ObjectiveTo investigate the association between immunoglobulin G （IgG）/immunoglobulin M （IgM） ratio and prognosis in patients with initially unresectable hepatocellular carcinoma （iuHCC） receiving TTP triple therapy with transcatheter arterial chemoembolization （TACE）， tyrosine kinase inhibitor （TKI）， and programmed cell death protein-1 （PD-1） inhibitors. MethodsA retrospective analysis was performed for the clinical data of 151 iuHCC patients who received TTP triple therapy in Department of Hepatobiliary Surgery， Guangxi Medical University Cancer Hospital， from November 2019 to December 2022， and according to IgG/IgM ratio， they were divided into high IgG/IgM group （IgG/IgM ratio >13.23） and low IgG/IgM group （IgG/IgM ratio ≤13.23）. The t-test was used for comparison of continuous data between groups， and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method and the log-rank test were used for survival analysis， and the Cox proportional hazards model was used to investigate the potential influencing factors for overall survival （OS）. ResultsThe 151 patients had a median OS of 26.7 months （95% confidence interval ［CI］： 19.8-not reached） and a median progression-free survival of 12.5 months （95%CI： 10.4 — 15.8）. The objective response rate was 83.4% and the disease control rate was 94.0%. There were no significant differences in baseline data between the high IgG/IgM group and the low IgG/IgM group （all P>0.05）. There was a significant difference in median OS between the high IgG/IgM group and the low IgG/IgM group （20.6 months vs not reached， P=0.016）. In both the high IgG/IgM group and the low IgG/IgM group， salvage hepatectomy was significantly associated with the improvement in OS （χ²=8.297 and 10.307， both P<0.05）. The multivariate analysis showed that high IgG/IgM ratio （hazard ratio ［HR］=1.799， 95%CI： 1.077 — 3.006， P=0.025）， baseline alpha-fetoprotein >400 ng/mL （HR=1.762， 95%CI： 1.017 — 3.050， P=0.043）， and BCLC stage （HR=2.265， 95%CI： 1.212 — 4.232， P=0.010） were independent influencing factors for OS. ConclusionHigh IgG/IgM ratio is associated with a poorer prognosis in iuHCC patients receiving TTP triple therapy， and salvage hepatectomy has a potential value in improving the prognosis of patients with a high IgG/IGM ratio.

Objective To explore the clinical features of fulminant type 1 diabetes mellitus (FT1DM). Methods The clinical data of 6 patients with FT1DM who were hospitalized in Jinshan Hospital of Fudan University from April 2020 to August 2024 were retrospectively analyzed. Their data were compared with that of 30 patients diagnosed with non-fulminant type 1 diabetes mellitus (NFT1DM) and diabetic ketosis or diabetic ketoacidosis (DKA) who were admitted to the hospital during the same period. The clinical characteristics of FT1DM were summarized. Results All 6 patients with FT1DM were male, with a disease course of 2.00 (1.75, 4.00) d. Three cases exhibited a history of prior infection, four tested positive for glutamic acid decarboxylase antibody (GADA), and five developed severe DKA. The glycated hemoglobin A_1C (HbA_1C) was (6.30±0.67) %, fasting C-peptide (FCP) was 0.07 (0.03, 0.15) ng/mL, 2-hour postprandial C-peptide (2h-CP) was 0.09 (0.03, 0.16) ng/mL. At discharge, all 6 patients received 4-injection insulin regimen, with a dose (0.69±0.15) U·kg⁻¹·d⁻¹. The body mass index (BMI), blood glucose/HbA_1C, blood potassium/HbA_1C, fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2h-PG), high-sensitivity C-reactive protein (hs-CRP), alanine aminotransferase (ALT), serum creatinine, and blood potassium levels in the FT1DM group were higher than those in the NFT1DM group (P＜0.05), while HbA_1C and glycated albumin (GA) levels were lower than NFT1DM group (P＜0.05). Conclusions FT1DM usually presents with an acute onset of DKA, may be accompanied by a history of preceding infection, and GADA can be positive. Patients with FT1DM have elevated blood glucose/HbA_1C, blood potassium/HbA_1C, FPG, 2h-PG, hs-CRP, ALT, serum creatinine, blood potassium levels, and require insulin therapy, while the HbA_1C and GA levels are lower.

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a high-grade neuroendocrine tumor with unique characteristics, and its treatment regimens are primarily derived from those for small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). In recent years, the incidence rate has been on the rise, and the prognosis are affected by the interaction of multiple factors such as individual, clinical stage and treatment mode, and the heterogeneity is significant. In the study of molecular subtypes, multiple subgroups were divided according to key gene mutations such as RB1 and TP53, and genomic subtypes were associated with survival, chemotherapy response, and efficacy of precision therapy. Targeted therapy excavates multiple targets, and the efficacy of drugs is different. Immunotherapy has made remarkable progress, and immune checkpoint inhibitors (ICIs) have been effective in all stages of chemotherapy alone or in combination with chemotherapy or radiation therapy, but there is a risk of hyperprogressive diseases, and accurate prognostic markers need to be explored urgently. This review reviews the latest research progress in the study of molecular subtypes and precision therapies such as targeted therapy and immunotherapy of pulmonary LCNEC, and points out that pulmonary LCNEC treatment will develop in the direction of precision and individualization in the future.
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Humans ; Lung Neoplasms/drug therapy* ; Carcinoma, Neuroendocrine/drug therapy* ; Precision Medicine ; Immunotherapy ; Carcinoma, Large Cell/drug therapy*

Integrin α _v β ₃ is overexpressed in various tumor cells and angiogenesis. To date, no drug has been proven to target it for therapy. A first-in-human study was designed to investigate the safety, pharmacokinetics, and dosimetry of ¹⁷⁷Lu-AB-3PRGD2, a novel integrin α _v β ₃-targeting radionuclide drug with an albumin-binding motif to optimize the pharmacokinetics. Ten patients (3 men, 7 women; aged 45 ± 16 years) with integrin α _v β ₃-avid tumors were recruited to accept ¹⁷⁷Lu-AB-3PRGD2 injection in a dosage of 1.57 ± 0.08 GBq (42.32 ± 2.11 mCi), followed by serial scans to obtain its dynamic distribution in the body. Safety tests were performed before and every 2 weeks after the treatment for 6-8 weeks. No adverse event over grade 3 was observed. ¹⁷⁷Lu-AB-3PRGD2 was excreted mainly through the urinary system, with intense radioactivity in the kidneys and bladder. Moderate distribution was found in the liver, spleen, and intestines. The estimated blood half-life was 2.85 ± 2.17 h. The whole-body effective dose was 0.251 ± 0.047 mSv/MBq. The absorbed doses were 0.157 ± 0.032 mGy/MBq in red bone marrow and 0.684 ± 0.132 mGy/MBq in kidneys. This first-in-human study of ¹⁷⁷Lu-AB-3PRGD2 treatment indicates its promising potential for targeted radionuclide therapy of integrin α _v β ₃-avid tumors. It merits further studies in more patients with escalating doses and multiple treatment courses.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To analyze clinical, immunopathological, therapeutic, and prognostic features of epidermolysis bullosa acquisita (EBA) .Methods:A retrospective study was conducted on patients with confirmed EBA at the Department of Dermatology, West China Hospital, Sichuan University from January 1, 2015 to July 30, 2022. Their clinical, immunopathological, therapeutic and prognostic features were analyzed. The autoimmune bullous skin disorder intensity score (ABSIS) was used to assess the severity of lesions in patients with EBA, and the visual analogue scale (VAS) to assess itch intensity. Descriptive statistical analysis was primarily carried out, and the correlation between disease severity scores and itch scores was analyzed using Pearson correlation analysis.Results:A total of 13 patients with EBA were included, including 9 males and 4 females, with the age at the clinic visit being 49.0 ± 20.6 years and ABSIS scores being 24.2 ± 10.7 points. One patient was diagnosed with classical EBA, while the remaining 12 patients with inflammatory EBA. Mucosal involvement was observed in 6 cases, whose oral mucosae were all affected. All patients had itching to varying degrees, with VAS scores of 5.6 ± 2.2 points; 9 of the 12 inflammatory EBA patients had VAS scores of ≥ 5 points, whereas 1 classical EBA patient had a VAS score of 2 points; there was no significant correlation between the ABSIS scores and VAS scores ( r = -0.02, P > 0.05). Histopathological examination showed subepidermal cleavages or blister formation and varying degrees of perivascular inflammatory cell infiltration in the superficial dermis of patients with inflammatory EBA. Direct immunofluorescence assay demonstrated linear IgG deposits along the basement membrane zone in all 13 patients, including 12 with concomitant linear C3 deposits in the basement membrane zone, 5 with linear IgA deposits, and 2 with IgM deposits. Indirect immunofluorescence on salt-split skin showed IgG deposition on the dermal side of the salt-split skin in the 13 patients. An elevated eosinophil count in the peripheral blood was observed in 1 out of 11 patients, while increased total IgE levels were noted in 3 out of 9 patients. Among the 13 EBA patients, 11 were treated with systemic glucocorticoids (equivalent to 10 - 100 mg/d of prednisone), and the other 2 were treated with compound glycyrrhizin tablets, sulfasalazine, hydroxychloroquine sulfate, and minocycline hydrochloride alone or in combination. During the follow-up period of 34.0 (27.5, 66.0) months in the 13 patients, 8 achieved complete remission after drug withdrawal, 2 achieved complete remission on therapy, 1 achieved partial remission on minimal therapy, and 2 presented with uncontrolled condition. The time to complete remission off/on therapy was 6.0 (3.8, 17.5) months. Conclusions:The inflammatory phenotype seems to be relatively common in EBA patients, with itching to varying degrees, and oral mucosa was the most commonly involved mucosa in those with mucosal damage. After treatment with systemic glucocorticoids alone or in combination with immunomodulators, most patients could achieve complete remission.

Objective To evaluate the effects of intermittent hypoxia-reoxygenation(IHR)on body weight,diet and water intake,circulating metabolites,and responses to central leptin injection in a rat model of diet-induced obesity(DIO).Methods Rat models of DIO established by 12-week high-fat diet(HFD)feeding were randomized into normoxia group(n=15),intermittent hypoxia group(6％O2,30 cycles/h,8 h/day for 4 weeks;n=15),and IHR group(2 weeks of intermittent hypoxia followed by 2 weeks of reoxygenation;n=15).Body weight,diet and water intake of the rats were recorded,and circulating leptin,IL-6,and Ang-Ⅱ levels were detected.After IHR treatment,the rats received intracerebroventricular injection of 4 μg leptin,and the hypothalamus and liver were taken 1 h later for detecting POMC,FRA-1 and FRA-2 expressions in the hypothalamus using immunohistochemistry,POMC,pSTAT3 and LepR expressions in the hypothalamus using Western blotting,and LepR mRNA expression in the hypothalamus and liver using RT-PCR.Results The rats in intermittent hypoxia group showed significantly increased weight gain,food intake and elevated systemic inflammatory cytokine levels.Intermittent hypoxia obviously inhibited the expression of POMC,lowered the expressions of FRA-1 and pSTAT3,reduced the responsiveness of the rats to exogenous leptin,and downregulated the mRNA and protein expression of LepR.Two weeks of reoxygenation treatment obviously reduced intermittent hypoxia-induced weight gain and metabolic disorder and improved leptin sensitivity of the rats.Conclusion Prolonged intermittent hypoxia impairs hypothalamic leptin signaling by downregulating LepR expression to promote weight gain in obese rats,which can be improved by reoxygenation treatment.

Objective To evaluate the effects of intermittent hypoxia-reoxygenation(IHR)on body weight,diet and water intake,circulating metabolites,and responses to central leptin injection in a rat model of diet-induced obesity(DIO).Methods Rat models of DIO established by 12-week high-fat diet(HFD)feeding were randomized into normoxia group(n=15),intermittent hypoxia group(6％O2,30 cycles/h,8 h/day for 4 weeks;n=15),and IHR group(2 weeks of intermittent hypoxia followed by 2 weeks of reoxygenation;n=15).Body weight,diet and water intake of the rats were recorded,and circulating leptin,IL-6,and Ang-Ⅱ levels were detected.After IHR treatment,the rats received intracerebroventricular injection of 4 μg leptin,and the hypothalamus and liver were taken 1 h later for detecting POMC,FRA-1 and FRA-2 expressions in the hypothalamus using immunohistochemistry,POMC,pSTAT3 and LepR expressions in the hypothalamus using Western blotting,and LepR mRNA expression in the hypothalamus and liver using RT-PCR.Results The rats in intermittent hypoxia group showed significantly increased weight gain,food intake and elevated systemic inflammatory cytokine levels.Intermittent hypoxia obviously inhibited the expression of POMC,lowered the expressions of FRA-1 and pSTAT3,reduced the responsiveness of the rats to exogenous leptin,and downregulated the mRNA and protein expression of LepR.Two weeks of reoxygenation treatment obviously reduced intermittent hypoxia-induced weight gain and metabolic disorder and improved leptin sensitivity of the rats.Conclusion Prolonged intermittent hypoxia impairs hypothalamic leptin signaling by downregulating LepR expression to promote weight gain in obese rats,which can be improved by reoxygenation treatment.

OBJECTIVE To analyse the prognosis and laryngeal function retention of patients undergoing minimally invasive and open surgery after induction chemotherapy.METHODS The clinical data of 54 hypopharyngeal carcinoma patients who received induction chemotherapy and underwent laryngeal preservation surgery in Beijing Tongren Hospital from 2016 to 2022 were retrospectively analyzed.The laryngeal function recovery and survival rate were compared between the two groups.RESULTS Twenty-eight patients underwent transoral minimally invasive surgery and 26 patients underwent partial laryngectomy and/or partial laryngectomy via external cervical approach.The 3-year survival rates of the two groups were 63%and 59%,respectively,and the difference was not statistically significant(P＞0.05).The differences were statistically significant(P＜0.05).CONCLUSION In patients with downstaged hypopharyngeal carcinoma after induction chemotherapy,the survival rate of transoral minimally invasive surgery is similar to that of open surgery,and the laryngeal function recovery of transoral minimally invasive surgery is better.

Objective To detect the expression of human telomerase reverse transcriptase(hTERT)and silent information regulatory factor 6(Sirt6)in serum of pregnant women with preeclampsia,and explore the value of hTERT and Sirt6 levels in the evaluation of disease severity and pregnancy outcome.Methods A total of 300 patients with preeclampsia who were treated in Shaanxi Provincial People's Hospital from January 2018 to December 2022 were selected as the preeclampsia group,and all pregnant women met the diagnostic criteria for preeclampsia in the Guidelines for the Diagnosis and Treatment of Hypertensive Disorders in Pregnancy(2015).Meanwhile,300 healthy pregnant women who underwent pregnancy examinations in Shaanxi Provincial People's Hospital during the same period were selected as the control group.Preeclampsia group was divided into mild preeclampsia group(n=180)and severe preeclampsia group(n=120)according to the severity of the disease.The preeclampsia group was divided into normal pregnancy group(n=165)and adverse pregnancy group(n=135)according to the occurrence of adverse pregnancy outcomes.Serum hTERT and Sirt6 levels were detected by enzyme-linked immunosorbent assay(ELISA).Spearman correlation analysis was applied to analyze the correlation between serum hTERT and Sirt6 levels and the severity of preeclampsia in patients.Receiver operating characteristic(ROC)curve was applied to evaluate the value of serum hTERT and Sirt6 levels in the diagnosis of preeclampsia and prediction of pregnancy outcomes.Results Compared with the control group serum levels of hTERT(22.15±5.82 ng/ml vs 30.12±9.56 ng/ml)and Sirt6(5.26±1.62 ng/ml vs 7.06±2.29 ng/ml)in preeclampsia group were decreased,and the differences were significant(t=12.334,11.114,all P＜0.001).Compared with the mild preeclampsia group,the serum levels of hTERT(18.28±4.11 ng/ml vs 24.73±6.96 ng/ml)and Sirt6(4.03±1.17 ng/ml vs 6.08±1.92 ng/ml)in the severe preeclampsia group were decreased,and the differences were significant(t=9.142,10.469,all P＜0.001).Compared with the normal pregnancy group,the serum levels of hTERT(17.75±4.61 ng/ml vs 25.75±6.81 ng/ml)and Sirt6(4.06±0.96 ng/ml vs 6.24±2.16 ng/ml)of preeclampsia pregnant women in the adverse pregnancy group were decreased,and the differences were significant(t=11.639,10.878,all P＜0.001).Spearman correlation analysis showed that the levels of hTERT and Sirt6 in serum were negatively correlated with the severity of preeclampsia in patients(r=-0.562,-0.604,all P＜0.001).ROC curve analysis results showed that the area under the curve(95％confidence interval)[AUC(95％CI)]of serum hTERT and Sirt6 in the diagnosis of preeclampsia were 0.711(0.673～0.747)and 0.727(0.689～0.762),respectively.The AUC(95％CI)of the combined diagnosis of preeclampsia was 0.788(0.753～0.820),which was higher than that of the combined diagnosis of preeclampsia(Z=2.719,2.154,P=0.007,0.031).The AUC of serum hTERT and Sirt6 for predicting adverse pregnancy outcomes of preeclampsia were 0.786(0.735～0.831)and 0.783(0.732～0.829),respectively.The AUC(95％CI)of serum HTERT and Sirt6 for predicting adverse pregnancy outcomes of preeclampsia was 0.849(0.804～0.888).It was higher than predicted by the two alone(Z=1.855,1.861,P=0.032,0.031).Conclusion The serum levels of hTERT and Sirt6 in pregnant women with preeclampsia were low,and they were negatively correlated with the disease severity of preeclampsia patients.They may have certain evaluation values for pregnancy outcomes.