Small Molecules Accelerate Skin Wound Healing: Shikonin Efficacy and Mechanism of Action in Mice / Las Moléculas Pequeñas Aceleran la Curación de Heridas en la Piel: Eficacia de Shikonin y Mecanismo de Acción en Ratones

SUMMARY: The objective of this study was to investigate the therapeutic wound healing potential and molecular mechanisms of shikonin as small molecules in vitro. A mouse burn model was used to explore the potential therapeutic effect of shikonin; we traced proliferating cells in vivo to locate the active area of skin cell proliferation. Through the results of conventional pathological staining, we found that shikonin has a good effect on the treatment of burned skin and promoted the normal distribution of skin keratin at the damaged site. At the same time, shikonin also promoted the proliferation of skin cells at the damaged site; importantly, we found a significant increase in the number of fibroblasts at the damaged site treated with shikonin. Most importantly, shikonin promotes fibroblasts to repair skin wounds by regulating the PI3K/AKT signaling pathway. This study shows that shikonin can effectively promote the proliferation of skin cell, and local injection of fibroblasts in burned skin can play a certain therapeutic role.

El objetivo de este trabajo fue investigar el potencial terapéutico de cicatrización de heridas y los mecanismos moleculares de la shikonina como moléculas pequeñas in vitro. Se utilizó un modelo de quemaduras en ratones para explorar el posible efecto terapéutico de la shikonina; Rastreamos las células en proliferación in vivo para localizar el área activa de proliferación de células de la piel. A través de los resultados de la tinción para patología convencional, encontramos que la shikonina tiene un buen efecto en el tratamiento de la piel quemada y promueve la distribución normal de la queratina de la piel en el sitio dañado. Al mismo tiempo, la shikonina también promovió la proliferación de células de la piel en el sitio dañado. Es importante destacar que encontramos un aumento significativo en la cantidad de fibroblastos en el sitio dañado tratado con shikonina. Lo más importante es que la shikonina promueve la función reparadora de fibroblastos en las heridas de la piel regulando la vía de señalización PI3K/ AKT. Este estudio muestra que la shikonina puede promover eficazmente la proliferación de células de la piel y que la inyección local de fibroblastos en la piel quemada puede desempeñar un cierto papel terapéutico.

The relationship between genetic polymorphism of CYP2C19 and the efficacy of Helicobacter pylori eradication therapy in children / 中华儿科杂志

Objective: To investigate the relationship between genetic polymorphisms of cytochrome P450 2C19 (CYP2C19) and the efficacy of Helicobacter pylori (Hp) eradication therapy in children. Methods: The retrospective cohort study was conducted on 125 children with gastroscopy and positive rapid urease test (RUT) from September 2016 to December 2018 who presented to the Children's Hospital of Zhejiang University School of Medicine due to gastrointestinal symptoms including nausea, vomiting, abdominal pain, bloating, acid reflux, heartburn, chest pain, vomiting blood and melena. Hp culture and drug susceptibility test were carried out with gastric antrum mucosa before treatment. All the patients completed 2 weeks of standardized Hp eradication therapy and had 13C urea breath test 1 month after that, which was used to evaluate the curative effect. The DNA of gastric mucosa after RUT was analyzed and CYP2C19 gene polymorphism was detected. Children were grouped according to metabolic type. Combined with the results of Hp culture and drug susceptibility, the relationship between CYP2C19 gene polymorphism and the efficacy of Hp eradicative treatment was analyzed in children. Chi square test was used for row and column variables, and Fisher exact test was used for comparison between groups. Results: One hundred and twenty five children were enrolled in the study, of whom 76 were males and 49 females. The genetic polymorphism of CYP2C19 in these children found poor metabolizer (PM) of 30.4% (38/125), intermediate metabolizer (IM) of 20.8% (26/125), normal metabolizer (NM) of 47.2% (59/125), rapid metabolizer (RM) of 1.6% (2/125), and ultrarapid metabolizer (UM) of 0. There were statistically significant in positive rate of Hp culture among these groups (χ2=124.00, P<0.001). In addition, the successful rates of Hp eradication in PM, IM, NM and RM genotypes were 84.2% (32/38), 53.8% (14/26), 67.8% (40/59), and 0, respectively, with significant differences (χ2=11.35, P=0.010); those in IM genotype was significantly lower than that in PM genotype (P=0.011). With the same standard triple Hp eradicative regimen, the successful rate of Hp eradication for IM type was 8/19, which was lower than that of PM (80.0%, 24/30) and NM type (77.3%, 34/44) (P=0.007 and 0.007, respectively). There was a significant difference in the efficacy of Hp eradication treatment among different genotypes (χ2=9.72, P=0.008). According to the clarithromycin susceptibility result, the successful rate of Hp eradication treatment for IM genotype was 4/15 in the sensitive group and 4/4 in the drug-resistant group (χ2=6.97, P=0.018). Conclusions: The genetic polymorphism of CYP2C19 in children is closely related to the efficacy of Hp eradication treatment. PM has a higher successful rate of eradication treatment than the other genotypes.

The association between Helicobacter pylori virulence factor genotypes and gastroduodenal diseases in children / 中华儿科杂志

Objective: To investigate the association between Helicobacter pylori (Hp) virulence factor genotypes and the degree and activity of gastric mucosa pathological changes in pediatric gastroduodenal diseases. Methods: This retrospective cohort study was conducted from May 2020 to October 2020. The frozen strains of Hp, which were cultured with the gastric mucosa of 68 children with gastroscopy confirmed gastroduodenal diseases who visited the children's hospital of Zhejiang University School of Medicine from April 2012 to December 2014, were resuscitated. After extracting DNA from these Hp strains, PCR amplification and agarose gel electrophoresis were performed to determine the detection rate of cytotoxin-associated protein A (cagA),vacuolating cytotoxin A (vacA)(s1a、s1b/s2,m1/m2), outer inflammatory protein A (oipA),blood group antigen binding adhesin (babA),duodenal ulcer promoting protein A (dupA) genes; oipA genes were sequenced to determine the gene status. The patients were divided into different groups according to the findings of gastroscopy and gastric mucosa pathology. The detection rates of various virulence factor genotypes among different groups were compared using χ2 tests or Fisher's exact tests. Results: The 68 Hp strains all completed genetic testing. According to the diagnostic findings of gastroscopy, the 68 cases were divided into 47 cases of superficial gastritis and 21 cases of peptic ulcer. Regarding the pathological changes of gastric mucosa, 8 cases were mild, and 60 cases were moderate and severe according to the degree of inflammation; 61 cases were active and 7 cases inactive according to the activity of inflammation. The overall detection rates of cagA, vacA, vacA s1/m2, functional oipA, babA2, and dupA virulence factor genes were 100% (68/68), 100% (68/68), 94% (64/68), 99% (67/68), 82% (56/68), and 71% (48/68), respectively. In the superficial gastritis group, their detection rates were 100% (47/47), 100% (47/47), 96% (45/47), 98% (46/47), 81% (38/47), and 70% (33/47), respectively; in the peptic ulcer group, their detection rates were 100% (21/21), 100% (21/21), 90% (19/21), 100% (21/21), 86% (18/21), and 71% (15/21), respectively. There was no statistically significant difference between the two groups (all P>0.05). In the mild gastric mucosa inflammation group, the detection rates of the above six genotypes were 8/8, 8/8, 8/8, 7/8, 7/8, and 5/8, respectively; and in the moderate to severe inflammation groups, the detection rates were 100% (60/60), 100% (60/60), 93% (56/60), 100% (60/60), 82% (49/60), and 72% (43/60), respectively, with no statistically significant difference between the two groups (all P>0.05). In the active inflammation group, the detection rate of six genotypes were 100% (61/61), 100% (61/61), 93% (57/61), 98% (60/61), 82% (50/61), and 72% (44/61), respectively; and in the inactive inflammation group, they were 7/7, 7/7, 7/7, 7/7, 6/7, and 4/7, respectively. Again, there was no statistically significant difference between the two groups (all P>0.05). There was no statistically significant difference in the detection rate of combinations of 4 or 5 virulence factor genes among the different groups (all P>0.05). Conclusions: CagA, vacA, vacA s1/m2, functional oipA, babA2, and dupA genes are not associated with superficial gastritis and peptic ulcer in children, or with the degree and activity of gastric mucosa pathological inflammation. Different gene combinations of cagA, vacA, oipA, babA2, and dupA have no significant effects on predicting the clinical outcome of Hp infection in children.

Analysis of measles antibody level and susceptibility of enterprise employees in Jinshan District，Shanghai in 2019 / 中国生物制品学杂志

@#Abstract：Objective To analyse the level of measles antibody and serological susceptibility of the enterprise employees in Jin⁃ shan District，Shanghai in 2019，to provide references for measles prevention and control of enterprise employees. Methods A total of 1 796 employees were selected from 6 enterprises in Jinshan District by using a stratified random sampling method，of which serum samples from intravenous blood were collected and determined for IgG antibody level of measles by ELISA. Geo⁃ metric mean concentration（GMC）of measles IgG antibody，antibody positive rate and antibody protection rate were calculated and the susceptibility factors of measles in enterprise employees were analyzed by using the unconditional multivariate Logistic regression model. Results The GMC of measles antibody in 1 796 monitoring objects was 639. 71 mIU／mL，the positive rate was 87. 58% and the protection rate was 29. 06%. Multivariate Logistic regression analysis showed that the odds ratio（OR）of measles susceptibility was 1. 55（95% CI：1. 14 ~ 2. 12）in native subjects compared with non⁃resident subjects，while 2. 35 （95% CI：1. 35 ~ 4. 08）in subjects aged 40 ~ 49 years compared with those aged ≥ 50 years. Conclusion In 2019，the measles antibody level of enterprise employees in Jinshan District of Shanghai was low，and people aged 40 ~ 49，especially the nativeadults，wereathighriskofsusceptibilitytomeasles. Supplementaryimmunizationwithmeaslesvaccineshouldbecarried out for high⁃risk enterprise employees to reduce the risk of measles infection and control the epidemic situation of measles.

A Pilot Clinical Study to Investigate the Hypomethylating Properties of Freeze-dried Black Raspberries in Patients with Myelodysplastic Syndrome or Myeloproliferative Neoplasm

Myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are bone marrow disorders characterized by cytopenias and progression to acute myeloid leukemia. Hypomethylating agents (HMAs) are Food and Drug Administration-approved therapies for MDS and MDS/MPN patients. HMAs have improved patients’ survival and quality of life when compared with other therapies. Although HMAs are effective in MDS and MDS/MPN patients, they are associated with significant toxicities that place a large burden on patients. Our goal is to develop a safer and more effective HMA from natural products. We previously reported that black raspberries (BRBs) have hypomethylating effects in the colon, blood, spleen, and bone marrow of mice. In addition, BRBs exert hypomethylating effects in patients with colorectal cancer and familial adenomatous polyposis. In the current study, we conducted a pilot clinical trial to evaluate the hypomethylating effects of BRBs in patients with low-risk MDS or MDS/MPN. Peripheral blood mononuclear cells (PBMCs) were isolated before and after three months of BRB intervention. CD45 + cells were isolated from PBMCs for methylation analysis using a reduced-representation bisulfite sequencing assay. Each patient served as their own matched control, with their measurements assessed before intervention providing a baseline for post-intervention results. Clinically, our data showed that BRBs were well-tolerated with no side effects. When methylation data was combined, BRBs significantly affected methylation levels of 477 promoter regions. Pathway analysis suggests that BRB-induced intragenic hypomethylation drives leukocyte differentiation. A randomized, placebo-controlled clinical trial of BRB use in low-risk MDS or MDS/ MPN patients is warranted.

Effect of dyslipidemia on clinical outcome of infertility patients receiving donor eggs / 中华妇产科杂志

Objective:To explore the effect of dyslipidemia on the clinical outcome of intracytoplasmic sperm injection-embryo transfer (ICSI-ET) in infertility patients receiving donor eggs.Methods:A total of 118 patients were selected to receive egg donors and ICSI-ET at the First Affiliated Hospital of Nanjing Medical University between April 2007 and December 2020. According to the levels of triacylglycerol, serum cholesterol, high density lipoprotein (HDL), and low density lipoprotein, they were divided into dyslipidemia group (35 cases) and normal blood lipids group (83 cases). The influence of body mass index (BMI) and age was adjusted by 1∶1 propensity score matching, and the general condition and clinical outcome of the two groups were analyzed retrospectively. Finally, the relationship between lipid composition and clinical outcome was analyzed according to patients′ age and BMI.Results:(1) Comparing the pre-matching dyslipidemia group with the normal blood lipids group, the BMI of the dyslipidemia group was significantly higher than that of the normal blood lipids group [(23.5±2.4) vs (22.4±2.7) kg/m 2], and the embryo implantation rate was significantly lower than that of the normal blood lipids group [13.6% (8/59) vs 27.3% (36/132)], the differences were statistically significant (both P<0.05). (2) There were no significant differences in years of infertility, number of pregnancies, number of abortions, number of transplanted embryos, protocol of endometrial preparation, endometrial thickness on transplantation day and high quality embryo rate between the two groups, through propensity score matching (all P>0.05). The biochemical pregnancy rate [28.6% (10/35)], embryo implantation rate [13.6% (8/59)] and live birth rate [20.0% (7/35)] in dyslipidemia group were significantly lower than those in the normal blood lipids group ( P<0.05). The clinical pregnancy rate was lower than that of the normal blood lipids group ( P>0.05). (3) The results of stratified analysis showed that the level of HDL in the clinically non-pregnant group was significantly lower than that in the pregnant group in patients ≤ 35 years old [(1.5±0.3) vs (1.8±0.5) mmol/L; P<0.05]. In the overweight recipient patients, the level of HDL of the clinically non-pregnant group was lower than that of the pregnant group ( P>0.05). Conclusions:Dyslipidemia significantly reduces the biochemical pregnancy rate, embryo implantation rate and live birth rate in patients with receiving donor eggs. Especially in patients aged ≤35 years old, the reduction of HDL is closely related to adverse pregnancy outcomes.

Changes of cytokine levels before and after anti-tuberculosis treatment / 中国热带医学

@#Abstract： Objective　To analyze the changes of cytokine levels in patients with sensitive pulmonary tuberculosis and drug-resistant pulmonary tuberculosis before and after anti-tuberculosis treatment. Methods　The clinical data of 213 pulmonary tuberculosis patients admitted to the Eighth Affiliated Hospital of Xinjiang Medical University from August 2019 to October 2020 were collected, and divided into a sensitive pulmonary tuberculosis group and a drug-resistant pulmonary tuberculosis group, of which 141 were in the sensitive group and 72 in the drug-resistant group , and the pro-inflammatory factors tumor necrosis factor-α (TNF-α), IL-6, IL-17, interferon-γ (IFN-γ) and anti-inflammatory factors IL-10 and IL-4 in plasma before treatment, 3 months and 6 months after treatment were compared. Results　Compared with the healthy group, the levels of plasma IL-6 in the sensitive group and the resistant group were significantly increased, difference was statistically significant (P<0.01). The plasma levels of IFN-γ and IL-17 in the sensitive group were increased, and the difference was statistically significant (P<0.05). Compared with before treatment, the levels of IL-6 and IL-4 in the plasma of the sensitive group after 6 months of treatment were lower than those after 3 months of treatment, and the difference was statistically significant (P<0.05), and IFN-γ was significantly decreased (P<0.001). After 6 months of treatment, the IL-10 content was lower than that before treatment, and the difference was statistically significant (P<0.05), and the IFN-γ decreased significantly (P<0.000 1). The levels of IFN-γ at 3 months were higher than those in the resistant group, and the difference was statistically significant (P<0.01). After 6 months of treatment, there was no significant difference in the content of IFN-γ between the sensitive group and the resistant group. The effective rate of CT absorption was 70% in the sensitive group and only 43.33% in the resistant group at 3 months of treatment, and there was no significant difference in the effective rate between the two groups after 6 months of treatment. Conclusions　Detection of pro-inflammatory cytokines and anti-inflammatory cytokines in plasma can provide reference for host-directed therapy of pulmonary tuberculosis. Understanding this important feature of cytokines on pathogen-host interactions can provide new insights into the study of virulence mechanisms and may provide new approaches for immune intervention in pulmonary tuberculosis.

Characterization and diagnostic efficacy of Rose-Bengal plate agglutination test, standard-tube agglutination test and enzyme-linked immunosorbent assay methods in detecting brucellosis / 中国热带医学

@#Abstract: Objective　To study the characteristics and diagnostic efficacy of Rose-Bengal plate agglutination test (RBPT), standard-tube agglutination test (SAT) and enzyme-linked immunosorbent assay (ELISA) in the diagnosis of brucellosis. Methods　A total of 489 suspected brucellosis patients with complete records, who admitted to Xing'anmeng People's Hospital from March 2020 to May 2021, were selected as the subjects. The diagnostic value of SAT, RBPT and ELISA for brucellosis was analyzed with exposure history + clinical symptoms + serological test/brucellosis isolation and culture as the gold standard. Results　Of the 489 suspected patients, 183 (37.42%) were diagnosed with brucellosis, while 234 (47.85%), 148 (30.27%) and 195 (39.88%) were positive by RBPT, ELISA and SAT, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of RBPT in the diagnosis of brucellosis were 95.08%, 80.39%, 74.36%, 96.47%, and 85.89%, respectively; the values of the above parameters for ELISA were 78.69%, 98.69%, 97.30%, 88.56%, and 91.21%, respectively; those values of SAT were 98.36%, 95.10%, 92.31%, 98.98%, and 96.32%, respectively. The sensitivity of RBPT was significantly higher than ELISA, but the specificity and accuracy were significantly lower than ELISA (all P<0.05). The sensitivity and accuracy of SAT diagnosis were significantly higher than ELISA, but the specificity was significantly lower than ELISA (all P<0.05). There was no significant difference between SAT and RBPT in the sensitivity of diagnosis, but the specificity and accuracy were significantly higher than those of RBPT (P<0.05). Conclusion　RBPT and SAT have high sensitivity in diagnosis of brucellosis, while ELISA has high specificity in diagnosis. RBPT with high sensitivity and convenient operation can be used for primary screening in field detection, and then the other two methods can be used for rechecking, so as to further improve the efficiency and accuracy of diagnosis of brucellosis.

Protocatechuic Acid, a Gut Bacterial Metabolite of Black Raspberries, Inhibits Adenoma Development and Alters Gut Microbiome Profiles in Apc Min/+ Mice

Administration of black raspberries (BRBs) and their anthocyanin metabolites, including protocatechuic acid (PCA), has been demonstrated to exert chemopreventive effects against colorectal cancer through alteration of innate immune cell trafficking, modulation of metabolic and inflammatory pathways, etc. Previous research has shown that the gut microbiome is important in the effectiveness of chemoprevention of colorectal cancer. This study aimed to assess the potency of PCA versus BRB dietary administration for colorectal cancer prevention using an Apc Min/+ mouse model and determine how bacterial profiles change in response to PCA and BRBs. A control AIN-76A diet supplemented with 5% BRBs, 500 ppm PCA, or 1,000 ppm PCA was administered to Apc Min/+ mice. Changes in incidence, polyp number, and polyp size regarding adenomas of the small intestine and colon were assessed after completion of the diet regimen. There were significant decreases in adenoma development by dietary administration of PCA and BRBs in the small intestine and the 5% BRB-supplemented diet in the colon. Pro-inflammatory bacterial profiles were replaced with anti-inflammatory bacteria in all treatments, with the greatest effects in the 5% BRB and 500 ppm PCA-supplemented diets ac-companied by decreased COX-2 and prostaglandin E 2 levels in colonic mucosa. We further showed that 500 ppm PCA, but not 1,000 ppm PCA, increased IFN-γ and SMAD4 levels in primary cultured human natural killer cells. These results suggest that both BRBs and a lower dose PCA can benefit colorectal cancer patients by inhibiting the growth and proliferation of adenomas and promoting a more favorable gut microbiome condition.

Transcranial sonography in differential diagnosis of Parkinson disease and other movement disorders / 中华医学杂志(英文版)

BACKGROUND@#Reports evaluating the efficacy of transcranial sonography (TCS) for the differential diagnosis of Parkinson disease (PD) and other movement disorders in China are scarce. Therefore, this study aimed to assess the application of TCS for the differential diagnosis of PD, multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and essential tremor (ET) in Chinese individuals.@*METHODS@#From 2017 to 2019, 500 inpatients treated at the Department of Dyskinesia, Beijing Tiantan Hospital, Capital Medical University underwent routine transcranial ultrasound examination. The cross-sections at the midbrain and thalamus levels were scanned, and the incidence rates of substantia nigra (SN) positivity and the incidence rates of lenticular hyperechoic area were recorded. The echo of the SN was manually measured.@*RESULTS@#Of the 500 patients, 125 were excluded due to poor signal in temporal window sound transmission. Among the 375 individuals with good temporal window sound transmission, 200 were diagnosed with PD, 90 with ET, 50 with MSA, and 35 with PSP. The incidence rates of SN positivity differed significantly among the four patient groups (χ2 = 121.061, P  0.017).@*CONCLUSION@#SN positivity could effectively differentiate PD from ET, PSP, and MSA in a Chinese population.

Dysregulated Free Fatty Acid Receptor 2 Exacerbates Colonic Adenoma Formation in ApcMin/+ Mice: Relation to Metabolism and Gut Microbiota Composition

Free fatty acid receptor 2 (FFAR2) has been reported as a tumor suppressor in colon cancer development. The current study investigated the effects of FFAR2 signaling on energy metabolism and gut microbiota profiling in a colorectal cancer mouse model (ApcMin/+). FFAR2 deficiency promoted colonic polyp development and enhanced fatty acid oxidation and bile acid metabolism. Gut microbiome sequencing analysis showed distinct clustering among wild-type, ApcMin/+, and ApcMin/+-Ffar2-/- mice. The relative abundance of Flavobacteriaceae and Verrucomicrobiaceae was significantly increased in the ApcMin/+-Ffar2-/- mice compared to the ApcMin/+ mice. In addition, knocking-down FFAR2 in the human colon cancer cell lines (SW480 and HT29) resulted in increased expression of several key enzymes in fatty acid oxidation, such as carnitine palmitoyltransferase 2, acyl-CoA dehydrogenase, longchain acyl-CoA dehydrogenase, C-2 to C-3 short chain, and hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase, alpha subunit. Collectively, these results demonstrated that FFAR2 deficiency significantly altered profiles of fatty acid metabolites and gut microbiome, which might promote colorectal cancer development.

Dysregulated Free Fatty Acid Receptor 2 Exacerbates Colonic Adenoma Formation in ApcMin/+ Mice: Relation to Metabolism and Gut Microbiota Composition

Free fatty acid receptor 2 (FFAR2) has been reported as a tumor suppressor in colon cancer development. The current study investigated the effects of FFAR2 signaling on energy metabolism and gut microbiota profiling in a colorectal cancer mouse model (ApcMin/+). FFAR2 deficiency promoted colonic polyp development and enhanced fatty acid oxidation and bile acid metabolism. Gut microbiome sequencing analysis showed distinct clustering among wild-type, ApcMin/+, and ApcMin/+-Ffar2-/- mice. The relative abundance of Flavobacteriaceae and Verrucomicrobiaceae was significantly increased in the ApcMin/+-Ffar2-/- mice compared to the ApcMin/+ mice. In addition, knocking-down FFAR2 in the human colon cancer cell lines (SW480 and HT29) resulted in increased expression of several key enzymes in fatty acid oxidation, such as carnitine palmitoyltransferase 2, acyl-CoA dehydrogenase, longchain acyl-CoA dehydrogenase, C-2 to C-3 short chain, and hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase, alpha subunit. Collectively, these results demonstrated that FFAR2 deficiency significantly altered profiles of fatty acid metabolites and gut microbiome, which might promote colorectal cancer development.

Efficacy and Safety of Emricasan in Liver Cirrhosis and/or Fibrosis

This study aimed to perform a meta-analysis to determine the efficacy and safety of emricasan. Nine databases were searched for clinical trials investigating the efficacy of emricasan treatment in patients with liver cirrhosis or fibrosis. A manual search was conducted to identify the missing trials. The quality of the included studies was assessed using the revised Cochrane risk of bias tool. Efficacy of emricasan treatment was defined as a positive change in apoptosis-related parameters from baseline to the last follow-up visit. Overall, emricasan treatment is more effective in patients with liver cirrhosis or fibrosis than placebo (standardized mean difference [SMD] [95% confidence intervals (CI)]=0.28 [0.14; 0.41]). No significant change in model for end-stage liver disease (MELD) score between the emricasan and placebo groups was noted (SMD [95% CI]=0.18 [-0.01; 0.36]; p=0.058). A 50 mg dose of emricasan had the highest efficacy rate compared to placebo (SMD [95% CI]=0.28 [0.06; 0.50]; p=0.012), followed by the 5 mg dosing regimen (SMD [95% CI]=0.28 [0.06; 0.50]; p=0.012). Treatment with emricasan resulted in significant reductions in ALT (mean difference (MD) [95% CI]=-5.89 [-10.59; -1.20]; p=0.014) and caspase3/7 levels (MD [95%CI]=-1215.93 [-1238.53; -1193.33]; p<0.001), respectively. No significant increase in the rate of overall adverse events was noted (OR [95% CI]=1.52 [0.97; 2.37]; p=0.069). Treatment with emricasan is more effective in improving liver function and apoptosis parameters compared to placebo, with a well-tolerated safety profile. However, due to the poor quality of the analyzed studies, the small number of trials and patients, and the short follow-up periods, more robust trials are still warranted.

Comparative analysis of the clinical symptoms and laboratory examination indexes between patients with HIV/AIDS infection complicated with tuberculosis and those with HIV/AIDS alone / 公共卫生与预防医学

Objective To explore the differences in clinical symptoms and laboratory examination indexes between patients with HIV/AIDS infection complicated with tuberculosis (TB) and those with HIV/AIDS alone, so as to provide a reference for early identification and diagnosis of HIV/AIDS infection with TB. Methods A total of 206 patients with HIV/AIDS infection and TB who were admitted to Suining Central Hospital from January 2015 to April 2019 were selected as the study group. 86 patients with pure HIV/AIDS were selected as the disease control group. Data of clinical diagnosis and treatment as well as follow-up of the patients were retrospectively analyzed. The clinical symptoms, laboratory examination indexes and clinical treatment outcomes were compared between the two groups. Results The incidence rates of fever, emaciation, electrolyte imbalance, hypoproteinemia, cough and chest pain in the study group were significantly higher than those in the disease control group (P0.05). The positive rates of sputum smear acid fast stain, sputum mycobacterium tuberculosis culture and PPD test in the study group were significantly higher than those in the disease control group, while the CD3+ count, CD4+ count and CD4+/CD8+ were obviously lower than the disease control group (P0.05). The ROC curve suggested that the areas under the curve of CD3+, CD4+, CD4+/ CD8+ and the three combined indicators to evaluate HIV/AIDS infection combined with TB were 0.799, 0.841, 0.913, and 0.935, respectively. The hospitalization time in the study group was significantly longer than that in the disease control group. The proportion of discharged patients (improved) in the study group was significantly lower than that in the disease control group, while the proportion of discharged patients (not improved) was significantly higher than that in the disease control group (P<0.05). Conclusion Although the clinical symptoms of patients with HIV/AIDS infection combined with TB are similar to those of patients with HIV/AIDS alone, the main symptoms of the former are fever, emaciation and electrolyte imbalance. The detection of laboratory immune function indexes is of positive significance for improvement of the diagnostic sensitivity and accuracy of HIV/AIDS infection with TB.

Anti-colonic Inflammation by Black Raspberries through Regulating Toll-like Receptor-4 Signaling in Interlukin-10 Knockout Mice

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon, with a steadily rising prevalence in Western and newly industrialized countries. UC patients have a cancer incidence as high as 10% after 20 years of the disease. Although the importance of fruits and vegetables in defense against UC is beginning to be appreciated, the mechanisms remain largely unclear. In the current study, we reported that dietary black raspberries (BRBs) decreased colonic inflammation in the mucosa and submucosa of interleukin (IL)-10 knockout (KO) mice. We then used colon, spleen, and plasma from those mice to investigate whether BRBs exert their anti-inflammatory effects by correcting dysregulated toll-like receptor (TLR)-4 signaling to downregulate prostaglandin E2 (PGE2). Other studies reported that spleen is the reservoir of macrophages and depletion of macrophages in IL-10 KO mice prevents the development of colitis. Our results showed that BRBs decreased the percentages of macrophages in spleens of IL-10 KO mice. Moreover, mechanistically, the BRB diet corrected dysregulated TLR-4 signaling in cells from the colon and spleen, decreased PGE2 and prostaglandin I2, and increased 15-lipoxygenase and its product, 13-S-hydroxyoctadecadienoic acid, in plasma of IL- 10 KO mice. Therefore, we have elucidated one of the anti-inflammatory mechanisms of BRBs, and have identified biomarkers that could be indicators of response in UC patients treated with them. Our findings with BRBs could well apply to many other commonly consumed fruits and vegetables.

Analysis on the main causes of death and years of life lost among youth aged 18-44 in Chongqing from 2011 to 2016 / 中华疾病控制杂志

Objective To estimate the mortality and years of life lost among youth aged 18-44 in Chongqing from 2011 to

Age distribution characteristics of intestinal segmented filamentous bacteria and their relationship with intestinal mucosal immunity in children / 中国当代儿科杂志

OBJECTIVE@#To investigate the age distribution characteristics of intestinal segmented filamentous bacteria (SFB) in children and their relationship with intestinal mucosal immunity.@*METHODS@#The fresh feces of 177 children and the ileocecal fluid of 47 children during colonoscopy were collected. The SFB was determined by real-time PCR. The concentration of secretory immunoglobulin A (sIgA) was determined by enzyme-linked immunosorbent assay. The numbers of interleukin 17A (IL-17A) cells and intraepithelial lymphocytes in the terminal ileum mucosa and the expression of transcription factors associated with the differentiation of T helper (Th) cells, T-box transcription factor (T-bet), forkhead box P3 (FOXP3), and retinoid-related orphan receptor gamma t (ROR-γt), were determined by immunohistochemistry.@*RESULTS@#The positive rate of intestinal SFB in these children was 19.2% (34/177). Trend analysis showed that the positive rate of SFB was correlated with age: the rates for children aged 0-, 1-, 2-, 3-, 4-, 5-, 6-, and 7-15 years were 40%, 47%, 32%, 15%, 12%, 13%, 15% and 4% respectively (P<0.001). The concentration of sIgA in intestinal fluid was significantly higher in SFB-positive children (n=24) than in SFB-negative children (n=23) (P<0.01). The number of intraepithelial lymphocytes in the terminal ileum mucosa and the expression of T-bet, FOXP3, and ROR-γt were not significantly different between the SFB-positive group (n=12) and the SFB-negative group (n=11), but the number of IL-17A cells in the terminal ileum mucosa was significantly lower in the SFB-positive group than in the SFB-negative group (P<0.05).@*CONCLUSIONS@#Intestinal SFB colonization in children is age-related, and the colonization rate is relatively high in children under 3 years old. In SFB-positive children, the secretion of intestinal sIgA is increased, while the number of IL-17A cells in the terminal ileum is reduced.

Diagnosis and treatment of congenital submandibular duct dilatation / 华西口腔医学杂志

OBJECTIVE@#To study the clinical features and treatments of congenital submandibular duct dilatation.@*METHODS@#Seven children with congenital submandibular duct dilatation from January 2008 to March 2018 were included in this study, whose average age was 5 months and 22 days. The clinical manifestations are unilateral swelling of the mouth floor. All seven children underwent sublingual gland resection, submandibular gland dilatation catheter resection, and catheter reroute under general anesthesia. Intraoperatively, the orifice of the submandibular gland was constricted and part of the catheter was dilated.@*RESULTS@#All seven patients had good healing without swelling or cyst formation.@*CONCLUSIONS@#Congenital submandibular duct dilatation occurs at a young age. Early diagnosis and treatment can help prevent further expansion of the catheter and avoid gland atrophy, feeding difficulty, and breathing obstruction. Simultaneous excision of the sublingual gland can avoid the formation of postoperative sublingual cyst.

Proprioception recovery after anterior cruciate ligament reconstruction with and without remnant preservation / 中国组织工程研究

BACKGROUND: Whether remnant preservation can improve proprioception of knee joint remains a controversy. Direct detection of proprioceptor, nerve growth and electrophysiological changes in the grafting tendon of remnant preservation in anterior cruciate ligament reconstruction can objectively evaluate the effect of remnant preservation on proprioception recovery. OBJECTIVE: To establish the animal models of anterior cruciate ligament reconstruction with remnant preservation (femoral tensioning and augmented suture), with remnant preservation (graft passing remnant anterior cruciate ligament sheath) and without remnant, and to compare the differences in postoperative knee proprioception among methods. METHODS: Ninety-six New Zealand rabbits were randomly divided into control group, anterior cruciate ligament reconstruction groups with remnant preservation (femoral tensioning and augmented suture), with remnant preservation (graft passing remnant anterior cruciate ligament sheath) and without remnant (n=24/group). At 3, 6 and 12 weeks after surgery, electrophysiological examination of knee joint was performed. The mRNA expression of neurotrophic factor 3 was detected by real-time fluorescent quantitative PCR. The number of proprioceptor in graft tendon in the anterior cruciate ligament reconstruction groups was detected by hematoxylin-eosin staining and immunohistochemistry. RESULTS AND CONCLUSION: (1) At postoperative 3, 6 and 12 weeks, there were no significant differences in mRNA expression of neurotrophic factor 3, number of proprioceptor and electromyography hamstring among anterior cruciate ligament reconstruction groups (P＞ 0.05). (2) To conclude, there is no significant difference in the proprioception recovery of knee joint between anterior cruciate ligament reconstruction with and without remnant preservation.

Apoptotic mechanisms in rabbits with blast-induced acute lung injury

Abstract Purpose: To investigate the apoptotic mechanisms in rabbits with blast-induced acute lung injury (ALI). Methods: A total of 40 rabbits were randomly divided into a blank control group (A, n=10) and an experimental group (EXP, n=30). Explosion-induced chest-ALI models were prepared and sampled at different time points (4, 12, and 24h after modeling, T1-T3) to test the lung dry weight/wet weight ratio (W/D) and arterial oxygen pressure (PaO2), apoptosis of lung tissue by the TUNEL assay, and Caspase-3, Bax, and Bcl-2 levels by immunohistochemical analysis. Furthermore, lung tissue was sampled to observe pathological morphology by microscopy. Results: Under a light microscope, Group EXP exhibited obvious edema in the pulmonary interstitial substance and alveoli, a large number of red blood cells, inflammatory cells, and serous exudation in the alveolar cavity, as well as thickening of the pulmonary interstitial fluid. Compared to Group A, the W/D ratio was significantly increased in Group EXP (P<0.01), while PaO2 was significantly reduced (P<0.01). The apoptosis index was significantly increased (P<0.01), and caspase-3 and Bax/Bcl-2 levels were increased (P<0.01). Conclusion: Apoptosis plays an important role in the occurrence and development of acute lung injury in rabbits by participating in lung injury and promoting the progression of ALI.