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

Sepsis is a systemic inflammatory response caused by severe infection or trauma, and is one of the common causes of acute lung injury(ALI) and acute respiratory distress syndrome(ARDS). Sepsis-acute lung injury(SALI) is a critical clinical condition with high morbidity and mortality. Its pathogenesis is complex and not yet fully understood, and there is currently a lack of targeted and effective treatment options. Pyroptosis, a novel form of programmed cell death, plays a key role in the pathological process of SALI by activating inflammasomes and releasing inflammatory factors, making it a potential therapeutic target. In recent years, the role of traditional Chinese medicine(TCM) in regulating signaling pathways related to pyroptosis through multi-components and multi-targets has attracted increasing attention. TCM may intervene in pyroptosis by inhibiting the activation of NLRP3 inflammasomes and regulating the expression of Caspase family proteins, thus alleviating inflammatory damage in lung tissues. This paper systematically reviews the molecular regulatory network of pyroptosis in SALI and explores the potential mechanisms and research progress on TCM intervention in cellular pyroptosis. The aim is to provide new ideas and theoretical support for basic research and clinical treatment strategies of TCM in SALI.
Pyroptosis/drug effects* ; Humans ; Sepsis/genetics* ; Acute Lung Injury/physiopathology* ; Animals ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Inflammasomes/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics*

OBJECTIVE: By analyzing the differential miRNA in seminal plasma between individuals with normal and abnormal sperm DNA fragmentation index（DFI）, we aim to identify miRNA that may impact sperm DNA integrity and target genes, and attempt to analyze their potential mechanisms of action. METHODS: A total of 161 study subjects were collected and divided into normal control group, DFI-medium group and DFI-abnormal group based on the DFI detection values. Differential miRNA were identified through miRNA chip analysis. Through bioinformatics analysis and target gene prediction, miRNA related to DFI and specific target genes were identified. The relative expression levels of differential miRNA and target genes in each group were compared to explore the impact of their differential expression on DFI. RESULTS: Through miRNA chip analysis, a total of 11 differential miRNA were detected. Bioinformatics analysis suggested that miR-26a-5p may be associated with reduced sperm DNA integrity. And gene prediction indicated that PTEN was a specific target gene of miR-26a-5p. Compared to the normal control group, the relative expression levels of miR-26a-5p in both the DFI-medium group and the DFI-abnormal group showed a decrease, while the relative expression levels of PTEN showed an increase. The relative expression levels of miR-26a-5p in all groups were negatively correlated with DFI values, while the relative expression levels of PTEN showed a positive correlation with DFI values in the DFI-medium group and the DFI-abnormal group. The AUC of miR-26a-5p in the DFI-medium group was 0.740 (P<0.05), with a sensitivity of 73.6% and a specificity of 71.5%; the AUC of PTEN was 0.797 (P<0.05), with a sensitivity of 76.5% and a specificity of 78.4%. In the DFI-abnormal group, the AUC of miR-26a-5p was 0.848 (P<0.05), with a sensitivity of 81.3% and a specificity of 78.1%. While the AUC of PTEN was 0.763 (P<0.05), with a sensitivity of 77.2% and a specificity of 80.2%. CONCLUSION miR-26a-5p affects the integrity of sperm DNA by regulating the expression of PTEN negatively. The relative expression levels of seminal plasma miR-26a-5p and PTEN have good diagnostic value for sperm DNA integrity damage, which can help in the etiological diagnosis and prognosis analysis of abnormal DFI. This provides a diagnostic and treatment approach for the study and diagnosis of DFI abnormalities without clear etiology.
Male ; Humans ; MicroRNAs/genetics* ; PTEN Phosphohydrolase/genetics* ; Spermatozoa ; Semen/metabolism* ; DNA Fragmentation

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

ObjectiveTo present the exploration and application of a prospective follow-up research method for acute infectious disease surveillance based on natural community populations， using COVID-19 infection as an example， and to provide a reference for improving the infectious disease surveillance and early warning system. MethodsA multi-stage probability proportional sampling method was employed to sample residents from all communities of 16 administrative districts in Shanghai， with households as the units. A cohort for acute infectious diseases based on natural community populations was established. The baseline survey was conducted for all cohort subjects， and COVID-19 antigen test kits were distributed. From December 21， 2022 to September 30， 2023， prospective follow-up monitoring of COVID-19 antigen and nucleic acid was carried out on the study subjects on a weekly basis. The baseline characteristics and follow-up information of the cohort subjects were described. ResultsThe cohort for acute infectious diseases included a total of 12 881 subjects， comprising 6 098 males （47.3%） and 6 783 females （52.7%）. The baseline survey revealed that 35.2% （4 540/12 881） of the subjects had a history of COVID-19 infection. During the follow-up period from December 21， 2022 to September 30， 2023， the average incidence density in the cohort was 0.61/person-year， with a higher incidence density in females （0.63/person-year） compared to males （0.59/person-year）. Individuals aged 60 and above （0.64/person-year） and those with underlying health conditions （0.67/person-year） had a higher incidence density. Healthcare workers showed a notably higher incidence density （0.84/person-year） than that in other occupational groups. As of September 30， 2023， a total of 340 subjects in the cohort experienced secondary infections， with a median interval of 170 days between the first and second infections. ConclusionThis study applies cohort study method to acute infectious disease surveillance， providing crucial data support for estimating infection rates and forecasting alerts for acute infectious diseases in the community. This method can be promoted and applied as a new approach for acute infectious disease surveillance.

Objective To investigate the effect of rats'injuries and its mechanism caused by specific dose of radiation combined with decompression exposure.Methods 81 male SD rats were randomly divided into control group(n=9),radiation group(n=18),radiation+low-load decompression group(n=18),radiation+medium-load decompression group(n=18),and radiation+high-load decompression group(n=18).In addition to control group,the rats were irradiated with 60Co γ rays at 4 Gy and then underwent rapid escape experiments.The high-pressure exposure schemes were to stay underwater 57 m for 30 min,45 min or 60 min and reduce to normal pressure within(30±5)s,respectively.The high-pressure exposure was not carried out in radiation group.The behavior and death of rats in each group were observed 0.5 h after leaving the cabin.Blood(abdominal aorta)and lung tissues were collected at 3 h and 72 h,respectively.The changes of lung wet-dry weight ratio(W/D),lung pathology and serum levels of interleukin(IL)-1β,IL-6,tumor necrosis factor-α(TNF-α),superoxide dismutase(SOD),malondialdehyde(MDA),nitric oxide(NO),intercellular adhesion molecule-1(ICAM-1)and thromboxane B2(TXB2)were analyzed.Results Compared with control group and radiation group,radiation+low-load decompression group showed no significant difference in the injury and death rate of rats(P＞0.05),while radiation+medium-load decompression group and radiation+high-load decompression group showed significantly increase of the injury and death rate of rats(P＜0.05).Compared with control group,other groups showed no significant change in pulmonary W/D at 3 h(P＞0.05),and increased at 72 h(P＜0.05).HE staining showed that compared with control group,radiation group showed mild lung interstitial edema,while radiation+low-load decompression group showed obvious pulmonary tissue edema and a small number of red blood cells exudated in the alveolar cavity.The edema,congestion and inflammatory cell infiltration of lung tissue were more serious in radiation+medium-load decompression group and radiation+high-load decompression group.Compared with control group and radiation group,all radiation+decompression groups showed an increase in serum levels of IL-1β,IL-6,TNF-α,MDA,NO,ICAM-1 and TXB2(P＜0.05),and a decrease in SOD activity(P＜0.05).Compared with radiation+low-load decompression group,radiation+medium-load decompression group and radiation+high-load decompression group showed increase in serum levels of IL-1β,IL-6,MDA,ICAM-1 and TXB2(P＜0.05),and decrease in activity of SOD(P＜0.05).Except for control group,serum levels of IL-1β,IL-6,TNF-α,MDA,NO,ICAM-1 and TXB2 were decreased at 72 h compared with 3 h(P＜0.05),and SOD activity was increased at 72 h in all groups(P＜0.05).Conclusions High-load decompression can increase the injury and death rate of rats exposed to radiation and high pressure.The potential mechanism of the combined injury effect of radiation and decompression was related to inflammation,immune stress,oxidative damage,vasomotor activity and coagulation mechanism.

Objective This study aims to develop and validate a dynamic web-based nomogram for predicting kinetophobia in patients following percutaneous coronary intervention(PCI).Methods A prospective design was employed to selectively enroll 330 PCI patients admitted to a hospital in Hangzhou from December 2022 to July 2023.Single-factor analysis and Lasso regression were utilized to identify independent risk factors for kinesophobia post-PCI.Logistic regression was performed using R software,and a nomogram was constructed.The model was assessed through the area under the receiver operating characteristic curve(AUC)and Hosmer-Lemeshow tests.Results There were 206 cases of kinesiophobia in 330 patients after PCI,and the incidence was 62.4％.Logistic regression analysis identified combined heart failure,emergency surgery,NYHA cardiac function grade,ADL level,sedentary behavior,Chinese version of PROMIS Physical Function Summary Table score,and Chinese version of Perceptive Social Support Scale score as independent influencing factors for kinesophobia after PCI(P＜0.05).The AUC value of the model was 0.821,with a sensitivity of 70.4％and specificity of 82.0％.The Hosmer-Lemeshow fit test yielded a non-significant result(x2=9.350,P=0.314).Calibration and decision curves demonstrated the model's favorable calibration and clinical practicability.The C-index of the nomogram prediction model was 0.778,0.774,and 0.800,respectively,by 5-fold cross-validation,10-fold cross-validation,and the Bootstrap method.Conclusion The dynamic nomogram model developed in this study effectively predicts kinesophobia in patients after PCI.It provides valuable references and support for clinical staff in early identification of high-risk patients,enabling the formulation of individualized health education strategies and exercise rehabilitation plans.

Autophagy is an essential cellular metabolic process that involves clearance of damaged organelles and protein aggregates in cells through lysosomes,providing energy for cells,and maintaining cellular tissue homeostasis.Impaired autophagy is closely related to the pathophysiology of a variety of diseases.In the pathogenesis of atherosclerosis(AS),the dysfunction of autophagy of vascular cells plays a crucial role in the formation and progression of AS.The functional status,survival or death of vascular cells,including endothelial cells,vascular smooth muscle cells and macrophages,can influence the formation and stability of plaques,thereby affecting the progression of AS.This review summarizes the relationship between autophagy and AS,and details the impact of autophagy dysfunction on vascular cell function in the process of AS,as well as the role of mitophagy and inflammasome in the development of AS,aiming to provide novel insights for the prevention and treatment of AS.

Objective To study the effects of different pellet feed hardness on the growth and reproduction,feed utilization rate,and environmental dust in laboratory mice.Methods One hundred of fifty 50 3-week-old SPF-grade C57BL/6JGpt and 150 ICR laboratory mice were randomly divided into three groups,with an equal number of males and females.They were fed diets with different hardness of 18.62 kg,23.15 kg,and 27.89 kg.Body weight,feed utilization rate,and dust levels in cages were recorded and calculated for mice aged 3-10 weeks.Forty-five 6-week-old male mice and ninety 4-week-old female mice from each strain were randomly divided into three groups and fed pellet feeds with three different hardness levels.After 2 weeks of adaptation to the same hardness feed,the mice were paired at a 1:2 male-to-female ratio and monitored for reproductive data for 3 months.Results At the age of 4 weeks,the body weight of male C57BL/6JGpt mice in 23.15 kg group was significantly higher than that in the 18.62 kg and 27.89 kg groups(P＜0.01),and the body weight of females in the 18.62 kg group was significantly higher than that in the 27.89 kg group(P＜0.05).There was no significant difference in body weight among ICR mice aged 3-10 weeks across different feed hardness groups(P＞0.05).For both strains,feed utilization rate for males was higher than that for females across different feed hardness groups at all weeks of age(P＜0.01).Compared to the 27.89 kg group,both the 18.62 kg and 23.15 kg groups showed a significant increase in the 50-mesh dust levels in cages for both strains aged 4-8 weeks(except for 7-week-old C57BL/6JGpt mice)(P＜0.05).For both C57BL/6JGpt and ICR mice,there was no significant difference in basic reproductive performance such as interval between the first litter and the monthly production index among the three feed hardness groups during the experimental period(P＞0.05).However,the monthly production index of C57BL/6JGpt mice first increased and then decreased with the increase of feed hardness,while that of ICR mice increased with increasing feed hardness,though these differences were not statistically significant(P＞0.05).Conclusion Different strains and genders had different tolerance to feed hardness.C57BL/6JGpt mice are more adapted to lower hardness feeds,while ICR mice are better suited to slightly higher hardness feeds.

Objective:This study aimed to share preliminary experiences of single-incision plus two ports laparoscopic proximal gastrectomy with right-sided overlap and single-flap valvuloplasty (ROSF).Methods:Following the 6th edition of the Japanese Gastric Cancer Treatment Guidelines, proximal gastrectomy with lymphadenectomy was performed. Using a single-port approach, the esophagus was transected at least 2 cm above the tumor's upper margin with linear staplers. The stomach was then extracted through a periumbilical incision, and the proximal stomach was subsequently transected extracorporeally, while ensuring appropriate resection margins on both the greater and lesser curvatures. A single flap was created before returning the remnant stomach to the abdominal cavity and re-establishing pneumoperitoneum. The No.2 clip was used to grasp and elevate the esophageal stump. An incision was made at the right lower edge of the esophageal stump to guarantee that the esophageal lumen was open. The linear stapler was then inserted into the openings of the stomach and esophagus to perform a side overlap anastomosis with a length of 3 cm. Another barbed suture was used to close the common opening of the esophagus and the stomach, and the same barbed suture were used to suture the gastric wall to the lower edge of the muscle flap. The first barbed suture was then used to sequentially suture the proximal brim of the flap to the esophagus and the right brim of the flap to the right brim of the mucosal window. After completion of anastomosis, a drainage tube was inserted through the right upper port. This procedure was employed from November 2023 to March 2024 on five patients diagnosed with adenocarcinoma of the esophagogastric junction and upper stomach. The cohort consisted of three males and two females, with an age range of 62 to 75 years and a body mass index (BMI) of 13.7 to 24.2 kg/m2. All cases were preoperatively staged as T1-2N0M0, confirmed by endoscopic biopsy and enhanced CT scans of the chest, abdomen, and pelvis.Results:All five patients successfully underwent the surgery. The median surgery time was 180-325 minutes, with the intraoperative blood loss of 30-50 ml. The number of lymph nodes harvested ranged from 18 to 27. The time to first flatus, and restore liquid diet and was 2.0-5.0 and 1.0-3.0 days, respectively. The postoperative length of stay was 9.0-11.0 days. The pain scores on the Numeric Rating Scale (NRS). On the first day, the pain scores were 3.0 in two cases, 2.0 in two cases, and 1.0 in one case. On the second day, the pain scores were 2.0 in two cases and 1.0 in three cases. On the third day, the pain scores were 1.0 in four cases and 2.0 in one case. No short-term postoperative complications were observed, and there were no perioperative deaths.Conclusion:Single-incision plus two ports laparoscopic proximal gastrectomy with ROSF is safe and feasible.