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.

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.

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 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.

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

Objective:To systematically evaluate the life experiences of young-onset dementia (YOD) patients and provide a basis for healthcare professionals to develop effective support service strategies.Methods:Qualitative studies on the life experiences of YOD patients were retrieved from PubMed, Embase, Medline, CINAHL, PsycINFO, Scopus, Web of Science, Cochrane Library, China National Knowledge Infrastructure, VIP, WanFang data, and China Biology Medicine disc. The search timeframe was from the establishment of the databases to December 10, 2023. A Meta-synthesis approach was used to integrate the results.Results:A total of 17 articles were included, from which 69 findings were extracted, forming 11 categories and synthesizing into four integrated results: the heavy physical and psychological burden borne by YOD patients, impairment in multiple roles and social isolation, unique needs of YOD patients, and various coping strategies of YOD patients.Conclusions:Healthcare professionals should focus on the personal stories of YOD patients, pay attention to their physiological, psychological, and social challenges, and continuously improve supportive care services to alleviate their psychological burden, promote social connections, assist in resuming life, and enhance their quality of life.

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.