Using chemoproteomic techniques, we first identified EIF2AK2, eEF1A1, PRDX3 and VPS4B as direct targets of berberine (BBR) for its synergistically anti-inflammatory effects. Of them, BBR has the strongest affinity with EIF2AK2 via two ionic bonds, and regulates several key inflammatory pathways through EIF2AK2, indicating the dominant role of EIF2AK2. Also, BBR could subtly inhibit the dimerization of EIF2AK2, rather than its enzyme activity, to selectively modulate its downstream pathways including JNK, NF-κB, AKT and NLRP3, with an advantage of good safety profile. In EIF2AK2 gene knockdown mice, the inhibitory IL-1β, IL-6, IL-18 and TNF-α secretion of BBR was obviously attenuated, confirming an EIF2AK2-dependent anti-inflammatory efficacy. The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target, and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammation-related disorders.

A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria. Compound 33a (IMBZ18G) is highly effective in vitro and in vivo against clinically intractable multi-drug-resistant (MDR) Gram-negative strains, with a highly druglike nature. The checkerboard assay reveals its significant synergistic effect with β-lactamase inhibitor avibactam, and the MIC values against MDR enterobacteria were reduced up to 4-512 folds. X-ray co-crystal and chemoproteomic assays indicate that the anti-MDR bacteria effect of 33a results from the dual inhibition of the common PBP3 and some class A and C β-lactamases. Accordingly, preclinical studies of 33a alone and 33a‒avibactam combination as potential innovative candidates are actively going on, in the treatment of β-lactamase-producing MDR Gram-negative bacterial infections.

Objective:To investigate the effects and potential mechanism of vitamin D supplementation on testicular function in aging rats induced by D-galactose.Methods:The aging rats were induced by D-galactose with subcutaneous injection. The animals were randomly divided into 6 groups: aging rats (DG), aging rats with low-dose vitamin D supplementation (LD), aging rats with high-dose vitamin D supplementation (HD), normal control rats(NC), normal rats with low-dose vitamin D supplementation(LN), normal rats with high-dose vitamin D supplementation (HN). The body weight, testicular weight, serum testosterone concentrations and sperm quality of the rats in each group were measured. The testis morphological changes were detected using light microscopy. The activity of superoxide dismutase (SOD) and level of malondialdehyde(MDA) were determined with spectrophotometer. The expression levels of Nrf2, GCLC, SOD2 and VDR in testis were detected by western blot.Results:At baseline, compared with NC group, testicular weight, serum testosterone level, SOD activity, Nrf2, GCLC and SOD2 expression levels were significantly decreased in DG group, while MDA level was significantly increased. After vitamin D supplementation, testicular weight, testosterone levels and SOD activity in both of HD and LD groups were significantly increased, while the MDA level was significantly decreased. The expression levels of Nrf2, GCLC, SOD2 and VDR were significantly increased.Conclusion:Vitamin D supplementation may enhance the testicular antioxidant capacity through activating Nrf2-ARE signaling pathway, and improve the testicular function in D-galactose-induced aging rats.

Chest trauma is one of the most common injuries. Venous thromboembolism (VTE) as a common complication of chest trauma seriously affects the quality of patients′ life and even leads to death. Although there are some consensus and guidelines on the prevention and treatment of VTE at home and abroad, the current literatures lack specificity considering the diagnosis, treatment and prevention of VTE in patients with chest trauma have their own characteristics, especially for those with blunt trauma. Accordingly, China Chest Injury Research Society and editorial board of Chinese Journal of Traumatology organized relevant domestic experts to jointly formulate the Chinese expert consensus on the diagnosis, treatment and prevention of chest trauma venous thromboembolism associated with chest trauma (2022 version). This consensus provides expert recommendations of different levels as academic guidance in terms of the characteristics, clinical manifestations, risk assessment, diagnosis, treatment, and prevention of chest trauma-related VTE, so as to offer a reference for clinical application.

Objective:To investigate the application value of digital single-operator peroral cholangioscopy on the preoperative evaluation of extrahepatic cholangiocarcinoma.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 172 patients with extrahepatic cholangiocarcinoma who were admitted to the First Affiliated Hospital of Army Medical University from December 1, 2017 to April 1, 2022 were collected. There were 91 males and 81 females, aged 65(range, 45?68)years. Of 172 patients, 36 cases undergoing preoperative digital single-operator peroral cholangioscopy examination were allocated into the experimental group, and 136 cases not undergoing preoperative digital single-operator peroral cholangioscopy examination were allocated into the control group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) surgical conditions. Propensity score matching was done by the 1:1 nearest neighbor matching method and caliper setting as 0.02. Measurement data with normal distribution were expressed as Mean± SD, and t test was used for comparison between groups. Measurement data with skewed distribution were expressed as M( Q1,Q3), and the Mann-Whitney U test was used for comparison between groups. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. The rank sum test was used for comparison of ordinal data. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of 172 patients, 60 cases were successfully matched, including 30 cases in the experiment group and 30 cases in the control group, respectively. Before propensity score matching, cases with or without preoperative bile drainage were 27, 9 in the experiment group, versus 62, 74 in the control group, showing a significant difference between the two groups ( χ2=9.86, P<0.05). The above indicators were 23, 7 in the experiment group, and 23, 7 in the control group after propensity score matching, showing no significant difference between the two groups ( χ2=0.00, P>0.05). The elimination of preoperative bile drainage confounding bias ensured comparability between the two groups. (2) Surgical conditions. After propensity score matching, there were 10 cases and 0 case without surgery in the two groups. Cases undergoing radical operation including R 0, R 1, R 2 resection were 16, 0, 4 in the experiment group, versus 18, 6, 6 in the control group, showing a significant difference between the two groups ( χ2=6.85, P<0.05). Conclusions:Preoperative digital single-operator peroral cholangioscopy exami-nation can improve the R 0 resection rate of extrahepatic cholangiocarcinoma.

Objective: To evaluate the effects of CYP2C19 genetic polymorphism on the plasma concentration of voriconazole in patients with hematological disease and the value of serial monitoring plasma concentrations in the treatment and prevention of invasive fungal disease (IFD). Methods: From January 2016 to December 2016, 65 hematological patients who received voriconazole intravenous administration for the treatment of invasive fungal disease were enrolled in this study. The population CYP2C19 polymorphism of voriconazole were performed using PCR-Pyrosequencing. The trough plasma concentrations of vriconazole (C_trough) was detected by ultra performance liquid chromatography tandem mass spectrometry. Results: Based on the genotype analysis, 65 subjects were identified as extensive metabolizers’ group (30 cases) and poor metabolizers’ group (35 cases). The C_trough of the 65 patients were detected for 169 times totally, and there was a significant difference of C_trough values between the two groups [0.98(0.38-2.08) mg/L vs 2.19(1.53-4.27) mg/L, z=10.286, P<0.001]. The medium of C_trough in 65 hematological patients were described. Lack of response to therapy was more frequent in patients with voriconazole levels <1.5 mg/L (50.0%) than in those with voriconazole levels >1.5 mg/L (20.5%) (P=0.052). And the risk of adverse events was more frequent in patients with voriconazole levels >5.5 mg/L (80.0%) than in those with voriconazole levels ≤5.5 mg/L (8.3%) (χ²=11.689, P=0.020). Conclusion Patients with CYP2C19 wild-type phenotype are extensive metabolizers, their C_trough of voriconazole are significantly lower than patients with CYP2C19 non-wild-type phenotype (poor metabolizers). Appropriate concentrations of vriconazole can improve the efficacy and safety during treatment.

Objective To evaluate the clinical effect of posterior decompression, internal fixation and interlaminar fusion for the treatment of severe osteoporotic vertebral fracture and collapse complicated with spinal canal encroachment. Methods A retrospective study was carried out in 27 cases of severe osteoporotic vertebral fractures complicated with spinal canal encroachment. The patients were treated with posterior decompression, internal fixation and interlaminar fusion during the period from January 1, 2009 to December 31, 2014. All patients were given vertebral pedicle screw fixation after pedicle augmentation with bone cement. The pain scores of visual analogue scale(VAS), Oswestry Disability Index(ODI), Cobb angle , thoracolumbar Cobb angle and the recovery of neurological function(estimated by Frankel grading system) of the patients were compared beforeoperation, one week after operation and at the end of follow-up. The incidences of internal fixation failure, adjacent vertebral fracture and bone cement leakage also were recorded. Results The patients were followed up for an average of 27 months. The spinal canal occupation rate caused by fracture fragment of posterior vertebral wall was 27.41%~63.85%, with an average of(43.24 ± 10.61)%. Postoperative VAS pain scores, ODI, Cobb angle and thoracolumbar Cobb angle were statistically different from those before operation (P < 0.05). The correction rate for Cobb angle and thoracolumbar Cobb angle was (63.31 ± 23.47)%, (61.91 ± 17.54)%respectively. At the end of the follow-up, the correction loss rate for Cobb angle and the thoracolumbar Cobb angle was (15.38 ± 39.92)%, (21.79 ± 32.20)% respectively, the difference being insignificant compared with those one week after operation(P>0.05). In respect of Frankel grading of neurological function at the end of the follow-up, 6 cases were in grade D and 19 cases were in grade E, but the differences were insignificant compared with those before operation (P > 0.05). None of the patients had surgical site infection, screw looseness or breakage, or rod breakage during the follow-up period. There were 8 patients with asymptomatic bone cement leakage after operation. Vertebral compression fractures recurred in 5 patients, of which 2 had adjacent vertebral fractures and 3 had non -adjacent segment. Conclusion The therapy of posterior decompression, internal fixation and interlaminar fusion is effective for the treatment of severe osteoporotic vertebral fracture and collapse complicated with spinal canal encroachment by obviously relieving pain, improving the physiological function of the spine and stabilizing the spine.

Objective To discuss the effect of syphilis treatment during pregnancy on serological test results in infants born to syphilis mothers.Methods Data of pregnant women with syphilis and their infants in Zhejiang Province between January 2013 and December 2014 were retrospectively analyzed and the effect of syphilis treatment during pregnancy on non-treponemal antigen serological test results in infants were compared.x2 test was used for positive rate of serological tests,incidence of congenital syphilis,and neonatal mortality in infants with syphilis,and rank sum test was used to compare the titers of rapid plasma reagin (RPR) test and tolulized red unheated serum teat (TRUST).Results A total of 3 953 infants were born to 3 901 mothers with syphilis.Of which 3 262 were tested,including 2 226 by RPR and 1 036 by TRUST.The rate of infants with positive RPR was significant lower in treated mothers (45.02％)compared with untreated mothers (55.04％;x2 =12.88,P＜0.01).The significant differences of titers of RPR or TRUST were observed among mothers with or without treatment (RPR:Z=-2.45,P=0.01;TRUST:Z=-2.65,P=0.01),different course of treatment (RPR:Z=-2.33,P=0.02;TRUST:Z=-2.60,P=0.01).Fifty-seven infants were diagnosed with congenital syphilis.The rate of congenital syphilis was 3.50％(27/772) born to untreated mothers,which was dramatically higher than treated mothers (0.96 ％,30/3 129,x2 =27.72,P＜ 0.01).Forty-two infants died.Neonatal mortality was also higher in the untreated group (2.59 ％,20/772) than the treated group (0.70％,22/3 129,x2 =20.72,P＜ 0.01).Conclusion Adequate treatment for women with syphilis during pregnancy could decrease serological tests of RPR and TRUST among new infants and improve the infants their outcomes.

Objective To investigate the incidence of adverse pregnancy outcomes among women with syphilis in Zhejiang province during 2013-2014,and to explore the influence of anti?syphilis treatment on pregnancy outcomes. Methods A retrospective study was carried out according to the Information Management System for preventing mother?to?child transmission(PMTCT)of syphilis in Zhejiang province during 2013-2014. The incidence of adverse pregnancy outcomes was compared between women with syphilis and general women without syphilis, between treated and untreated women with syphilis, as well as between women with syphilis receiving and not receiving standard anti?syphilis treatment. The effects of anti?syphilis treatment and standard anti?syphilis treatment on pregnancy outcomes were analyzed. Results Data were collected from 3 985 women with syphilis and their children. Of these women, 12 had a stillbirth, and 3 973 a live birth. Totally, 3 210(80.55%)women received anti?syphilis treatment, 967(30.12%, 967/3 210) women received substandard treatment, and 775(19.45%)did not receive anti?syphilis treatment. Of the 3 985 fetuses or neonates born to women with syphilis, 45(1.13%)had abnormal clinical symptoms/signs. The incidence rates of low birth weight and early neonatal death were 7.00%(279/3 985) and 1.13%(45/3 985) respectively in fetuses or neonates born to women with syphilis, both significantly higher than those in fetuses or neonates born to general women without syphilis (3.18%[26 092/819494] and 0.13%[1 029/819 494], respectively, both P < 0.01). Among 775 untreated women with syphilis, the incidence rates of premature birth, low birth weight, early neonatal death, congenital syphilis and abnormal neonatal symptoms/signs were 15.61%(121/775), 10.84%(84/775), 2.45%(19/775), 3.48%(27/775)and 2.84%(22/775)respectively, all significantly higher than those in 3 210 women receiving anti?syphilis therapy (8.26%, 6.07%, 0.81%, 0.81% and 1.03%,respectively, all P < 0.01). Besides, the 967 women receiving substandard anti?syphilis treatment showed higher incidence rates of premature birth, low birth weight, early neonatal death, congenital syphilis and abnormal neonatal symptoms/signs than the 2 243 women receiving standard treatment (10.44%vs. 7.31%, 8.17%vs. 5.17%, 1.55%vs. 0.49%, 1.65%vs. 0.45%, 1.96%vs. 0.62%, respectively, all P<0.01). Conclusions The incidence of adverse pregnancy outcomes is high among women with syphilis in Zhejiang province during 2013-2014. Untreated and inadequately treated maternal syphilis is strongly associated with adverse pregnancy outcomes.

OBJECTIVEDiagnosis and prenatal diagnosis to a family of hemoglobin variant with α-thalassemia.

METHODSWhole blood cell analysis, hemoglobin analysis by capillary zone electrophoresis (CZE), Gap-PCR, polymerase chain reaction-reverse dot blot (PCR-RDB) assay and DNA sequencing.

RESULTSHb Zurich Albisrieden with α°-thalassemia lead to severe anemia. The genotype of fetus is also Hb Zurich Albisrieden with α°-thalassemia.

CONCLUSIONAbnormal hemoglobin with α-thalassemia may lead to severe anemia, Prenatal diagnosis of thalassemia has the vital significance for eugenic birth.

Adult ; Base Sequence ; Child, Preschool ; Female ; Fetal Diseases ; blood ; diagnosis ; genetics ; Hemoglobins, Abnormal ; genetics ; metabolism ; Humans ; Male ; Molecular Sequence Data ; Pregnancy ; Prenatal Diagnosis ; Young Adult ; alpha-Thalassemia ; blood ; diagnosis ; embryology ; genetics