Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study.

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.

Optimizing the indication of initial radioiodine oncolytic treatment for metastatic differentiated thyroid cancer by diagnostic 131I scan.

AIM: As a classic theranostic radiopharmaceutical, radioiodine (131I) has been utilized in the management of differentiated thyroid cancer (DTC) for more than 8 decades, and the refinement of its clinical practice has been raised recently. This study was conducted to evaluate the efficiency of a diagnostic (Dx) 131I scan in optimizing the indication of initial radioiodine oncolytic treatment (ROT) for metastatic DTC by predicting therapeutic outcomes. RESULTS: A total of 100 patients (Dx positive, n=29; Dx negative, n=71) were eligible for patient-based analysis. The matching rate was 83.0% between the Dx and the post-therapeutic scans (kappa = 0.648, P<0.001). The biochemical remission rate and structural shrinkage rate induced by the initial ROT in the Dx-positive group were, respectively, greater than those in the Dx-negative group (83.3% vs. 17.4%, P<0.001; 37.9% vs. 4.2%, P<0.001). Notably, the predictive values of positive Dx scans for ROT responsiveness and negative Dx scans for ROT nonresponsiveness reached up to 89.7% and 84.5%, respectively. CONCLUSION: This Dx scan approach seems viable in characterizing the 131I-avidity of metastatic DTC and plays a pivotal role in optimizing the indication of initial ROT for metastatic DTC.

[The effect of ubiquitin ligase Cullin3 on the proliferation, migration and invasion of triple-negative breast cancer cells and exploration of its mechanism].

Objective: To investigate the effects of ubiquitin ligase Cullin3 (CUL3) on the proliferation, migration and invasion ability of triple-negative breast cancer (TNBC) cells and its mechanism of action. Methods: Bioinformatics-based methods were used to obtain CUL3 gene and protein expression data in TNBC tissues, and to assess the expression of CUL3 in tumour tissues of TNBC patients (n=160) and in normal breast tissues (n=572), and its relationship with clinical prognosis. The effects of overexpression of CUL3 on the proliferation, migration and invasion ability of TNBC cells in vitro were detected by CCK8 cell proliferation assay, scratch assay and transwell assay; proteins that might interact with CUL3 were screened by immunoprecipitation combined with mass spectrometry analysis, and the substrate protein regulated by CUL3 was identified as Glutathione S-Transferase Pi 1 (GSTP1); the effects of overexpression of GSTP1 on the migration and invasion ability of TNBC cells were detected by scratch assay and Transwell assay, and it was explored whether overexpression of CUL3 could reverse the effects of GSTP1 on the migration and invasion ability of cells; and the effects of overexpression of GSTP1 on the migration and invasion ability of cells were detected by Western blot and IP (Immunoprecipitation) to detect the effect of CUL3 on the ubiquitination modification of GSTP1 protein, and to verify the molecular mechanism by which CUL3 regulates the expression of GSTP1 to affect TNBC migration and invasion. Results: CUL3 expression was significantly higher in TNBC (P<0.000 1), and high CUL3 expression was closely associated with poor prognosis of TNBC patients (OS, P=0.018; RFS, P=0.008); overexpression of CUL3 significantly increased the proliferation of TNBC cells (F=11.97, P=0.002 for the 231-cell group, F=51.92, P<0.001 for the 468-cell group), migration [74.7±4.0 and 128.0±6.1 perforating cells in the overexpression groups of 231 and 468 cell lines, compared with 21.0±2.7 and 70.0±6.6 in the blank control (NC) group, and the t-values of 231 and 468 cell groups were-19.24 and-11.23, with P-values<0.001] and invasive ability (48 h cell proliferation rates were 56.6%±4.4% and 51.6%±3.7% in the 231 and 468 cell line overexpression groups, compared with 40.5%±2.9% and 32.9%±4.8% in the NC group, respectively, t=-5.26, P=0.006 3 in the 231 cell group; t=-5.38 in the 468 cell group, P=0.005 8); GSTP1 expression was reduced in TNBC, and up-regulation of GSTP1 inhibited TNBC cell migration (the number of membrane-penetrating cells in the overexpression groups of 231 and 468 cell lines were 16.3±6.5 and 33.0±6.2, respectively, compared with 34.3±2.5 and 77.3±5.0 in the NC group, and t=5.44 in the 231 cell group, P=0.006; 468 cell group t=7.20, P=0.002) and invasion (48 h cell proliferation rates of 49.6%±1.7% and 36.2%±1.4% in the 231 and 468 cell line overexpression groups, compared to 59.4%±4.7% and 53.0%±1.7% in the NC group, t=3.42, P=0.027 in the 231 cell group; 468 cell group t=13.18, P<0.001), whereas up-regulation of CUL3 reversed the effects of GSTP1 on cell migration (37.0±1.0 and 67.0±5.3 membrane-penetrating cells in the overexpression groups of 231 and 468 cell lines, respectively, 231 cell group t=-3.97, P=0.017; 468 cell group t=-6.12, P=0.004), and invasion (48 h cell proliferation rates of 71.9%±3.6% and 59.4%±2.1% in the 231 and 468 cell line overexpression groups, respectively, with t-values of -9.61 and -16.01 in the 231 and 468 cell groups, respectively, P-values<0.001) inhibitory effects; and CUL3, by increasing GSTP1 ubiquitylation modification, promotes ubiquitin-proteasome system to degrade GSTP1 protein, thereby reducing the stability of GSTP1 protein. Conclusion: Overexpression of CUL3 promotes TNBC development by promoting GSTP1 ubiquitination degradation inducing cell migration and invasion.

[Epidemiological characteristics of a local cluster epidemic caused by the BA.2 evolutionary branch of Omicron variant].

Descriptive epidemiological methods were used to analyze the epidemiological characteristics of the local cluster of COVID-19 in the logistic park of Yuhang District in Hangzhou in March 2022. The cluster epidemic was detected by a case who actively visited the fever clinic. The epidemic lasted for 8 days, and a total of 58 cases (53 workers, 2 students, 1 farmer, 1 teacher and 1 unemployed) were found, including 40 males and 18 females. The age was (33.29±12.22) years. There cases were mainly in Yuhang District (48 cases, 82.77%) and Shangcheng District (7 cases, 12.07%) of Hangzhou. The real-time regeneration number peaked at 2.31 on March 10th and decreased to 0.37 on March 15th. The sequencing result of the indicated case was 100% homologous with the sequence uploaded from South Korea on March 4th, 2022.

[Accelerating the construction of digital and intelligentialized pathology and the prospects].

With the continuous development of informatization, digitalization and artificial intelligence technology, the working mode of the pathology department has gradually changed from the traditional manual check, paper circulation and physical carrier storage to the informatization process and digital storage. The traditional pathology discipline has ushered in unprecedented opportunities and challenges. Digital pathology department also emerge as the times require. Simultaneously, with the full integration of artificial intelligence technology in pathology department, the concept of "department of digital and intelligentialized pathology" was proposed. Based on information and digital technology, the digital intelligent pathology department integrates intelligent management system, optimizes the previous cumbersome management and workflow of the pathology department, develops advanced technologies such as intelligent material extraction, unmanned organization processing, artificial intelligence quality control, artificial intelligence diagnosis, and promotes the intelligent construction of the pathology department.

[Clinical research progress in non-invasive positive pressure ventilation in 2023].

Non-invasive positive pressure ventilation (NPPV) is a widely used method of providing respiratory support in a variety of clinical settings, including emergency departments, general wards, and intensive care units. The relevant research articles on NPPV published between 1st October 2022 and 30th September 2023 were retrieved from Medline and reviewed. In the management of acute respiratory failure (ARF) associated with COVID-19, studies have highlighted the significant influence of regional economic status on the choice of respiratory support strategies. It has been observed that NPPV is more suitable for patients with mild to moderate acute respiratory distress syndrome (ARDS) than for those with severe ARDS, as the latter group has an increased risk of delayed intubation. In addition, patients with severe dyspnea tended to benefit more from NPPV compared with high flow nasal cannula (HFNC) and conventional oxygen therapy, with a reduced risk of self-induced lung injury. For non-COVID-19-related ARF, research shows no significant differences in mortality and intubation rates between HFNC and NPPV in patients with hypercapnic ARF. The updated HACOR score and ROX score have been validated to have a high predictive value for clinical outcomes in patients receiving NPPV for hypoxemic ARF. With regard to weaning from invasive mechanical ventilation, immediate application of NPPV after extubation showed a lower mortality rate compared to continued invasive weaning. Moreover, NPPV with active humidification significantly decreased the reintubation rate within 7 days after extubation compared with HFNC. The choice between using NPPV and HFNC should be based on the specific etiology of the patient's condition. The potential effect of noninvasive high-frequency oscillatory ventilation on CO2 clearance was also investigated.

[Comparison of the efficacy of different surgical strategies in the treatment of patients with initially resectable gastric cancer liver metastases].

Objective: To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM). Methods: This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging (M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results: (1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95%CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference (P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options (HR=1.98, 95%CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients' prognosis (HR=2.01, 95%CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors (HR=2.84, 95%CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver (HR=2.06, 95%CI 1.19 to 3.57, P=0.010). Conclusions: In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

[Exploration of detection methods for free silica with different crystal forms in dust].

Objective: To investigate the differences and applicability of free silica detection methods of different crystal forms in dust, and to provide a basis for the selection of various methods. Methods: From December 2021 to June 2022, dust samples from 20 enterprises in different industries in 18 cities in Henan Province were randomly selected as the investigation objects. X-ray diffraction (XRD) method was used to analyze the samples and classify the samples. Based on GBZ/T 192.4-2007 "Determination of Dust in the Air of Workplace-Part 4: Content of Free Silica in Dust", pyrophosphate method and infrared spectrophotometry were used for quantitative determination. The measured results were analyzed by paired sample t test to evaluate the advantages and disadvantages of the two methods and their applicable scope. Results: The XRD results of 20 dust samples could be divided into α, ß, γ crystal types and the mixed type of α and γ. There was no significant difference between pyrophosphate method and infrared spectrophotometry (P=0.180). The pyrophosphate method results of ß, γ and α, γ mixed crystalline free silica were significantly higher than those of infrared spectrophotometry, and the difference was statistically significant (P<0.001) . Conclusion: Pyrophosphate method and infrared spectrophotometry are suitable for α-type free silica, while pyrophosphate method is suitable for ß, γ and α, γ mixed crystalline free silica.

Uniaxial cyclic stretch enhances osteogenic differentiation of OPLL-derived primary cells via YAP-Wnt/ß-catenin axis.

The pathogenesis of posterior longitudinal ligament ossification (OPLL) remains inadequately understood. Mechanical stimulation is one of the important pathogenic factors in OPLL. As one of the mechanical stimulation transduction signals, the yes-associated protein (YAP) interacts with the Wnt/ß-catenin signalling pathway, which plays an important role in osteogenic differentiation. This study aimed to demonstrate the role of YAP-Wnt/ß-catenin axis in cell differentiation induced by mechanical stress. Primary cells extracted from posterior longitudinal ligament tissues from OPLL or non-OPLL patients were subjected to sinusoidal uniaxial cyclic stretch (5 %, 0.5 Hz, 3 d). The expression of runt-related transcription factor 2, collagen I, osterix, osteocalcin and alkaline phosphatase were compared between the static and the experimental groups. In addition, the cytoskeleton was detected using phalloidin staining while YAP phosphorylation states and nuclear location were identified using immunofluorescence. The results showed that mechanical stretching loading increased the expression of osteogenic genes and proteins in the OPLL group, while it had no significant effect on the control group. When OPLL cells were stretched, YAP exhibited an obvious nuclear translocation and the Wnt/ß-catenin pathway was activated. Knocking down YAP or ß-catenin could weaken the impact upon osteogenic differentiation induced by mechanical stimulation. YAP-mediated mechanical stimulation promoted osteogenic differentiation of OPLL cells through Wnt/ß-catenin pathway and this progress was independent of the Hippo pathway.

Association of non-alcoholic fatty liver disease with total testosterone in non-overweight/obese men with type 2 diabetes mellitus.

PURPOSE: Non-alcoholic fatty liver disease (NAFLD) is considered as both a vital risk factor and a consequence of type 2 diabetes mellitus (T2DM). Low total testosterone (TT) is common in men with T2DM, contributing to increased risks of metabolic diseases. This study aimed to investigate the association between TT levels and the prevalence of NAFLD in men with T2DM. METHODS: In this cross-sectional study, 1005 men with T2DM were enrolled in National Metabolic Management Center (MMC) of First Affiliated Hospital of Wenzhou Medical University between January 2017 and August 2021. NAFLD was diagnosed using ultrasound as described by the Chinese Liver Disease Association. Overweight/obesity was defined as body mass index (BMI) ≥ 25 kg/m2 according to WHO BMI classifications. RESULTS: Individuals without NAFLD had higher serum TT levels than those with NAFLD. After adjustments for potential confounding factors, the top tertile was significantly associated with lower prevalence of NAFLD compared with the bottom tertile of TT level [odds ratio (OR) 0.303, 95% confidence interval (CI) 0.281-0.713; P < 0.001]. The association between TT with NAFLD in individuals with normal weight (OR 0.175, 95% CI 0.098-0.315; P < 0.001) was stronger than in individuals with overweight/obesity (OR 0.509, 95% CI 0.267-0.971; P = 0.040). There was a significant interaction of TT with overweight/obesity (P for interaction = 0.018 for NAFLD). CONCLUSION: Higher serum TT was significantly associated with a lower prevalence of NAFLD in men with T2DM. We found that the relationship of TT and NAFLD was stronger in individuals with non-overweight/obesity.

Postoperative pulmonary complications in older patients undergoing elective surgery with a supraglottic airway device or tracheal intubation.

The two most commonly used airway management techniques during general anaesthesia are supraglottic airway devices and tracheal tubes. In older patients undergoing elective non-cardiothoracic surgery under general anaesthesia with positive pressure ventilation, we hypothesised that a composite measure of in-hospital postoperative pulmonary complications would be less frequent when a supraglottic airway device was used compared with a tracheal tube. We studied patients aged ≥ 70 years in 17 clinical centres. Patients were allocated randomly to airway management with a supraglottic airway device or a tracheal tube. Between August 2016 and April 2020, 2900 patients were studied, of whom 2751 were included in the primary analysis (1387 with supraglottic airway device and 1364 with a tracheal tube). Pre-operatively, 2431 (88.4%) patients were estimated to have a postoperative pulmonary complication risk index of 1-2. Postoperative pulmonary complications, mostly coughing, occurred in 270 of 1387 patients (19.5%) allocated to a supraglottic airway device and 342 of 1364 patients (25.1%) assigned to a tracheal tube (absolute difference -5.6% (95%CI -8.7 to -2.5), risk ratio 0.78 (95%CI 0.67-0.89); p < 0.001). Among otherwise healthy older patients undergoing elective surgery under general anaesthesia with intra-operative positive pressure ventilation of their lungs, there were fewer postoperative pulmonary complications when the airway was managed with a supraglottic airway device compared with a tracheal tube.

Effects of lysolecithins on performance, egg quality, blood profiles and liver histopathology in late-phase laying hens.

1. This study investigated the effects of lysolecithins (LL) on performance, egg quality, blood profiles, relative organ weight and liver histopathology in laying hens.2. A total of 480 healthy 65-week-old Lohmann laying hens were randomly allocated into four treatments in a 2 × 2 factorial arrangement design with two levels of energy (AMEn, 11.08 MJ/kg and 12.94 MJ/kg) and two levels of LL (0 and 0.05%).3. Birds fed high energy diets had lower (P < 0.05) average daily intake and feed conversion rate during weeks 0-4, 5-8 and 0-8, but higher (P < 0.05) average egg weight (AEW) during trial weeks 0-4. There was an interaction in (P < 0.05) AEW during trial weeks 0-14 and 0-8 for energy and LL. The high energy diets increased yolk colour at the end of weeks 2 and 4, while addition of LL increased albumen height at the end of week 2. There was an interaction (P < 0.05) in yolk colour between energy and LL at the end of week 2. There was an interaction (P < 0.05) in serum superoxide dismutase and LDL-C throughout the experiment.4. The high energy diets increased (P < 0.05) the relative weight of abdominal fat compared with low energy diets. The high energy diets increased (P < 0.05) liver ether extract content and liver pathological injury score compared with low energy diets at the end of week 8, while the addition of LL decreased (P < 0.05) liver pathological injury score.5. The supplementation of LL in high energy diets could alleviate some negative effects on liver injury in late laying hens.

[Comparison of air filled anterior approach of sternocleidomastoid muscle and space of sternocleidomastoid muscle for treatment of thyroid papillary carcinoma under axillary endoscope].

Objective: To evaluate the application of the anterior sternocleidomastoid muscle approach in transaxillary endoscopic thyroidectomy. Methods: The clinical data of 180 patients undergoing transaxillary endoscopic thyroidectomy for thyroid cancer in the Department of General Surgery of the Affiliated Hospital of Nantong University from March 2021 to March 2023 were retrospectively analyzed. There were 27 males and 153 females, aged (37.5±8.0)years, range: 27 to 52 years. The anterior approach of sternocleidomastoid muscle was used in 100 cases, and the interspace approach of sternocleidomastoid muscle was used in 80 cases between the two groups. The postoperative efficacy, complications and satisfaction of the two groups were compared. Results: There was no difference between the two groups in the number of lymph node dissection (using nano carbon tracer), hospital stay, and postoperative complications (transient decrease in parathyroid function, laryngeal nerve injury) (P>0.05). The anterior approach of sternocleidomastoid muscle had shorter cavity building time[(17.8±2.9)vs(20.1±3.7) min], less drainage volume the second day after operation[(18.7±5.2)vs(23.5±6.3) ml], and less discomfort in the neck (P<0.05). Conclusion: The anterior approach of sternocleidomastoid muscle under complete transaxillary endoscopy has certain advantages in the time of cavity construction, the drainage volume the second day after the operation, and the reduction of cervical discomfort after the operation. The operation is safe and reliable.

[Clinical update in non-invasive positive pressure ventilation for respiratory failure in 2022].

In this article, we searched the research literatures related to clinical investigation of non-invasive positive pressure ventilation (NPPV) in acute respiratory failure(ARF)/chronic respiratory failure(CRF) between 1st October 2021 and 30th September 2022 through Medline, and reviewed the important advances. Three prospective randomized controlled studies related to the efficacy and safety of NPPV and/or high-flow nasal cannula oxygen therapy (HFNC) on patients with COVID-19 with ARF were reported, showing that NPPV (including continuous positive airway pressure and bilevel positive airway pressure) was able to reduce the intubation rate, but the efficacy of HFNC was contradictory. In addition, progress has been made in outcome prediction models for ARF treated with NPPV, NPPV-related cardiac arrest, and the impact of human-machine interface on NPPV treatment outcomes. The effects of NPPV as preoxygenation method before intubation was reported to be able to reduce severe desaturation during intubation, especially in obese population. The use of NPPV in extubated patients resulting in reduced reintubation rate was also studied. With regard to long-term home application of NPPV, five indicators of successful initiation were proposed, but the success rate was low in clinical practice. Some reports showed that psychological support could improve the adherence to NPPV. The results of these studies contributed to the rational selection and optimal application of NPPV in clinical practice.

The association between sociodemographic status and COPD and asthma mortality, DALY and YLD in southern China, 2005-2015.

BACKGROUND: Little is known about the disease burden of chronic obstructive pulmonary disease (COPD) and asthma in southern China. METHOD: We calculated the mortality, disability-adjusted life-years (DALY), years lived with disability (YLD) and years of life lost (YLL) for COPD and asthma in Guangdong province between 2005 and 2015. We examined the significance of trends of mortality, DALY, YLD and YLL rates for COPD and asthma with the Cochran-Armitage trend test. We also analyzed their association with sociodemographic factors by negative binomial models. RESULT: The age-standardized mortality, DALY, YLD and YLL rates of COPD and asthma decreased significantly in Guangdong, except for an increase of 11.3% in the age-standardized YLD rate of COPD between 2005 and 2015 (all P < 0.05). Compared with females, the respective adjusted mortality rate ratio of males was 2.11 for COPD, and 0.74 for asthma. Compared with other regions, the richest region, Pearl River Delta, had the lowest mortality, DALY, YLD and YLL rate ratios (RR) of COPD and asthma (all P < 0.05). COPD and asthma mortality, DALY, YLD and YLL rates increased substantially with age. Specifically, when compared with the 25-49 years age group, the respective adjusted DALY RR of asthma was 1.91, 2.02 and 22.21 for 0-24, 50-74 and ≥75 years age group; the respective adjusted YLD RR was 2.27, 1.33 and 7.17 for 0-24, 50-74 and ≥75 years age group. CONCLUSIONS: Disease burden of COPD and asthma decreased in Guangdong province in southern China between 2005 and 2015; however, a disproportionate burden of COPD and asthma in terms of age, sex and regions was observed. The relatively high disease burden and high rate of impaired public health from the less developed regions highlight the need for focused policy making to address the problem.

[Novel MFN2, BSCL2 and LRSAM1 variants in a cohort of Chinese patients with Charcot-Marie-Tooth disease].

Objective: Charcot-Marie-Tooth disease (CMT) comprises a group of clinically and genetically heterogeneous inherited neuropathies with an estimated prevalence of 1 in 2500. This study aimed to analyze the clinical and mutational characteristics of Chinese CMT patients with MFN2, BSCL2 and LRSAM1 variants. Methods: In this study, genetic analysis was performed in 206 Chinese patients at Chinese PLA General Hospital from December 2012 to March 2020 with clinical diagnosis of CMT, and reported variants of MFN2, BSCL2 and LRSAM1 related to CMT2. Results: We reported ten MFN2 mutations in ten unrelated patients (7 male, 3 female), two of whom had positive family history. Three novel mutations were detected including c.475-2A>G (splicing); c.687dupA (p.E230Rfs*16) and c.558dupT (p.S186fs). We reported three BSCL2 mutations of four unrelated patients, including c.461C>G (p.S154W), c.461C>T(p.S154L), and novel variants of c.1309G>C (p.A437P) and c.845C>T (p.A282V). Furthermore, two novel variants of LRSAM1, including c.1930G>T (p.G644C) and c.1178T>A (p.L393Q) were detected in two unrelated patients. Conclusion: Mutational spectrum of MFN2-, BSCL2-and LRSAM1-related CMT disease is expanded with the identification of novel variants in Chinese patients.

[Clinical features of immune checkpoint inhibitor-related myositis in patients with urological cancer].

OBJECTIVE: Immune checkpoint inhibitors (ICI) have significantly improved the treatment efficacy of a variety of malignant tumors. However, patients may experience a series of special side effects during treatments with ICI. Immune-related myositis after ICI treatment is characterized by autoimmune rheumatic and musculoskeletal damage, which is relatively rare. To analyze the clinical characteristics and outcomes of ICI-associated myositis in urological tumors, we summarized the clinical manifestations, electrophysiological and pathological characteristics, treatments and outcomes in 8 patients. METHODS: The clinical data of the 8 patients with immune-related myositis after ICI treatment for urological tumors treated in the Department of Urology, Peking University First Hospital from March 2018 to March 2022 were retrospectively analyzed for demographic characteristics, drug regimen, clinical symptoms, laboratory indices, electromyography examination, pathological manifestations and outcomes. RESULTS: The eight patients included 2 females and 6 males with a median age of 68 years, all treated with ICI for urological neoplasms, including 2 upper tract urothelial carcinoma (UTUC), 3 renal cell carcinoma (RCC), and 3 bladder cancer (BCa). The median time between the first ICI treatment and the detection of immune-related myositis was 39.5 days, and the median duration of treatment was 2 sessions. The main symptoms were muscle pain and weakness, 5 cases with ptosis, 3 cases with secondary rhabdomyolysis, 5 cases with myocarditis, 1 case with myasthenia gravis, and 1 case with enterocolitis. Among them, patients with immune-related myocarditis had a shorter interval from the first anti-programmed cell death protein-1 (PD-1) therapy to the onset of immune-related myositis (P=0.042) compared with patients without myocarditis. The 8 patients had significant elevation of transaminases and muscle enzyme profile indexes, and 5 patients showed positive auto-antibodies. 3 patients had perfected muscle biopsies and showed typical skeletal muscle inflammatory myopathy-like pathological changes with CD3+, CD4+, CD8+, CD20+ lymphocytes and CD68+ macrophage infiltration. After the diagnosis of immune-related myositis, all the 8 patients immediately discontinued ICI therapy and improved after intravenous administration of methylprednisolone alone or in combination with gamma-globulin. CONCLUSION: Immune-related myositis after ICI treatment is an immune-related adverse reactions (irAEs) with unique clinical and pathological features, commonly combined with cardiovascular adverse reactions. Immediate discontinuation of ICI and initiation of glucocorticoid therapy may improve the patient's condition in a timely manner.

[The efficacy and prognostic factors of immunotherapy in advanced non-small cell lung cancer patients with different driver gene mutations].

Objective: To explore the efficacy and prognostic factors of immunotherapy in advanced non-small cell lung cancer (NSCLC) patients with different driver gene mutations. Methods: Medical records of advanced NSCLC patients who harbored driver gene mutations (EGFR, KRAS, ALK and etc.) and received PD-1 inhibitors in Henan Cancer Hospital from April 2016 to May 2021 were collected. Treatment patterns, progression free survival (PFS), overall survival (OS) and prognostic factors of patients with driver gene mutations were estimated. Results: A total of 120 patients were included. There were 70 males and 50 females, with a median age [M(Q1,Q3)] of 57 (50, 65) years. Of these, 52 patients harbored KRAS mutations, 42 patients harbored EGFR mutations, 16 patients harbored ERBB2 mutations, 5 patients harbored MET mutations or amplifications, 5 patients harbored ROS-1 mutations, 2 patients harbored BRAF mutations, and the last 2 patients harbored ALK and RET mutations, respectively. The PFS and OS [M (95%CI)] were 6.4 (5.1-7.8) and 31.2 (22.0-40.3) months in 120 participated patients. Patients with KRAS mutations showed the greatest survival benefit from Immune checkpoint inhibitors (ICIs) with the PFS of 9.7 (4.8-14.6) months and OS of 31.2 (19.4-50.6) months. They mostly received the first-line (34.6%, 18/52) and second-line (38.5%, 20/52) ICIs. The PFS and OS of EGFR mutant patients were 3.9 (1.8-6.1) months and 18.0 (12.1-23.8) months, respectively. They tended to receive ICIs after resistance to EGFR-tyrosine kinase inhibitors (TKIs), and the proportion of second-, third-, fourth or further-line drugs was 38.1% (16/42), 11.9% (5/42), and 47.6% (20/42), respectively. PD-L1 expression level (negative vs ≥50% positive: HR=3.710, 95%CI: 1.372-10.031, P=0.010; 1%-49% positive vs ≥50% positive: HR=2.738, 95%CI: 0.841-8.912, P=0.094), age (every additional year: HR=0.957, 95%CI: 0.933-0.982, P=0.001) and different driver mutations status (EGFR vs KRAS: HR=2.676, 95%CI: 1.317-5.436, P=0.006; ERBB2 vs KRAS: HR=3.411, 95%CI: 1.493-7.792, P=0.004; other mutations vs KRAS: HR=0.727, 95%CI: 0.322-1.643, P=0.444) were prognostic factors for PFS. While PD-L1 expression level (negative vs ≥50% positive: HR=2.305, 95%CI: 0.748-7.103, P=0.146; 1%-49% positive vs ≥50% positive: HR=1.286, 95%CI: 0.337-4.913, P=0.713), and treatment lines of ICIs (first-line vs ≥ third-line: HR=0.322, 95%CI: 0.114-0.914, P=0.033; second-line vs ≥ third-line: HR=0.375, 95%CI: 0.178-0.789, P=0.010) were prognostic factors for OS. Conclusions: KRAS mutant NSCLC patients mostly receive ICIs at the front line, and have best survival benefits from immunotherapy. While EGFR mutant NSCLC patients tend to receive ICIs at the back line, and obtain reasonable survival benefits. PD-L1 expression level, age, and different driver mutations status are prognostic factors for PFS, and PD-L1 expression level and treatment lines of ICIs are prognostic factors for OS.

[Effect of reducing-opioids consumption on postoperative delirium incidence in elderly patients after gastric cancer surgery].

Objective: To evaluate the effect of reducing-opioids on postoperative delirium (POD) incidence in elderly patients with gastric cancer surgery. Methods: From July 2016 to September 2021, 130 elderly patients undergoing scheduled gastric cancer surgery in Zhejiang Cancer Hospital were selected and divided into conventional opioid general anesthesia group (group A) and reducing-opioids general anesthesia group (group B) according to random number table. Postoperative analgesic pump formula: group A: 0.2% ropivacaine and 1 µg/ml sufentanil solution; Group B: 0.2% ropivacaine solution. POD assessment was performed once daily between 8 am and 8 pm for 3 days after surgery. The primary outcome measures were POD incidence 3 days after surgery, and the secondary outcome measures included anaesthesia related adverse events 3 days after surgery, such as nausea and vomiting, postoperative fever and fatigue. Results: Among the 130 patients, 7 patients were excluded because they did not comply with the POD test after operation. Finally, 123 elderly patients completed the study. There were 59 cases in group A, aged (73±5) years, including 45 males, and 64 cases in group B, aged (71±6) years, including 56 males. The incidence of total POD 3 days after surgery in group A and B was 30.5% (18/59) and 18.8% (12/64), respectively, with no statistical significance (P>0.05). However, POD incidence at 48 and 72 h after operation in group A [27.1% (16/59) and 16.9% (10/59)] was higher than that in group B [10.9% (8/64) and 4.7% (3/64), both P<0.05]. The incidence of nausea and vomiting in group A was higher than that in group B [15.3% (9/59) vs 1.6% (1/64), P<0.05]. Conclusion: Reducing-opioids consumption have no effect on the incidence of total POD 3 d after gastric cancer surgery in elderly patients, but can reduce the risk of POD 48-72 h after surgery.

[Clinical features and prognostic factors of severe hemophagocytic syndrome in children].

Objective: To explore the clinical characteristics, prognostic risk factors and effective treatment of severe hemophagocytic syndrome (HPS) in children, so as to provide reference for the clinical diagnosis and treatment of the disease. Methods: The clinical data of 83 children with severe HPS admitted in Affiliated Hospital of Zunyi Medical University from January 2014 to April 2021 were collected, and their clinical characteristics, prognosis and prognostic risk factors were analyzed. The children were divided into central nervous system (CNS) dysfunction group and non-CNS dysfunction group according to whether they were accompanied with CNS dysfunction, and were divided into blood purification group and non-blood purification group according to whether they received blood purification, then the survival differences were compared. Results: Among the 83 children, there were 43 males and 40 females, aged[M(Q1,Q3)] 36(15,27)months. A total of 51 children were induced by infection, among which 41 children (80.4%) were infected with EB virus. All the children were accompanied by multiple organ dysfunction (MODS), and dysfunction of the blood system (72.3%), liver (71.1%), respiratory system (53.0%) and CNS (37.3%) were common. By the end of follow-up, 40 cases (48.2%) survived, 38 cases (45.8%) died, and 5 cases (6.0%) were lost to follow-up. CNS dysfunction was a risk factor (HR=3.358, 95%CI: 1.445-7.803, P=0.005) and blood purification was a protective factor (HR=0.362, 95%CI: 0.179-0.730, P=0.005) affecting the prognosis of children. The mortality of CNS dysfunction group was statistically higher than that of non-CNS dysfunction group (74.2% vs 28.8%) (P<0.001); The mortality of blood purification group was statistically lower than that of non-blood purification group (31.0% vs 61.0%) (P=0.010). Conclusions: Severe HPS in children was dangerous and had a poor overall prognosis. CNS dysfunction was a risk factor for death. Blood purification could significantly improve the prognosis and improve the survival rate of children.