Research progress in treatment of tuberculous meningitis / 中华临床感染病杂志

Tuberculous meningitis is the most common and serious type of central nervous system tuberculosis, with high mortality and disability rate, which has attracted extensive attention of global public health. The high mortality rate and disability rate of tuberculosis meningitis may be related to its lack of specific clinical and imaging characteristics, insufficient attention from clinicians, lack of early sensitive and specific diagnostic testing techniques, delay in treatment, and restricted penetration of anti-TB drugs into the blood-brain barrier or/and MDR-TB, etc. This article reviews the disease burden of TBM, chemotherapy drugs and regimens, anti-inflammatory agents, aspirin, interventional and surgical treatment to provide reference for clinical management of this disease.

Research progress of Delamani in treatment of multidrug-resistant/extensively drug-resistant tuberculosis / 中华临床感染病杂志

The treatment of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) is prone to more time-consuming, complex, toxic and ineffective. MDR-TB has low treatment success rate (52%) and high fatality rate (17%), as well as high rate of lost visits(15%), while the treatment success rate of XDR-TB is only 26%. It’s urgent to develop new drugs and chemotherapy regimens to improve the efficacy for MDR/XDR-TB. Delamanid (Dlm) has a strong killing effect on Mycobacterium tuberculosis (MTB) in vitro and in vivo. When MDR-TB patients are treated with optimized background regimen containing Dlm, the two-month sputum negative conversion rate is increased, case fatality is decreased and the prognosis is improved. This article reviews the progress on characteristics, in vitro activity, animal tests, clinical efficacy and safety of Dlm.

Influences of initiation of epidural analgesia pain relief in early labor on uterine myoelectrical activity / 中华围产医学杂志

Objective To assess the influences of early implementation of patient-controlled epidural analgesia (PCEA) in labor on uterine myoelectrical activity and delivery outcomes. Methods A prospective study was conducted on 240 singleton cephalic primiparae with spontaneous labor at Guangzhou Women and Children's Medical Center from January 2015 to October 2018. Those women, who were ready to accept PCEA, were randomly assigned to early- or late-PCEA group based on cervical dilation of 0-3 cm or 3-6 cm at the time of commencing PCEA, while those who refused PCEA in labor were classified as non-PCEA group. Uterine electromyographic activity and visual analogue score (VAS)were recorded before and 1 h and 2 h after PCEA. Patient satisfaction with labor, duration of the first stage of labor, volume of postpartum bleeding within 2 h after delivery and neonatal Apgar score were compared between different groups using multivariate analysis of variance, repeated measures analysis of variance, LSD-t test or Chi-square test. Results The VAS values 1 h after PCEA in the early- and late-PCEA group were both lower than that in the non-PCEA group (2.08±1.34 and 2.00±1.28 vs 7.65±1.04, LSD-t were － 27.713 and － 27.663, P<0.001) and those before PCEA (7.65±0.91 and 7.62±0.86, LSD-t were －32.879 and －33.349, P<0.001). The VAS values 2 h after PCEA in the early- and late-PCEA group were both lower than that in the non-PCEA group (1.63±1.53 and 1.41±1.56 vs 7.66±0.87, LSD-t were －27.018 and －27.823, P<0.001) and those before PCEA (LSD-t were －31.379 and －32.718, P<0.001).The patient satisfaction rate with labor was higher in the early-PCEA group comparing to the late-PCEA group [80.0% (72/90) vs 61.1% (55/90), P<0.001], and the two figures above were both higher than that of the non-PCEA group [20.0% (12/60), both P<0.001]. There was no significant difference in the duration of the first stage of labor, the volume of postpartum blood loss 2 h after delivery, oxytocin usage rate, the rate of convertion to cesarean section, neonatal birth weight or Apgar score at 1 or 5 min among the three groups (all P>0.05). There was also no significant difference in uterine electromyographic parameters among the three groups before or 2 h after PCEA (all P>0.05). The number and duration of burst, power density spectrum peak frequency, root mean square and total power 1 h after PCEA in the early- and later-PCEA group were all lower than those in the non-PCEA group [4.80±2.49 and 5.54±3.04 vs 9.67±2.44; (34.41±1.21) and (36.94±1.18) vs (41.68±1.53) s; (0.36±0.08) and (0.36±0.07) vs (0.48±0.05) Hz ; (0.05±0.04) and (0.05±0.05) vs (0.07±0.05) mV; (4.33±0.51) and (5.36 ±0.59) vs (9.90±1.43) pV2; all P<0.05]. Conclusions The effect of PCEA on uterine myoelectrical activity has no association with the commencing time. While early PCEA could alleviate the labor pain as soon as possible, which enable us to improve the efficacy of labor analgesia, patient satisfaction and maternal and neonatal safety without increasing cesarean section rate.

Effects on human peripheral erythrocytes of long-term occupational contact with chromate / 中华预防医学杂志

Objective@#To investigate the effects on human peripheral blood erythrocytes of long-term occupational contact with chromate.@*Methods@#A dynamic cohort study was conducted of chromate-exposed workers (343 cases) and non-chromate-exposed workers (73 cases) at a chromate production enterprise who were selected according to specific inclusion and exclusion criteria from 2010 to 2015. Personal information and chromate exposure information were obtained by questionnaire. A generalized estimating equation was employed to analyze the effects on human peripheral blood erythrocytes of long-term occupational contact with chromate, controlling for age, gender, smoking, alcohol consumption and body mass index.@*Results@#The mean ages and working ages of those entering the cohort study were 36.67 ±6.78 and 38.47 ± 7.18, respectively, for the exposure group and 8.39 ± 6.02 and 12.86 ± 8.34, respectively, for the control group. The erythrocyte content [(4.73±0.46), (4.81±0.53), (4.41±0.45)]×1012/L in the peripheral blood in the chromate exposure group was lower than that [(4.76±0.42), (4.95±0.45), (4.47±0.39)]×1012/L in the control group for the years 2010, 2011, 2012 and 2014 (t values were 0.38, 1.96, 0.92 and 1.21; P values were 0.703, 0.051, 0.358 and 0.227, respectively). The correlations between the years 2010 and 2011, 2011 and 2012, 2012 and 2014, and 2014 and 2015 were 0.667, 0.464,-0.070 and 0.020, respectively (P<0.001). The RR for males and those that consumed alcohol were 0.661 (95% CI: 0.616-0.709) and 0.910 (95% CI: 0.811- 1.201), respectively. Compared with the control group, the risk of reduced erythrocyte levels in the peripheral blood was increased by 0.915 (95% CI: 0.852- 0.982) in the chromate-exposed group.@*Conclusions@#The erythrocyte content of peripheral blood was reduced after long-term exposure to chromate. Maleness and alcohol consumption were factors that increased the risk of reduced peripheral blood erythrocytes in the chromate-exposed population.

Three-dimensional finite element analysis of artificial femoral head replacement for unstable femoral intertrochanteric fractures / 中国组织工程研究

BACKGROUND:Artificial femoral head replacement provides a new idea for the repair of unstable intertrochanteric fracture. Artificial prosthesis replacement may affect original femoral biomechanical stability and lead to a variety of adverse consequences. OBJECTIVE:To analyze the stress distribution of femoral head replacement in the treatment of unstable femoral intertrochanteric fractures with three-dimensional finite element analysis. METHODS:One male old volunteer was randomly selected from population who underwent health examination. The left femur was scanned with spiral CT, and the three-dimensional finite element models of the human femur and prosthesis were established. The three-dimensional finite element model was used to simulate the actual working conditions of human climbing stairs, and the stress distribution of the bone channels around the surface of the femur and the prosthesis was analyzed with three-dimensional finite element analysis. RESULTS AND CONCLUSION: Under normal condition, the stress of the human femur was in a consistent state. Stress changed gradualy from the proximal end to the distal end. The stress of the prosthesis was concentrated in the middle section. The prosthesis of inner stress distribution was analyzed to obtain stress distribution of prosthesis and femur cancelous bone interface. The analysis found that stress change trend was consistent. The results suggest that artificial femoral head replacement does not have a significant effect on the overal stress distribution of the human femur, and the overal stress distribution does not change, and the maximum stress region is located in the middle of the whole femur. After the reconstruction, the stress concentration of the femur is not observed.

Structural insight into substrate specificity of human intestinal maltase-glucoamylase

Human maltase-glucoamylase (MGAM) hydrolyzes linear alpha-1,4-linked oligosaccharide substrates, playing a crucial role in the production of glucose in the human lumen and acting as an efficient drug target for type 2 diabetes and obesity. The amino- and carboxyl-terminal portions of MGAM (MGAM-N and MGAM-C) carry out the same catalytic reaction but have different substrate specificities. In this study, we report crystal structures of MGAM-C alone at a resolution of 3.1 Å, and in complex with its inhibitor acarbose at a resolution of 2.9 Å. Structural studies, combined with biochemical analysis, revealed that a segment of 21 amino acids in the active site of MGAM-C forms additional sugar subsites (+ 2 and + 3 subsites), accounting for the preference for longer substrates of MAGM-C compared with that of MGAM-N. Moreover, we discovered that a single mutation of Trp1251 to tyrosine in MGAM-C imparts a novel catalytic ability to digest branched alpha-1,6-linked oligosaccharides. These results provide important information for understanding the substrate specificity of alpha-glucosidases during the process of terminal starch digestion, and for designing more efficient drugs to control type 2 diabetes or obesity.