Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC_{50, SMS2} = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t _{1/2, cornea} = 1.11 h; t _{1/2, meibomian glands} = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.

Objective:To investigate the occurrence of work-related musculoskeletal disorders (WMSDs) in bus drivers in Zhuhai City, analyze the ergonomic factors, and explore the prevention and control measures of WMSDs.Methods:From March to May 2023, 1675 active bus drivers from 5 branches of a bus group in Zhuhai were selected by stratified sampling method. The incidence of WMSDs among bus drivers in the past 12 months was investigated by using the modified Chinese Version of Musculoskeletal Disorders Questionnaire. The influencing factors of WMSDs were analyzed by χ2 test and generalized linear model. Results:The total incidence of WMSDs in bus drivers in the past 12 months was 47.2% (790/1675) , and the incidence of WMSDs in neck and shoulder and lower back was 36.9% (618/1675) and 31.7% (531/1675) , respectively. The χ2 test showed that there were statistically significant differences in the incidence of WMSDs among bus drivers with different individual factors such as body mass index (BMI) , physical exercise and looking down at mobile phones ( P<0.05) . There were significant differences in the incidence of WMSDs in the neck and shoulder of bus drivers with different years of service and number of stops on their routes ( P<0.05) . There were statistically significant differences in the incidence of WMSDs in the lower back of bus drivers with different one-way driving time, shift patterns, and rest breaks during work ( P<0.05) . Abnormal BMI, professional working years >12 years, uncomfortable working posture, frequent turning, slightly forward neck posture, large forward neck posture and long shoulder posture were the risk factors for WMSDs of bus drivers ( P<0.05) , and comfortable seat was the protective factor ( P<0.05) . One-way driving time >70 min, shift work schedules, uncomfortable working posture, slightly forward back posture, and frequent turning were the risk factors leading to lower back WMSDs ( P<0.05) , and physical exercise, comfortable driving cabin space, and seat comfort were the protective factors ( P<0.05) . Conclusion:The total incidence of WMSDs in bus drivers is higher, and ergonomic factors are related to the occurrence of WMSDs. In the implementation of bus driving space comfort, human-computer interaction interface friendliness and seat comfort, employers should be reasonable allocation of fitness facilities, regular training, reasonable shift organization and other measures to prevent and control the occurrence of bus drivers WMSDs.

Objective:To investigate the occurrence of work-related musculoskeletal disorders (WMSDs) in bus drivers in Zhuhai City, analyze the ergonomic factors, and explore the prevention and control measures of WMSDs.Methods:From March to May 2023, 1675 active bus drivers from 5 branches of a bus group in Zhuhai were selected by stratified sampling method. The incidence of WMSDs among bus drivers in the past 12 months was investigated by using the modified Chinese Version of Musculoskeletal Disorders Questionnaire. The influencing factors of WMSDs were analyzed by χ2 test and generalized linear model. Results:The total incidence of WMSDs in bus drivers in the past 12 months was 47.2% (790/1675) , and the incidence of WMSDs in neck and shoulder and lower back was 36.9% (618/1675) and 31.7% (531/1675) , respectively. The χ2 test showed that there were statistically significant differences in the incidence of WMSDs among bus drivers with different individual factors such as body mass index (BMI) , physical exercise and looking down at mobile phones ( P<0.05) . There were significant differences in the incidence of WMSDs in the neck and shoulder of bus drivers with different years of service and number of stops on their routes ( P<0.05) . There were statistically significant differences in the incidence of WMSDs in the lower back of bus drivers with different one-way driving time, shift patterns, and rest breaks during work ( P<0.05) . Abnormal BMI, professional working years >12 years, uncomfortable working posture, frequent turning, slightly forward neck posture, large forward neck posture and long shoulder posture were the risk factors for WMSDs of bus drivers ( P<0.05) , and comfortable seat was the protective factor ( P<0.05) . One-way driving time >70 min, shift work schedules, uncomfortable working posture, slightly forward back posture, and frequent turning were the risk factors leading to lower back WMSDs ( P<0.05) , and physical exercise, comfortable driving cabin space, and seat comfort were the protective factors ( P<0.05) . Conclusion:The total incidence of WMSDs in bus drivers is higher, and ergonomic factors are related to the occurrence of WMSDs. In the implementation of bus driving space comfort, human-computer interaction interface friendliness and seat comfort, employers should be reasonable allocation of fitness facilities, regular training, reasonable shift organization and other measures to prevent and control the occurrence of bus drivers WMSDs.

Objective To investigate and analyze a group occupational acute dimethylacetamide (DMA) poisoning incident occurred during the post-fire cleaning operation in a spandex manufacturing enterprise. Methods This study focused on the involved enterprise, employing units, poisoning patients, and workers with similar occupational exposure history from a group occupational acute chemical poisoning incident in Guangdong Province in 2023. Occupational health on-site investigation data, clinical records of poisoned patients, and occupational disease diagnostic data were collected to determine the cause of the poisoning. Results The incident occurred at a spandex manufacturing enterprise during the cleaning of polymerization reaction vessels after a fire, resulting in poisoning of six cleaning workers. The clinical symptoms of patients included varying degrees of liver function abnormalities and skin damage. All six patients wore long-tube air-supplied full-face masks during work. The patients were in a confined work space with poor ventilation, and worked more than 8 hours per day. Patients felt unwell after 5-13 days of work. Post-incident investigation revealed that the DMA exposure concentration of short term near the reaction vessels was 36.06 mg/m³. DMA accounted 13.74% to 30.09% of the volatile organic compounds in the raw and auxiliary materials and waste in the vessel. N-methylacetamide was detected in the urine of these six patients, with levels up to 1 639.78 mg/g creatinine, exceeding the occupational exposure limit (20.00 mg/g creatinine). All six patients were diagnosed as occupational acute DMA poisoning. Conclusion Occupational acute DMA poisoning mainly causes liver damage, has a latent onset, and poses a risk of group occurrence. The main causes of group poisoning are confined work space, inadequate management, insufficient protective measures, and excessive working hours.

The Choledochal cyst is an extremely rare congenital anomaly of the bile duct. Early cyst resection and Roux-en-Y hepatojejunostomy are the primary surgical methods for treating choledochal cyst. With the emergence of enhanced recovery after surgery, laparoscopic surgery has effectively reduced the incidence of biliary complications and wound infections, but it still does not meet people's requirements for minimally invasive surgery. Robotic surgery system has the potential to enhance surgical precision and the maneuverability of surgeons due to clear surgical visualization and flexible mechanical arms. The authors review the relevant literatures and conduct a Meta-analysis to evaluate the efficacy of robot-assisted surgery and laparoscopic surgery for choledochal cyst.

Objective:This study aims to explore the relationship between non-suicidal self-injurious (NSSI) behaviors and childhood trauma and peer rejection in adolescents with depressive disorders and, to examine whether childhood trauma and peer rejection can predict NSSI behaviors in these adolescents.Methods:A total of 412 depressed adolescents (263 with NSSI and 149 without NSSI) were included in the test data set, while another 161 depressed adolescents (99 with NSSI and 62 without NSSI) were in the validation set. This study firstly analyzed the differences in the scores of the Children's Depression Inventory (CDI), Childhood Trauma Questionnaire (CTQ), and Social Peer Rejection Scale (SPR) between the two groups using the test set. Then, a hierarchical logistic regression model was used to analyze the independent effects of these environmental factors on NSSI behaviors and to determine the diagnostic model. Finally, the diagnostic model was applied using the validation data set to calculate the actual predictive efficacy of the model.Results:Compared to those without NSSI, adolescent patients with NSSI showed significantly higher scores in CDI ( t=10.04, P<0.001), CTQ ( t=9.11, P<0.001), SPR ( t=5.30, P<0.001), and their subscale scores. Then, the scores of the low self-esteem factor of CDI ( OR=1.12, P=0.002), the emotional neglect factor of CTQ ( OR=1.08, P=0.037), and the insult factor ( OR=1.10, P=0.050) and somatic aggression factor ( OR=0.89, P=0.049) of SPR were significantly associated with NSSI behaviors. The diagnostic model was well established (area under the ROC curve=0.84, P<0.001). In addition, in the validation data set, the diagnostic model had a significant predictive effect (area under the ROC curve=0.85, P<0.001). Conclusion:Childhood emotional neglect and peer insult might be crucially influential factors triggering NSSI behaviors among adolescents with depressive disorders. Childhood trauma and peer rejection were of considerable importance when diagnosing and predicting the development of NSSI behaviors in depressive adolescents.

Objective:This study aims to explore the relationship between non-suicidal self-injurious (NSSI) behaviors and childhood trauma and peer rejection in adolescents with depressive disorders and, to examine whether childhood trauma and peer rejection can predict NSSI behaviors in these adolescents.Methods:A total of 412 depressed adolescents (263 with NSSI and 149 without NSSI) were included in the test data set, while another 161 depressed adolescents (99 with NSSI and 62 without NSSI) were in the validation set. This study firstly analyzed the differences in the scores of the Children's Depression Inventory (CDI), Childhood Trauma Questionnaire (CTQ), and Social Peer Rejection Scale (SPR) between the two groups using the test set. Then, a hierarchical logistic regression model was used to analyze the independent effects of these environmental factors on NSSI behaviors and to determine the diagnostic model. Finally, the diagnostic model was applied using the validation data set to calculate the actual predictive efficacy of the model.Results:Compared to those without NSSI, adolescent patients with NSSI showed significantly higher scores in CDI ( t=10.04, P<0.001), CTQ ( t=9.11, P<0.001), SPR ( t=5.30, P<0.001), and their subscale scores. Then, the scores of the low self-esteem factor of CDI ( OR=1.12, P=0.002), the emotional neglect factor of CTQ ( OR=1.08, P=0.037), and the insult factor ( OR=1.10, P=0.050) and somatic aggression factor ( OR=0.89, P=0.049) of SPR were significantly associated with NSSI behaviors. The diagnostic model was well established (area under the ROC curve=0.84, P<0.001). In addition, in the validation data set, the diagnostic model had a significant predictive effect (area under the ROC curve=0.85, P<0.001). Conclusion:Childhood emotional neglect and peer insult might be crucially influential factors triggering NSSI behaviors among adolescents with depressive disorders. Childhood trauma and peer rejection were of considerable importance when diagnosing and predicting the development of NSSI behaviors in depressive adolescents.

Objective To study the clinical features and risk factors of acute pulmonary reperfusion injury after operation in neonates with severe pulmonary stenosis or pulmonary atresia.Method From February 2014 to February 2018,a retrospective analysis was performed in patients with critical pulmonary stenosis or pulmonary atresia who received percutaneous balloon pulmonary valvuloplasty (PBPV) in the neonatal intensive care unit of our hospital.Clinical characteristics,perioperative cardiac structure,hemodynamic data and biochemical results were collected.The neonates were assigned into injury group if they had acute lung reperfusion injury,and non-injury group if not.The risk factors of acute lung reperfusion injury were analyzed using multi-variate Logistic regression model.Result A total of 32 patients (24 prenatal diagnosis and 8 postnatal diagnosis) with severe pulmonary stenosis or pulmonary atresia with intact ventricular septum were enrolled.The main manifestations were dyspnea and cyanosis.Intravenous prostaglandin E was administered to keep the ductus arteriosus open.The age of operation ranged from 1 to 52 days and the median age was 7.5 days.Postoperative acute lung reperfusion injury occurred in 7 cases (21.9％).Preoperative and intraoperative pulmonary valve annulus diameter,balloon diameter,preoperative hemoglobin,hematocrit and blood albumin were significantly lower in the injury group.The operation duration,total length of hospital stay and postoperative duration were longer than in the non-injury group,the differences were statistically significant (P ＜ 0.05).Multi-variate Logistic regression analysis showed that the diameter of pulmonary valve annulus (OR =5.814,95％CI 1.106 ～30.568),preoperative blood albumin (OR =1.361,95％ CI 1.063 ～ 1.742),and hematocrit (OR =1.173,95％ CI 1.010 ～ 1.363) were risk factors of acute lung reperfusion injury,with statistically significant differences (P ＜ 0.05).Conclusion Acute lung reperfusion injury is one of the common complications after the operation of severe pulmonary stenosis or pulmonary atresia.The severity of pulmonary valve annulus stenosis,preoperative hematocrit and blood albumin level may be the risk factors of postoperative acute lung reperfusion injury.

Objective To investigate the potential dose-response relationship between PCDD/Fs inhalational exposure and oxidative damage to DNA and lipid in foundry workers.Methods The participants were divided into three groups,including exposure group,administrator group and control group.The concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in air environment were determined by isotope dilution high resolution capillary column gas chromatography/high resolution mass spectrometry (HRGC-HRMS).The inhalational dose of PCDD/Fs were evaluated by Houmen's model.Urinary 8OHdG was analyzed by high performance liquid chromatography-electrochemical detector (HPLC-ECD).Urinary 8-iso-PGF2a were determined by ELISA.Results The PCDD/Fs environmental concentrations of three groups (pg· TEQ/m) were 0.21 +0.08,0.03 ±0.01,0.0012 ±0.0007 (P＜0.05),respectively.The inhalational dose of exposure group (92.54 (32.90～264.49) fg· TEQ/kg· d) was 5.4 folds higher than the administrator group,and was 201 times more than control group.The levels of urinary 8-OHdG(nmol/L crea) of three groups were 3.25 (1.07～15.36),2.72(0.75～16.07),2.17(0.38～17.07) (P＜0.05) and the levels of urinary 8-iso-PGF2n (nmol/L crea)were 19.11(9.33～76.50),20.95(8.40～79.31),11.48(4.85～37.80)(P＜0.05),respectively.The multiple linear regression analysis revealed that there were significantly increased trend for levels of urinary 8-OHdG and 8-iso-PGF2a as PCDD/Fs exposure levels increased,after adjustment for age,sex,smoking statue,alcohol use and BMI (P＜0.01).Conclusion There was a dose-response relationship between PCDD/Fs inhalational exposure and oxidative damage in foundry workers.

Objective To investigate the potential dose-response relationship between PCDD/Fs inhalational exposure and oxidative damage to DNA and lipid in foundry workers.Methods The participants were divided into three groups,including exposure group,administrator group and control group.The concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in air environment were determined by isotope dilution high resolution capillary column gas chromatography/high resolution mass spectrometry (HRGC-HRMS).The inhalational dose of PCDD/Fs were evaluated by Houmen's model.Urinary 8OHdG was analyzed by high performance liquid chromatography-electrochemical detector (HPLC-ECD).Urinary 8-iso-PGF2a were determined by ELISA.Results The PCDD/Fs environmental concentrations of three groups (pg· TEQ/m) were 0.21 +0.08,0.03 ±0.01,0.0012 ±0.0007 (P＜0.05),respectively.The inhalational dose of exposure group (92.54 (32.90～264.49) fg· TEQ/kg· d) was 5.4 folds higher than the administrator group,and was 201 times more than control group.The levels of urinary 8-OHdG(nmol/L crea) of three groups were 3.25 (1.07～15.36),2.72(0.75～16.07),2.17(0.38～17.07) (P＜0.05) and the levels of urinary 8-iso-PGF2n (nmol/L crea)were 19.11(9.33～76.50),20.95(8.40～79.31),11.48(4.85～37.80)(P＜0.05),respectively.The multiple linear regression analysis revealed that there were significantly increased trend for levels of urinary 8-OHdG and 8-iso-PGF2a as PCDD/Fs exposure levels increased,after adjustment for age,sex,smoking statue,alcohol use and BMI (P＜0.01).Conclusion There was a dose-response relationship between PCDD/Fs inhalational exposure and oxidative damage in foundry workers.