Background Staff in tertiary hospitals are a high-risk group for occupational burnout. Timely identification and precise intervention are crucial for improving healthcare service quality. However, comparative studies on perceived stress and occupational burnout among hospital staff in different positions are lacking. Objective To describe the status of perceived stress and occupational burnout among hospital staff in different positions and compare the differences, explore the relationship between perceived stress and occupational burnout, and identify the influencing factors of occupational burnout. Methods In May 2022, 1526 hospital staff members were selected by convenience sampling from six tertiary hospitals in Guangzhou. Data were collected using a general information questionnaire, the Chinese Perceived Stress Scale (CPSS), and the Maslach Burnout Inventory-Human Services Survey (MBI-HSS) to assess demographic characteristics, perceived stress, and occupational burnout. Chi-square test, one-way ANOVA, and Kruskal-Wallis H test were used to compare differences in perceived stress and occupational burnout among staff in different positions. Pearson correlation analysis was used to explore possible correlation between perceived stress and occupational burnout. Multiple linear regression was conducted to identify influencing factors of occupational burnout. Results A total of 1388 valid questionnaires were collected, with an effective response rate of 90.96%. Among them, 437 nurses (57.0%), 273 physicians (58.6%), 24 pharmacists (57.1%), and 62 administrators (54.9%) reported positive perceived health risk stress (P=0.892). Additionally, 392 nurses (51.1%), 213 physicians (45.7%), 19 pharmacists (45.2%), and 53 administrators (46.9%) reported positive occupational burnout (P=0.005). Perceived stress was positively correlated with occupational burnout among nurses, physicians, pharmacists, and administrators (r=0.5973, 0.5687, 0.5464, and 0.5276, respectively; P＜0.01). The multiple linear regression identified perceived stress (b=1.4587, P＜0.001), job satisfaction (b=−7.4195, P＜0.001), self-rated health (b=−2.0428, P＜0.001), working years (b=−0.1135, P=0.016), and being a nurse (compared with an administrators) (b=3.2435, P=0.045) as significant factors for occupational burnout (P<0.001). Conclusion Perceived health risk stress and occupational burnout are common among hospital staff, with nurses experiencing significantly higher levels of occupational burnout compared to other positions. Hospital managers should pay more attention to staff with higher perceived stress, lower job satisfaction, poorer self-rated health, and shorter working years, particularly nurses.

Therapies for tumors continue to develop,and tumor immunotherapy has emerged as an effective means of controlling tumor progression.Given the limitations of immunotherapy,only some specific patients can benefit from immunotherapy.Since the complex tumor microenvironment is highly influenced by individual variability,immunotherapy will be subjected to different degrees of immune suppression in different tumor microenvironments and thus cannot exert its full effect.In the tumor microenvironment,regulatory T(Treg)cell plays as an immunosuppressive role.Numerous Treg cells infiltrate in indifferent tumor types,resulting in immune escape of tumor tissues,which will have a negative impact on treatment and prognosis.CC chemokine receptor 8(CCR8)belongs to the CC chemokine receptor family.CCR8 is specifically expressed on Treg cell in the tumor microenvironment and expressed at low level in the surrounding normal tissues and peripheral blood thus it can be a specific marker for Treg cell.CCR8 is a potential therapeutic target and biomarker.This review summarized the research progress of CCR8 in different tumor types in recent years,so as to provide reference for subsequent research.

OBJECTIVE To assess the profiles of elements in benzo[a]pyrene(BaP)induced carci-nogenesis,and explore the joint effects of copper with cisplatin or vinorelbine on cell proliferation.METHODS Forty-four elements were measured using an inductively coupled plasma mass spectrometer in 16HBE cells and BaP malignantly transformed 16HBE(T-16HBE-C1)cells.Partial least square was used to validate the robustness of cell classification of elements.Cell viability was measured by MTT assay for copper(0,237,340,487,1000 and 1432 μmol·L-1),cisplatin(0,4.4,6.1,8.6,12.0 and 16.8 μmol·L-1),and vinorelbine(0,3.8,9.8,25.0,40.0 and 64.0 μmol·L-1)to acquire their half maximal inhibitory concentra-tion(IC50).Mixtures of copper and chemotherapeutics were prepared according to the ratio of each IC50.Their joint effects on cell viability were assessed by MTT assay and isobolographic analysis.Inhibition effect of copper(0,50,100,200,400 and 800 μmol·L-1)with IC50 of cisplatin or vinorelbine on prolifera-tion of T-16HBE-C1 cells was also assessed.RESULTS A total of 29 elements were quantified in 16HBE and T-16HBE-C1 cells,among which concentrations of copper,zinc,silver,selenium and rubidium decreased(P<0.05,P<0.01),while those of molybdenum,arsenic,lithium,germanium,strontium,nickel,lanthanum,mercury,iron,and cesium increased(P<0.05,P<0.01)in T-16HBE-C1 cells.Element concen-tration could be used to distinguish T-16HBE-C1 cells from 16HBE cells.Copper concentration-dependently inhibited proliferation of both cells,with a statistically significant lower IC50 of(613±16)μmol·L-1 in 16HBE cells than(776±15)μmol·L-1 in T-16HBE-C1 cells(P<0.01).Mixtures of copper and cisplatin(1∶69.5)or vinorelbine(1∶33.4)could inhibit cell proliferation,and copper had additive effects with cisplatin or vinorelbine.When copper concentration was higher than 400 μmol·L-1,copper combined with IC50 of cisplatin or vinorelbine inhibited cell proliferation of T-16HBE-C1 cells compared with IC50 of cisplatin(11.2 μmol·L-1)or vinorelbine(23.2 μmol·L-1)alone.CONCLUSION Element profiles and correlations can change significantly after 16HBE cells are malignantly transformed by BaP.Copper could inhibit the proliferation of T-16HBE-C1 cells and have additive effects with cisplatin or vinorelbine in higher concentration.

Purpose/Significance To solve the problem that regional clinical research data are difficult to integrate efficiently,and to promote"Chinese evidence"and"Chinese protocol"in the global clinical research community.Method/Process Based on the standard-ization theory,the data standardization system is proposed,and the construction and application methods of the regional clinical research data platform are explored with the integration of multi-center clinical research data as the starting point.Result/Conclusion The theo-retical framework of the regional clinical research data platform has been preliminarily established,and the clinical research capabilities of tertiary hospitals in Shanghai have been significantly improved.

Background::Although the treatment of peripheral T-cell lymphoma (PTCL) has undergone advancements during the past several years, the response rate and long-term effects with respect to patients with PTCL remain unsatisfactory—particularly for relapsed or refractory (R/R) patients. This phase II trial was designed to explore the efficacy and safety of an all-oral regimen of chidamide plus prednisone, cyclophosphamide, and thalidomide (CPCT) for R/R PTCL patients who could not tolerate the standard chemotherapy for a variety of reasons.Methods::We conducted a multicenter phase II clinical trial in which we combined chidamide (30 mg twice weekly) with prednisone (20 mg daily after breakfast), cyclophosphamide (50 mg daily after lunch), and thalidomide (100 mg daily at bedtime) (the CPCT regimen) for a total of fewer than 12 cycles as an induction-combined treatment period, and then applied chidamide as single-drug maintenance. Forty-five patients were ultimately enrolled from August 2016 to April 2021 with respect to Chinese patients at nine centers. Our primary objective was to assess the overall response rate (ORR) after the treatment with CPCT.Results::Of the 45 enrolled patients, the optimal ORR and complete response (CR)/CR unconfirmed (CRu) were 71.1% (32/45) and 28.9% (13/45), respectively, and after a median follow-up period of 56 months, the median progression-free survival (PFS) and overall survival (OS) were 8.5 months and 17.2 months, respectively. The five-year PFS and OS rates were 21.2% (95% confidence interval [CI], 7.9-34.5%) and 43.8% (95% CI, 28.3-59.3%), respectively. The most common adverse event was neutropenia (20/45, 44.4%), but we observed no treatment-related death.Conclusion::The all-oral CPCT regimen was an effective and safe regimen for R/R PTCL patients who could not tolerate standard chemotherapy for various reasons.Trial Registration::ClinicalTrials.gov, NCT02879526.

Objective:To investigate the influence of maternal autoimmune diseases and anticoagulants, including low-molecular-weight heparin (LMWH) and aspirin, on the fetal fraction of maternal plasma cell-free DNA of non-invasive prenatal testing (NIPT).Methods:A prospective cohort study was conducted on women with singleton pregnancies receiving NIPT in the Nanjing Drum Tower Hospital from March 2021 to July 2022. NIPT was carried out using a polymerase chain reaction (PCR)-free amplification platform. In this study, four types of maternal autoimmune diseases, which were antiphospholipid syndrome, undifferentiated connective tissue disease, Sj?gren's syndrome, and systemic lupus erythematosus (SLE), and two anticoagulants, LMWH and aspirin, were studied. Univariate and multivariate linear regression models were used to analyze the factors influencing fetal fraction of maternal plasma cell-free DNA.Results:A total of 4 102 singleton pregnant women were enrolled in the prospective cohort, and 3 948 were finally included after excluding the cases with unclear dosing time of LMWH or aspirin, other autoimmune diseases, conceiving through ovulation induction alone, and having true positive or failed NIPT result. There were 96 cases with antiphospholipid syndrome, 35 with undifferentiated connective tissue disease, 34 with Sj?gren's syndrome, and 18 with SLE. A total of 108 patients only received LMWH treatment, 121 only received aspirin treatment, and 113 received both LMWH and aspirin treatment. Univariate linear regression analysis showed that maternal body mass index at blood collection ( B=－0.423), conceived by assisted reproductive technology ( B=－0.803), male fetus ( B=－0.458), undifferentiated connective tissue disease ( B=1.774), and SLE ( B=3.467) had influence on the fetal fraction (all P<0.05). Multivariate linear regression analysis showed that maternal body mass index at blood collection ( B=－0.415), conceived by assisted reproductive technology ( B=－0.585), male fetus ( B=－0.322), SLE ( B=3.347) and undifferentiated connective tissue disease ( B=1.336) were factors influencing fetal fraction (all P<0.05). Conclusions:Maternal use of LMWH or aspirin does not affect fetal fraction when performing NIPT on a PCR-free amplification platform, but undifferentiated connective tissue disease and SLE are the influencing factors. Therefore, pregnant women should be informed before the NIPT that the fetal fraction of maternal plasma cell-free DNA may be affected by maternal autoimmune diseases.

Objective:To evaluate the role of spinal cord mitochondrial autophagy in alleviation of diabetic neuropathic pain (DNP) by curcumin in mice.Methods:SPF healthy male C57BL/6 mice, aged 2 months, weighing 20-25 g, in which DNP model was established by intraperitoneal injection of streptozotocin (STZ) 130 mg/kg, were used in this study.A total of 36 mice with successfully established DNP model were divided into 3 groups ( n=12 each) using the random number table method: DNP group, DNP + curcumin group (DPR group), and DNP + curcumin + cyclosporine A group (DRC group). Another 12 C57BL/6 mice were selected and served as normal control group (NC group), and the equal volume of normal saline was intraperitoneally injected.In group DPR, curcumin 200 mg/kg was administered by intragastric gavage, once a day, for 7 consecutive days.In group DRC, the mitochondrial autophagy inhibitor cyclosporine A 10 mg/kg was intrathecally injected once a day for 7 consecutive days before each administration of curcumin.The equal volume of normal saline was administered by intragastric gavage at the same time point, once a day, for 7 consecutive days in group NC and group DNP.The mechanical paw withdrawal threshold (MWT) was measured before intragastric gavage and at 1, 3, 5 and 7 days after intragastric gavage.After the last behavioral testing, the L 4-6 spinal cord tissues were removed for determination of the mitochondrial membrane potential and ROS content (by JC-1 and DCFH-DA combined with flow cytometry), expression of microtubule-associated protein light chain 3 (LC3), Beclin1 and P62 (by Western blot), and mitochondrial autophagosomes (by transmission electron microscopy) and for microscopic examination of the co-expression of LC3-Ⅱwith mitochondrial translocase outer membrane protein 20 (TOM20) (using immunofluorescence double-labeling technique). Results:Compared with group NC, the MWT and mitochondrial membrane potential were significantly decreased, the ROS content and LC3-Ⅱ/Ⅰ ratio were increased, the expression of Beclin1 was up-regulated, the expression of P62 was down-regulated ( P<0.05), the number of mitophagosomes developed was increased, and the co-expression of LC3-Ⅱwith TOM20 was increased in group DNP.Compared with group DNP, the MWT and mitochondrial membrane potential were significantly increased, the ROS content was decreased, and LC3-Ⅱ/Ⅰ ratio was increased, the expression of Beclin1 was up-regulated, the expression of P62 was down-regulated ( P<0.05), the number of mitophagosomes developed was increased, and the co-expression of LC3-Ⅱwith TOM20 was increased in group DPR.Compared with group DPR, the MWT and mitochondrial membrane potential were significantly decreased, the ROS content was increased, LC3-Ⅱ/Ⅰ ratio was decreased, the expression of Beclin1 was down-regulated, the expression of P62 was up-regulated ( P<0.05), the number of mitophagosomes developed was decreased, and the co-expression of LC3-Ⅱ with TOM20 was decreased in group DRC. Conclusions:The mechanism by which curcumin reduces DNP may be related to the up-regulation of mitochondrial autophagy in the spinal cord and improvement in mitochondrial function in mice.

ObjectiveThis study aimed to understand the epidemiological characteristics of hand-foot-mouth disease （HFMD） in Minhang District， Shanghai from 2009 to 2020， and provide a scientific basis for the prevention and control of HFMD. MethodsThe case information of HFMD was collected from the National Notifiable Infectious Diseases Reporting System of Chinese Center for Disease Control and Prevention. We used descriptive epidemiological methods to analyze the population characteristics， temporal and spatial distribution of HFMD， the pathogen composition of the case and its changing trend. ResultsFrom 2009 to 2020， a total of 66，198 cases of HFMD were reported in Minhang District， Shanghai， including 377 severe cases （severe case rate 0.57%） and 3 deaths （severs case fatality rate 0.80%）. There were more cases of HFMD in boys than in girls （1.5∶1）. HFMD patients aged under 5 years predominated， accounting for 88.91% of all cases. Majority of the cases （91.42%） were in scattered children （55.80%） and children in kindergartens （35.62%）. The incidence showed a cyclical trend， with low incidence years and high incidence years appearing alternately. The peak period was from April to July， and sometimes there were small peaks during October to December. A total of 12 years time-space scanning analysis revealed 3 clusters. The cluster centers were located in Wujing Town， Huacao Town and Xinzhuang Town， respectively. The proportion of EV71 in common cases was generally decreasing， and reduced to zero in 2019. The proportion of CoxA6 had increased year by year， and reached 75.00% in 2020. CoxA6 became the dominant pathogen in recent years. The number of severe cases had decreased year by year since 2010， and the dominant pathogen was EV71 （90.03% on average） in severe cases. ConclusionThe incidence of HFMD in Minhang District of Shanghai has a downward trend from 2014. The dominant pathogen changes from EV71 to CoxA6， and the dominant pathogen in severe cases is EV71. The discovered temporal and spatial clustering pattern is helpful for in-depth understanding of the distribution and epidemic trend of HFMD in Minhang District， and provides a scientific basis for epidemic prevention and control.

OBJECTIVE: To analyze the clinical phenotype and genetic basis for a male neonate featuring hypoparathyroidism, sensorineural hearing loss, and renal dysplasia (HDR) syndrome. METHODS: The child was subjected to genome-wide copy number variation (CNVs) analysis and whole exome sequencing (WES). Clinical data of the patient was analyzed. A literature review was also carried out. RESULTS: The patient, a male neonate, had presented with peculiar facial appearance, simian crease and sacrococcygeal mass. Blood test revealed hypocalcemia, hypoparathyroidism. Hearing test suggested bilateral sensorineural deafness. Doppler ultrasound showed absence of right kidney. Copy number variation sequencing revealed a 12.71 Mb deletion at 10p15.3-p13 (chr10: 105 001_12 815 001) region. WES confirmed haploinsufficiency of the GATA3 gene. With supplement of calcium and vitamin D, the condition of the child has improved. CONCLUSION The deletion of 10p15.3p13 probably underlay the HDR syndrome in this patient.
DNA Copy Number Variations ; Hearing Loss, Sensorineural/genetics* ; Humans ; Hypoparathyroidism/genetics* ; Infant, Newborn ; Kidney/abnormalities* ; Male ; Syndrome ; Urogenital Abnormalities/genetics*

Objective:To explore the clinical features and survival of newly diagnosed follicular lymphoma (FL) patients with diffuse large B-cell lymphoma (DLBCL) component.Methods:1845 newly diagnosed FL patients aged ≥ 18 years with grades 1-3a in 11 medical centers in China from 2000 to 2020 were included, and patients with DLBCL component were screened. The clinical data and survival data of the patients were retrospectively analyzed, and the prognostic factors were screened by univariate and multivariate analysis.Results:146 patients (7.9% ) with newly diagnosed FL had DLBCL component. The median age was 56 (25-83) years, 79 males (54.1% ) . The pathology of 127 patients showed the proportion of DLBCL component. Patients were divided into two groups according to whether the proportion of DLBCL component was ≥ 50% . The study found that patients with DLBCL component ≥ 50% had higher grade 3 ratio (94.3% vs 91.9% , P=0.010) , Ki-67 index ≥ 70% ratio (58.5% vs 32.9% , P=0.013) and PET-CT SUVmax ≥ 13 ratio (72.4% vs 46.3% , P=0.030) than patients with DLBCL component<50% . All patients received CHOP or CHOP like ± rituximab chemotherapy. The overall response rate (ORR) was 88.2% , and the complete response (CR) rate was 76.4% . In the groups with different proportions of DLBCL component, there was no significant difference in the remission rate after induction treatment and the incidence of disease progression within 2 years after initiation of treatment (POD24) ( P<0.05) . The overall estimated 5-year progression free survival (PFS) rate was 58.9% , and the 5-year overall survival (OS) rate was 90.4% . The 5-year OS rate of POD24 patients was lower than that of non POD24 patients (70.3% vs 98.5% , P<0.001) . Compared with non maintenance treatment of rituximab, maintenance treatment of rituximab could not benefit the 5-year PFS rate (57.7% vs 58.8% , P=0.543) , and the 5-year OS rate had a benefit trend, but the difference was not statistically significant (100% vs 87.8% , P=0.082) . Multivariate analysis showed that failure to reach CR after induction treatment was an independent risk factor for PFS ( P=0.006) , while LDH higher than normal was an independent risk factor for OS ( P=0.031) . Conclusion:FL patients with DLBCL component ≥50% have more invasive clinical and pathological features. CHOP/CHOP like ± rituximab regimen can improve the clinical efficacy of patients. Rituximab maintenance therapy can not benefit the PFS and OS of patients. Failure to reach CR after induction therapy was the independent unfavorable factor for PFS.