Objective:To explore the efficacy of different second-line treatment strategies in the real world after progression of first-line immunotherapy and its combination therapies in patients with driver gene-negative advanced non-small cell lung cancer (NSCLC) .Methods:A retrospective analysis was conducted on the clinical data of 93 driver gene-negative advanced NSCLC patients who received first-line immunotherapy and its combination therapies from January 1, 2018 to December 31, 2023 at the First Affiliated Hospital of Xinxiang Medical University and Xinxiang Central Hospital. Patients were categorized into immune checkpoint inhibitors (ICIs) -resistant ( n=43) and ICIs-responsive ( n=50) groups according to whether progression free survival (PFS) exceeded 6 months after first-line treatment. Patients were categorized into ICIs-treated ( n=55) and non-ICIs-treated ( n=38), anti-angiogenic-treated ( n=51) and non-anti-angiogenic-treated ( n=42) groups according to the different second-line treatment strategies after progression of first-line immunotherapy and its combination therapies. The median PFS2 (mPFS2) and median overall survival (mOS) 2 after second-line treatment of each group were compared. The Kaplan-Meier method was used for survival analysis. Results:The mPFS2 and mOS2 of 93 advanced NSCLC patients who progressed after first-line ICIs treatment were 4.9 months (95% CI: 4.1-5.7 months) and 14.7 months (95% CI: 11.2-18.2 months). The mPFS2 of patients in the first-line ICIs-responsive and ICIs-resistant groups were 6.0 and 3.8 months, respectively, with no statistically significant difference ( χ2=2.00, P=0.157), and the mOS2 were 25.3 and 11.3 months, respectively, with a statistically significant difference ( χ2=12.13, P<0.001). The mPFS2 of patients in the second-line ICIs-treated group and the non-ICIs-treated group were 5.2 and 4.6 months, respectively, with no statistically significant difference ( χ2=0.16, P=0.687). The mOS2 were 15.1 and 12.7 months, respectively, with no statistically significant difference ( χ2=0.01, P=0.930). The mPFS2 of patients in the second-line anti-angiogenic-treated and non-anti-angiogenic-treated groups were 4.5 and 6.0 months, respectively, with no statistically significant difference ( χ2=0.41, P=0.525), the mOS2 were 14.7 and 16.8 months, respectively, with no statistically significant difference ( χ2=0.01, P=0.943) . Conclusions:After progression of first-line ICIs therapy in patients with driver gene-negative advanced NSCLC, first-line ICIs-responsive patients have significantly longer OS after second-line treatment compared with ICIs-resistant patients. The efficacy of second-line therapy in patients after progression of first-line ICIs therapy does not show significant differences due to the type of treatment strategies.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To evaluate the efficacy and safety of rituximab (RTX) in the treatment of idiopathic membranous nephropathy (IMN), explore the influencing factors of the therapeutic effect and construct a nomogram model for predicting the therapeutic effect.Methods:A single retrospective study was conducted in IMN patients in the First Affiliated Hospital of Zhejiang University School of Medicine from January 2017 to December 2022. All patients received monotherapy with RTX and were followed up for at least 12 months. RTX regimen adopted a B-cell guided regimen to achieve 0 cells/μl of peripheral blood CD19+ B cells through multiple administrations, followed by monitoring every 2?3 months and adding doses as needed to maintain this state. The complete response rate, partial response rate, and composite response rate at 6 months, 12 months and the end of follow up were analyzed. Logistic stepwise regression and R language were applied to construct a nomogram model for efficacy prediction. The receiver operating characteristic (ROC) curve, calibration curve and Hosmer-Lemeshow test were used to internally validate the nomogram model.Results:A total of 147 IMN patients were included in the study, with age of 56 (47, 65) years, 99 (67.4%) males. There were 69 (46.9%) newly treated patients, 78 (53.1%) retreatment patients. The follow-up time was 14.4 (12.0, 15.0) months. The total RTX dose was 1 800 (1 200, 2 400) mg. The composite response rates at 6 months, 12 months and the end of the follow-up were 36.7% (54/147), 59.9% (88/147) and 63.3% (93/147), respectively. The complete remission rates at 6 months, 12 months and the end of the follow-up were 6.1% (9/147), 13.6% (20/147) and 19.7% (29/147), respectively. Logistic stepwise regression analysis showed that age ≥ 65 years ( OR=0.335, 95% CI 0.135?0.833), retreatment ( OR=0.333, 95% CI 0.144?0.771), high cholesterol ( OR=0.716, 95% CI 0.577?0.888), high serum creatinine ( OR=0.978, 95% CI 0.963?0.993) and B-cell reconstruction within 6 months ( OR=0.273, 95% CI 0.115?0.645) were independent correlated factors affecting composite remission. Based on these factors, a nomogram model for predicting the therapeutic effect of RTX in IMN patients was constructed. The ROC curve indicated that the accuracy of this model in predicting composite remission was good ( AUC=0.814, 95% CI 0.744-0.883). The calibration curve showed that the predicted composite response rate had a good fit with the actual response rate (Hosmer-Lemeshow test χ2=11.917, P=0.155). Conclusions:RTX has good efficacy and safety as a monotherapy for IMN patients. The constructed nomogram prediction model has high discrimination and accuracy to predict the efficacy of RTX treatment for IMN.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To evaluate the efficacy and safety of rituximab (RTX) in the treatment of idiopathic membranous nephropathy (IMN), explore the influencing factors of the therapeutic effect and construct a nomogram model for predicting the therapeutic effect.Methods:A single retrospective study was conducted in IMN patients in the First Affiliated Hospital of Zhejiang University School of Medicine from January 2017 to December 2022. All patients received monotherapy with RTX and were followed up for at least 12 months. RTX regimen adopted a B-cell guided regimen to achieve 0 cells/μl of peripheral blood CD19+ B cells through multiple administrations, followed by monitoring every 2?3 months and adding doses as needed to maintain this state. The complete response rate, partial response rate, and composite response rate at 6 months, 12 months and the end of follow up were analyzed. Logistic stepwise regression and R language were applied to construct a nomogram model for efficacy prediction. The receiver operating characteristic (ROC) curve, calibration curve and Hosmer-Lemeshow test were used to internally validate the nomogram model.Results:A total of 147 IMN patients were included in the study, with age of 56 (47, 65) years, 99 (67.4%) males. There were 69 (46.9%) newly treated patients, 78 (53.1%) retreatment patients. The follow-up time was 14.4 (12.0, 15.0) months. The total RTX dose was 1 800 (1 200, 2 400) mg. The composite response rates at 6 months, 12 months and the end of the follow-up were 36.7% (54/147), 59.9% (88/147) and 63.3% (93/147), respectively. The complete remission rates at 6 months, 12 months and the end of the follow-up were 6.1% (9/147), 13.6% (20/147) and 19.7% (29/147), respectively. Logistic stepwise regression analysis showed that age ≥ 65 years ( OR=0.335, 95% CI 0.135?0.833), retreatment ( OR=0.333, 95% CI 0.144?0.771), high cholesterol ( OR=0.716, 95% CI 0.577?0.888), high serum creatinine ( OR=0.978, 95% CI 0.963?0.993) and B-cell reconstruction within 6 months ( OR=0.273, 95% CI 0.115?0.645) were independent correlated factors affecting composite remission. Based on these factors, a nomogram model for predicting the therapeutic effect of RTX in IMN patients was constructed. The ROC curve indicated that the accuracy of this model in predicting composite remission was good ( AUC=0.814, 95% CI 0.744-0.883). The calibration curve showed that the predicted composite response rate had a good fit with the actual response rate (Hosmer-Lemeshow test χ2=11.917, P=0.155). Conclusions:RTX has good efficacy and safety as a monotherapy for IMN patients. The constructed nomogram prediction model has high discrimination and accuracy to predict the efficacy of RTX treatment for IMN.

Objective:To evaluate the relationship between the mechanism underlying electroacupuncture-induced reduction of postoperative cognitive dysfunction and microglial nuclear factor kappa B (NF-κB)/NOD-like receptor protein 3 (NLRP3) signaling pathway in aged mice.Methods:Sixty SPF healthy male C57BL/6 mice, aged 18 months, weighing 27-30 g, were allocated into 4 groups ( n=15 each) using a random number table method: control group (C group), operation group (O group), operation plus sham electroacupuncture group (O+ SE group) and operation plus electroacupuncture group (O+ Egroup). In O+ E group, the mice received electrical stimulation at the Baihui and Shenting acupoints for a duration of 30 min. The electroacupuncture entailed the utilization of a continuous wave with a frequency of 10 Hz, an intensity of 1 mA, and a daily application for 5 consecutive days. The mice in Y group underwent the same procedure as O+ E group, except that no electrical stimulation was administered. Laparotomy was performed on the mice following a 3% isoflurane anesthesia in O, O+ SE, and O+ E groups. The open field test was conducted in the morning of 6th day after surgery to assess the spontaneous activity and anxiety-like behavior. The novel object recognition test was subsequently performed in the afternoon of 6th day after surgery. The fear conditioning test was performed on 7th day postoperatively. The mice were sacrificed under deep anesthesia at the end of behavioral testing, and the hippocampal tissue was extracted for determination of the expression of phosphorylated NF-κB p65 (p-NF-κB p65), NLRP3, postsynaptic density protein-95 (PSD-95), and synaptic vesicle protein (SYN) (by Western blot) and the co-staining area of NLRP3 and ionized calcium-binding adapter molecule 1 (Iba1, a specific marker for microglia) (by immunofluorescence staining) and for measurement of the dendritic length and dendritic spine density of neurons in the hippocampal CA1 region (using Golgi staining). Results:No statistically significant differences were observed in terms of movement speed, distance traveled, and time of center stay during the open field test among the four groups ( P>0.05). Compared to C group, the percentage of novel object exploration and discrimination index were significantly decreased, the freezing time was prolonged, the expression of p-NF-κB p65 and NLRP3 in the hippocampal tissue was up-regulated, the co-staining area of NLRP3 and Iba1 was increased, the expression of PSD-95 and SYN was down-regulated, and the dendritic length and dendritic spine density of hippocampal neurons were decreased in O, O+ SE and O+ E groups ( P<0.05). Compared to O group, the percentage of novel object exploration and discrimination index were significantly increased, the freezing time was shortened, the expression of p-NF-κB p65 and NLRP3 in the hippocampal tissue was down-regulated, the co-staining area of NLRP3 and Iba1 was decreased, the expression of PSD-95 and SYN was up-regulated, and the dendritic length and dendritic spine density of hippocampal neurons were increased in O+ E group ( P<0.05), and no significant change was found in each parameter in O+ SE group ( P>0.05). Compared to O+ SE group, the percentage of novel object exploration and discrimination index were significantly increased, the freezing time was shortened, the expression of p-NF-κB p65 and NLRP3 in the hippocampal tissue was down-regulated, the co-staining area of NLRP3 and Iba1 was decreased, the expression of PSD-95 and SYN was up-regulated, and the dendritic length and dendritic spine density of hippocampal neurons were increased in O+ E group ( P<0.05). Conclusions:The mechanism by which electroacupuncture attenuates postoperative cognitive dysfunction is associated with inhibition of activation of NF-κB/NLRP3 signaling pathway in microglial cells and improvement in synaptic plasticity in aged mice.

Objective:To analyze the differences in clinical outcomes and toxicities between postoperative radiotherapy alone and postoperative radiochemotherapy for soft tissue sarcoma (STS), as well as the related factors affecting clinical prognosis of STS patients.Methods:Retrospective analysis of patients diagnosed with primary STS admitted to Zhejiang Cancer Hospital from May 2012 to May 2019 was performed, who received adjuvant radiotherapy after surgery, combined with or without postoperative chemotherapy. A total of 100 patients were enrolled and divided into postoperative radiotherapy group ( n=52) and postoperative radiochemotherapy group ( n=48). The median follow-up time was 65 months (24-124 months). The local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), overall survival (OS), and treatment-related toxicities were recorded in two groups. The survival rate was calculated by Kaplan-Meier analysis. Log-rank test was used for univariate analysis, and Cox model was used for multivariate analysis. Results:In multivariate analysis, the maximum tumor diameter was an independent predictor of local tumor recurrence ( HR=4.80, 95% CI=1.16-19.85, P=0.031), distant metastasis ( HR=4.67, 95% CI=1.53-14.26, P=0.007) and OS ( HR=4.10, 95% CI=1.35-12.48, P=0.013). In addition, the degree of myelosuppression in patients in postoperative radiochemotherapy was significantly higher than that in their counterparts in postoperative radiotherapy group ( P<0.001). Conclusions:In the limited number of patients, radiochemotherapy has no advantages over radiotherapy alone in distant metastasis or survival rate. Besides, it increases toxicities, but the overall tolerability is favorable. It is necessary to conduct prospective randomized studies in a large population and subgroup analysis of histological subtypes, aiming to obtain results with better reference value.

The stability of virus-like particles (VLPs) is currently the main factor affecting the quality of foot-and-mouth disease VLPs vaccines. In order to further improve the quality of the VLPs vaccine of foot-and-mouth disease (FMD), three amino acid modification sites were designed and screened through kinetic analysis software, based on the three-dimensional structure of FMDV. The three mutant recombinant plasmids were successfully prepared by the point mutation kit, transformed into Escherichia coli strain BL21 and expressed in vitro. After purification by Ni ion chromatography column, SDS-PAGE proved that the three amino acid mutations did not affect the expression of the target protein. The results of the stability study of three FMD mutant VLPs obtained by in vitro assembly show that the introduction of internal hydrophobic side chain amino acids made the morphology of VLPs more uniform (N4017W), and their stability was significantly improved compared to the other two VLPs. The internal hydrophobic force of the capsid contributes to the formation of VLPs and helps to maintain the stability of the capsid, providing new experimental ideas for improving the quality of VLPs vaccines, and helping to promote the development of VLPs vaccines.
Amino Acids ; Animals ; Capsid Proteins/genetics* ; Foot-and-Mouth Disease/prevention & control* ; Foot-and-Mouth Disease Virus/genetics* ; Kinetics ; Vaccines, Virus-Like Particle/genetics* ; Viral Vaccines/genetics*

PURPOSE: To evaluate the prognosis of nasopharyngeal carcinoma (NPC) patients who developed bone-only metastasis after primary treatment and the stratification of these patients into different risk groups based on independent prognostic factors. MATERIALS AND METHODS: Eighty NPC patients who developed bone-only metastasis after definitive radiotherapy from October 2005 to December 2010 were enrolled. All these patients received palliative treatment for bone metastasis, including chemotherapy and/or radiotherapy. Clinical features, treatment modality, and laboratory parameters were examined with univariate and multivariate analyses. RESULTS: The median follow-up time was 15.5 months (range, 2-67 months) for the whole cohort. The median overall metastatic survival (OMS) time and the 2-year estimate OMS rate were 26.5 months and 52%, respectively. Multivariate analysis indicated that patients with short metastases-free interval, multiple bone metastases sites, high serum lactic dehydrogenase levels, and treated with radiotherapy or chemotherapy alone had significantly worse outcomes. Patients were stratified into three different risk groups based on the number of adverse factors present. The OMS curves of the three groups were all significantly different (p<0.001). CONCLUSION: Severl prognostic factors were found to be associated with worse outcomes. According to the number of adverse factors present, bone-only metastasis patients can be stratified into three risk groups with significantly different prognoses. Such grouping may help in improving the design of clinical trials and in guiding individualized treatment for NPC patients with bone-only metastasis.
Adolescent ; Adult ; Aged ; Bone Neoplasms/mortality/*secondary/therapy ; Combined Modality Therapy ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Nasopharyngeal Neoplasms/mortality/*pathology/therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Survival Rate ; Young Adult

Background and purpose:Currently, subjective questionaire is the most frequently used methods to evaluate swallowing dysfunctions after radiotherapy in nasopharyngeal carcinoma patients, while lacking of effective objective examinations. This study aimed to explore effective methods to evaluate swallowing dysfunctions after radiotherapy in nasopharyngeal carcinoma patients, and gain knowledge of the incidence and severity of swallowing dysfunctions. Methods: From Oct. 2013 to Dec. 2013, 128 consecutive outpatients with previously treated nasopharyngeal carcinoma received esophageal barium lfuoroscopy examination at there regularly follow-ups to evaluate swallowing function. Among these patients, 89 were primary treated with intensity modulated radiation therapy (IMRT) and 39 with conventional radiotherapy (CRT). In this study, each patient received esophageal barium lfuoroscopy examination for 3 times with thin, thick and pasty barium and were dynamically observed using X-ray fluoroscopy from front and lateral direction. Swallowing dysfunctions were defined as follows:①The bolus could not be swallowed and blocked in the mouth;②The dilute barium diverted to the glottis or trachea;③Residual barium delayed in the pyriform sinus and vallecula;④The movement of the hyoid bone or epiglottis were restricted;⑤Bolus prolong through the pharynx;⑥Barium slowed down when went though the esophageal entrance. Results:Of the 128 patients, incidence of dysphagia was 60.2%for the entire cohort, 52.8%for IMRT group and 76.9%for CRT group. Incidence of dysphagia for IMRT group was signiifcantly lower than CRT group (P=0.018). Dysphagia incidence within 1 year, 1 to 2 years and more than 2 years after RT were 63.1%, 33.3%and 69.0%, respectively (P=0.019). Conclusion:There was a high incidence of swallowing dysfunction for the nasopharyngeal carcinoma patients treated with radiotherapy and dysphagia incidence decreased when treated with IMRT. Esophageal barium lfuoroscopy examination is objective method to evaluate the incidence and severity of the swallowing dysfunction.