Magnesium promotes vascularization and osseointegration in diabetic states / 国际口腔科学杂志·英文版

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues. Magnesium has been proved to promote bone healing under normal conditions. Here, we elucidate the mechanism by which Mg2+ promotes angiogenesis and osseointegration in diabetic status. We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised, with significantly decreased angiogenesis. We then developed Mg-coating implants with hydrothermal synthesis. These implants successfully improved the vascularization and osseointegration in diabetic status. Mechanically, Mg2+ promoted the degradation of Kelch-like ECH-associated protein 1 (Keap1) and the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) by up-regulating the expression of sestrin 2 (SESN2) in endothelial cells, thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia. Altogether, our data suggested that Mg2+ promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.

Screening and correction of myopia in children and adolescents from the Gannan region / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To understand the screening and correction of myopia in children and adolescents from the Gannan region of Gansu Province, and to provide guidance for the prevention and control of myopia.METHODS: A cross-sectional stratified cluster sampling study was conducted to select 2 kindergartens and 12 primary and secondary schools in Hezuo City and Zhouqu County, Gannan region of Gansu Province, two classes were randomly selected from each grade, and the whole class was used as a unit for screening. The screening and correction of myopia in children and adolescents were collected for statistical analysis.RESULTS: A total of 5 072 children and adolescents were selected, and 4 806 valid data were finally included after excluding unqualified records. The overall prevalence of myopia was 45.55%, and the prevalence of myopia showed an increasing trend with the increase of grade(P<0.001). The prevalence of myopia in girls(48.66%)was higher than that in boys(42.18%; P<0.001). The prevalence of myopia increased with age(P<0.001), and the age group of 10-12 years old was the fastest growing for myopia, increasing from 25.62% to 60.57%. Furthermore, moderate myopia and high myopia showed an increasing tread with the increase of the grade(all P<0.001). The overall glasses wearing rate of the Gannan region was 28.55%, with a full correction rate of 50.72%, and the glasses wearing rate showed an increasing trend with the increase of grades(P<0.001). The glasses wearing rate of female students(30.84%)was higher than that of male students(26.69%; P=0.008). The full correction rates of low, moderate and high myopia in junior high were the lowest among the 3 phases of studying. The full correction rate of high myopia was the lowest in all phases of studying.CONCLUSION: The prevalence of myopia in children and adolescents from the Gannan region is lower than the national average, but the myopia of children and adolescents is still a trend of young age and high incidence, and the glasses wearing rate of myopia and full correction rate are low.

LncRNA SBF2-AS1 Regulates Invasion and Proliferation of Hepatocellular Carcinoma Cells Through miR-372-3p/CDK6 Axis / 肿瘤防治研究

Objective To investigate the effects of lncRNA SBF2-AS1 on the proliferation and invasion of hepatoma cells by regulating the miR-372-3p/CDK6 pathway. Methods Bel7402 and SK-hep1 cells were selected as research objects. The expression levels of SBF2-AS1, miR-372-3p, and CDK6 were up- or down-regulated according to different experimental stages, while the expression levels of miR-372-3p and CDK6 in cells were detected by real-time fluorescence quantitative PCR and Western blot. Dual luciferase reporter assay verified the targeting relationships between SBF2-AS1 and miR-372-3p as well as miR-372-3p and CDK6, respectively. CCK-8, colony formation assay, Transwell, cell cycle assay, and flow cytometry were used to analyze cell proliferation, colony formation, migration/invasion ability, cell cycle activity, and apoptosis. Results SBF2-AS1 was highly expressed in hepatocellular carcinoma cells (P<0.05). SBF2-AS1 knockdown resulted in decreased proliferation and invasion of Bel7402 and SK-hep1 cells (P<0.05). After miR-372-3p knockdown, the proliferation capacity and invasion number of Bel7402 cells were significantly increased. However, the above results were reversed after SBF2-AS1 knockdown (P<0.05). In addition, miR-372-3p targeted CDK6 and inhibited its expression, although over-expressing SFB2-AS1 could reverse the above results (P<0.05). Over-expressing CDK6 could reverse the inhibition of over-expressing miR-372-3p on the proliferation and invasion of Bel7402 cells. Conclusion LncRNA SBF2-AS1 can positively regulate the expression of CDK6 through miR-372-3p. It can also influence the distribution of cell cycle and affect the proliferation and invasion abilities of hepatocellular carcinoma cells.

Effects of RNA M6A demethylase ALKBH5 gene deficiency on morphology and function of cerebellum in aged mice / 中华病理学杂志

Objective: To investigate the effects of RNA m6A demethylase ALKBH5 gene deficiency on cerebellar morphology and function in the aged mice, and to explore the role of ALKBH5 in cerebellar degeneration. Methods: Western blot was performed to detect the protein level of ALKBH5 in the cerebellum of wild-type mice of various ages. The expression of NeuN, Calbindin-D28K, MAP2, GFAP and other proteins in the cerebella of middle-aged (12-month-old) and aged (18-month-old) wild-type mice and ALKBH5-/- mice was examined using immunohistochemistry. The balance beam test and gait analysis were performed to test the balance ability and motor coordination of the mice. Results: With aging of the mice, the expression of ALKBH5 in the cerebellum increased gradually in an age-dependent manner. In the aged mice, but not middle-aged mice, the body weight, whole brain weight and cerebellum weight of ALKBH5-/- mice decreased by 15%, 10% and 21%, respectively (P<0.05). The expression of ALKBH5 in the Purkinje cells was much higher than that in other types of neural cells. Correspondingly, ALKBH5-deficiency caused 40% reduction in the number of Purkinje cells, as well as the length and density of neuronal dendrites in the aged mice (P<0.01). In addition, the time for the aged ALKBH5-/- mice to pass the balance beam was 70% longer than that of the wild type mice of the same age, with unstable gaits (P<0.01). Conclusions: Gene deficiency of RNA m6A demethylase ALKBH5 causes cerebellar atrophy, Purkinje neuron loss and damage in the aged mice. These changes eventually affect mice's motor coordination and balance ability. These results suggest that imbalanced RNA m6A methylation may lead to neurodegenerative lesions in the cerebellum of mice.

Research progress on mosaic embryo transfer and pregnancy risk / 中华预防医学杂志

Mosaic embryos contain two or more genetically distinct cell lines, which can be detected by pre-implantation genetic testing for aneuploidy. At present, it has been reported that mosaic embryo transfer can lead to healthy live births. In order to prevent severe adverse pregnancy outcomes, such as implantation failure, abortion, congenital malformation and neonatal death after implantation of mosaic embryos, it is critical to carry out genetic counseling, prenatal diagnosis and pregnancy supervision for mosaic embryo transfer. This article reviews the selection of mosaic embryos, the pregnancy outcomes of mosaic embryo transfer, and the safety of offspring, in order to provide references for the clinical practice of mosaic embryo transfer.

Analysis of characteristics of drug resistance gene mutation in HBV RT region of hepatitis B infected patients / 中华预防医学杂志

Objective: This article investigated the clinical characteristics and distribution of drug resistance mutation sites in HBV RT region of hepatitis B infected patients. Methods: Retrospective analysis was made on 1 948 patients with HBV infection, who had been tested for NAs resistance mutation and had a medical history of NAs in the Laboratory Department of the Fifth Medical Center of the PLA General Hospital from January 2020 to December 2021. Basic clinical information and drug resistance related mutation information were recorded. Meanwhile, the serological index data of hepatitis B were collected. Drug resistance gene mutant group and non-mutated group were grouped according to whether the drug resistance genes had a mutation in HBV RT region, and the clinical characteristics and genotype distribution of the two groups were statistically analyzed. The pattern of drug resistance gene mutation, number of mutation sites, drug resistance type and mutation of NAs resistance-related sites were analyzed in 917 patients with drug resistance gene mutation in HBV RT region. χ2 Inspection was used for counting data. Meanwhile, two independent samples t-test and Wilcoxon rank sum test were used for measurement data. Results: Among the 1 948 patients with chronic HBV infection, 917 patients had drug resistance gene mutation in RT region (47.07%). The proportion of patients with acute hepatitis B and CHB in HBV RT resistance gene mutant group was lower than that in the non-mutated group, while the proportion of patients with HBV-related cirrhosis was higher than that in the non-mutated group, these differences were statistically significant. Compared with the non-mutated group in HBV RT region, the age, the positive rates of HBeAg and HBV DNA, and HBV DNA load of these patients were increased in drug resistance gene mutant group, these differences were statistically significant. Genotypes of patients in both groups were dominated by C, followed by B and D. The proportion of patients with genotype C in HBV RT drug resistance gene mutant group was higher than that of non-mutated group, the difference was statistically significant. There were 53 gene mutation patterns in 917 patients with drug resistance gene mutation in HBV RT region, and the main pattern was rtL180M+rtM204V+rtS202G (9.70%). The mutation sites were dominated by 3 (20.74%). There were 5 types of drug resistance, LAM+Ldt (21.25%) was the most. Among the 18 sites that were clearly associated with LAM, ADV, ETV and Ldt resistance in the HBV RT region, 14 sites were mutated, and the most common mutation sites were rtL180M, rtM204V, rtM204 and rtS202G. what's more, the proportion of patients with NAs drug resistance was LAM>Ldt>ETV>ADV. Conclusion: In order to prevent adverse consequences of this study such as disease recurrence or disease progression caused by HBV drug resistance, HBV infected patients, who have long-term use of NAs antiviral therapy, should monitor the level of HBV DNA and drug resistance genes in HBV RT region in order to optimize the treatment plan in time or guide individualized treatment.

AI Rudi's Experience in Differentiating and Treating Facial Hormone-dependent Dermatitis by Stages Using the method of Clearing Heat and Protecting Yin / 中医杂志

This paper summarized the clinical experience of AI Rudi in the treatment facial hormone-dependent dermatitis with the method of clearing heat and protecting yin. It is believed that the key pathogenesis is the heat toxin accumulation， yin depletion and collaterals obstruction. The clinical treatment should focus on “heat exuberance” and “yin depletion”. It is advocated that “half treatment is from heat and half from yin” is the general principle， and the treatment is staged. In the acute phase， the treatment is half from cooling blood and dispersing wind to dispel heat pathogen， and half from protecting fluid and moisturizing skin to strengthen yin； and the modified Liangxue Xiaofeng Powder （凉血消风散） could be used. In the chronic phase， half treatment is from clearing residual toxin to eliminate heat pathogen， and half from nourishing yin and unblocking collaterals to strengthen yin， for which Xuanmai Ganju Decoction and Erzhi Pills （玄麦甘桔汤合二至丸） can be used and modified according to the symptoms. At the same time， we should pay attention to the simultaneous internal and external treatment， and emphasize the importance of daily protection in the treatment of the disease.

AI Rudi's Experience in Differentiating and Treating Facial Hormone-dependent Dermatitis by Stages Using the method of Clearing Heat and Protecting Yin / 中医杂志

@#This paper summarized the clinical experience of AI Rudi in the treatment facial hormone-dependent dermatitis with the method of clearing heat and protecting yin. It is believed that the key pathogenesis is the heat toxin accumulation， yin depletion and collaterals obstruction. The clinical treatment should focus on “heat exuberance” and “yin depletion”. It is advocated that “half treatment is from heat and half from yin” is the general principle， and the treatment is staged. In the acute phase， the treatment is half from cooling blood and dispersing wind to dispel heat pathogen， and half from protecting fluid and moisturizing skin to strengthen yin； and the modified Liangxue Xiaofeng Powder （凉血消风散） could be used. In the chronic phase， half treatment is from clearing residual toxin to eliminate heat pathogen， and half from nourishing yin and unblocking collaterals to strengthen yin， for which Xuanmai Ganju Decoction and Erzhi Pills （玄麦甘桔汤合二至丸） can be used and modified according to the symptoms. At the same time， we should pay attention to the simultaneous internal and external treatment， and emphasize the importance of daily protection in the treatment of the disease.

Efficiency analysis and management strategies of hospital beds based on diagnosis-related groups / 中华医院管理杂志

Objective:To improve the evaluation method of hospital beds efficiency based on diagnosis-related groups (DRG), and to provide a basis for hospitals to allocate beds reasonably and improve bed efficiency.Methods:Taking a tertiary hospital in Beijing as the research object, the types of beds were evaluated by the beds utilization matrix with the time consumption index as the X-axis and the bed utilization rate as the Y-axis. The types of beds in the department were divided into efficiency type, pressure type, turnover type, and idle type. The efficiency of medical services and the level of diagnosis and treatment were evaluated by the weight of DRG per bed. The calculation method of theoretical number of beds was improved by incorporating hospital case mix index as a risk adjustment factor into the formula to evaluate the status of beds allocation. Combining the bed type, DRG weight per bed, and bed allocation status, the improvement emphasis and management strategy of bed utilization could be comprehensively analyzed.Results:Among the 24 departments in the hospital, there were 5, 9, 1 and 9 departments being efficiency type, pressure type, turnover type and idle type, respectively. The weight per bed of 11 departments was higher than the average level of the hospital. There were 16, 5, and 3 departments with appropriate, fewer, and excessive beds, respectively.Conclusions:The comprehensive analysis of beds utilization type, allocation status and weight of each bed based on DRG is an effective method to evaluate the efficiency of hospital beds, and can provide decision-making basis for hospital bed resource allocation, hospital operation focus adjustment, and subject development planning.

Weekly gestational weight gain in women with obesity and its association with risk of macrosomia / 中华围产医学杂志

Objective:To explore the characteristics of weekly gestational weight gain (GWG) in women with obesity and its correlation with the risk of macrosomia.Methods:Clinical data of women with singleton pregnancy and pre-pregnancy body mass index (PPBMI) ≥28 kg/m 2 were retrospectively analyzed, from January 2014 to December 2019, in Beijing Obstetrics and Gynecology Hospital, Capital Medical University (Beijing Maternal and Child Health Care Hospital). The participants were divided into three groups based on their PPBMI: group A (28-<30 kg/m 2), group B (30-<32 kg/m 2), and group C (≥32 kg/m 2). The study compared the characteristics of GWG among the three groups, explored the correlation between the weekly weight gain during each gestational stage and the risk of macrosomia, and discussed the impacts of the GWG pattern in women with different PPBMI on the risk of macrosomia. Chi-square (or Fisher's exact), Kruskal-Wallis, and Mann-Whitney U tests were performed for statistical analysis. Multivariate logistic regression was used to analyze the impact of weekly weight gain in specific gestational stages on macrosomia. Results:(1) A total of 2 046 participants were included in the study, with 982 in group A, 588 in group B, and 476 in group C. For all of the 2 046 cases, the median PPBMI was 30.1 kg/m 2 (29.0-31.9 kg/m 2), GWG was 10.5 kg (7.3-14.0 kg), and neonatal birth weight was 3 520 g (3 215-3 816 g) with 60 (2.9%) ≥4 500 g, and the biggest baby weighed 5 580 g. Out of the births analyzed, macrosomia occurred in 318 cases (15.5%). (2) Among the three groups (A, B and C), the differences in maternal age [32.0 years (29.0-35.0 years), 32.0 years (29.0-35.0 years) and 32.0 years (29.0-34.0 years), H=6.58] and women with a history of type 2 diabetes mellitus [0.9% (9/982), 0.3% (2/588) and 1.9% (9/476), χ2=6.61] were statistically significant (all P<0.05). (3) The weekly weight gain in each group exhibited a gradual upward trend before 20-24 weeks, reached a plateau at 24-32 weeks, peaked at 32-36 weeks, and subsequently declined. The weekly weight gain of group A in the pre-pregnancy to 14 weeks [0.14 kg/week (0.00-0.25 kg/week)], 14 to 20 weeks [0.25 kg/week (0.17-0.42 kg/week)], and 20 to 24 weeks [0.38 kg/week (0.25-0.63 kg/week)] were higher than those of group B [0.07 kg/week (－0.03-0.21 kg/week), 0.25 kg/week (0.10-0.42 kg/week), and 0.38 kg/week (0.22-0.60 kg/week)], respectively ( Z value was－3.73,－2.16, and－2.01, all P<0.05). Likewise, the weekly weight gain of group B in the above three stages were all higher than those of group C [0.07 kg/week (－0.10-0.21 kg/week), 0.17 kg/week (0.05-0.33 kg/week), and 0.25 kg/week (0.08-0.50 kg/week)], respectively ( Z value was－2.55,－3.28, and－3.25, all P<0.05). (4) The risk of macrosomia increased with the weekly weight gain in specific gestational stages in different PPBMI groups. In group A, the stages correlated with increased risk were 14-20 weeks [adjusted odd ratio ( aOR)=2.669, 95% CI: 1.378-5.169] and 20-24 weeks ( aOR=1.764, 95% CI: 1.143-2.723), while the stages were 20-24 weeks ( aOR=2.149, 95% CI: 1.156-3.996) and 36 weeks until delivery ( aOR=1.888, 95% CI: 1.268-2.810) in group B, and pre-pregnancy to 14 weeks ( aOR=3.515, 95% CI: 1.158-10.665) and 14-20 weeks ( aOR=3.021, 95% CI: 1.058-8.628) in group C (all P<0.05). The risk of macrosomia increased when the weekly weight gain of both risk-related stages in group A ( aOR=2.255, 95% CI: 1.029-4.940) ≥50th percentile, and group B ( aOR=4.399, 95% CI: 1.017-19.023) ≥75th percentile, and for group C ( aOR=3.404, 95% CI: 1.004-11.543) when the weekly weight gain above 25th percentile (all P<0.05). Conclusions:Weekly GWG demonstrates an observable gradual acceleration pattern in women with obesity. Therefore, clinical attention should be directed towards monitoring fluctuations in the weekly weight gain in this population, as excessive weekly weight gain before 24 gestational weeks is associated with an elevated risk of macrosomia.

Factors affecting the geometry variations of surgical clips in radiotherapy after breast-conserving surgery / 中华放射医学与防护杂志

Objective:To investigate the variations and related influencing factors of the volumes, positions, and morphologies of geometries formed by surgical clips in intensity-modulated radiation therapy (IMRT) for whole breasts after breast-conserving surgery.Methods:A retrospective analysis was conducted on 18 patients treated with IMRT from October 2021 to September 2022 after breast-conserving surgery. Set-up errors were obtained by reading the coordinate information of tumor bed surgical clips according to the cone beam CT (CBCT) images at 0, 10, 20, 30, 40, and 50 Gy sequentially. Geometries were constructed using the convex hull program, and the volumes ( Vct and V0-5) of geometries were then calculated based on the localization CT images and the six CBCT images, respectively. The centroid displacements ( D0-5) and degrees of inclusion ( DI0-5) of these geometries were compared. The t-test or rank-sum test was used to analyze the effects of radiation doses on V0-5, D0-5, and DI0-5. The Pearson correlation analysis was conducted to analyze the correlations between D0-5 and corresponding set-up errors in three-dimensional directions, and the correlations of average V0-5 variation ( AV), average D0-5 ( AD), and average DI0-5 ( ADI) with the body mass index (BMI), the volume of a breast ( VB), the breast axial height ( H), and the time interval from surgery to radiotherapy ( T) each. The influences of quadrants ( Q) where geometries are located and states ( S) of geometries adhering to or away from the chest walls on AV, AD, and ADI were analyzed through one-way ANOVA. Results:The differences between D5 and D0, between D5 and D1, and between D5 and D2 were statistically significant ( t = -3.27, -4.52, -3.38, P < 0.05), respectively. The differences between DI5 and DI0, between DI5 and DI1, between DI5 and DI2 were statistically significant ( t = 2.53, 2.70, 2.64, P < 0.05), respectively. D1 and D4 correlated with the set-up errors in the superior-inferior dimension, and D3 correlated with the set-up errors in the left-right dimension ( r = 0.50, 0.56, 0.53, P < 0.05). The AD was related to BMI, VB, and H ( r = 0.54, 0.48, 0.50, P < 0.05). There were statistically significant differences in AV and ADI of geometries away from ( S3) and near ( S2) chest walls ( F = 2.66, 3.83, P < 0.05). The AD differences of geometries between S3 and the state adhering to chest walls ( S1) and between S3 and S2 were statistically significant ( F = 7.46, P < 0.05), respectively. Conclusions:The geometries are relatively constant volumes during whole-breast radiotherapy. However, their positions and morphologies vary greatly in the late course. The volume variation ratios, centroid displacements, and degrees of inclusion of geometries are all affected by the states of their attachments to the chest walls. The centroid displacements correlate with breast morphologies and BMI. The radiotherapy plan modification can be individualized.

The proportion of Th17 cells in patients with systemic sclerosis: a Meta-analysis / 中华风湿病学杂志

Objective:To clarify peripheral Th17 level in SSc patients and its correlation with disease.Methods:Chinese databases CNKI, CBM, Wanfang and VIP, and English databases PubMed, EMBASE, Web of Science, Cochrane Library and Science Direct were searched to collect a case-control study on the content of Th17 cells in peripheral blood of patients with SSc. The papers published when the database was first developed in 25 February 2021. Meta-analysis was conducted using Stata 12.0 software, and I2 and Egger tests were used to evaluate the heterogeneity and publication bias between studies. Results:A total of 26 case-controls were included in the study, including 1 160 patients with SSc and 778 healthy controls. Overall, the percentage of Th17 cells in SSc patients was higher than in healthy controls [SMD(95% CI)=1.85 (1.33, 2.38), P<0.001], which was most significant in IL-17 +Th17 concentration [SMD(95% CI)=1.88 (1.28, 2.48), P<0.001]. As for disease activity, the proportion of Th17 cells in active SSc patients was much higher than those of patients in remission [SMD(95% CI)=1.92 (1.12, 2.71), P<0.001]. SSc patients had a reduced Th17 level after receiving DMARDs treatment [SMD(95% CI)=-0.74 (-1.05, -0.42), P=0.029]. Conclusion:The number of Th17 cells increase significantly in the peripheral blood of patients with SSc, and is related to disease activity. DMARDs can be used to treat this disease by downregulating Th17 levels.

Efficacy of 3D-printed guide plate assisted versus freehand placement of cannulated screws for the treatment of Sanders type II and III calcaneal fractures / 中华创伤杂志

Objective:To compare the efficacy of 3D-printed guide plate assisted versus freehand placement of cannulated screws for the treatment of Sanders type II and III calcaneal fractures.Methods:A retrospective cohort study was conducted to analyze the clinical data of 29 patients with Sanders type II and III calcaneal fractures admitted to Chonggang General Hospital from June 2020 to October 2022. Among them, there were 18 males and 11 females, with an age range of 22-69 years [(40.1±11.5)years]. Nineteen patients were treated with individualized 3D-printed guide plate assisted placement of cannulated screws (3D-printed group) and 10 were treated with freehand placement of cannulated screws (freehand group). The surgical time, fluoroscopy times, postoperative 6-month calcaneal morphology (length, width, height, B?hler angle and Gissane angle), and American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and Maryland functional score assessed at 3, 6 months after operation and at the final follow-up were compared between the two groups. The incision healing and complications were observed.Results:The patients were followed up for 6-24 months [(11.3±2.5)months]. The surgical time and fluoroscopy times in the 3D-printed group were (53.4±9.1)minutes and (7.3±1.1)times, respectively, which were shorter than (90.2±16.0)minutes and (16.0±3.2)times in the freehand group (all P<0.01). At 6 months after operation, there was no significant difference in calcaneal length between the two groups ( P>0.05); the calcaneal width, height, B?hler angle and Gissane angle in the 3D-printed group [(34.0±1.8)mm, (47.2±1.6)mm, (27.8±1.0)°, (129.2±2.8)°] were superior than those in the freehand group [(37.5±2.0)mm, (43.0±2.7)mm, (25.8±1.5)°, (125.9±2.5)°] (all P<0.01). At 3, 6 months after operation and at the final follow-up, the values of AOFAS ankle-hindfoot score in the 3D-printed group [(72.2±2.3)points, (79.7±2.3)points, (86.5±4.4)points] were higher than those in the freehand group [(64.2±6.9)points, (73.4±4.2)points, (81.8±3.1)points] (all P<0.05); the values of Maryland score in the 3D-printed group [(71.4±7.7)points, (84.7±2.6)points, (91.5±2.5)points] were higher than those in the freehand group [(65.2±5.6)points, (79.1±3.8)points, (87.1±2.9)points] (all P<0.05). All surgical incisions were healed in stage I. In the 3D-printed group, there were no complications regarding infection, iatrogenic vascular or nerve injury, or fixation failure after surgery. In the freehand group, one patient with lateral sural cutaneous nerve injury was resolved spontaneously without specific treatment. Conclusion:Compared with freehand placement of cannulated screws, 3D-printed guide plate assisted placement of percutaneous placement has the advantages of shorter surgical time, fewer fluoroscopy times, lower reduction loss, better ankle joint function recovery, and less complications in treating Sanders type II and III calcaneal fractures.

Clinical characteristics of patients with acquired immunodeficiency syndrome complicated with nontuberculous mycobacteria disease / 中华传染病杂志

Objective:To explore the clinical characteristics of acquired immunodeficiency syndrome (AIDS) complicated with nontuberculous mycobacteria (NTM) disease.Methods:The clinical data of 190 patients with AIDS complicated with NTM disease diagnosed by Shanghai Public Health Clinical Center, Fudan University from January 1, 2019 to December 31, 2021 were analyzed retrospectively. NTM diseases were divided into disseminated NTM disease group and non-disseminated NTM disease group. The independent sample t test, Mann Whitney U test and chi-square test were used for statistical analysis. Results:The 190 patients with AIDS complicated with NTM disease included 182 males and eight females. The age was (42±13) years old, and the first hospital stay was 15(6, 26) days. Pneumocystis carinii pneumonia was the most common co-infection in 12.1%(23/190) of patients, 87 cases (45.8%) were disseminated NTM disease. The clinical symptoms of patients were common in fever (55.8%(106/190)), cough (50.0%(95/190)), and expectoration (28.9%(55/190)). The proportions of fatigue (31.0%(27/87) vs 7.8%(8/103)), poor appetite (21.8%(19/87) vs 10.7%(11/103)) in the AIDS patients with disseminated NTM disease group were higher than those in the non-disseminated NTM disease group, and the differences were statistically significant ( χ2=16.99, P<0.001 and χ2=4.42, P=0.036, respectively). There was no significant difference in the proportions of deaths between AIDS patients with disseminated NTM disease and those without disseminated NTM disease (17.2%(15/87) vs 12.6%(13/103), χ2=0.80, P=0.371). The most common NTM species was Mycobacterium avium (67.1%(49/190)), followed by Mycobacterium kansasii (15.1%(11/190)). Hemoglobin ((90.3±23.9) g/L vs (110.1±24.2) g/L), albumin ((29.7±5.5) g/L vs (34.7±5.6) g/L), CD4 + T lymphocyte count (11(5, 30)/μL vs 52(16, 96)/μL) and CD8 + T lymphocyte count ((362±320)/μL vs (496±352)/μL) in the disseminated NTM disease group were lower than those in non-disseminated NTM disease group ( t=-5.63, P<0.001; t=-6.18, P<0.001; Z=-5.90, P<0.001; and t=-2.73, P=0.007, respectively), while procalcitonin (0.24(0.10, 0.77) μg/L vs 0.10 (0.04, 0.51) μg/L) was higher than that in the non-disseminated NTM disease group ( Z=-3.09, P=0.002), with statistical significance. The most common imaging features were lung patch and strip shadow (67.4%(128/190)). Conclusions:The most common type of AIDS patients complicated with NTM disease is disseminated NTM disease, and Mycobacterium avium is the most common NTM species. The clinical manifestations (fatigue, anorexia) and laboratory tests (hemoglobin, albumin, procalcitonin, CD4 + T lymphocyte count, CD8 + T lymphocyte count) of AIDS patients with disseminated NTM disease and non-disseminated NTM disease are different, while the prognosis is not significantly different.

Changing trends of the clinical and epidemiological characteristics of acquired immunodeficiency syndrome-associated talaromycosis in Shanghai City / 中华传染病杂志

Objective:To analyze the clinical and epidemiological characteristics and changing trends of acquired immunodeficiency syndrome (AIDS)-associated talaromycosis in Shanghai City.Methods:The clinical data of patients with AIDS-associated talaromycosis hospitalized at Shanghai Public Health Clinical Center, Fudan University from Janauary 1, 2014 to December 31, 2021 were collected. The medical information included age, gender, place of origin, clinical symptoms, imaging manifestations, blood routine test, CD4 + T lymphocyte count. The chi-square test or Fisher exact probability test was used for statistical analysis. Univariate logistic regression was used to analyze the related risk factors for death. Results:From 2014 to 2021, a total of 12 165 AIDS patients were admitted, including 169 (1.4%) AIDS-assiociated talaromycosis patients. The proportions of AIDS-associated talaromycosis in AIDS inpatients from 2014 to 2021 were 1.8%(21/1 149), 1.1%(14/1 307), 1.3%(19/1 446), 0.9%(15/1 610), 1.2%(20/1 626), 1.2%(22/1 778), 1.7%(28/1 624) and 1.8%(30/1 625), respectively, which had not changed much. There was no statistically significant difference in the proportion of AIDS-associated talaromycosis in AIDS inpatients in different years ( χ2=9.50, P=0.218). Among the 169 patients, 157 cases (92.9%) were male, with the age of (37.9±12.2) years, and 35 were from Jiangxi Province, 31 from Shanghai Municipality, 29 from Zhejiang Province, 17 from Anhui Province, 14 from Fujian Province, 11 from Jiangsu Province, eight from Hunan Province, four from Heilongjiang Province, three cases each from Guangxi Zhuang Autonomous Region, Guizhou Province and Henan Province, two cases each from Hubei Province, Shandong Province, Shanxi Province, Yunnan Province and Guangdong Province, and one case from Chongqing Municipality. Patients from non-traditional endemic areas did not find a clear history of living in traditional endemic areas. Of 169 patients, 143(84.6%) cases had fever, 73(43.2%) had respiratory symptoms, and 26(15.4%) had rash during the course of the disease, 147(87.0%) had pulmonary imaging abnormalities, 94(55.6%) were complicated by other pathogens, and 44(26.0%) had hepatosplenomegaly, 137(81.1%) had CD4 + T lymphocyte count <50/μL. Twenty-three patients died, with the total fatality rate of 13.6%. The overall mortality rate showed a downward trend year by year. There was a statistically significant difference in the case fatality rate of AIDS-associated talaromycosis in different years (Fisher exact probability test, P=0.046). The result of univariate logistic regression model showed that patients with platelet count<50×10 9/L had an increased risk of death (odds ratio ( OR)=3.33, 95% confidence interval ( CI) 1.13 to 9.81, P=0.029). Conclusions:The overall change of AIDS-associated talaromycosis inpatients in Shanghai is not significant, while the prevalence rate has increased slightly in recent two years. The case fatality rate is declining year by year. The proportions of patients without a history of living in or traveling to epidemic areas and without rash as the first manifestation are high, and the main clinical manifestation is multi-system damage. Patients with platelet count<50×10 9/L have an increased risk of death.

Analysis of chest imaging features of novel coronavirus pneumonia, bacterial pneumonia and viral pneumonia / 中华危重病急救医学

Objective:To investigate and summarize the chest CT imaging features of patients with novel coronavirus pneumonia (COVID-19), bacterial pneumonia and other viral pneumonia.Methods:Chest CT data of 102 patients with pulmonary infection due to different etiologies were retrospectively analyzed, including 36 patients with COVID-19 admitted to Hainan Provincial People's Hospital and the Second Affiliated Hospital of Hainan Medical University from December 2019 to March 2020, 16 patients with other viral pneumonia admitted to Hainan Provincial People's Hospital from January 2018 to February 2020, and 50 patients with bacterial pneumonia admitted to Haikou Affiliated Hospital of Central South University Xiangya School of Medicine from April 2018 to May 2020. Two senior radiologists and two senior intensive care physicians were participated to evaluated the extent of lesions involvement and imaging features of the first chest CT after the onset of the disease.Results:Bilateral pulmonary lesions were more common in patients with COVID-19 and other viral pneumonia, and the incidence was significantly higher than that of bacterial pneumonia (91.6%, 75.0% vs. 26.0%, P < 0.05). Compared with other viral pneumonia and COVID-19, bacterial pneumonia was mainly characterized by single-lung and multi-lobed lesion (62.0% vs. 18.8%, 5.6%, P < 0.05), accompanied by pleural effusion and lymph node enlargement. The proportion of ground-glass opacity in the lung tissues of patients with COVID-19 was 97.2%, that of patients with other viral pneumonia was 56.2%, and that of patients with bacterial pneumonia was only 2.0% ( P < 0.05). The incidence rate of lung tissue consolidation (25.0%, 12.5%), air bronchial sign (13.9%, 6.2%) and pleural effusion (16.7%, 37.5%) in patients with COVID-19 and other viral pneumonia were significantly lower than those in patients with bacterial pneumonia (62.0%, 32.0%, 60.0%, all P < 0.05), paving stone sign (22.2%, 37.5%), fine mesh sign (38.9%, 31.2%), halo sign(11.1%, 25.0%), ground-glass opacity with interlobular septal thickening (30.6%, 37.5%), bilateral patchy pattern/rope shadow (80.6%, 50.0%) etc. were significantly higher than those of bacterial pneumonia (2.0%, 4.0%, 2.0%, 0%, 22.0%, all P < 0.05). The incidence of local patchy shadow in patients with COVID-19 was only 8.3%, significantly lower than that in patients with other viral pneumonia and bacterial pneumonia (8.3% vs. 68.8%, 50.0%, P < 0.05). There was no significant difference in the incidence of peripheral vascular shadow thickening in patients with COVID-19, other viral pneumonia and bacterial pneumonia (27.8%, 12.5%, 30.0%, P > 0.05). Conclusions:The probability of ground-glass opacity, paving stone and grid shadow in chest CT of patients with COVID-19 was significantly higher than those of bacterial pneumonia, and it was more common in the lower lungs and lateral dorsal segment. In other patients with viral pneumonia, ground-glass opacity was distributed in both upper and lower lungs. Bacterial pneumonia is usually characterized by single lung consolidation, distributed in lobules or large lobes and accompanied by pleural effusion.

Clinical efficacy of da Vinci Xi surgical system assisted laparoscopic exocytosis for hepatic echinococcosis / 中华消化外科杂志

Objective:To investigate the clinical efficacy of da Vinci Xi surgical system assisted laparoscopic exocytosis for hepatic echinococcosis.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 7 patients who underwent da Vinci Xi surgical system assisted laparoscopic exocytosis for hepatic echinococcosis in Xinjiang Uiger Municipal People′s Hospital from October 2019 to July 2021 were collected. There were 3 males and 4 females, aged (43±12)years. Observation indicators: (1) surgical situations; (2) complications; (3) follow-up. Mea-surement data with normal distribution were represented as Mean±SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Surgical situations. All 7 patients underwent da Vinci Xi surgical system assisted laparoscopic exocytosis for hepatic echinococcosis successfully, without conversion to laparotomy and laparoscopic surgery. None of the 7 patients underwent intraoperative blood transfusion and the operation time, volume of intraoperative blood loss, time to postoperative first and flatus, time to postoperative initial liquid food intake, time to postoperative abdominal drainage tube removal, time to postoperative urethral catheter removal, duration of postoperative hospital stay of 7 patients was (225±45)minutes, 100(range, 50-200)mL, (1.9±0.7)days, (4.2±1.2)days, (7±4)days, (2.9±0.8)days, (7±4)days, respectively. (2) Complications. None of the 7 patients had postoperative complications such as bile leakage, abdominal hemorrhage, incision infection, hydatid cavity infection, secondary operation, intestinal obstruction, pulmonary infection and deep venous thrombosis of lower limbs. (3) Follow-up. All 7 patients were followed up for 7 (range, 3-12) months. None of the 7 patients had recurrence of hepatic echinococcosis or peritoneal implantation and incision implantation, and all patients survived during follow-up.Conclusion:da Vinci Xi surgical system assisted laparoscopic exocytosis for hepatic echinococcosis is safe and feasible.

CT-Based Weighted Radiomic Score Predicts Tumor Response to Immunotherapy in Non-Small Cell Lung Cancer / 中国医学科学院学报

Objective To develop a CT-based weighted radiomic model that predicts tumor response to programmed death-1(PD-1)/PD-ligand 1(PD-L1)immunotherapy in patients with non-small cell lung cancer.Methods The patients with non-small cell lung cancer treated by PD-1/PD-L1 immune checkpoint inhibitors in the Peking Union Medical College Hospital from June 2015 to February 2022 were retrospectively studied and classified as responders(partial or complete response)and non-responders(stable or progressive disease).Original radiomic features were extracted from multiple intrapulmonary lesions in the contrast-enhanced CT scans of the arterial phase,and then weighted and summed by an attention-based multiple instances learning algorithm.Logistic regression was employed to build a weighted radiomic scoring model and the radiomic score was then calculated.The area under the receiver operating characteristic curve(AUC)was used to compare the weighted radiomic scoring model,PD-L1 model,clinical model,weighted radiomic scoring + PD-L1 model,and comprehensive prediction model.Results A total of 237 patients were included in the study and randomized into a training set(n=165)and a test set(n=72),with the mean ages of(64±9)and(62±8)years,respectively.The AUC of the weighted radiomic scoring model reached 0.85 and 0.80 in the training set and test set,respectively,which was higher than that of the PD-L1-1 model(Z=37.30,P<0.001 and Z=5.69,P=0.017),PD-L1-50 model(Z=38.36,P<0.001 and Z=17.99,P<0.001),and clinical model(Z=11.40,P<0.001 and Z=5.76,P=0.016).The AUC of the weighted scoring model was not different from that of the weighted radiomic scoring + PD-L1 model and the comprehensive prediction model(both P>0.05).Conclusion The weighted radiomic scores based on pre-treatment enhanced CT images can predict tumor responses to immunotherapy in patients with non-small cell lung cancer.

Highly efficient production of L-valine by multiplex metabolic engineering of Corynebacterium glutamicum / 生物工程学报

As a branched chain amino acid, L-valine is widely used in the medicine and feed sectors. In this study, a microbial cell factory for efficient production of L-valine was constructed by combining various metabolic engineering strategies. First, precursor supply for L-valine biosynthesis was enhanced by strengthening the glycolysis pathway and weakening the metabolic pathway of by-products. Subsequently, the key enzyme in the L-valine synthesis pathway, acetylhydroxylate synthase, was engineered by site-directed mutation to relieve the feedback inhibition of the engineered strain. Moreover, promoter engineering was used to optimize the gene expression level of key enzymes in L-valine biosynthetic pathway. Furthermore, cofactor engineering was adopted to change the cofactor preference of acetohydroxyacid isomeroreductase and branched-chain amino acid aminotransferase from NADPH to NADH. The engineered strain C. glutamicum K020 showed a significant increase in L-valine titer, yield and productivity in 5 L fed-batch bioreactor, up to 110 g/L, 0.51 g/g and 2.29 g/(L‧h), respectively.

Regulation of intracellular level of ATP and NADH in Escherichia coli to promote succinic acid production / 生物工程学报

Succinic acid is an important C4 platform chemical that is widely used in food, chemical, medicine sectors. The bottleneck of fermentative production of succinic acid by engineered Escherichia coli is the imbalance of intracellular cofactors, which often leads to accumulation of by-products, lower yield and low productivity. Stoichiometric analysis indicated that an efficient production of succinic acid by E. coli FMME-N-26 under micro-aeration conditions might be achieved when the TCA cycle provides enough ATP and NADH for the r-TCA pathway. In order to promote succinic acid production, a serial of metabolic engineering strategies include reducing ATP consumption, strengthening ATP synthesis, blocking NADH competitive pathway and constructing NADH complementary pathway were developed. As result, an engineered E. coli FW-17 capable of producing 139.52 g/L succinic acid and 1.40 g/L acetic acid in 5 L fermenter, which were 17.81% higher and 67.59% lower than that of the control strain, was developed. Further scale-up experiments were carried out in a 1 000 L fermenter, and the titer of succinic acid and acetic acid were 140.2 g/L and 1.38 g/L, respectively.