Occupational chronic n-hexane poisoning incidents have been effectively curtailed in traditional printing and footwear industries, but its hazards are emerging in new industries. In recent years, two cluster incidents involving eight patients with occupational chronic n-hexane poisoning had occurred in Longgang District, Shenzhen City. Unlike the cleaning processes of electronic components in the electronics industry, these two incidents occurred during cleaning operations of non-electronic products. The rapid on-site detection tubes indicated the presence of n-hexane in the organic solvents used at the work site, and subsequent analysis of volatile components of the organic solvents further confirmed the involvement of n-hexane. Although the n-hexane exposure concentration of short term in the workplace air samples were below its occupational exposure limit, all eight cases were diagnosed as occupational chronic n-hexane poisoning, based on occupational exposure history, clinical manifestations, field investigations, and laboratory test results. These two poisoning incidents highlight that in air-conditioned or enclosed workshops with substandard occupational disease prevention facilities, the use of n-hexane containing organic solvents may result in occupational chronic n-hexane poisoning, even when the air monitoring results do not exceed the occupational exposure limits.

Abstract: This study aims to find out the causes for the dissolution of unqualified samples found during evaluation sampling of lansoprazole enteric-coated preparations by the laser infrared imaging system and orbitrap high resolution mass spectrometry, with suggestions for improvement. Lansoprazole enteric-coated preparations were tested by current standard, the dissolution of a batch of samples was below the limit and other items were in line with the standard. Considering that this product is unstable to acid and alkali, the following exploratory experiments were designed from different dimensions, based on the conclusion of the unannounced inspection of the company, to explore the reasons for the unqualified batch, including the influence of high-temperature and high-humidity storage environment on the key quality properties of the sample, the influence of 2-hour acid resistance test on dissolution result, the imaging of the core and the measure of coating layer thickness, the optimization of chromatographic conditions of related substances, and the analysis of the source of impurities. It was found that improper storage in circulation and poor coating process caused the low dissolution of this batch: the high-temperature and high-humidity storage environment possible in the circulation process led to the decreasing efficacy of disintegrating agent in the samples and thus the difficulty to release the active pharmaceutical ingredient fully; the coating solution could not be uniformly sprayed on the core, resulting in thin isolation layer and different thickness, which then affected the protection of the main drug against acid degradation. The above two reasons together resulted in unqualified dissolution of this batch. The overall quality of lansoprazole enteric-soluble preparation is good, but the formulation and process in some companies need to be optimized; and the temperature and humidity in the circulation process need to be controlled in strict accordance with the regulations.

Objective To investigate the effect of subanesthetic dose of esketamine on remifentanil-in-duced hyperalgesia after cesarean section under general anesthesia,and its effect on serum homocysteine(Hcy)level and postpartum depression.Methods A total of fifty patients undergoing cesarean section under general anesthesia were randomly divided into the esketamine group and the control group(25 cases in each group).The two groups were given esketamine 0.2 mg/kg and the same amount of normal saline by slow in-jection 10 min after fetal delivery.Then,the extubation time,visual analogue scale(VAS)score within two hours after operation,and consumption of morphine while in the post-anaesthesia care unit(PACU)were compared between the two groups.The Edinburgh Postnatal Depression Scale(EPDS)scores were compared at one day before surgery,one day,four days,and one month after surgery.Serum Hcy levels were measured at one day before surgery,one day and four days after surgery.Results There was no significant difference in extubation time between the two groups(P>0.05).Compared with the control group,it took a longer time for patients in the esketamine group to have a VAS score≥4 for the first time,but the time from morphine injection to a VAS score<4 was shortened(P<0.05).The amount of morphine used in the esketamine group was lower than that in the control group in PACU(P<0.05).Compared with the control group,the VAS scores of the esketamine group decreased at 15 min,30 min,45 min,one hour,and 90 min after surgery(P<0.05),while there was no statistical significance difference in VAS scores at two hours after surgery(P<0.05).EPDS scores in the esketamine group were lower than those in the control group at one day and four days after surgery(P>0.05),but there was no statistically significant between the two groups at one month after surgery(P>0.05).Serum Hcy level in the esketamine group was lower than that in the control group at one day and four days after surgery(P<0.05).Conclusion The subanesthetic dose of esketamine during caesarean section under general anesthesia can effectively relieve remifentanil-induced postoperative hy-peralgesia and prevent the occurrence of postpartum depression.

OBJECTIVE To predict the core ingredients, targets and signaling pathways of Sanhuang ointment in the treatment of haemorrhoids based on network pharmacology, and preliminarily discuss the mechanism of action preliminarily by means of molecular docking and experimental verification. METHODS Active ingredients, targets and haemorrhoid related targets of Sanhuang ointment were obtained through literature research and database screening. Association networks were constructed and core targets were screened by Cytoscape, and gene function analysis and pathway enrichment analysis were conducted. Autodock Vina was used for molecular docking verification, and the regulatory effects of Sanhuang ointment on core targets were verified by ELISA and immunohistochemistry. RESULTS The 77 active ingredients and 61 potential targets of Sanhuang ointment for treating haemorrhoids were collected. KEGG showed that Sanhuang ointment could regulate calcium signaling pathways, neuroactive ligand receptor interactions, cGMP-PKG pathway, etc. Affect 6 core targets of CGRP, NK-1R, TRPV1, VEGF, IL-6 and TNF-α. Molecular docking showed that Sanhuang ointment had a good affinity with target protein, and animal experiments verified that Sanhuang ointment could inhibit the expression of IL-6, CGRP, substance P, and promote the expression of VEGF. CONCLUSION Sanhuang ointment may act on CGRP, NK-1R and other targets, regulate Calcium signaling pathway and PI3K-Akt pathways, and exert analgesic and anti-inflammatory effects, promoting blood circulation and removing blood stasis to treat haemorrhoids.

Objective To investigate the neurobehavioral development of young children aged 24 to 60 months in Shunde and explore the factors influencing the development of young children and provide reference for the interven-tion of neurobehavioral development delays in young children.Methods A retrospective cohort study was used to enroll the young children who were initially screened by the Pediatric Neuropsychological Developmental Scale(Pe-diatric Heart Scale)with a score of ≤85 was included in the study.With a score of ≤85,the young children might be at risk of developmental delays,and needed to be further diagnosed by the GESELL Developmental Diagnostic Scale,the basic information of the young children and their mothers at the time of birth were investigated,as well as basic information about the young children at the time of completing the GESELL Developmental Diagnostic Scale was collected.Results A total of 271 young children were included,196 males and 75 females.Young children had the lowest developmental quotient(DQ)in the language domain among the five domains(P＜0.001).Multiple lin-ear regression models showed:compared with girls,the language domain DQ of boys decreased by 5.321 points(P=0.049,95％CI:-10.620--0.021),and the personal-social domain DQ decreased by 4.474 points(P=0.023,95％CI:-8.316--0.631).Compared with young children via natural vaginal delivery(NVD),the gross motor domain DQ of young children via caesarean section(CS)decreased by 4.890 points(P=0.008,95％CI:-8.499--1.281),the fine motor domain DQ decreased by 3.373 points(P=0.037,95％CI:-6.532--0.213),the language domain DQ decreased by 7.621 points(P=0.004,95％CI:-12.826--2.416),per-sonal-social domain DQ decreased by 6.232 points(P=0.001,95％CI:-10.006--2.457).The results of bi-nary logistic regression models showed,compared with young children via NVD,the risk of gross motor domain retar-dation in young children increased(OR=1.763,95％CI:1.003-3.100),the risk of fine motor domain retardation increased(OR=2.217,95％CI:1.235-3.980),the risk of language domain retardation increased(OR=3.306,95％CI:1.080-10.124).Conclusion Young children with suspected neurobehavioral delays were more likely to have delayed development in language domain than in other domains,boys had lower DQ in language domain and personal-social domain than girls,and the development of young children via CS was slower than that via NVD.Fo-cus should be on the language development of young children especially on the language and personal-social devel-opment of boys.Carefully chose delivery way.Focus should be placed on assessment of young children's comprehen-sive neurobehavioral development in early time.

Objective:To investigate the clinical manifestations, endoscopic characteristics, and prognostic factors of patients with colorectal extranodal NK/T cell lymphoma.Methods:The clinical data of 52 patients with colorectal extranodal NK/T cell lymphoma admitted to the First Affiliated Hospital of Zhengzhou University from January 2013 to January 2023 were retrospectively analyzed. Their clinical manifestations and endoscopic characteristics were summarized, and the prognostic factors were analyzed by Cox regression model.Results:Among the 52 patients with colorectal extranodal NK/T cell lymphoma, there were 35 males and 17 females, with a male-to-female ratio of 2.06∶1. Among the general symptoms, abdominal pain was the most common (39 cases), and B symptoms occurred in 47 patients, among which fever was the most common lymphoma B symptom (42 cases), and gastrointestinal perforation was the most common complication (18 cases). Forty-three patients underwent colonoscopy, and the main manifestations under endoscopy were the ulceration type (24 cases). The ulcers were irregular at the edges and often covered with moss at the bottom. The median survival time was 4.3 months. Multivariate Cox regression analysis showed that hemocytic syndrome ( HR=8.50,95% CI: 1.679-8.328, P=0.001), serum albumin ( HR=3.59,95% CI: 1.017-6.551, P=0.048), and with or without chemotherapy ( HR=0.31, 95% CI: 0.246-1.061, P=0.025) were independent factors influencing the overall survival of patients with colorectal extranodal NK/T cell lymphoma. Conclusions:Colorectal extranodal NK/T cell lymphoma is a rare disease with a very poor prognosis. When patients present with abdominal pain and lymphoma B symptoms, and when ulcers with irregular edges and moss covering the bottom are found under endoscopy, the disease should be considered, and endoscopic biopsy should be taken in time for pathological diagnosis. The prognosis of patients with hemophagocytic syndrome and hypoproteinemia is poor. This disease should be treated with chemotherapy and surgery, and on this basis, hemophagocytic syndrome and hypoproteinemia should be treated to improve the prognosis of patients.

Objective:To investigate the iodine nutrition level and thyroid function status of pregnant women in Hubei Province.Methods:According to the requirements of "the National Iodine Deficiency Disorders Monitoring Program (2016 Edition)", in 2020, using a cross-sectional survey method, two mountainous counties and two plain areas in Hubei Province were divided into five districts: east, west, south, north, and central. One township (street) was selected from each district, and 20 pregnant women were selected from each township (street) as survey subjects. Urine iodine content and thyroid function indicators [serum free triiodothyronine (FT 3), free thyroxine (FT 4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb)] were tested. Abnormal thyroid function rate and antibody positive rate were analyzed, and correlation analysis of thyroid function indicators was conducted (Spearman method). Results:A total of 321 pregnant women were included, including 43, 114, and 164 in early, middle, and late pregnancy, respectively; The median urinary iodine was 164.80 μg/L. The median serum FT 3, FT 4, TSH, TPOAb, TgAb levels were 4.10, 12.83 pmol/L, 1.85 mU/L, 15.84 and 13.35 U/ml, respectively. There were statistically significant differences in FT 3, FT 4, and TSH levels among different trimesters ( P < 0.05). According to Spearman's correlation analysis, FT 3 in early stage of pregnancy was negatively correlated with TSH and TPOAb levels ( r = - 0.46, - 0.33, P < 0.05), while TSH was positively correlated with TPOAb level ( r = 0.33, P = 0.032); there was a positive correlation between FT 4 and TgAb levels in middle stage of pregnancy ( r = 0.21, P = 0.032); there was a negative correlation between FT 3 and TPOAb levels in late stage of pregnancy ( r = - 0.19, P = 0.017); FT 3 and FT 4, TPOAb and TgAb levels were positively correlated throughout pregnancy ( P < 0.05). There was no correlation between urinary iodine content and thyroid function indicators ( P > 0.05). The total abnormal rate of thyroid function was 7.79% (25/321), with 16.28% (7/43), 5.26% (6/114), and 7.32% (12/164) in early, middle, and late pregnancy, respectively. There was no statistically significant difference in the abnormal rate of thyroid function among different pregnancy periods (χ 2 = 4.83, P = 0.097). The detection rates of hypothyroxinemia, hypothyroidism, subclinical hypothyroidism, hyperthyroidism, and subclinical hyperthyroidism were 4.36% (14/321), 0.31% (1/321), 2.49% (8/321), 0.31% (1/321), and 0.31% (1/321), respectively. The positive detection rate of autospecific antibodies was 10.28% (33/321), with a TPOAb positive detection rate of 9.97% (32/321) and a TgAb positive detection rate of 5.30% (17/321). Conclusions:The iodine nutrition level of pregnant women in Hubei Province is at a suitable level, and the rates of abnormal thyroid function and thyroid autospecific antibody positive are relatively low. It is necessary to continuously monitor the iodine nutrition and thyroid function indexes of pregnant women, strengthen health education on the hazards of iodine deficiency during pregnancy, and minimize the harm to maternal and infant health caused by iodine deficiency.

Objective: To analyze the trend of the burden of leukemia among people under 35 years in China from 1990 to 2019. Methods: Incidence, mortality and disability-adjusted life years (DALY) of leukemia among people under 35 years in China from 1990 to 2019 were collected by using the Global Burden of Disease (GBD) Study Database 2019. The trends in leukemia incidence, mortality and DALY rates were analyzed using the average annual percent change (AAPC) and age-period-cohort model. Results: From 1990 to 2019, the incidence, mortality and DALY rates of leukemia among people under 35 years in China showed a downward trend (AAPC=-2.336%, -3.604% and -3.589%, all P<0.05), with more pronounced downward trends in females (AAPC=-3.209%, -3.787% and -3.818%, all P<0.05) than in males (AAPC=-2.521%, -3.292% and -3.306%, all P<0.05). According to the age-period-cohort model, the risks of leukemia incidence, mortality and DALY rates decreased with increasing age. Among them, the children under 5 years had the highest risks of leukemia incidence, mortality and DALY rates (RR=4.697, 2.718 and 3.059). Over time, the risks of leukemia incidence, mortality and DALY rates also decreased from 1990-1994 (RR=1.217, 1.264 and 1.296) to 2015-2019 (RR=0.901, 0.696 and 0.691). With regard to birth cohorts, the risks of leukemia incidence, mortality and DALY rates first increased and then decreased, peaking in the 1986-1990 birth cohort (RR=1.335, 1.192 and 1.231). Conclusions The incidence, mortality and DALY rates of leukemia among people under 35 years in China from 1990 to 2019 showed a downward trend. Males and children under 5 years were the key populations for leukemia prevention and control.

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).