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.

Stress and illness connection is complex and involves multiple physiological systems. Panax ginsengs, reputed for their broad-spectrum "cure-all" effect, are widely prescribed to treat stress and related illnesses. However, the identity of ginseng's "cure-all" medicinal compounds that relieve stress remains unresolved. Here, we identify ginsentides as the principal bioactives that coordinate multiple systems to restore homeostasis in response to stress. Ginsentides are disulfide-rich, cell-penetrating and proteolytic-stable microproteins. Using affinity-enrichment mass spectrometry target identification together with in vitro, ex vivo and in vivo validations, we show that highly purified or synthetic ginsentides promote vasorelaxation by producing nitric oxide through endothelial cells via intracellular PI3K/Akt signaling pathway, alleviate α1-adrenergic receptor overactivity by reversing phenylephrine-induced constriction of aorta, decrease monocyte adhesion to endothelial cells via CD166/ESAM/CD40 and inhibit P2Y12 receptors to reduce platelet aggregation. Orally administered ginsentides were effective in animal models to reduce ADP-induced platelet aggregation, to prevent collagen and adrenaline-induced pulmonary thrombosis as well as anti-stress behavior of tail suspension and forced swimming tests in mice. Together, these results strongly suggest that ginsentides are the principal panacea compounds of ginsengs because of their ability to target multiple extra- and intra-cellular proteins to reverse stress-induced damages.

Objective: To investigate the current status and relationship between loneliness and negative emotional symptoms among first generation college students in the family, so as to provide reference for improving mental health of this population. Methods: A convenience sampling method was used to select 3 017 college students from 10 colleges and universities in Guangdong Province and Yunnan Province, China, in May 2023. Questionnaires were administered to the students, and the Depression Anxiety Stress Scale (DASS-21) and the short form of the University of California at Los Angeles Loneliness Scale (ULS-6) were employed. Results: The total ULS-6 score of first generation college students in the family was (12.38±4.16), while the score of non first generation college students in the family was (11.89±4.38), with a statistically significant difference ( t=2.79, P <0.05). The total DASS-21 score of first generation college students in the family was (71.13±26.97), while the score of non first generation college students in the family was (70.20±26.66), with a statistically significant difference ( t=2.69, P <0.05). Among the first generation college students in the family, male students experienced more DASS-21 score (77.55±29.36) than female students (70.43±25.03)( t =5.79, P <0.05). Urban students (12.00±4.15, 70.34±25.68) reported lower levels of loneliness score and DASS- 21 score than rural students (12.62±4.15, 74.93±27.63), and the depression subscale scores showed statistically significant differences among students with different professional achievement rankings ( t/F =-3.42, -3.94, 4.25, P <0.05). There was a positive correlation between loneliness, depression, anxiety, pressure and DASS-21 scales of first generation college students in the family ( r=0.64, 0.62, 0.64, 0.66, P <0.01). The linear regression analysis results showed a positive correlation between loneliness and all dimensions and total scores of the DASS-21, explaining 44% of the variance in negative emotional symptoms. Conclusions A positive correlation is found between loneliness and negative emotional symptoms among first generation college students in the family. Improving the loneliness of the first generation college students in the family can reduce their negative emotional symptoms and improve their mental health level.

Objective To investigate the relationship between the development of terminal rectal ganglion and spinal cord/sacral abnormalities in boys with complex anorectal malformations(ARMs)in order to improve the understanding of rectal ganglion development abnormalities in ARMs patients.Methods A retrospective trial was conducted on the male patients with complex ARMs admitted to our hospital from 2015 to 2021.The terminal rectal specimens were taken from them during anoplasty.According to the findings on development of terminal rectal ganglion after HE staining,the patients were classified into G1 group(ganglion cells observed)and G2 group(no ganglion cells observed).Imaging techniques were used to evaluate whether there were abnormalities in the spinal cord and sacrum,and their correlation with the terminal rectal ganglion development was analyzed.Results A total of 139 patients were enrolled,and their median age at anoplasty was 5.77(4.57,6.97)months.There were no significant differences between the G1(n=80,57.6％)and G2(n=59,42.4％)groups in ARMs pathological type(P=0.706)and age at surgery(P=0.140).Radiological findings showed there were 48 cases(34.5％)of spinal cord anomalies(SCA),25 cases(18.0％)of sacral abnormalities and 18 cases(12.9％)of coccyx abnormalities.No significant differences were observed in the incidences of SCA and sacral abnormalities between the G1 and G2 groups(P＜0.05).Moreover,the differences of fatty filum terminale and syrinx were statistically significant(P＜0.05).In addition,the ratio of sacrum to coccyx between the G1 and G2 groups were 0.72±0.10 vs 0.67±0.12(P＜0.05)of the anteroposterior position and 0.77±0.09 vs 0.72±0.09(P＜0.05)of the lateral position.Multivariate logistic regression analysis showed that sacral abnormalities,fatty filum terminale and syrinx were independent predictors of rectal terminal ganglion absence in male patients with complex ARMs.Conclusion The development of terminal rectal ganglia in male patients with ARMs is closely associated with the abnormalities of spinal cord and sacrum.Sacral abnormalities,fatty filum terminale and syrinx are independent predictors of rectal terminal ganglion absence in male patients with complex ARMs.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective:To analyze the performance characteristics of the energy output of defibrillation device at different lifecycle stages of the equipment,and to improve the level of management,so as to ensure the safety and effectiveness of using the device.Methods:A total of 90 defibrillation devices of using 10 types included 861290 and CardioServ(included scrapped devices)during the period of 2015-2022 were retrospectively analyzed.The detected data of energy output of defibrillation device were analyzed as statistical method,and the error of releasing energy was calculated.A total of 36 defibrillation devices that were in the early stages of use(at the first three years of device use)were divided into the first year,the second year and the third year,and the data of energy outputs of devices among three years were compared.The data of the type A and type B defibrillation devices,which were the largest number of devices in the normal stage of use(the middle stage of use),were calibrated according to the energy release in the three years between 2018 and 2000.The difference of releasing energy at the preseted value of 100J between the two types of devices was analyzed.Finally,the errors of energy releases of 8 devices,which energy outputs exceeded the deadline,in the scrap period between 2015 and 2022 were summarized.Results:In the data of three groups of devices in the early stages of use,the differences at the first and second year of device use among 100J,150J and 200J of the energy releases of the preseted values were significant(t=-0.17,-0.17,-0.58,P>0.05).The difference of the measured values between the first and third years of device use was not significant(Z=-0.70,-0.38,-0.86,P>0.05).The results of variance analysis of repeated measurement of the energy releases of the devices in normal stage indicated that the difference of the energy release at 100J preseted point among different types of 41 devices was significant(F=4.40,P<0.05).The energy release of type X defibrillator appeared constantly high,and the relative error increased with the increasing of preseted values.The repeatability of the device was better,and the relationship between preseted energy(x)and release energy(y)conformed to linear relationship(R2=0.9985).In these defibrillation devices that were using,the qualified rate of energy output of>100J preseted point was 97.68%.Conclusion:There is slight difference in the mean value of energy release between different type of defibrillation devices within the qualified range,and the energy release still is a performance indicator that should be highly focused for defibrillation devices.We should combine with the maintenance and repair data of device to conduct in-depth analysis,so as to grasp the operating status of the device,and optimize the strategy of quality control,and ensure the safety of defibrillator in clinical use.