[Expression of DARS2 in colorectal cancer and its clinical significance].

Objective: To investigate the expression of DARS2 and its clinical significance in colorectal cancer. Methods: In this study, bioinformatics tools, especially gene expression profile interactive analysis 2 (GEPIA2), were used to conduct an in-depth analysis of DARS2 expression in colorectal cancer tissues. Immunohistochemical staining was carried out in 108 colorectal cancer specimens and 30 normal colorectal tissues obtained from the First Affiliated Hospital of Nanchang University, Nanchang, China. Colorectal cancer cell lines (HCT116 and SW480) were transfected with small interfering RNA (siRNA) and DARS2 overexpression plasmid to examine the effects of DARS2 knockdown and overexpression on cell function. To assess the effects on cell function, CCK8 and transwell migration assays were used to assess proliferation and cell motility, respectively. Additionally, protein immunoblotting was employed to scrutinize the expression of proteins associated with the epithelial-mesenchymal transition of colorectal cancer cells. Results: DARS2 exhibited a pronounced upregulation in expression within colorectal cancer tissues compared to their normal epithelial counterparts. Furthermore, DARS2 expression was higher in colorectal cancer of stage Ⅲ-Ⅳ than those of stage Ⅰ-Ⅱ, exhibiting a significant correlation with N staging, M staging, and pathological staging (P<0.05). Kaplan-Meier analyses showed a decreased overall survival rate in colorectal cancer with DARS2 expression compared to those without DARS2 expression (P<0.05). In the siRNA transfection group, there was a significant reduction in cell proliferation and migration (P<0.01 and P<0.05, respectively). Conversely, the transfection of DARS2 overexpression plasmids substantially increased both cell proliferation and migration (P<0.05). Additionally, immunoblotting revealed that DARS2 knockdown led to an upregulation of E-cadherin expression and a downregulation of N-cadherin and vimentin expression. In contrast, DARS2 overexpression resulted in increased N-cadherin and vimentin expression, coupled with reduction in E-cadherin expression. Conclusions: There is a strong association between DARS2 expression and colorectal cancer progression. Silencing DARS2 inhibits cell proliferation and migration, exerting a discernible influence on the epithelial-mesenchymal transition process.

[Pituitary Crooke cell neuroendocrine tumor of adrenocorticotropic hormone differentiation-specific transcription factor lineage: a clinicopathological analysis of six cases].

Objective: To investigate the clinicopathological features of Crooke cell tumor of adrenocorticotropic hormone differentiation specific transcription factor (TPIT, also known as transcription factor 19, TBX19) lineage neuroendocrine tumors. Methods: Six cases of Crooke cell tumor diagnosed at the First Affiliated Hospital of University of Science and Technology of China, Hefei, China from October 2019 to October 2023 were collected. The clinical and pathological features of these cases were analyzed. Results: Among the six cases, one was male and five were female, with ages ranging from 26 to 75 years, and an average age of 44 years. All tumors occurred within the sella turcica. Clinical presentations included visual impairment in two cases, menstrual disorders in one case, Cushing's syndrome in one case, headache in one case, and one asymptomatic case discovered during a physical examination. Preoperative serum analyses revealed elevated levels of cortisol and adrenocorticotropic hormones in two cases, elevated cortisol in two cases, elevated adrenocorticotropic hormone in one case, and one case with a mild increase in prolactin due to the pituitary stalk effect. Magnetic resonance imaging revealed uneven enhancement of masses with maximum diameters ranging from 1.7 to 3.2 cm, all identified as macroadenomas. Microscopically, tumor cells exhibited irregular polygonal shapes, solid sheets, or pseudo-papillary arrangements around blood vessels. The cell nuclei were eccentric or centrally located, varying in size, with abundant cytoplasm. Some tumor cells showed perinuclear halo. Immunohistochemistry demonstrated diffuse strong positivity for TPIT in five cases, focal weak positivity for TPIT in one case, diffuse strong positivity for adrenocorticotropic hormone in all cases, and faint staining around the nuclei in a few cells. CK8/18 showed a strong positive ring pattern in more than 50% of tumor cells, focal weak positive expression of p53, and the Ki-67 positive index ranged 1%-5%. Periodic acid-Schiff staining revealed positive cytoplasm and negative perinuclear areas. Conclusions: Crooke cell tumor is a rare type of pituitary neuroendocrine tumors. Its pathological characteristics include a distinctive perinuclear clear zone and immunohistochemical markers, such as CK8/18 exhibiting a ring or halo pattern. This entity represents a high-risk subtype among pituitary neuroendocrine tumors, displaying a high risk of invasion and a propensity for recurrence. Accurate diagnosis is crucial for the postoperative follow-up and multimodal treatment planning.

[Safety and immunogenicity of freeze-dried rabies vaccine (Vero-cells) for human use in healthy people aged 9-65 years].

Objective: To assess the safety and immunogenicity of freeze-dried rabies vaccine (Vero-cells) for human use on different immunization procedures in healthy people aged 9-65 years. Methods: A randomized, blind, positive-controlled clinical study was conducted in March 2015. The eligible residents aged 9-65 were recruited in Dengfeng city and Biyang County, Henan Province. A total of 1 956 subjects were enrolled. The subjects were randomly (1∶1∶1) assigned to 5-dose control group, 4-dose trial group and 5-dose trial group, with 652 subjects in each group. The subjects of 5-dose control group were immunized with control vaccine on days 0, 3, 7, 14 and 28. The subjects of 4-dose trial group were immunized with trial vaccine on days 0, 7 and 21 (2-1-1 phases) and the subjects of 5-dose trial group were immunized with trial vaccine on days 0, 3, 7, 14 and 28. A combination of regular follow-up and active reporting was used to observe local and systemic adverse reactions till 30 days after the first and full immunization, and the incidence rate of adverse reactions in three groups was analyzed and compared. The venous blood was collected before the first immunization, 7 days after the first immunization, 14 days after the first immunization and 14 days after the full immunization. The neutralizing antibody of rabies virus was detected by rapid fluorescent focus inhibition test (RFFIT), and the seropositive conversion rate and geometric mean concentration (GMC) of antibody were calculated. Results: The adverse reaction rates in 5-dose control group, 4-dose trial group and 5-dose trial group were 41.87% (273/652), 35.43% (231/652) and 34.97% (228/652), respectively. The adverse reaction rates of 4-dose trial group and 5-dose trial group were lower than those of the 5-dose control group (P<0.05). The local reactions were mainly pain, itching, swelling and redness in injection site, while the systemic reactions were mainly fever, fatigue, headache and muscle pain. The severity of adverse reactions was mainly mild (level 1), accounting for 85.33% (518/607), 89.02% (373/419) and 88.96% (427/480) of the total number of adverse reactions in each group. At 14 days after the first immunization and 14 days after the full immunization, the antibody positive conversion rates of three groups were all 100%. At 7 days, 14 days after the first immunization and 14 days after the full immunization, the GMCs of three groups were 0.60, 0.72, 0.59 IU/ml, 20.42, 23.99, 24.38 IU/ml and 22.95, 23.52, 24.72 IU/ml, respectively, with no significant difference (P>0.05). Conclusion: The freeze-dried rabies vaccine (Vero-cells) for human use has good safety and immunogenicity when inoculated according to 5-dose and 4-dose immunization procedures.

[Medium-term efficacy and safety analysis of Ex-PRESS shunt implantation for the treatment of secondary glaucoma in Sturge-Weber syndrome].

Objective: To evaluate the medium-term efficacy and safety of Ex-PRESS shunt implantation in the treatment of secondary glaucoma associated with Sturge-Weber Syndrome (SWS). Methods: This was a retrospective case series study. Medical records of patients diagnosed with secondary glaucoma due to SWS who underwent Ex-PRESS shunt implantation at Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, between January 2013 and February 2020 were collected. Only the right eye were included in the analysis when both eyes were affected. Follow-up visits were scheduled at postoperative week 1, 3 months, 6 months, 1 year, 2 years, and 3 years. Clinical data including intraocular pressure (IOP), vertical cup-to-disc (C/D) ratio, corneal horizontal diameter, visual field, anterior chamber condition, anti-glaucoma medication usage, and additional surgeries were evaluated and analyzed before and after the procedure. Surgical success rates and procedure-related complications at each follow-up time point were assessed. Statistical analyses were performed using t-test, Mann-Whitney U test, and χ2 test. Results: A total of 21 patients (21 eyes) were included in the study, comprising 10 females and 11 males. Among them, 15 eyes were on the right side, and 6 eyes were on the left side. The patients' ages ranged from 3 to 51 years, with a median age of 8.1 (6.3, 11.9) years. The follow-up period ranged from 3 to 53 months, with a median of 11 (6, 24) months. Preoperatively, the IOP in the 21 operated eyes was (32.9±9.1) mmHg (1 mmHg=0.133 kPa), significantly higher than the IOP in the 19 healthy eyes, which was (17.1±4.3) mmHg (t=5.80, P<0.001). The C/D ratio in the operated eyes was (0.75±0.13), also significantly higher than that in the healthy eyes, which was (0.32±0.10) (t=11.22, P<0.001). At the 1-year, 2-year, and 3-year follow-up, 8 eyes out of 16 operated eyes, 6 eyes out of 9 operated eyes, and 7 eyes out of 10 operated eyes achieved overall surgical success (complete success+conditional success), respectively. The number of eyes with complete success at the three follow-up time points was 3, 2, and 4, respectively. The IOP in the operated eyes was significantly reduced at all follow-up time points compared to preoperative values (all P<0.05), while there was no statistically significant difference in C/D ratio before and after surgery (all P>0.05). Two operated eyes experienced retinal detachment or choroidal leakage postoperatively, both of which recovered after conservative treatment. One eye developed postoperative degree Ⅰ shallow anterior chamber, and it resolved spontaneously on the third day after surgery. No serious surgical complications, such as bleb-related complications, malignant glaucoma, expulsive choroidal hemorrhage, or endophthalmitis, were observed postoperatively. Conclusions: Ex-PRESS shunt implantation for the treatment of secondary glaucoma in SWS demonstrated a relatively high level of safety. The medium-term IOP in the operated eyes significantly decreased compared to preoperative values. However, the majority of operated eyes did not achieve complete surgical success.

[An area under curve-based nomogram to predicts vancomycin-associated nephrotoxicity in critically ill patients: a retrospective cohort study].

Objective: To develop an area under curve (AUC)-based nomogram to predict vancomycin-associated nephrotoxicity in critically ill patients. Methods: This retrospective cohort study included adult patients treated with vancomycin in the intensive care unit at a tertiary teaching hospital from January 2015 to December 2017. Baseline clinical characteristics before vancomycin treatment and pharmacokinetic parameters were collected to establish a prediction model of nephrotoxicity. Univariate analysis was used to screen variables, and multivariate logistic regression analysis was used to establish the prediction model and nomogram. Results: A total of 159 patients met the inclusion criteria, sixty-four were included in the final analysis. Sixteen patients (25%, 16/64) developed vancomycin-associated nephrotoxicity. The following variables were incorporated into the prediction model: vancomycin AUC, estimated glomerular filtration rate (GFR), and combined nephrotoxic drugs. The following equation was established to calculate the probability of nephrotoxicity: logit (P)=-4.83+0.009×AUC-2.87×1 (if GFR>60 ml/min)+2.53×1 (if number of combined nephrotoxic drugs≥2). A nomogram was generated based on the equation. The receiver-operating characteristic curve demonstrated that the AUC of the prediction model was 0.927 (95%CI 0.851-1.000). The cut-off value of the probability of nephrotoxicity was 26.48%. The sensitivity and specificity were 87.5% and 87.5% respectively. Conclusion: The incidence of vancomycin-associated nephrotoxicity is high. The AUC-based nomogram can effectively predict vancomycin-associated nephrotoxicity in critically ill patients.

[Immunogenicity of group A+C meningococcal polysaccharide conjugate vaccine in infants: A phase â ¢ clinical trial study].

Objective: To evaluate the immunogenicity of group A+C meningococcal polysaccharide conjugate vaccine in infants under 2 years old. Methods: From March 2017 to June 2018, 1 932 healthy infants in Biyang County, Henan Province, who were not vaccinated with meningococcal meningitis vaccine and whose axillary temperature was ≤37.0 ℃, were recruited as participants. The 3 months and 6-11 months old infants were allocated to the experiment group and the control group in a ratio of 1∶1. Infants aged 12-23 months were allocated to the 1-dose group, the 2-dose group and the control group in a ratio of 1∶1∶1, with 276 infants in each group. The infants in the experiment group were intramuscularly injected with freeze-dried group A+C meningococcal polysaccharide conjugate vaccine to be evaluated, and infants in the control group received intramuscular injection of commercially available freeze-dried group A+C meningococcal conjugate vaccine. The venous blood of infants was collected 30 days before the first dose and after the last dose of inoculation, and the antibody seroconversion of each group was determined and compared. Results: The completion rate of immunogenicity study was 95.2% (1 839/1 932). Before inoculation, there was no statistical difference in the geometric mean titer and positive rate of group A+C antibodies between the experiment group and the control group in 3 months and 6-11 months old infants (all P values >0.05). The geometric mean titers and positive rate of group A antibodies in the 1-dose group were higher than those in the control group (all P values <0.05), but there was no statistical difference between the 2-dose group and the control group (all P values >0.05) in infants aged 12-23 months. After inoculation, the differences (95%CI) in the positive conversion rate of group A+C antibodies between the experiment group and the control group were -0.12% (-6.01%-5.77%) and 0.82% (-4.23%-5.86%) in the 3 months old infants. At the age of 6-11 months, the differences were 6.75% (1.71%-11.79%) and -4.32% (-8.73%-0.08%), respectively. At the age of 12-23 months, the differences were 1.02% (-3.80%-5.83%) and -4.40% (-7.79%- -1.01%) in the 2-dose group and -7.22% (-12.90%- -1.54%) and -18.61% (-23.75%- -13.46%) in the 1-dose group, respectively. The geometric mean titers of group A+C antibodies in the 3 months old infants were 48.50 and 63.12, respectively, which had no significant difference from the control group (43.02 and 57.99, respectively) (both P values <0.05). The geometric mean titers of group A+C antibodies in the 6-11 months and 12-23 months old infants were 84.09 and 92.51 (2-dose group), which were higher than those in the corresponding control group (43.10 and 61.83, respectively) (all P values <0.001). Conclusion: Group A+C meningococcal conjugate vaccine has good immunogenicity in infants under 2 years old.

[A phase â ¢ clinical trial study on the safety and immunogenicity of ACYW135 group meningococcal conjugate vaccine inoculated in 3 month old infants].

Objective: The aim of this study was to evaluate the safety and immunogenicity of the first domestic ACYW135 meningococcal conjugate vaccine and a control vaccine named AC group meningococcal conjugate vaccine for 3 months (90-119 days) infants. Methods: From February 2017 to June 2018, a randomized, blinded, and similar vaccine-controlled clinical trial design was adopted at the Henan Vaccine Clinical Research Base. The subjects were 3 months old healthy infants, a total of 720, based on a 1∶1 ratio. The random allocation table for entry was randomly assigned to the experimental group and the control group. According to the 3, 4, and 5 month-old vaccination procedures, the subjects were vaccinated with test vaccine (ACYW135 group meningococcal conjugate vaccine) and control vaccine (group A group C meningococcal polysaccharide conjugate vaccine), of which 720 were given the first dose, 696 were given the second dose (test group: 346; control group: 350), and 692 were given the third dose (test group: 344; Control group: 348). Results: The overall adverse reaction rate of the test vaccine was 21.90% (230 cases), which was lower than the 32.04% (339 cases) of the control vaccine (P<0.001). The incidence of systemic adverse reactions was 19.52% (205 cases), which was lower than that of the control vaccine (27.69%) (293 cases) (P<0.001). The local adverse reaction rate was 3.04% (32 cases), which was lower than the control group (7.84%) (83 cases) (P<0.001). The graded adverse reaction test vaccine was 0.57% (6 cases), which was lower than the control group of 2.36% (25 cases) (P<0.001). The positive conversion rate of anti-bacterial serum antibodies showed that there was no significant difference between the test vaccine group A (91.42%), C (88.76%) and the control vaccine (92.92%) (87.02%) (P>0.05). Group Y and W135 was 88.17% (298 cases), 99.41% (336 cases), respectively. The GMT results showed that the test vaccine group A was 56.24, the control vaccine was 57.43 (P>0.05); the group C test vaccine (43.53) was higher than the control group (27.28) (P<0.001). The group Y and W135 are 89.22 and 140.66, respectively. Among them, the proportion of the group C GMT antibody ≥ 1∶128 for test vaccine (31.07%, 105 cases) was higher than the control vaccine (16.22%, 55 cases) (P<0.001). Conclusion: ACYW135 group meningococcal conjugate vaccine has more safety and immunogenicity after application to 3 month old infants.

[Analysis of prognosis factors for reintervention after endovascular aneurysm repair in patients with abdominal aortic aneurysm].

Objectives: To examine the prognosis factors for readmission after endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA) patients in the Chinese population. Methods: A total of 1 129 AAA patients who underwent EVAR at Department of Vascular Surgery, Zhongshan Hospital, Fudan University, from January 2010 to December 2017 were enrolled. There were 948 males and 181 females, with an age of (71.2±9.6) years (range: 18 to 93 years). Comorbidities included primary hypertension found in 630 patients, diabetes mellitus in 129 patients and coronary heart disease in 163 patients. A total of 214 patients had a history of smoking, and 11 patients had a history of previous aortic intervention.Clinical data including baseline information, laboratory examinations and follow-up data before December 31, 2019 were retrospectively collected. The primary end point was readmission. Cox regression analysis was used to analyze the prognosis factors for the end point. Results: All patients completed at least one follow-up with a follow-up time of 22.7(42.6) months (range: 1 to 120 months). The readmission rate of 1 year post-operation was 4.52% (51/1 129). The overall readmission rate was 11.34% (128/1 129) during the whole follow-up duration. The main reasons of readmission included endoleak in 60 patients with readmission, iliac limb occlusion in 25 patients and distal iliac aneurysm in 12 patients. Age (HR=0.972, 95%CI: 0.956 to 0.987, P<0.01) and elevated pre-operative fibrinogen level (HR=2.213, 95%CI: 1.185 to 4.134, P=0.013) were found to be the prognosis factors for the survival time free from aortic-related readmission in univariate Cox regression analysis. Elevated pre-operative fibrinogen level (HR=2.542, 95%CI: 1.353 to 4.776, P=0.004) was found to be the prognosis factor for the survival time free from aortic-related readmission in multivariate Cox regression analysis. Conclusions: The most common reason for readmission was endoleak, followed by iliac limb occlusion and distal iliac aneurysm. Elevated pre-operative fibri nogen level was the risk factor for the survival time free from aortic-related readmission, though further researches were warranted for exploring the underlying mechanism.

[Immunocheckpoint inhibition in head and neck squamous cell carcinoma: the current status and progress].

Over the past decades, although the clinical efficacy of advanced head and neck squamous cell carcinoma (HNSCC) has been moderately improved by the combination of cetuximab and chemotherapy, no remarkable treatment has emerged. The prognosis of HNSCC is still unsatisfied. With the deeper exploration of tumor immunological therapy, immunocheckpoint inhibitors such as monoclonal antibodies targeting on programmed cell death protein 1 (PD-1)/ cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) have shown appreciable anti-tumor effect on cancers such as melanoma and non-small cell lung cancer. Some successful clinical studies on HNSCC have also been reported, which provide a new opportunity for the improvement of HNSCC prognosis.Here we systemically review the progress of checkpoint inhibitors and its combination therapy in HNSCC, some immunotherapy efficacy-related biomarkers are also discussed.

[The influencing factors achieving target vancomycin trough level in critically ill patients].

Objective: To assess the rate achieving the target vancomycin trough level (VTL) and its influencing factors in critically ill patients. Methods: The retrospective observational study recruited adult patients treated with intravenous vancomycin in the intensive care unit (ICU) at Zhongda Hospital from January 2015 to December 2017. Serum VTL was tested at steady state. Patients' demographics, the sites of infection, microbial culture results, the severity of illness, laboratory data and vancomycin regimen were obtained at the baseline. The rate achieving target VTL (15-20 mg/L) was analyzed based on renal function. Linear regression was performed to determine the influencing factors of VTL. Results: A total of 85 patients were enrolled, among whom only 23.5% (20/85) achieved the target VTL. In patients with normal renal function, the achieving rate was only 11.4% (4/35), and 80.0% (28/35) was lower than the target trough level multiple linear regression analysis showed that procalcitonin (PCT), estimated glomerular filtration rate (eGFR) and acute physiology and chronic health disease classification system Ⅱ (APACHE Ⅱ) score were independent factors associated with VTL. Conclusion: Achieving target VTL in critically ill patients is not satisfactory. Further study to optimize the administration is needed to facilitate prompt attainment of target VTL.

[The propensity score method and it's application].

Propensity score method, as an analytical strategy for adjusting multiple covariates, has been widely used in observational comparative effectiveness research. This paper introduces this method covered basic principles, case illustration and software implementation, in order to help readers understand propensity score method, apply it correctly in their researches, improve the efficiency of data utilization, and enhance the level of statistical analysis.

[Screening of optimal siRNA interference sequence of CIT gene and its inhibition expression in hepatoma SK-Hep-1].

Objective: To construct and screen optimal siRNA interference sequence of CIT gene and to detect its interference efficiency as well as proliferation effect in human hepatoma cell line SK-Hep-1. Methods: Three siRNA target spots were designed and synthesized according to the CIT gene sequence. SK-Hep-1 HCC cells were transfected by liposome transfection. The knockdown efficiency of the target CIT gene was detected by real-time PCR and Western blot. Expressional change of CIT in SK-Hep-1 cells after 48 hours of siRNA interference were observed by immunohistochemistry and confocal microscopy. The proliferation of SK-Hep-1 cells after 48 hours of siRNA interference was detected by EdU cell proliferation assay. A t-test was used to compare the mean of two samples, and one-way ANOVA was used to compare the mean of multiple samples. Results: Western blot results showed that the three interference sequences were targeted at different target spots. The expression level of CIT protein in KD-1,-2, and-3 groups were decreased (P < 0.01) than control, while the protein expression level of KD1 group was the lowest. Real-time PCR results showed that compared with the control group, the expression level of CIT mRNA in KD-1, -2, and -3 groups decreased (P < 0.01), while that in KD1 group was the lowest. Laser confocal microscopy also confirmed that the morphological expression of CIT attenuated significantly after transfection with siRNA. The results of EdU proliferation assay showed that siRNA transfected with CIT significantly attenuated the proliferation of SK-Hep-1 hepatoma cells (P < 0.05). Conclusion: The successful construction and screening of siRNA fragments can effectively inhibit the expression and proliferation of CIT gene in hepatoma SK-Hep-1.

[Overexpression of protein phosphatase 2 regulatory subunit B''α gene effect on proliferation and invasion of hepatoma cells].

Objective: To study the overexpression of protein phosphatase 2 regulatory subunit B''α gene effects on the proliferation and invasion of hepatoma cells. Methods: Immunohistochemistry method was used to analyze the expression of PPP2R3A in cancerous and paracancerous tissues. Hepatocellular carcinoma cell lines (Huh-7 and HepG2) with stably overexpressing PPP2R3A were constructed by lentiviral vector. Biological behavioral transition in hepatocellular carcinoma cell proliferation, cell cycle, apoptosis, invasion and metastasis were detected by cell counting kit-8 assay (CCK-8), flow cytometry, and transwell assay. A subcutaneous nude tumor mice model was constructed to validate the growth of hepatoma cells. Two independent sample t-tests were used to compare the groups. Results: The expression of PPP2R3A gene in human hepatocarcinoma tissues was higher than paracancerous tissues. The absorbance (A value) of hepatoma cells was increased (P < 0.05) after overexpression of PPP2R3A gene. The transition from G1-to-S phase was significantly increased i.e., the G1 phase of the cell cycle was reduced (Huh-7: t = 3.04, P = 0.0384; HepG2: t = 4.06, P = 0.0153), while the S phase was increased (Huh-7: t = 3.47, P = 0.0255; HepG2: t = 4.46, P = 0.0112). Early apoptotic rate was decreased (Huh-7: t = 7.34, P = 0.0018; HepG2: t = 4.06, P = 0.0153). The number of Huh-7 cells migrating to the lower chamber was increased (t = 3.18, P = 0.0334), and after the use of matrigel the number of cells reaching to the lower chamber was also increased (t = 2.84, P = 0.0464). The results of animal experiments showed that the subcutaneous tumor growth (t = 4.31, P = 0.0035) was significantly overexpressed in nude mice group. The results of Western blot showed that the expression of PARP and P53 protein in the spliced ​​forms decreased, while the accumulation of ß-catenin protein in the liver cancer cells was increased. Conclusion: Overexpressed PPP2R3A gene may promote proliferation, migration and invasion ability, inhibit apoptosis, induce G1/S phase transition, and participate in the biological behavior of hepatoma cells.

[Analysis of factors affecting the noise-induced high frequency hearing loss of male workers in a vehicle manufacturing enterprise].

Objective: To analyze the relationships between the exposure of occupational noise and the occurrence of noise-induced high frequency hearing loss in automobile manufacturing industry. Methods: From June to November 2017, 1579 male workers were selected for exposure to noise hazards in the automobile manufacturing industry in Guangzhou for more than one year (including one year) using the convenient sampling method. According to the hearing test results, 276 people in the high frequency hearing loss group and 1303 in the normal hearing group were surveyed, occupational health tests were conducted, and the noise intensity in the workplace was measured. The cumulative noise exposure (CNE) was calculated. The relationship between shift work and high frequency hearing loss of noise work is analyzed. Results: Compared with the normal hearing group, the noise exposure intensity, age, length of service, marital status, working system, and physical exercise of the high frequency hearing loss group were statistically significant (P<0.05). Through logistic regression analysis, after correcting the effects of organic solvent contact, marital status, and physical exercise, CNE, age, and shift operations (double-shift operations, three-shift operations) are the risk factors for high frequency hearing loss to occur. Conclusion: The risk of hearing loss of workers exposed to noise in the whole vehicle manufacturing industry may be related to CNE, age, and shift work. Two-shift and three-shift work are possible risk factors for noise-induced high frequency hearing loss.

[An analysis of work-related musculoskeletal disorders and ergonomic loads in male welders in shipbuilding industry].

Objective: To investigate the prevalence of work-related musculoskeletal disorders (WMSDs) in male welders in different work areas of shipbuilding industry based on their operational working position and body position characteristics and to analyze the operational positions and ergonomic loads. Methods: In February 2017, 412 male welders from the hull and block work areas of a large ship factory were selected by stratified sampling. The prevalence and effects of WMSDs within a year were investigated using the Nordic Musculoskeletal Disorders Questionnaire, and a rapid exposure checklist was used to obtain the ergonomic load index by comprehensive scoring; the exposure-response relationship between the ergonomic loads and WMSDs symptoms of subjects in the hull and block work areas was evaluated. Results: Among the male welders working in the hull work area of shipbuilding industry, WMSDs occurred more commonly in the neck, lower back/waist, and legs, accounting for 53.16% (126/237) , 51.90% (123/237) , and 41.77% (99/237) , respectively; among those working in the block work area, WMSDs occurred more commonly in the lower back/waist, wrist, and legs, accounting for 52.57% (92/175) , 49.14% (86/175) , and 45.14% (79/175) , respectively. There were significant differences in the distribution of cases of pain within the last 7 days and one month, pain lasting more than one month, or absence from work due to pain within a year in the four positions between the two work areas (P<0.05). In the hull work area, high and extremely high exposure levels were mainly seen in the neck, lower back/waist, and legs, accounting for 76.79%(182/237), 69.20%(164/237), and 59.49%(141/237), respectively; in the block work area, high and extremely high exposure levels were mainly seen in the lower back/waist, wrist, and legs, accounting for 77.71%(136/175), 50.29% (88/175), and 46.29% (81/175), respectively. The detection rates of WMSDs in these four positions significantly increased as the exposure levels rose (P<0.01). Conclusion: The WMSDs of male welders working in the hull and block work areas of shipbuilding industry occurs more commonly in the lower back/waist and legs. The risk of WMSDs symptoms increases with the rise of ergonomic load.

Dietary exposure assessment of cyadox based on tissue depletion of cyadox and its major metabolites in pigs, chickens, and carp.

The tissue kinetics of cyadox, an antibacterial agent used in food animals, and its major metabolites in pigs, chickens, and carp were investigated followed by a complete dietary exposure assessment to evaluate the food safety of cyadox. Cyadox and its major metabolites, bisdeoxycyadox (Cy1), 4-desoxycyadox (Cy2), N-(quinoxaline-2-methyl)-cyanide acetyl hydrazine (Cy4), quinoxaline-2-carboxylic acid (Cy6), and 2-hydromethyl-3-hydroxy-quinoxaline (Cy12), were simultaneously quantitated with a high-performance liquid chromatography-ultraviolet (HPLC-UV) method. Pigs, chickens, and carp were fed with 150 mg/kg cyadox in feed for consecutive 60, 40, and 30 days, respectively. The residue amount of cyadox and its major metabolites in liver, kidney, muscle, and fat (skin) tissues was determined. Cy2 was below the limit of quantitation even at the withdrawal time of 6 hr, cyadox, Cy4, Cy6, and Cy12 could be detected at 6-24 hr with low level less than 50 µg/kg. By contrast, Cy1 persisted for 3 days in the kidney of pigs and chickens, and in the liver of carp. Based on these residue depletion data and previous toxicology results, the global estimated chronic dietary exposure assessment of cyadox for general population was conducted, indicating a zero withdrawal time (WDT) may be appropriate for cyadox in food animals when used in feed for prolonged administration. These results provide analytical techniques and safety standards suitable for residue monitoring of cyadox in food animals.

Diffusion-limited PBPK model for predicting pulmonary pharmacokinetics of florfenicol in pig.

For most bacterial lung infections, the concentration of unbound antimicrobial agent in lung interstitial fluid has been thought to be responsible for antimicrobial efficacy. In this study, a diffusion-limited physiologically based pharmacokinetic (PBPK) model was developed to predict the pulmonary pharmacokinetics of florfenicol (FF) in pigs. The model included separate compartments corresponding to blood, diffusion-limited lung, flow-limited muscle, liver, and kidney and an extra compartment representing the remaining carcass. The absorption rate constant and renal and hepatic clearance of FF were determined in vivo. Other parameters were taken from the literature or optimized based on existing pharmacokinetic data. All mathematical operations during the development of the model were performed using acslXtreme version 3.0.2.1 (Aegis Technologies Group, Inc., Huntsville, AL, USA). The model accurately predicted the concentration-time courses of FF in lung interstitial fluid, serum, and plasma following different dosing schedules, except at the dose of 15 mg/kg. When compared with the tissue residue data, the model generally underestimated the FF concentration at the injection site, whereas it gave good predictions of FF concentrations in lung, liver, and kidney at early time points. The model predictions provide a scientific basis for the dosage regimen design of FF.

[Antiretroviral treatment discontinuation and its influencing factors among HIV-infected patients who initiated ART from 2012 to 2015 in Wenshan prefecture, Yunnan Province].

Objective: To understand the antiretroviral treatment (ART) discontinuation rate and its influencing factors among HIV infected patients who initiated ART between 2012 and 2015 in Wenshan prefecture, Yunnan province. Methods: Demographic characteristics, baseline informations of ART, initial treatment regimens and follow-up status of a total of 4 354 patients who initiated ART from 2012 to 2015 in Wenshan prefecture were collected. A historical cohort study was used to describe the discontinuation incidence rate of ART. Life table was used to estimate cumulative retention rate and Cox proportional hazard model was used to determine the influencing factors of ART discontinuation. Results: The percentage and incidence rate of discontinuation were 25.1% (1 092/4 354) and 14.53 per 100 person-years among patients who initiated ART from 2012 to 2015 in Wenshan prefecture. ART retention rates were 88%, 83%, 78%, 74% at 6(th) month, 12(th) month, 18(th) month, 24(th) month, respectively. The multivariate Cox proportional hazard regression model showed that male patients were at a higher risk of discontinuation (HR=1.24, 95%CI: 1.09-1.41) than female patients, patients aged ≥50 years were at a higher risk of discontinuation (HR=1.27, 95%CI: 1.06-1.53) than patients aged<30 years, discontinuation hazard among patients who were unmarried or divorced or widowed was 1.30 times (HR:1.30, 95%CI: 1.14-1.48) as patients who were married or cohabitation, discontinuation hazard among patients infected with HIV through injection drug use (IDU) was 1.49 times (HR:1.49, 95%CI: 1.23-1.82) as those infected through heterosexual transmission, patients with a baseline CD4 cell count<350/µl (HR=1.34, 95%CI: 1.13-1.58) or ≥500/µl (HR=1.36, 95%CI: 1.09-1.71) were at a higher risk of discontinuation than those with a baseline CD4 cell count from 350/µl to 500/µl, patients initiating ART in 2014 (HR=1.25, 95%CI: 1.04-1.50) or in 2015 (HR=1.26, 95%CI: 1.02-1.55) were at a higher risk of discontinuation than those initiating ART in 2012. Conclusion: There is an uptrend for ART discontinuation rate in Wenshan prefecture. Male, 50 years or older, unmarried or divorced or widowed, transmission route as IDU, baseline CD4 count <350/µl or ≥500/µl are risk factors of ART discontinuation.

[Current prevalence and prevention of work-related musculoskeletal disorders among physicians for internal medical examination in tertiary hospitals in a city of China].

Objective: To investigate the current prevalence and prevention of work-related musculoskeletal disorders (WMSDs) among physicians for internal medical examination, and to provide a theoretical basis for the prevention and treatment of WMSDs in physicians for internal medical examination. Methods: In February 2017, 326 physicians for internal medical examination were randomly selected from 5 general tertiary hospitals and 2 specialized tertiary hospitals in a city of China. A questionnaire was designed according to the Nordic Musculoskeletal Questionnaire and the occupational features of doctors in China to investigate the prevalence of musculoskeletal pain over the past year, the cognitive attitude to WMSDs, the knowledge of WMSDs prevention, and ways to get the knowledge of WMSDs prevention. Results: In the tertiary hospitals of this city, the symptoms of WMSDs were mainly seen in the wrist (75.78%) , neck (67.19%) , and lower back (58.59%) among male physicians, and in the wrist (73.74%) , lower back (70.95%) , and upper back (60.89%) among female physicians. Compared with the female physicians, the male physicians had a significantly increased detection rate of symptoms of WMSDs in the neck (P<0.05) and significantly reduced detection rates of symptoms of WMSDs in the upper and lower back (P<0.05). There were significant differences between the detection rates of symptoms of WMSDs in the neck, wrist, and lower back within the past 12 months, 7 days, and >1 month (P<0.01). The rates of knowledge of the severity and prevention of WMSDs were significantly different between the physicians with different working years and professional titles (P<0.01) . Conclusion: Among the physicians for internal medical examination in the tertiary hospitals of this city, WMSDs are mostly seen in the wrist, neck, and waist, and the knowledge of WMSDs prevention varies with different working years and professional titles.