Objective To explore the mechanism by which zinc-regulated transporters, iron-regulated transporter-likeprotein 4 (ZIP4) regulates glycolysis and its impact on tumor progression in cholangiocarcinoma (CCA), providing a theoretical basis for targeted therapy of CCA. Methods ZIP4 expression in CCA was analyzed using the GEPIA database. Immuno-histochemistry (IHC) was used to detect ZIP4 expression in 20 paired CCA and adjacent non-tumor tissues. Stable ZIP4-overexpressing CCA cell lines (ZIP4-OE) were established. Gene set enrichment analysis was used to screen differentially expressed genes and pathways in ZIP-OE CCA cells. ZIP4, N-myc proto-oncogene protein (MYCN), and histone-lysine N-methyltransferase 2E (KMT2E) were knocked down using small interfering RNAs (siRNAs). The expression of glycolysis-related gene (glucose transporter 1 [Glut1], hexokinase 2 [HK2], and lactate dehydrogenase A [LDHA]) was measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Glycolytic activity was assessed by measuring the extracellular acidification rate (ECAR). Cell proliferation was evaluated using colony formation assays, and cell migration was assessed using Transwell assays. A xenograft mouse model was constructed to examine CCA tumor growth. Protein levels of ZIP4, KMT2E, H3K4me3 (tri-methylation of lysine 4 on histone H3), and MYCN were detected by Western blotting. Results GEPIA database analysis and IHC results confirmed significantly higher ZIP4 expression levels in CCA tissues compared to adjacent non-tumor tissues (P＜0.05). Compared to the control group, the ZIP4-OE group exhibited a significantly increased ECAR, along with significantly enhanced proliferation and migration abilities (P＜0.01). Conversely, knockdown of ZIP4 suppressed CCA cells proliferation and migration. GEPIA analysis indicated that ZIP4 upregulates the transcription of oncogene MYCN, as well as glycolysis-related genes. Knockdown of MYCN abolished the ZIP4 overexpression-induced upregulation of Glut1, HK2, and LDHA gene transcription, reduced glycolysis, and significantly inhibited CCA cell proliferation and migration (P＜0.05). Mechanistic studies demonstrated that ZIP4 increases H3K4me3 level via KMT2E, leading to MYCN transcription. Knockdown of KMT2E in CCA cells suppressed the ZIP4 overexpression-induced enhancement in H3K4me3 modification, resulting in MYCN downregulation and significantly reduced CCA cells proliferation and migration (P＜0.05). Conclusions ZIP4 upregulates H3K4me3 modification through KMT2E, which recruits transcription factors to activate the transcription of MYCN. This subsequently enhances cellular glycolysis and promotes the proliferation and migration of CCA cells.

{L-End}Objective To understand the prevalence of work-related musculoskeletal disorders (WMSDs) and sickness absence due to WMSDs among key industry workers in Shenzhen City. {L-End}Methods A total of 14 949 workers exposed to dust, noise, chemical and radiation (hereinafter referred to as "traditional occupational groups") in some key industries in Shenzhen City, as well as bus drivers, teachers, medical staff, policemen, courier, sanitation workers and video operators were selected as the research subjects using stratified cluster sampling. The Musculoskeletal Disorders Questionnaire was used to investigate the prevalence of WMSDs and sickness absence due to WMSDs in the past year. {L-End}Results The overall prevalence of WMSDs among the study subjects was 56.3% (8 423/14 949). The prevalence of WMSDs in different body parts from high to low was neck, waist, shoulder, back, knee, wrist, ankle, hip, and elbow, which was 37.6%, 35.7%, 31.7%, 25.2%, 18.3%, 15.4%, 14.9%, 12.4%, and 11.6%, respectively (P<0.01). The overall prevalence of WMSDs among different occupational groups from high to low was teachers, video operators, bus drivers, couriers, medical staff, policemen, traditional occupational groups, and sanitation workers, which was 82.2%, 75.7%, 74.9%, 73.9%, 67.9%, 64.3%, 43.3%, and 31.9%, respectively (P<0.01). The overall rate of sickness absence due to WMSDs was 18.3% (2 736/14 949). The overall rate of sickness absence among different occupational groups from high to low was bus drivers, couriers, teachers, traditional occupational groups, policemen, video operators, medical staff, and sanitation workers, which was 31.6%, 24.5%, 20.9%, 20.2%, 15.2%, 12.4%, 9.3%, and 6.7%, respectively (P<0.01). Among different parts of the body, the highest correlation coefficient of WMSDs was found between neck and shoulder ［correlatioon cofficient (r)=0.648, P<0.01］, while the lowest was between neck and ankle (r=0.303, P<0.01). {L-End}Conclusion The prevalence of WMSDs and sickness absence due to WMSDs among key industry workers in Shenzhen City is relatively high. Comprehensive prevention and control measures should be taken according to the characteristics of occupational population to reduce the impact of WMSDs on the health of occupational population.

{L-End}Objective To investigate the prevalence of neck and waist work-related musculoskeletal disorders (WMSDs) and its relationship with occupational stress among express delivery workers. {L-End}Methods A total of 437 express delivery workers in Shenzhen City were selected as the research subjects using convenient sampling method. The prevalence of neck and waist WMSDs and the level of occupational stress were investigated by the Musculoskeletal Disorder Questionnaire and Work Content Questionnaire. {L-End}Results The prevalences of neck and waist WMSDs among the workers in the past year were 47.6% (208/437) and 60.2% (263/437), respectively. The detection rate of occupatioonal stress was 51.5%(225/437). The prevalences of neck and waist WMSDs among the workers of the occupational stress group were higher than that in the non-occupational stress group (51.9% vs 42.6%, 66.4% vs 53.0%, both P<0.01). The results of multivariate logistic regression analysis showed that the risk of neck WMSDs was higher in workers with weekly working hours >40 hours, workers with poor working posture, and workers with occupational stress compared with workers with weekly working hours ≤40 hours, workers without poor working posture, and workers without occupational stress, respectively (all P<0.05). The risk of waist WMSDs was higher in workers without weekly exercise, workers with poor working posture, and workers with occupational stress compared with workers with weekly exercise, workers without poor working posture, and workers without occupational stress, respectively (all P<0.05). {L-End}Conclusion The prevalence of neck and waist WMSDs, which may be influenced by occupational stress and poor working postures, is relatively high among express delivery workers.

Objective:To analyze the biological characteristics, phylogenic features and clinical significance of SQ219 and SQ220 isolated from clinical sputum and midstream urine specimens.Methods:The culture and biochemical characteristics of the two strains were observed. VITEK2 System, drug sensitivity testing and MALDI-TOF mass spectrometry were used for bacterial identification. Phylogenetic analysis based on 16S rRNA and core genome was performed. The average nucleotide identity (ANI) based on whole genome sequences was calculated.Results:SQ219 and SQ220 were Gram-stain-negative, aerobic, catalase- and oxidase-positive, and non-motile bacteria. Their optimum growth was observed in NaCl-free medium at 30℃ and pH7. Flexirubin-type pigments were produced by SQ220 on Colombia blood agar, but not by SQ219. Both SQ219 and SQ220 were resistant to aztreonam, amikacin, tobramycin and colistin, which was consistent with the drug resistance phenotype of genus Chryseobacterium. The genome sequences of SQ219 and SQ220 were 5.08 Mb and 4.80 Mb in length, and the G+ C contents were 36.72% and 36.36%, respectively. Both strains carried β-lactam resistance gene ( blaCGA). 16S rRNA phylogenetic analysis showed that SQ219 and SQ220 were closely related to Chryseobacterium gambrini DSM18014 T with the similarities of 98.93% and 98.36%, respectively. Core genome phylogenetic analysis revealed that SQ219 and SQ220 were highly homologous to Chryseobacterium gambrini DSM18014 T. However, the ANI values between the two strains and Chryseobacterium gambrini DSM18014 T were 92.49% and 93.27%, respectively, below the threshold for prokaryotic species identification. Conclusions:Based on the phenotypic and phylogenetic data, SQ219 and SQ220 represent a novel species of the genus Chryseobacterium. This study would help promote the understanding of the evolution of Chrysobacterium and provide reference for the identification of new species of Chrysobacterium.

Objective:To understand the occurrence of occupational injuries among sanitation workers in Shenzhen, and provide a scientific basis for the prevention of occupational injuries among sanitation workers.Methods:From May to November 2020, a cluster sampling method was used to select some street sanitation workers in Shenzhen to conduct a questionnaire survey. A total of 2200 questionnaires were recovered, of which 2167 were valid (98.5% effective recovery rate) . The socio-demographic data, length of service, type of work and occurrence of occupational injuries of sanitation workers were collected, and the distribution characteristics of occupational injuries and their relationship with factors such as type of work were analyzed.Results:Among the 2167 sanitation workers, 240 (11.1%) had experienced occupational injuries. The most common occupational injuries among sanitation workers were sharp injury, heat stroke and motor vehicle traffic accident, with the incidence rates of 6.1% (133/2167) , 2.4% (53/2167) and 1.7% (36/2167) respectively. There were statistically significant differences in the distribution of occupational injuries among sanitation workers with different lengths of work and types of work ( P<0.05) . The incidence of occupational injury among sanitation workers with more than 5 years of service was significantly higher than that of workers with less than 5 years of service ( P<0.05) . The incidence of sharp injury among garbage sorting and transportation personnel was higher (7.9%, 21/265) , the incidence of heat stroke among manual cleaners was higher (3.1%, 42/1366) , and the incidence of motor vehicle traffic accident among mechanized cleaners was higher (5.4%, 10/184) . Conclusion:There are many cases of occupational injuries among sanitation workers in Shenzhen. Targeted measures should be taken to prevent the occurrence of different types of work and different types of occupational injuries, and to improve the occupational health level of sanitation workers.

Objective:To understand the occurrence of occupational injuries among sanitation workers in Shenzhen, and provide a scientific basis for the prevention of occupational injuries among sanitation workers.Methods:From May to November 2020, a cluster sampling method was used to select some street sanitation workers in Shenzhen to conduct a questionnaire survey. A total of 2200 questionnaires were recovered, of which 2167 were valid (98.5% effective recovery rate) . The socio-demographic data, length of service, type of work and occurrence of occupational injuries of sanitation workers were collected, and the distribution characteristics of occupational injuries and their relationship with factors such as type of work were analyzed.Results:Among the 2167 sanitation workers, 240 (11.1%) had experienced occupational injuries. The most common occupational injuries among sanitation workers were sharp injury, heat stroke and motor vehicle traffic accident, with the incidence rates of 6.1% (133/2167) , 2.4% (53/2167) and 1.7% (36/2167) respectively. There were statistically significant differences in the distribution of occupational injuries among sanitation workers with different lengths of work and types of work ( P<0.05) . The incidence of occupational injury among sanitation workers with more than 5 years of service was significantly higher than that of workers with less than 5 years of service ( P<0.05) . The incidence of sharp injury among garbage sorting and transportation personnel was higher (7.9%, 21/265) , the incidence of heat stroke among manual cleaners was higher (3.1%, 42/1366) , and the incidence of motor vehicle traffic accident among mechanized cleaners was higher (5.4%, 10/184) . Conclusion:There are many cases of occupational injuries among sanitation workers in Shenzhen. Targeted measures should be taken to prevent the occurrence of different types of work and different types of occupational injuries, and to improve the occupational health level of sanitation workers.

Rheumatoid arthritis (RA) is an autoimmune disease and is mainly characterized by abnormal proliferation of fibroblast-like synoviocytes (FLS). The up-regulated cellular membrane expression of G protein coupled receptor kinase 2 (GRK2) of FLS plays a critical role in RA progression, the increase of GRK2 translocation activity promotes dysfunctional prostaglandin E4 receptor (EP4) signaling and FLS abnormal proliferation. Recently, although our group found that paeoniflorin-6'-

Objective:To evaluate the safety and efficacy of eltrombopag combined with immunosuppressive therapy in patients with aplastic anemia (AA) in China.Methods:We investigated and analyzed the clinical data of AA patients from 14 hematological treatment centers who were treated with oral eltrombopag for at least 3 mon.Results:We enrolled 56 AA patients, including 19 treatment-na?ve patients and 37 IST-refractory patients. The median administration period for eltrombopag was 7 (3-31) months, and the median maximum stable dosage was 75 mg/d (50-150 mg/d) . The 3-month hematological response (HR) rate was 60%, and the complete response (CR) rate was 30% in 10 SAA patients who were treated with first-line eltrombopag and standard IST (ATG+CsA) . Eight of 9 eltrombopag and CsA ± androgen first-line treated SAA patients responded (8/9, 89%) and 4 (44%) gave CR. The overall HR and CR rates were 79% and 52.6%, respectively, among these 19 patients by the end of the follow-up period. Of the 19 AA patients who were refractory to CsA ± androgen, 11 achieved HR (57.9%) at 3 mon, and the best HR rate was 44% in standard IST (ATG+CsA) refractory 18 patients after eltrombopag treatment. Fifty-one percent of the patients experienced mild or moderate adverse events, and gastrointestinal discomfort was the most common adverse effect reported by the study subjects.Conclusion:Adding Eltrombopag in first-line IST can accelerate the acquisition and improve the quality of hematological responses in AA patients. AA with relatively more residual hematopoietic cells may be well treated with eltrombopag and non-ATG IST. Eltrombopag can be used as salvage therapy for CsA±androgen refractory patients. Eltrombopag was generally safe and well tolerated by AA patients in China.

Objective:To investigate the risk factors associated with anastomotic leakage after robotic surgery in mid-low rectal cancer.Methods:A retrospective case-control study method was conducted. Inclusion criteria: (1) 18 to 80 years old; (2) pathologically confirmed rectal cancer; (3) distance <10 cm from tumor to anal margin; (4) robotic anterior rectal resection. Patients with previous history of colorectal cancer surgery, distant metastases or other malignant tumors, undergoing emergency surgery, with severe abdominal adhesions or those receiving combined organ resection were excluded. Based on the above criteria, 636 patients undergoing robotic radical sphincter-preserving surgery for mid-low rectal cancer in Zhongshan Hospital from January 2015 to December 2018 were included in this study, including 398 males (62.6%) and 238 females (37.4%) with a mean age of (61.9±11.3) years. Sixty-eight cases (10.7%) received neoadjuvant chemoradiotherapy. Amony the 636 included patients, 123(19.3%) underwent natural orifice specimen extraction surgery (NOSES) and 15 (2.3%) underwent preventive stoma. According to the cirteria developed by the International Rectal Cancer Research Group in 2010, the anastomotic leakage was classified as grade A (no requirement of intervention), B (requirement of intervention), and C (requirement of operation). Logistic regression was used to analyze the relationship between anastomotic leakage and clinicopathological factors. Factors in univariate analysis with P<0.05 were included in the multivariate analysis. Results:Anastomotic leakage occurred in 38 cases (6.0%). The grading of anastomotic leakage was grade A in 13 cases (2.0%), grade B in 19 cases (3.0%), and grade C in 6 cases (0.9%). The 3-year disease-free survival rate of patients with anastomotic leakage and without anastomotic leakage was 83.5% and 83.6% respectively ( P=0.862); the 3-year overall survival rate of the two group was 85.1% and 87.5% respectively ( P=0.296). The results of univariate logistic regression analysis showed that male ( P=0.011), longer operation time ( P=0.042), distance ≤5 cm from tumor to anal margin ( P=0.012), more intraoperative blood loss ( P=0.048) were associated with anastomotic leakage (all P<0.05). NOSES was not associated with anastomotic leakage ( P=0.704). Multivariate analysis confirmed that male (OR=3.03, 95%CI: 1.37 to 7.14, P=0.010), operation time ≥180 minutes (OR=2.04, 95%CI: 1.03 to 3.99, P=0.040), distance ≤5 cm from tumor to anal margin (OR=2.56, 95%CI:1.28 to 5.26, P=0.008) were independent risk factors for anastomotic leakage. Conclusion:Male, short distance from tumor to anal margin, and long operation time are independent risk factors for anastomotic leakage in patients undergoing robotic mid-low rectal cancer radical surgeries. These patients need to be cautiously treated during surgery.

Objective:To investigate the risk factors associated with anastomotic leakage after robotic surgery in mid-low rectal cancer.Methods:A retrospective case-control study method was conducted. Inclusion criteria: (1) 18 to 80 years old; (2) pathologically confirmed rectal cancer; (3) distance <10 cm from tumor to anal margin; (4) robotic anterior rectal resection. Patients with previous history of colorectal cancer surgery, distant metastases or other malignant tumors, undergoing emergency surgery, with severe abdominal adhesions or those receiving combined organ resection were excluded. Based on the above criteria, 636 patients undergoing robotic radical sphincter-preserving surgery for mid-low rectal cancer in Zhongshan Hospital from January 2015 to December 2018 were included in this study, including 398 males (62.6%) and 238 females (37.4%) with a mean age of (61.9±11.3) years. Sixty-eight cases (10.7%) received neoadjuvant chemoradiotherapy. Amony the 636 included patients, 123(19.3%) underwent natural orifice specimen extraction surgery (NOSES) and 15 (2.3%) underwent preventive stoma. According to the cirteria developed by the International Rectal Cancer Research Group in 2010, the anastomotic leakage was classified as grade A (no requirement of intervention), B (requirement of intervention), and C (requirement of operation). Logistic regression was used to analyze the relationship between anastomotic leakage and clinicopathological factors. Factors in univariate analysis with P<0.05 were included in the multivariate analysis. Results:Anastomotic leakage occurred in 38 cases (6.0%). The grading of anastomotic leakage was grade A in 13 cases (2.0%), grade B in 19 cases (3.0%), and grade C in 6 cases (0.9%). The 3-year disease-free survival rate of patients with anastomotic leakage and without anastomotic leakage was 83.5% and 83.6% respectively ( P=0.862); the 3-year overall survival rate of the two group was 85.1% and 87.5% respectively ( P=0.296). The results of univariate logistic regression analysis showed that male ( P=0.011), longer operation time ( P=0.042), distance ≤5 cm from tumor to anal margin ( P=0.012), more intraoperative blood loss ( P=0.048) were associated with anastomotic leakage (all P<0.05). NOSES was not associated with anastomotic leakage ( P=0.704). Multivariate analysis confirmed that male (OR=3.03, 95%CI: 1.37 to 7.14, P=0.010), operation time ≥180 minutes (OR=2.04, 95%CI: 1.03 to 3.99, P=0.040), distance ≤5 cm from tumor to anal margin (OR=2.56, 95%CI:1.28 to 5.26, P=0.008) were independent risk factors for anastomotic leakage. Conclusion:Male, short distance from tumor to anal margin, and long operation time are independent risk factors for anastomotic leakage in patients undergoing robotic mid-low rectal cancer radical surgeries. These patients need to be cautiously treated during surgery.