BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of subsequent radiotherapy (RT) following first-line treatment with durvalumab plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). METHODS: A total of 122 patients with ES-SCLC from three hospitals during July 2019 to December 2021 were retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to address potential confounding factors. The primary focus of our evaluation was to assess the impact of RT on progression-free survival (PFS) and overall survival (OS). RESULTS: After IPTW analysis, 49 patients received durvalumab plus platinum-etoposide (EP) chemotherapy followed by RT (Durva + EP + RT) and 72 patients received immunochemotherapy (Durva + EP). The median OS was 17.2 months vs . 12.3 months (hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.17-0.85, P = 0.020), and the median PFS was 8.9 months vs . 5.9 months (HR: 0.56, 95% CI: 0.32-0.97, P = 0.030) in Durva + EP + RT and Durva + EP groups, respectively. Thoracic radiation therapy (TRT) resulted in longer OS (17.2 months vs . 14.7 months) and PFS (9.1 months vs . 7.2 months) compared to RT directed to other metastatic sites. Among patients with oligo-metastasis, RT also showed significant benefits, with a median OS of 17.4 months vs . 13.7 months and median PFS of 9.8 months vs . 5.9 months compared to no RT. Continuous durvalumab treatment beyond progression (TBP) prolonged OS compared to patients without TBP, in both the Durva + EP + RT (NA vs . 15.8 months, HR: 0.48, 95% CI: 0.14-1.63, P = 0.238) and Durva + EP groups (12.3 months vs . 4.3 months, HR: 0.29, 95% CI: 0.10-0.81, P = 0.018). Grade 3 or 4 adverse events occurred in 13 (26.5%) and 13 (18.1%) patients, respectively, in the two groups; pneumonitis was mostly low-grade. CONCLUSION Addition of RT after first-line immunochemotherapy significantly improved survival outcomes with manageable toxicity in ES-SCLC.
Humans ; Small Cell Lung Carcinoma/therapy* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Lung Neoplasms/therapy* ; Aged ; Antibodies, Monoclonal/therapeutic use* ; Adult ; Immunotherapy/methods* ; Aged, 80 and over

Intervention in chronically activated microglia-mediated neuroinflammation is a novel approach to treat Alzheimer's disease (AD). The low permeability of the blood‒brain barrier (BBB) and non-selective distribution in the brain severely restrict AD drugs' disease-modifying efficacy. Here, an immunosuppressant TREM2-lowing antisense oligonucleotides (ASOs) and resveratrol co-loaded cationic liposome is developed as an immune reprogramming nanomodulator modified by acid-cleavable BBB-targeting peptide and microglia-targeting peptide (Res@TcMNP/ASO) for AD management. Res@TcMNP/ASO can enter brain endothelial cells via D-T7 peptides. Then D-T7 undergoes an acid-responsive cleavage, facilitating the escape of Res@MNP/ASO from endo/lysosomes to cross the BBB. The detached Res@MNP/ASO specifically targets M1-phenotype microglia via exposed MG1 peptides to prompt the simultaneous delivery of two drugs into activated microglia. This nanomodulator can not only restore the immune function of microglia through TREM2-lowing ASO but also mitigate the immune stimulation to microglia caused by reactive oxygen species (ROS) through resveratrol, thereby synergistically inhibiting the chronic activation of microglia to alleviate neuroinflammation in AD. Our results indicate that this combination treatment can achieve significant behavioral and cognitive improvements in late APP/PS1 mice.

Objective:To conduct a systematic review of reported cases of autosomal dominant tubulointerstitial kidney disease (ADTKD) caused by uromodulin ( UMOD) gene mutations (ADTKD- UMOD) in China, summarize the clinical, pathological and genetic variation characteristics, and analyze the genotype-phenotype correlation. Methods:It was a retrospective systematic analysis study. The search terms "UMOD", "ADTKD-UMOD", "uric acid kidney disease (UAKD)", "medullary cystic kidney disease type 2 (MCKD2)", and "familial juvenile hyperuricemic nephropathy type 1 (FJHN1)" were used, and relevant literature on ADTKD- UMOD cases in China were retrieved from PubMed, CNKI, Wanfang Data and Chinese Medical Journal Full-text Database. The data of the cases involved in the literature were collected and summarized, and the clinical and pathological characteristics and genetic variation features of Chinese ADTKD- UMOD patients were analyzed. The patients were divided into exon 3 mutation group and non-exon 3 mutation group based on the mutation sites, and the differences of clinical phenotypes between the two groups were compared. The patients were also divided into domain 8 cysteine (D8C) mutation group and non-D8C mutation group based on the mutation regions, and the differences of clinical phenotypes between the two groups were compared. Results:A total of 17 relevant articles on ADTKD- UMOD cases in China were retrieved, involving 57 patients from 34 families. The age at first diagnosis was 24.0 (20.0, 39.5) years. Fifty-three patients (93.0%) had a family history of nephropathy or hyperuricemia. Among the 48 patients with recorded blood uric acid levels, 36 patients (75.0%) had hyperuricemia, with age of 24.0 (20.3, 37.3) years. Fifty-four patients had chronic kidney disease assessment records, among which 46 patients (85.2%) developed chronic kidney disease, and 21 patients (38.9%) developed end-stage renal disease. The age of end-stage renal disease was 39.0 (24.0, 46.0) years, with age of 33.0 (21.0, 46.5) years in males and 39.5 (25.5, 45.5) years in females ( Z=-0.649, P=0.516). Twenty patients underwent renal biopsies, and 19/20 patients had tubular or interstitial lesions, and 9/20 patients had glomerular lesions, mainly manifested as focal segmental or global glomerulosclerosis. Forty patients had renal ultrasound examination records, among which 36 patients (90.0%) had abnormal results, with renal cysts being the most common type (12 patients, 30.0%). Among the 34 family cases, no ADTKD- UMOD hotspot mutation was found in the UMOD gene mutations. Thirty-two families (94.1%) were missense mutations, 26 families (76.5%) had mutation sites in exon 3, and 16 families (47.1%) had mutation regions in D8C. The proportion of hypertension in the non-exon 3 mutation group was higher than that in the exon 3 mutation group ( χ2=9.84, P=0.002). The proportion of males in the non-D8C mutation group was higher than that in the D8C mutation group ( χ2=4.97, P=0.026). Conclusions:The main clinical manifestations of Chinese ADTKD- UMOD patients are hyperuricemia, and the main renal histopathological changes are tubular and interstitial lesions. Some patients have glomerular lesions, which need to be differentiated from focal segmental glomerulosclerosis. Renal cysts detected by renal ultrasound can suggest the diagnosis of the disease. Missense mutation is the main type of UMOD gene mutations. The gene mutation region may be correlated with hypertension and gender.

Objective:To explore the surgical strategies and clinical efficacy of open partial nephrectomy in the treatment of renal angiomyolipoma (AML) with inferior vena cava tumor thrombus.Methods:A retrospective analysis was conducted on the clinical data of 5 patients with renal AML and inferior vena cava tumor thrombus who underwent partial nephrectomy at Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine from October 2014 to December 2022. There were 2 male and 3 female patients, with a median age of 37 years, ranged from 33 to 45 years. All patients were identified during routine physical examinations. Four patients presented with right-sided lesions, while one had a left-sided lesion. The diameter of the primary tumor within the kidney ranged from 3.0 to 7.0 cm, with a median diameter of 5.5 cm.The length of the tumor thrombus within the inferior vena cava ranged from 1.0 to 6.0 cm, with a median length of 1.5 cm. Among them, 2 patients underwent laparoscopic nephrectomy combined with extracorporeal workbench tumor resection and autologous kidney transplantation (the workbench surgery group), while 3 patients underwent open in-situ partial nephrectomy combined with removal of inferior vena cava tumor thrombus (the in-situ nephron-sparing surgery group). The surgical method of the workbench surgery group: The patients first underwent laparoscopic nephrectomy on the affected side combined with inferior vena cava tumor thrombus removal, then the incision was extended to remove the affected kidney, and table partial nephrectomy was performed. After completely removing the tumor and tumor thrombus within the affected kidney and renal vein, autologous kidney transplantation was performed in the iliac fossa. The surgical method of the in-situ kidney preservation surgery group: The affected kidney, renal artery and vein on the affected side, inferior vena cava, and contralateral renal vein were dissected and exposed. The distal end of the inferior vena cava, the contralateral renal vein, the proximal end of the inferior vena cava, and the renal artery on the affected side were blocked respectively. The venous wall was opened in the middle of the renal vein, and the tumor thrombus was gradually pulled out. According to the pre-marked tumor boundary, the tumor within the kidney was gradually removed by alternate blunt and sharp dissection combined with suction, and the wound surface was sutured layer by layer. The perioperative conditions, complications, and follow-up results of the patients were analyzed.Results:All 5 surgeries were successfully completed, with a median operation time of 100 to 450 minutes and a median operation time of 200 minutes. The intraoperative bleeding volume was 100 to 600 ml, with the median of 150 ml. In the in-situ nephron-sparing surgery group, the renal artery occlusion time was 28 to 41 minutes, and the median occlusion time was 34 minutes. All patients were discharged safely after surgery, and there were no serious perioperative complications. The postoperative pathology of all 5 patients was renal angiomyolipoma, without any epithelioid components. The patients were followed up for 12 to 90 months, with a median follow-up duration of 24 months. None of the 5 patients had tumor recurrence or metastasis, and no patient developed chronic kidney dysfunction during follow-ups.Conclusions:Renal AML with venous tumor thrombus is a challenging clinical problem. In situ open partial nephrectomy or the combined approach through the workbench and autologous kidney transplantation can effectively remove the tumor thrombus and maximize the protection of renal function. For cases of ① multiple or complex renal AML; ② complex vascular system structure within the renal sinus requiring precise anatomy; ③ renal AML with a previous history of hemorrhage, complex adhesions around, and difficult dissociation, table partial nephrectomy combined with inferior vena cava tumor thrombus removal and autologous kidney transplantation can be selected. For cases where the expected surgical operation is simple, in situ open partial nephrectomy can significantly shorten the operation time and reduce surgical trauma.

Objective:Comparative analysis of the mNUTRIC and NRS-2002 scores for evaluating nutritional risk and predicting clinical outcomes in end stage liver disease patients.Method:A retrospective cohort study method was used to screen 114 cases with end-stage liver disease admitted to the intensive care unit (ICU) of the First Hospital of Lanzhou University from December 1, 2016 to March 31, 2021 according to the inclusion and exclusion criteria. The patient's demographic data, blood routine, blood biochemical indexes, coagulation function indexes, arterial blood gas analysis and imaging examination data were collected. The mNUTRIC score, NRS-2002 score, sequential organ failure (SOFA) score, model for end-stage liver disease (MELD) score, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, Child-Pugh grade, and clinical outcomes at 28 and 90 days at 24 h post-ICU admission were collected. The differences in clinical indicators between the mNUTRIC high group (≥5 points) and the low group, and the NRS-2002 high group (≥3 points) and the low group were compared. Spearman correlation analysis was used to explore the correlation between the mNUTRIC score and NRS-2002 score, clinical indicators, and 28 and 90-day mortality rates. Multivariate logistic regression analysis was used to determine the risk factors associated with 28-day and 90-day mortality in patients. The value of mNUTRIC score and NRS-2002 score in assessing the clinical outcomes of patients with end-stage liver disease was explored by receiver operating characteristic (ROC) curve.Results:The clinical indicators related to nutritional status of patients were worse in the high-mNUTRIC group than those in the low-mNUTRIC group, and the 28-day and 90-day mortality rates were significantly higher than those in the low-mNUTRIC group [89.0%(65/73) vs. 29.2%(12/41), 97.2%(71/73) vs. 39.0%(16/41), P<0.001]. There was no statistically significant difference in the incidence rate of hepatic encephalopathy, esophageal variceal bleeding, and ascites between the high and low mNUTRIC group. The clinical indicators related to nutritional status were worse in the high-NRS-2002 group than those in the low-NRS-2002 group of patients, and the 28-day and 90-day mortality rates were significantly higher than those in the low-group [73.0%(73/100) vs. 4/14, 81.0%(81/100) vs. 6/14, P=0.008, 0.004]. The NRS-2002 high-score group did not differ significantly from the low-score group in terms of hepatic encephalopathy, esophagogastric variceal bleeding, or ascites prevalence. Patient's age, white blood cell count (WBC), urea nitrogen (BUN), creatinine (UREA), uric acid (UA), total cholesterol (TG), Child-Pugh, MELD, SOFA, APACHE Ⅱscores were significantly positively correlated with the mNUTRIC score. Conversely, albumin (Alb) and Glasgow Coma Scale (GCS) were significantly negatively correlated. Patient's age, WBC, CREA, BUN, UREA, UA, Child-Pugh, MELD, SOFA, APACHE Ⅱwere significantly positively correlated with the NRS-2002 score.Conversely, albumin (Alb) and Glasgow Coma Scale (GCS) were significantly negatively correlated ( P<0.05). The 28-day and 90-day mortality rates of patients increased with the increase in the mNUTRIC scores. The mNUTRIC score was an independent predictor of death within 28 and 90 days in patients with end-stage liver disease. The area under the curve (AUC) of mNUTRIC for predicting patient death at 28 days was 0.864 (95% CI: 0.794-0.934). The AUC of NRS-2002 for predicting patient death at 28 days was 0.683 (95% CI: 0.573-0.792). The AUC of the two indicators combined for predicting patient death at 28 days was 0.868 (95% CI: 0.799-0.936). The AUC of mNUTRIC for predicting patient death at 90 days was 0.915 (95% CI: 0.861-0.969). The AUC of NRS-2002 for predicting patient death at 90 days was 0.715 (95% CI: 0.599-0.832). The AUC of the two indicators combined for predicting patient death at 90 days was 0.922 (95% CI: 0.871-0.972). Conclusion:mNUTRIC score and NRS-2002 score can better evaluate the nutritional status in patients with end-stage liver disease. The mNUTRIC score is a good predictor of 28-day and 90-day mortality in patients with end-stage liver disease, and its application value efficacy is enhanced when combined with NRS-2002.

Objective:To observe the effects of RasGRP4 gene deletion on the structure and function of the retina in diabetic mice, and to explore the mechanism of RasGRP4 in diabetic retinopathy (DR) by transcriptome sequencing in conjunction with bioinformatics analysis. Methods:A total of 12 male C57BL/6J mice were divided into normal group, diabetic group (DM group), with 6 mice in each group. Six male RasGRP4 knockout mice were uesd as RasGRP4 knockout diabetic group (DM-KO group). Mice in the DM group and DM-KO group were fed with high-fat diet combined with intraperitoneal injection of streptozotocin to establish diabetic model and body weight and blood glucose were monitored regularly. Three months after modeling, optical coherence tomography was used to detect the retinal thickness and ganglion cell layer thickness. Electroretinography was used to detect the function of the retina in mice under dark-adapted conditions. Total RNA was extracted from the retinas of mice in DM group and DM-KO group, and transcriptomic sequencing was performed to screen differentially expressed genes (DEG). Core genes were screened using MCODE and Cytohubba plug-ins of Cytoscape v3.8.2 software. At the same time, the functional enrichment analysis of gene samples (GO) of the selected DEG was performed. The mRNA relative expression levels of interleukin-8, transforming growth factor-β (TGF-β), interferon-γ (IFN-γ), NOd-like receptor thermal protein domain protein 3 (NLRP3), Caspase-1 and IL-1β in each group were detected by real-time quantitative polymerase chain reaction. t test was used to compare the two groups. One-way analysis of variance was used to compare the three groups. Results:Compared with the DM group, there was no significant difference in blood glucose and body weight in the DM-KO group with the extension of high-fat diet ( t=0.12, 2.02, 0.22, 0.10, 0.59, 0.41, 1.35, 0.31, 1.12, 1.58, 1.47, 1.20, 1.24, 0.39, 0.66, 0.14; P>0.05). The retinal thickness and ganglion cell layer thickness of mice in the three groups were significantly reduced in the DM group compared with the normal group, while DM-KO was significantly increased compared with the DM group, and the differences were statistically significant ( F=30.43, 7.81; P<0.000 1, 0.01). Comparison of a-wave and b-wave amplitudes among the three groups showed that the DM group was significantly lower than the normal group, while the DM-KO was significantly higher than the DM group, and the differences were statistically significant ( F=16.46, 35.58; P<0.001, 0.000 1). Compared with the DM group, 184 differential genes (DEG) were screened in the DM-KO group, among which 39 up-regulated and 145 down-regulated genes were detected, respectively. The results of the MCODE plug-in analysis showed that Col1a2, Fbln1, Fbn1, Col6a3, Fmod, Ogn, Tgfb, Mfap4, Vcan, Nid2, and Col18a1 were core genes in the DEG. Cytohubba plug-in analysis showed that Col1a2, Mrc1, Cd47, Fbn1, Cybb, Cd163, Fbln1, Fmod, Adgre1, and Col6a3 were the core genes in DEG. The results of the GO functional enrichment analysis showed that DEG was mainly involved in hemoglobin complexes, MHC class Ⅱ protein complex, apical plasma membrane, inflammasome complex, immunological synapse, response to bacterium, inflammatory response, immune system processe, response to hypoxia, and cell adhesion were significantly enriched. Comparison of mRNA relative expression levels of IL-8, TGF-β, IFN-γ, NLRP3, Caspase-1 and IL-1β in the three groups showed that the DM group was significantly higher than the normal group, while the DM-KO was significantly lower than the DM group, with statistical significance ( F=12.43, 15.41, 70.09, 29.04, 11.79, 41.28; P<0.01). Conclusion:RasGRP4 deficiency plays a therapeutic role in the development of DR through inhibition of inflammatory factor secretion and NLRP 3 inflammasome pathway activation.

Objective To analyze the current quality of treatment for hospitalized cancer patients in Bei-jing,identify major issues in treatment practices,and propose improvements.Methods Nine hospitals in Beijing were selected for examination.Expert on-site interviews and medical record sampling were conducted.The"Bei-jing Cancer Diagnosis and Treatment Quality Control Checklist"was used to assess the hardware,management,anti-cancer drug therapy,radiation therapy,and surgical treatment during cancer treatment at these hospitals from January to October 2023.The relevant problems were analyzed.Results Among the nine hospitals,two(22.2％)were equipped with laminar flow rooms,and three(33.3％)had intravenous drug preparation centers.In terms of institutional management,seven hospitals(77.8％)had standardized anti-cancer drug prescription authority management,eight(88.9％)had complete emergency plans,and five(55.6％)had oncology specialist pharmacists.Regarding anti-cancer drug therapy,the areas with higher completion rates included pathology diag-nosis support(97.6％),routine pre-treatment examinations(96.3％),adverse reaction evaluation(92.7％),discharge summaries(95.1％),and admission records(91.5％).However,the accuracy of tumor staging before treatment(70.7％)and the evaluation of therapeutic efficacy after drug treatment(76.9％)needed improvement.The oncology specialty significantly outperformed the non-oncology specialty in terms of the accuracy rate of TNM staging(86.0％vs.46.9％,P＜0.001),the completeness of informed consent forms(100％vs.68.8％,P＜0.001),the completeness of drug indication evaluation(96.0％vs.78.1％,P=0.025),the completeness of admission medical history records(98.0％vs.81.3％,P=0.008),the rationality of drug dosage(96.0％vs.75.0％,P=0.005),the rationality of drug infusion time(100％vs.62.5％,P＜0.001),and the rationality of the order of drug infusion(100％vs.87.5％,P=0.010).Although the quality of radiation therapy was high,the subsequent evaluation of therapeutic efficacy(39.3％)requires enhancement.In surgical treatment,the preoper-ative pathology diagnosis support rate(78.1％)and the accuracy of tumor staging(37.5％)were relatively low,indicating issues with incomplete preoperative evaluation and the absence of multidisciplinary discussions.Conclusions There remains significant room for improvement in the quality of cancer treatment in China.It is recommended to standardize tumor staging assessment processes,strengthen entry assessments for non-oncology departments,promote the implementation of multidisciplinary treatment models,and establish a multi-department collaborative management model.Continuous monitoring of cancer diagnosis and treatment quality indicators is es-sential to promote ongoing improvements in cancer treatment quality.

Objective:To explore the core factors of self-management and quality of life (QOL) in patients with chronic obstructive pulmonary disease (COPD) and the internal relationship between these two constructs.Methods:A convenience sampling method was used to enroll 210 COPD patients who visited the Fifth Affiliated Hospital, Sun Yat-sen University from January to December 2022. Data were collected using Self-Management Scale and 36-item Short-Form. A relationship network between self-management and QOL was constructed via network analysis, and centrality indicators and network stability were calculated.Results:A total of 210 questionnaires were distributed, and 205 valid questionnaires were recovered, with an effective recovery rate of 97.6%. Emotional management was identified as the core node in both the overall network and the self-management subnetwork (2.064), while vitality was the core node in the QOL subnetwork (0.730). The relationship between self-management and QOL was mainly manifested through the strong association between emotional management and role-emotion.Conclusions:Emotional management is the core factor in the relationship between self-management and QOL in COPD patients. The overall network of self-management and QOL is influenced by the strong association between emotional management and role-emotion.

Tooth extraction is one of the most common procedures in oral surgery.Poor wound healing is a common problem after tooth extraction.Poor wound healing may not only lead to eating difficulties and impaire psychological health,but also increase the difficulty and cost of treatment,prolong the treatment period and lead to osteonecrosis of the jaw in severe cases.Currently,there is a lack of systematic integration and evaluation of domestic and international studies related to post-extraction wound healing.In this study VOSviewer,Bibliometrix and CiteSpace software were used to econometrically analyse the literature on post-extraction wound healing from 2013 to 2023,with the aim of providing a reference for developing more scientific and systematic strategies for post-ex-traction wound management and prevention of the complications.

Objective:To analyze the relationship between folate and thyroid antibody in early pregnancy and adverse pregnancy outcome in pregnant women with hypothyroidism during pregnancy.Methods:The data of 97 pregnant women with hypothyroidism from Jul. 2020 to Mar. 2023 in the Obstetrics Department of Liaocheng Second People’s Hospital were retrospectively analyzed. The levels of folate, thyroglobulin antibody (TGAb) and thyroid peroxidase antibody (TPOAb) were detected in the first trimester. According to whether adverse pregnancy outcome occurred in pregnant women with hypothyroidism during pregnancy, they were divided into occurrence group and non-occurrence group. The clinical data of the occurrence group and the non-occurrence group were compared. Logistic regression was used to analyze the influencing factors of adverse pregnancy outcomes in pregnant women with hypothyroidism during pregnancy, and receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of folic acid, TGAb, TPOAb and their combination on adverse pregnancy outcomes in pregnant women with hypothyroidism during pregnancy.Results:Among 97 pregnant women, the incidence of adverse pregnancy outcome was 14.43% (14/97) .The folate level in the occurrence group was lower than non-occurrence group ( P<0.05) , and the TGAb and TPOAb levels in the occurrence group were higher than non-occurrence group ( P<0.05) . The occurrence group with alanine aminotransferase (ALT) , glutamine transpeptidase (GGT) and aspartate aminotransferase (AST) were all higher than non-occurrence group ( P<0.05) .The folate, TGAb, and TPOAb levels were factors influencing adverse pregnancy outcomes in pregnant women with hypothyroidism ( P<0.05) . The area under the curve (AUC) values of folate, TGAb, TPOAb and their combined prediction of adverse pregnancy outcomes in pregnant women with hypothyroidism during pregnancy were 0.804, 0.843, 0.799, 0.909 ( P<0.05) , while the combined three with AUC values were higher ( P<0.05) . Conclusion:The folate, TGAb and TPOAb levels in early pregnancy can be used to evaluate adverse pregnancy outcomes in hypothyroidism pregnant women, and the combination of the three has a higher evaluation value.