiangtang Jieyu prescription against damage to hippocampal synaptic microenvironment via suppressing glutamate receptor 2 （GluR2）/Parkin signal-mediated mitophagy in rats with diabetes-related depression （DD）. MethodsEighty male SD rats underwent adaptive feeding for 5 days before the study. Ten rats were randomly assigned to the normal group. The model of DD rats was established with the rest by 2-week high-fat diet + streptozotocin （STZ） tail intravenous injection + 28 days of chronic unpredictable mild stress （CUMS） combined with isolation. The rats were randomly divided into a normal group， a model group， a GluR2 blocker group （5 μg·kg^-1）， a GluR2 agonist group （10 μg·kg^-1）， a metformin + fluoxetine group （0.18 g·kg^-1 metformin + 1.8 mg·kg^-1 fluoxetine）， and high- and low-dose Zuogui Jiangtang Jieyu prescription groups （20.52 and 10.26 g·kg^-1， respectively）. The rats in the GluR2 blocker group and the GluR2 agonist group were continuously injected with CNQX and Cl-HIBO in the dentate gyrus of the hippocampus once a week starting from stress modeling， respectively， while the metformin + fluoxetine group and the high- and low-dose Zuogui Jiangtang Jieyu prescription groups were continuously given intragastric administration for 28 d at the same time of stress modeling. Depression-like behavior was evaluated by open field and forced swimming experiments. The levels of serum insulin and adenosine triphosphate （ATP） in hippocampus were detected by biochemical analysis. The levels of 5-hydroxytryptamine （5-HT） and dopamine （DA） in hippocampus were detected by enzyme-linked immunosorbent assay （ELISA）. The autophagosomes of hippocampal neurons were observed by transmission electron microscopy. The morphology and structure of dendrites and spines of hippocampal neurons were evaluated by Golgi staining. Western blot detected the expression levels of GluR2 and Parkin proteins in hippocampus. The expression levels of GluR2， Parkin， regulating synaptic membrane exocytosis protein 3 （RIMS3）， and postsynaptic density protein 95 （PSD95） in the dentate gyrus of the hippocampus were detected by immunofluorescence. ResultsCompared with the normal group， the model group exhibited reduced total activity distance in the open field and increased immobility time in forced swimming （P<0.01）， lowered levels of serum insulin and ATP， 5-HT， and DA in hippocampus （P<0.01）， increased autophagosomes of hippocampal neurons， significantly damaged morphology and structure of dendrites and spines of hippocampal neurons， decreased expression levels of GluR2， RIMS3， and PSD95 in hippocampus， and an increased Parkin expression level （P<0.05， P<0.01）. Compared with the model group， the GluR2 blocker group and the GluR2 agonist group showed aggravation and alleviation of the above abnormal changes， respectively （P<0.05， P<0.01）. The above depression-like behavior was significantly improved in the high- and low-dose Zuogui Jiangtang Jieyu prescription groups to different degrees. Specifically， the two groups saw elevated levels of serum insulin and ATP， 5-HT， and DA in hippocampus （P<0.05， P<0.01）， restrained increase in autophagosomes and damage to morphology and structure of dendrites and spines of hippocampal neurons， up-regulated protein expression levels of GluR2， RIMS3， and PSD95， and down-regulated Parkin expression level （P<0.05， P<0.01）. ConclusionZuogui Jiangtong Jieyu prescription can ameliorate the mitophagy-mediated damage to hippocampal synaptic microenvironment in DD rats， the mechanism of which might be related to the regulation of GluR2/Parkin signaling pathway.

Clinical data of a patient with alveolar soft part sarcoma (ASPS) treated at Zhongshan Hospital, Fudan University were retrospectively analyzed. The patient was initially diagnosed with abdominal ASPS with multiple lung metastases. After 6 weeks of treatment with nivolumab and ipilimumab, the patient achieved stable disease (SD). In the 7th week, the treatment was changed to a combination of nivolumab (30 mg, d1, q3w), anlotinib (8 mg, d1-14, q3w) and ipilimumab (50 mg, d1, q6w). The patient remained SD at the 12th week. The patient then underwent iliac artery embolization and intensity-modulated radiation therapy for the lesion in the psoas major muscle, while continuing the combination treatment. By the 24th week, the evaluation showed partial remission (PR) of both primary tumor and lung metastases. The patient experienced mild adverse reactions during treatment.

Objective:To analyze the death cases in Beijing municipal hospitals, identify possible medical quality issues in unexpected death cases, so as to provide a basis for medical quality management in medical institutions.Methods:A total of 432 death cases from Beijing municipal hospitals were included, and their acute physiology and chronic health status were evaluated. Based on the evaluation results and the death risk level determined by the diagnosis-related groups, an average of 10 cases were selected from each hospital. A total of 186 cases from 20 hospitals were selected for clinical diagnosis and treatment process evaluation, those cases with problems in the diagnosis and treatment process were defined as unexpected deaths.Results:According to expert judgment, 19.89% (37/186) of the examined deaths had medical quality issues. The main medical quality issues included delayed diagnosis and treatment of patient condition changes (15 cases), inadequate preoperative evaluation (12 cases), failure to consult as required(11 cases), and inadequate prevention of venous thromboembolism (7 cases).Conclusions:Medical institutions should attach importance to the analysis of death cases, address the medical quality issues in the diagnosis and treatment of unexpected death cases, continuously improve medical quality management.

Objective To explore the effect and mechanism of Zuogui Jiangtang Jieyu Formula(ZGJTJYF)in treating diabetes-related depression by regulating glutamate receptor 2(GluR2).Methods The primary isolated and cultured hippocampal neurons of SD rats were used.The experiment consisted of normal,model,blank serum(10％blank serum),positive drug(10％[metformin+fluoxetine]drug-containing serum),20％ZGJTJYF group,10％ZGJTJYF group,10％ZGJTJYF+GluR2 knockdown group,and 10％ZGJTJYF+GluR2 overexpression group(with corresponding volume fractions of ZGJTJYF drug-containing serum added).The ZGJTJYF+GluR2 knockdown and overexpression groups,were transfected with lentivirus to obtain hippocampal neurons with either GluR2 overexpression or knockdown.The glucose(150 mmol/L)and corticosterone(200 μmol/L)were used for 18 h to establish an in vitro cell model of hippocampal neurons in diabetes-related depression.After 24 h of successful modeling,the corresponding serum was added to each group for intervention.After 24 h of intervention,the morphological structure of hippocampal neurons was observed using an optical microscope.Biochemical methods were used to determine the glucose and insulin content in cell supernatant.An enzyme-linked immunosorbent assay was used to detect 5-hydroxytryptamine(5-HT)and dopamine(DA)levels in the cell supernatant,and the microtubule-associated protein 1A/1B light chain 3 autophagy double-labeled adenovirus(mRFP-GFP-LC3)autophagy fluorescence double labeling method was used to detect the average fluorescence intensity of LC3 protein in hippocampal neurons.Nissl staining was used to observe synaptic damage in hippocampal neurons,and an immunofluorescence method was used to detect the protein expression of Parkin,phosphatase and tensin homolog-induced putative kinase 1(PINK1),regulating synaptic membrane exocytosis 3(RIMS3),synapsin 1(SYN1),postsynaptic density-95(PSD-95),synapse-associated protein 102(SAP 102),and GluR2 in hippocampal neurons.Realtime fluorescence PCR was used to detect GluR2 mRNA expression in hippocampal neurons,while Western blotting was employed to assess the expression of mitophagy proteins Parkin and PINK1 in these neurons.Results Compared to the normal group,the model group and blank serum group showed structural damage to hippocampal neurons,increased glucose content in cell supernatant,decreased insulin,5-HT,and DA content,increased average fluorescence intensity of LC3,Parkin,and PINK1,decreased average fluorescence intensity of RIMS3,SYN1,PSD-95,SAP 102,and GluR2,decreased GluR2 mRNA expression,increased protein expression of Parkin and PINK1(P＜0.05),and decreased Nissl bodies.Compared to the model group and blank serum group,the above indicators in each administration group were improved to varying degrees(P＜0.05).Compared to the positive drug group,the average fluorescence intensity of LC3,Parkin,and PINK1 decreased,Parkin and PINK1 protein expression decreased,and the average fluorescence intensity of GluR2,SYN1,and PSD-95 increased in 10％ZGJTJYF,20％ZGJTJYF group,and 10％ZGJTJYF+GluR2 overexpression group(P＜0.05).Compared to 10％and 20％ZGJTJYF groups,10％ZGJTJYF+GluR2 knockdown group showed a decrease in 5-HT content,an increase in average fluorescence intensity of LC3 and Parkin,a decrease in average fluorescence intensity of SYN1,PSD-95,and GluR2,a decreased in GluR2 mRNA expression,and an increase of Parkin and PINK1 protein expression(P＜0.05).In contrast,the above indicators were improved to varying degrees in 10％ZGJTJYF+GluR2 overexpression group(P＜0.05).Compared to 10％ZGJTJYF+GluR2 knockdown group,the above abnormal indicators in 10％ZGJTJYF+GluR2 overexpression group were reversed to varying degrees(P＜0.05).Conclusion ZGJTJYF has a protective effect on synaptic damage of hippocampal neurons in diabetes-related depression,and its mechanism may be related to the upregulation of GluR2 and the inhibition of mitophagy over activation.

Objective To explore the effect and mechanism of Zuogui Jiangtang Jieyu Formula(ZGJTJYF)in treating diabetes-related depression by regulating glutamate receptor 2(GluR2).Methods The primary isolated and cultured hippocampal neurons of SD rats were used.The experiment consisted of normal,model,blank serum(10％blank serum),positive drug(10％[metformin+fluoxetine]drug-containing serum),20％ZGJTJYF group,10％ZGJTJYF group,10％ZGJTJYF+GluR2 knockdown group,and 10％ZGJTJYF+GluR2 overexpression group(with corresponding volume fractions of ZGJTJYF drug-containing serum added).The ZGJTJYF+GluR2 knockdown and overexpression groups,were transfected with lentivirus to obtain hippocampal neurons with either GluR2 overexpression or knockdown.The glucose(150 mmol/L)and corticosterone(200 μmol/L)were used for 18 h to establish an in vitro cell model of hippocampal neurons in diabetes-related depression.After 24 h of successful modeling,the corresponding serum was added to each group for intervention.After 24 h of intervention,the morphological structure of hippocampal neurons was observed using an optical microscope.Biochemical methods were used to determine the glucose and insulin content in cell supernatant.An enzyme-linked immunosorbent assay was used to detect 5-hydroxytryptamine(5-HT)and dopamine(DA)levels in the cell supernatant,and the microtubule-associated protein 1A/1B light chain 3 autophagy double-labeled adenovirus(mRFP-GFP-LC3)autophagy fluorescence double labeling method was used to detect the average fluorescence intensity of LC3 protein in hippocampal neurons.Nissl staining was used to observe synaptic damage in hippocampal neurons,and an immunofluorescence method was used to detect the protein expression of Parkin,phosphatase and tensin homolog-induced putative kinase 1(PINK1),regulating synaptic membrane exocytosis 3(RIMS3),synapsin 1(SYN1),postsynaptic density-95(PSD-95),synapse-associated protein 102(SAP 102),and GluR2 in hippocampal neurons.Realtime fluorescence PCR was used to detect GluR2 mRNA expression in hippocampal neurons,while Western blotting was employed to assess the expression of mitophagy proteins Parkin and PINK1 in these neurons.Results Compared to the normal group,the model group and blank serum group showed structural damage to hippocampal neurons,increased glucose content in cell supernatant,decreased insulin,5-HT,and DA content,increased average fluorescence intensity of LC3,Parkin,and PINK1,decreased average fluorescence intensity of RIMS3,SYN1,PSD-95,SAP 102,and GluR2,decreased GluR2 mRNA expression,increased protein expression of Parkin and PINK1(P＜0.05),and decreased Nissl bodies.Compared to the model group and blank serum group,the above indicators in each administration group were improved to varying degrees(P＜0.05).Compared to the positive drug group,the average fluorescence intensity of LC3,Parkin,and PINK1 decreased,Parkin and PINK1 protein expression decreased,and the average fluorescence intensity of GluR2,SYN1,and PSD-95 increased in 10％ZGJTJYF,20％ZGJTJYF group,and 10％ZGJTJYF+GluR2 overexpression group(P＜0.05).Compared to 10％and 20％ZGJTJYF groups,10％ZGJTJYF+GluR2 knockdown group showed a decrease in 5-HT content,an increase in average fluorescence intensity of LC3 and Parkin,a decrease in average fluorescence intensity of SYN1,PSD-95,and GluR2,a decreased in GluR2 mRNA expression,and an increase of Parkin and PINK1 protein expression(P＜0.05).In contrast,the above indicators were improved to varying degrees in 10％ZGJTJYF+GluR2 overexpression group(P＜0.05).Compared to 10％ZGJTJYF+GluR2 knockdown group,the above abnormal indicators in 10％ZGJTJYF+GluR2 overexpression group were reversed to varying degrees(P＜0.05).Conclusion ZGJTJYF has a protective effect on synaptic damage of hippocampal neurons in diabetes-related depression,and its mechanism may be related to the upregulation of GluR2 and the inhibition of mitophagy over activation.

A 71-year-old man with undifferentiated sarcoma was treated with palliative first-line regimen(epirubicin,anlotinib and penpulimab)for 6 cycles and maintained with anlotinib and penpulimab for 30 cycles.He was admitted to the hospital due to chest pain 25 months after the first treatment.The laboratory examination showed cardiac troponin T 1.26 ng·mL-1,N terminal pro B type natriuretic peptide 8,545 pg·mL-1,coronary computed tomography angiography(CTA)showed non-calcified plaque in the left proximal anterior descending branch,severe lumen stenosis,nearly complete occlusion.Emergency CTA was performed on the same day,showing 50％stenosis of the distal left main coronary artery(LMCA);95％stenosis of the left anterior descending(LAD)branch ostium,the LAD branch was medium-sized and showed no stenosis;50％stenosis of the left circumflex branch(LCx),and a cardiac stent was implanted into the LAD branch.The patient has recovered after coronary artery stent implantation.Naranjo's Assessment Scale was used to evaluate the association of suspected drugs,the acute myocardial infarction of this patient was likely associated with the combination of penpulimab and anlotinib.Myocardial infarction is a rare but severe adverse drug reaction of anti-tumor treatment.This article summarizes the related risks and treatment measures to provide a reference for clinical medication safety.

Objective: To investigate the effects of Zuogui Jiangtang Jieyu Formula (ZGJTJYF) on histone H3 lysine 18 lactylation (H3K18la) in the hippocampus of rats with diabetes mellitus complicated with depression (DD) and predict the regulatory genes of H3K18la. Methods: Male Sprague-Dawley rats were divided into control, model, and positive drug (metformin [0.18 g/kg] and fluoxetine [1.8 mg/kg]) groups, and the three groups were treated with high, medium, and low ZGJTJYF doses (20.52, 10.26, and 5.13 g/kg, respectively), with 10 rats per group. After treatment, the forced swimming and water maze tests were performed to assess depressive-like behaviors and cognitive function. An enzyme-linked immunosorbent assay was used to measure blood insulin, glycosylated hemoglobin, lactate levels, and lactate content in the hippocampus. Western blotting was used to detect H3K18la expression in the hippocampus. Cleavage Under Targets and lagmentation(CUT&Tag) experiments targeted hippocampal H3K18la epigenetic modification regions to analyze the transcription factors bound by H3K18la. Kyoto Encyclopedia of Genes and Genomes and Protein-Protein Interaction networks were constructed to identify key pathways and target genes regulated by H3K18la. Results: Compared with the normal group, the model group rats showed prolonged immobility time in the forced swim test, increased escape latency in the water maze experiment, decreased target quadrant distance ratio (P<0.01), increased serum lactate content, and decreased lactate content in hippocampal homogenate (P<0.01), as well as decreased H3K18la protein expression in the hippocampus (P<0.01). Compared with the model group, ZGJTJYF reduced the immobility time in the forced swim test and the escape latency in the water maze test (P<0.01), while the distance ratio in the target quadrant increased (P<0.01) in model rats. Lowered fasting blood glucose, insulin, and glycosylated hemoglobin levels (P<0.05, P<0.01) were also observed. ZGJTJYF also increased the lactate content and H3K18la protein expression in hippocampal homogenate (P<0.05, P<0.01). The DNA sequences bound by H3K18la were predominantly enriched at the transcription start sites. ZGJTJYF modulated H3K18la-associated pathways, including cell adhesion junctions, tumor growth factor-beta (TGF-β) signaling, stem cell pluripotency regulation, mitogen-activated protein kinase(MAPK) signaling pathway, and insulin resistance, leading to the identification of 12 target genes. Conclusion ZGJTJYF enhances hippocampal lactate levels and H3K18la modification in DD rats, which may regulate neural cell interactions, neurogenic stem cell function, TGF-β signaling, MAPK signaling, and insulin resistance pathways.

Acute symptomatic osteoporotic thoracolumbar compression fracture (ASOTLF) can lead to chronic low back pain, kyphosis deformity, pulmonary dysfunction, loss of mobility, and even life-threatening complications. Vertebral augmentation is currently the mainstream treatment method for this condition. In 2019, the Editorial Board of Chinese Journal of Trauma and the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association collaboratively led the development of Clinical guideline for vertebral augmentation for acute symptomatic osteoporotic thoracolumbar compression fractures. Six years later, with advances in clinical diagnosis and treatment techniques as well as accumulating evidence in related fields, the 2019 guideline requires updating. To this end, the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association, the Spinal Health Professional Committee of China Human Health Science and Technology Promotion Association, and the Minimally Invasive Orthopedics Professional Committee of Shaanxi Medical Doctor Association have organized experts in the field to develop the Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures ( version 2025) , based on the latest evidence-based medical researches. This guideline incorporates 3 recommendations retained from the 2019 version with updated strength of evidence, along with 12 new recommendations. It provides recommendations from six aspects of diagnosis, pain management, treatment option selection, prevention of postoperative complications, anti-osteoporosis therapy, and postoperative rehabilitation, aiming to provide a reference for standard treatment of vertebral augmentation for ASOTLF in hospitals at all levels.

Objective:To evaluate the efficacy of eculizumab in treating hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA) .Methods:This retrospective study included 11 patients who developed TA-TMA after allogeneic hematopoietic stem cell transplantation and subsequently received eculizumab treatment at Peking University People′s Hospital between June 2018 and May 2024. The incidence of TA-TMA, treatment details, and clinical outcomes were analyzed.Results:Among the 11 included patients [4 males, 7 females; median age: 29 years (range: 9-56) ], underlying diseases were severe aplastic anemia (SAA) in 5 patients, acute lymphoblastic leukemia (ALL) in 3 patients, and acute myeloid leukemia (AML) in 3 patients. The median time to TA-TMA diagnosis was 48 days post-transplantation (range: 4-213 days), and all patients met the diagnostic criteria for high-risk TA-TMA. The median interval from TA-TMA diagnosis to the initiation of eculizumab treatment was 12 days (range: 1-56 days). Patients received a median of 3 doses of eculizumab (range: 1-14). Ten of the 11 patients were assessed as having no response (NR) to eculizumab at the end of treatment or at death. One patient achieved a partial response (PR) but subsequently died after TA-TMA relapsed due to infection. At the last follow-up, all patients were either lost to follow-up or had died. The median follow-up duration was 88 days (range: 33-326 days), and the median time from TA-TMA diagnosis to the last follow-up was 31 days (range: 21-113 days) .Conclusion:Eculizumab demonstrated poor efficacy in this TA-TMA cohort. This might be attributable to the critical and complex condition of the patients, delayed initiation of eculizumab treatment, and insufficient dosage.

Objective:To investigate the clinicopathological and molecular genetic characteristics of pan cytokeratin (CKpan)-positive EWSR1/FUS::CREB fusion malignant tumors in abdominopelvic cavity.Methods:Four cases of malignant tumor with CKpan-positive EWSR1/FUS::CREB fusion were selected from January 2019 to July 2024 in the Department of Pathology, Tianjin Medical University Cancer Hospital, Tianjin, China. Their clinical, pathological, and immunohistochemical characteristics were examined. Their molecular genetic characteristics were analyzed using fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS).Results:Among the 4 patients, there were 2 males and 2 females, aged 44, 44, 48 and 66 years, respectively. The tumor sites included 1 case located between the stomach and transverse colon, 1 case on the serous surface of the gastric wall, 1 case in the transverse mesocolon, and 1 case in transverse mesocolon and small mesentery. The clinical manifestations were mostly abdominal distension and abdominal pain. The maximum diameter of the tumor in the surgical resection specimen was 3.5-8.5 cm. The tumor′s cut surface was grayish-white and gray-yellow in color, with medium consistency. Microscopically, the tumor cells were mainly composed of epithelioid tumor cells, and 2 of the tumors showed that tumor cells arranged in a solid sheet or multinodular pattern, and the cytoplasm of the tumor cells was abundant, lightly stained, and the boundaries were unclear, accompanied by the formation of capsules or microcapsules, and lymphocyte and plasma cell sleeves were seen. In one case, the pseudopapillary arrangement was present, and the tumor cells were radially distributed around the fibrovascular axis. In another case, it was arranged in a pseudoacinar pattern, and the nest was surrounded by slender reticular fibers. Immunohistochemistry showed that tumor cells expressed CKpan (4/4) and WT1 (4/4, including 1 focal positive). Vimentin, CK8/18, D2-40 and S-100 were expressed in various intensities, while Calretinin was locally positive or negative. FISH showed that 2 cases had EWSR1 break-apart and 2 cases had FUS break-apart. NGS confirmed the presence of EWSR1::CREM fusion (1 case) and FUS::CREM fusion (2 cases), respectively. Except for 1 recently diagnosed case, 3 cases were followed up: 1 patient died due to tumor recurrence and metastasis (overall survival was 33 months), and 2 patients survived (1 case had recurrence 58 months after surgery, and 1 case had no recurrence or metastasis after surgery).Conclusions:CKpan-positive EWSR1/FUS::CREB fusion malignant tumor is a rare malignancy tumor with undetermined classification that tends to occur in the abdominopelvic cavity and often involves the gastrointestinal tract. Molecular testing such as FISH and NGS is helpful for a definitive diagnosis.