A 71-year-old female patient underwent laparoscopic right hemicolectomy due to intestinal obstruction caused by malignant colon tumor. The patient had a fever 7 hours after surgery. Because of suspected abdominal infection, intravenous infusion of 2 g mezlocillin was given once every 8 hours on the day of operation. Three days later, the patient was given simnotrelvir (0.75 g)/ritonavir (0.1 g) once every 12 hours because of the positive nucleic acid test of novel coronavirus. Two days later after medication, the patient′s serum creatinine (Scr) increased from 40.2 μmol/L before treatment to 165.1 μmol/L, and the estimated glomerular filtration rate (eGFR) decreased from 100.6 ml/(min·1.73 m 2) before treatment to 26.7 ml/(min·1.73 m 2), without significant oliguria. Drug-induced acute kidney failure (AKI) was suspected, and mezlocillin and simnotrelvir/ritonavir were discontinued. After 3 days of drug withdrawal, the patient′s renal function was improved, with Scr 78.1 μmo1/L; after 15 days, the Scr was 49.7 μmo1/L and eGFR was 93.8 ml/(min·1.73 m 2). It was considered that the patient′s AKI was likely to be related to simnotrelvir/ritonavir. However, the possibility of nephrotoxicity enhancement due to the combination of simnotrelvir/ritonavir and mezlocillin could not be excluded.

A 71-year-old female patient underwent laparoscopic right hemicolectomy due to intestinal obstruction caused by malignant colon tumor. The patient had a fever 7 hours after surgery. Because of suspected abdominal infection, intravenous infusion of 2 g mezlocillin was given once every 8 hours on the day of operation. Three days later, the patient was given simnotrelvir (0.75 g)/ritonavir (0.1 g) once every 12 hours because of the positive nucleic acid test of novel coronavirus. Two days later after medication, the patient′s serum creatinine (Scr) increased from 40.2 μmol/L before treatment to 165.1 μmol/L, and the estimated glomerular filtration rate (eGFR) decreased from 100.6 ml/(min·1.73 m 2) before treatment to 26.7 ml/(min·1.73 m 2), without significant oliguria. Drug-induced acute kidney failure (AKI) was suspected, and mezlocillin and simnotrelvir/ritonavir were discontinued. After 3 days of drug withdrawal, the patient′s renal function was improved, with Scr 78.1 μmo1/L; after 15 days, the Scr was 49.7 μmo1/L and eGFR was 93.8 ml/(min·1.73 m 2). It was considered that the patient′s AKI was likely to be related to simnotrelvir/ritonavir. However, the possibility of nephrotoxicity enhancement due to the combination of simnotrelvir/ritonavir and mezlocillin could not be excluded.

Objective To investigate the correlation between 23 metals and metalloids elements in the urine and thyroid function indicators in the blood of traffic police. Methods A cross-sectional study was performed to assess the effects of 23 metals and metalloids elements in the urine on blood thyroid function indicators in 166 traffic policemen (122 field staff and 44 internal staff) in Wuhan, Hubei Province. Each subject received an occupational health examination. Results After multiple corrections for false detection rates, in the polymetallic model, the levels of urinary manganese and urinary uranium were positively correlated with the levels of thyroid peroxidase antibody (TPOAb) in the blood (β = 66.57, 95% CI 2.92-130.22, P = 0.040 and β = 62.43, 95% CI 14.37-110.49, P = 0.011), and the level of urinary uranium was positively correlated with thyroid stimulating hormone (TSH) levels in the blood (β = 6.20, 95% CI 2.68-9.72 , P = 0.001). Urinary uranium level was negatively correlated with free thyroxine level in the blood (FT4) (β = -2.03, 95 % CI (-3.67 )- (-0.39), P = 0.015), and urinary lead level was negatively correlated with blood TSH level (β = -4.59, 95% CI (-8.67) - (-0.51), P = 0.027). Conclusion Manganese exposure is related to the increase of TPOAb level in blood, uranium exposure is related to the increase of TPOAb and TSH levels and the decrease of FT4 level in blood, and lead exposure is related to the decrease of TSH level in blood, suggesting that more attention should be paid to the effects of heavy metals on the thyroid of traffic police.

[摘 要] 目的：探讨在靶向HER2的CAR的CD3ζ链胞内区引入YRHQ基序对CAR-T细胞的特异性杀伤活性及免疫记忆形成的影响。方法：通过DNA合成获得包含靶向HER2的编码抗原受体H28ζ或H28ζ(YRHQ)的DNA片段，通过慢病毒载体将不同CAR的DNA片段分别转导健康人外周血T细胞，制备靶向HER2的H28ζ-CAR-T及H28ζ(YRHQ)-CAR-T细胞。扩增过程中对不同CAR-T细胞进行计数，FCM检测CAR的表达率。将CAR-T细胞分别与HER2阳性的SKOV3、MDA-MB-453或HER2阴性的MCF-7细胞共培养，LDH释放法检测其杀伤活性，ELISA法检测IL-2、IFN-γ和颗粒酶B的水平，WB法检测STAT3磷酸化水平及免疫检查点分子TIM-3和PD-1的表达，通过FCM检测CCR7、CD45RO的表达，分析CAR-T细胞的表型。结果：H28ζ-CAR-T和H28ζ(YRHQ)-CAR-T细胞扩增能力较好，体外培养7 d时扩增4~5倍。H28ζ-CAR和H28ζ(YRHQ)-CAR表达率分别为（33.3±2.85）%和（28.30±3.2）%。H28ξ(YRHQ)-CAR-T细胞的杀伤活性较H28ζ-CAR-T细胞更高（P<0.05）。经HER2抗原刺激后，与T细胞或H28z-CAR-T细胞比较，H28ξ(YRHQ)-CAR-T细胞的STAT3磷酸化水平较H28ξ-CAR-T细胞明显升高（P<0.01）；而两者间PD-1和TIM-3的表达无明显差异。未经抗原刺激的CAR-T细胞CCR7和CD45RO表达与正常T细胞比较差异无统计学意义（均P>0.05），与SKOV3细胞共培养后，与T细胞或H28z-CAR-T细胞比较，H28ξ(YRHQ)-CAR-T细胞中TEM细胞比例明显增加、TCM细胞比例明显减少（均P<0.05）。结论：在CD3胞内区引入YRHQ基序可在一定程度上提高CAR-T细胞的杀伤潜力。

Objective:To observe the effects of estradiol on expression of plasma membrane Ca 2+-ATPase isoform 2 in inner ear of rats. Methods:Twenty-five Three-months-old female Sprague-Dawley rats were randomly and equally divided into five groups by random number table mathod,with five rats in each group. Animals in Sham group were sham-operated while others were bilateral ovariactmized. One month after modeling, the OVX groups were supplemented with estradiol (E2 group), progesterone (P group), estradiol and progesterone (E2+P group)and vehicle sesame oil (Veh group), while the Sham operation group (Sham group) was supplemented with vehicle sesame oil.All rats were sacrificed and otocysts were obtained immediately. Enzyme-linked immunosorbent assay was used to detect the changes in serum estradiol and progesterone levels of each group of rats before operation, before treatment and before sacrifice. Western blot and quantitative real-time polymerase chain reaction were used to detect the expression of total PMCA2 protein and mRNA in the inner ear of each group.Results:There was no significant difference in serum estradiol and progesterone levels among the five groups before operated( P>0.05). Before treatment, the serum estradiol and progesterone levels of rats in each group were significantly lower than those in Sham group ( P<0.05). The serum estradiol level in E2 group and E2+P group was not significantly different from that in Sham group ( P>0.05), while the serum estradiol level in P group and Veh group was significantly different from that in Sham group ( P<0.05). The level of progesterone in P group and E2+P group was higher than that in Sham group ( P<0.05), while the level of progesterone in Veh group and E2 group was lower than that in Sham group ( P<0.05). Protein and mRNA expression of PMCA2 in P and Veh groups were significantly decreased compared with that of Sham group ( P<0.05) while the expression levels underwent no significantly change in E2 and E2+P groups ( P<0.05). Conclusion:The decrease of serum estradiol level can reduce the expression of otolith regulatory protein PMCA2 in rats, and then affect otolith metabolism, which may be an important link of estrogen affecting otolith metabolism.

Objective:To investigate the prognosis of severe hyperbilirubinemia in full-term infants who met the exchange transfusion criteria and were treated by blood exchange transfusion and phototherapy.Methods:A total of 168 full-term infants with severe hyperbilirubinemia who met the criteria for exchange transfusion and were hospitalized in the Neonatology Department of seven tertiary hospitals in Hebei Province from June 2017 to December 2018 were retrospectively included. According to the treatment protocol, they were divided into two groups: exchange transfusion group (38 cases) and phototherapy group (130 cases). Two independent sample t-test and Chi-square test were used to compare the clinical manifestations and follow-up results between the two groups. Multivariate logistic regression was used to analyze the risk factors for poor prognosis. Results:Neonatal severe hyperbilirubinemia in the exchange transfusion and phototherapy group were both mainly caused by hemolytic disease [42.1%(16/38) and 29.2%(38/130)], sepsis [28.9%(11/38) and 11.5%(15/130)] and early-onset breastfeeding jaundice [15.8%(6/38) and 11.5%(15/130)]. Total serum bilirubin level on admission in the exchange transfusion group was significantly higher than that in the phototherapy group [(531.7±141.3) vs (440.0±67.4) μmol/L, t=3.870, P<0.001]. Moreover, the percentage of patients with mild, moderate and severe acute bilirubin encephalopathy in the exchange transfusion group were higher than those in the phototherapy group [15.8%(6/38) vs 3.8%(5/130), 7.9%(3/38) vs 0.8%(1/130), 13.2%(5/38) vs 0.0%(0/130); χ2=29.119, P<0.001]. Among the 168 patients, 135 were followed up to 18-36 months of age and 12 showed poor prognosis (developmental retardation or hearing impairment) with four in the exchange transfusion group (12.9%, 4/31) and eight in the phototherapy group (7.7%, 8/104). Multivariate logistic regression analysis showed that for full-term infants with severe hyperbilirubinemia who met the exchange transfusion criteria, phototherapy alone without blood exchange transfusion as well as severe ABE were risk factors for poor prognosis ( OR=14.407, 95% CI: 1.101-88.528, P=0.042; OR=16.561, 95% CI: 4.042-67.850, P<0.001). Conclusions:Full-term infants who have severe hyperbilirubinemia and meet the exchange transfusion criteria should be actively treated with blood exchange transfusion, especially for those with severe ABE, so as to improve the prognosis.

Objective:To investigate the influence of the prevalence and co-prevalence of risk factors for metabolic syndrome on the scores of different levels of metabolic syndrome in people receiving physical examination in Urumqi.Methods:Using the 2017 Xinjiang Health Examination Database, a total of 175 927 people from 7 districts and 1 county in Urumqi were selected as subjects. Face-to-face survey and body measurements were used to collect cardiovascular risk factors and metabolic syndrome scores. Metabolic syndrome scores were used. For the 0-5 points at 6 levels, χ2, χ2 trend test, correlation analysis of ordered variable Kendall’s tau-b, and logistic regression analysis of ordered results were used to analyze the influence of prevalence and co-prevalence of behavioral risk factors on the MS scores. Results:The percentages of 6 metabolic syndrome scores in the sample population were 23.82 %, 27.87 %, 22.41 %, 16.03 %, 8.02 %, and 1.85 %, respectively. The scores of metabolic syndrome were different in different age groups, ethnic groups, groups with different drinking rates, and groups with different dietary types, with the differences all significant ( P<0.05).The MS score in men increased with the increase of oil/salt rate and excessive drinking rate ( P<0.01). The score in women increased with the increase of the current smoking rate, oil/salt rate, and increased with the decrease of physical activity ( P≤0.01). There was no significant difference in the distribution of regular drinking rates between different score groups ( P>0.05). The scores of metabolic syndrome increased with the increase of risk factors ( P<0.05). Ordered results logistic analysis found that in the men with ≥3 risk factors and the metabolic syndrome score was 1.15 (1.06-1.26) times higher than that in the men without risk factor, as well as in women with 2 risk factors and≥3 risk factors. The metabolic syndrome scores were 1.38 (1.22-1.55), 2.02 (1.53-2.66) times higher than those in the women without risk factors. Conclusions:The physical examination group in Urumqi, the more the metabolic syndrome disease behavior risk factors clustered, the higher the metabolic syndrome score was. Therefore, comprehensive intervention measures should be taken to control the different forms of metabolic syndrome to prevent the occurrence and progress of the disease.

Objective To investigate the mechanism of Qinggan-Huoxue recipe in the treatment of alcoholic liver disease by observing its function on alcoholic liver disease rat fibroblast growth factor -21 (FGF21). Methods The rats were randomly divided into the blank group (n=10), the carbon tetrachloride group (n=10), the model group (n=11), the Qinggan-Huoxue recipe group (n=10), the Qinggan recipe group (n=9) and the Huoxue recipe group (n=10). Except for the blank group and the carbon tetrachloride group, the other rats were given 10 ml/kg alcohol, corn oil and pyrazole mixture (4.5 ml: 2 ml: 25 mg), once a day, 0.3 ml/kg carbon tetrachloride olive oil solution (carbon tetrachloride: olive oil =1: 3) intraperitoneally, and twice a week for 12 weeks to prepare the alcoholic liver disease model. In the ninth week, the Qinggan-Huoxue recipe group was treated with 4.75 g/kg of Qinggan-Huoxue recipe, the Qinggan recipe group was treated with 1.5 g/kg of Qinggan recipe, and the Huoxue recipe group was treated with 3.25 g/kg of Huoxue recipe, once a day, and 28 d for continuous administration. The pathological changes of liver tissue were observed by HE staining and Masson staining. The serum levels of AST and ALT were detected in rats. The changes of FGF21 protein and mRNA expression were detected by immunohistochemistry, Western blotting and fluorescence quantitative PCR. Results Compared with the model group, the liver weight and liver body ratio in the Qinggan recipe group, Qinggan-Huoxue recipe group and Huoxue recipe group were significantly lower (P<0.01). Compared with the model group, the serum ALT (41.95 ± 26.78 U/L, 46.63 ± 21.00 U/L, 37.57 ± 27.85 U/L vs. 138.34 ± 43.35 U/L), AST (102.74 ± 23.55 U/L, 111.50 ± 21.26 U/L, 83.72 ± 37.57 U/L vs. 257.41 ± 162.31 U/L) in the Qinggan recipe group, Qinggan-Huoxue recipe group and Huoxue recipe group significantly decreased (P<0.01 or P<0.05). Compared with the model group, the expression of FGF21 protein (1.19 ± 0.07, 1.24 ± 0.12 vs. 0.92 ± 0.04) in Qinggan recipe group and Qinggan-Huoxue recipe group significantly increased (P<0.05), and the expression of FGF21 mRNA (1.25 ± 0.08 vs. 0.95 ± 0.05) in Qinggan-Huoxue recipe group significantly increased (P<0.05). Conclusions FGF21 plays an important role in the alcoholic liver disease. During the process of liver injury, FGF21 increases continuously. Qinggan-Huoxue recipe can improve the content of FGF21 in the treatment of alcoholic liver disease.

Objective To explore the clinical efficacy and indications of kyphoplasty with movement and secondary en?largement of balloon for the compression fracture of vertebral body with ruptured posterior wall. Methods A retrospective analy?sis was carried out on the data of 29 patients (10 males, 19 females;age range:55-86 years old;mean age:71 years old;29 verte?bral bodies in total) who suffered from compression fracture of the thoracolumbar spine and below, and underwent kyphoplasty through the movement and secondary enlargement of balloon within the vertebral body and were followed up from January 2011 to November 2014. These patients had backache, accompanied by lowered support, limitation of movement, no symptom of nervous lesion on both lower extremities and no past history of balloon kyphoplasty. All fractured vertebral bodies were at T 11 or below, in?cluding 1 case at T11, 4 cases T12, 11 cases L1, 9 cases L2 and 4 cases L3. The causes of injury included fall (19 cases), car accident (8 cases) and unknown reasons (2 cases). All patients underwent kyphoplasty with the movement and secondary enlargement of bal?loon within the vertebral body. Photos were taken immediately after the surgery, at 1 month, 3 months, 6 months and 12 months, and these patients were assessed and analyzed in terms of vertebral height, Cobb angle, visual analogue score (VAS) and Oswestry disability index (ODI). Results The operation time (including the formation and solidification of bone cement) of 29 patients was 40 to 65 min and the mean time was 55 ± 7 min;the blood loss during operation was 2 to 15 ml and the mean blood loss was 5 ± 2 ml;the injected volume of bone cement was 2.5-7.5 ml and the mean volume was 5.5±0.5 ml. Post?operative pain was relieved and ambulation was performed under the protection of lumbar orthosis brace. Statstical analysis was conducted on VAS, ODI, vertebral height and Cobb angle before operation and at 1 month, 3 months, 6 months and 12 months after operation, showing statistically significant differences. X ray examination found that there was no alternation or displacement of bone cement location, and no change in vertebral morphology, the vertebral height and cobb angle remained the post?operative status, and posterior wall rupture of the vertebral body was recovered well. CT revealed that the morphology of bone cement was irregular and closely integrated with bone substance, and no cavity or fissure was seen. Conclusion Kyphoplasty with movement and secondary enlargement of bal?loon within the vertebral body has a good, definite clinical efficacy in treating compression vertebral fracture with incomplete pos?terior wall of the vertebral body without obvious displacement of fractured bone and symptom of nervous lesion on both lower ex?tremities. This surgery is easy to operate, and has an immediate analgesic effect, which could recover vertebral height as well as re?duce kyphosis deformity and improve patient’s prognosis.

Objective To explore the clinical efficacy and safety of modified Ponticelli regimen in treating patients with idiopathic membranous nephropathy (IMN).Methods A retrospective analysis was performed in 90 patients with IMN (type Ⅰ / Ⅱ,79/11 respectively) diagnosed by clinical data and renal biopsy.The patients were divided into modified Ponticelli group (n =23),steroid plus cyclophosphamide (CTX) (CTX group,n =39) and steroid plus cyclosporine A(CsA) (CsA group,n =28) according to the treatment.Liver function,renal function,serum lipid,proteinuria were recorded before and after treatment.Efficacy and adverse reactions were evaluated in three groups.Results (1) In all three groups,the quantity of proteinuria after treatment for 3 months [(3.33 ± 1.53) g/d,(4.70 ± 2.97) g/d,(3.92 ± 2.57) g/d],6 months [(1.60 ± 1.10) g/d,(2.34 ± 1.61) g/d,(2.25 ± 1.78) g/d] was significantly decreased compared with baseline level[(7.26 ± 2.06) g/d,(7.50 ± 2.55) g/d,(7.54 ± 2.70) g/d;P ＜ 0.05].Serum albumin levels at 3 months [(31.42 ± 3.86) g/d,(30.59 ± 5.79) g/d,(30.90 ± 7.87) g/d],6 months [(36.25 ± 4.20) g/d,(34.70 ± 6.70) g/d,(35.36 ± 8.29) g/d] were significantly increased compared with baseline levels [(24.13 ± 2.61) g/d,(23.98 ± 3.79) g/d,(22.94 ± 4.57) g/d;P ＜ 0.05],whereas serum creatinine at 3 and 6 months had no significant changes (P ＞ 0.05).(2) After treatment for 3 months,partial remission rates in modified Ponticelli group,CTX group and CsA group were 39.1％,35.9％,35.7％ respectively and complete remission rates were 8.7％,5.1％,10.7％,which were not statistically significant in all three groups (P ＞ 0.05).At 6 months,partial remission rates in three groups were 56.5％,41.0％,42.9％ respectively and complete remission rates were 21.7％,20.5％,28.6％,which did not suggested significant difference in all three groups either (P ＞ 0.05).(3) In modified Ponticelli group,steroid diabetes,impaired liver dysfunction,infections and gastrointestinal adverse events occurred in 1,1,2 and 2 patients,respectively.In CTX group,steroid diabetes,infections and gastrointestinal adverse events occurred in 5,8 and 2 patients,respectively.In CsA group,steroid diabetes and infections occurred in 1 and 3 patients,respectively.Conclusion Modified Ponticelli regimen to treat patients with IMN has a trend of better outcome than classic CTX regimen.The efficacy is not inferior to CsA regimen with fewer side effects.