Based on the interaction between supramolecules of traditional Chinese medicine and enterobacteria to explore the material basis of combination of Rhei Radix et Rhizoma - Coptidis Rhizoma / 药学学报

Based on the interaction between supramolecule of traditional Chinese medicine and enterobacteria, the material basis of Rhei Radix et Rhizoma and Coptidis Rhizoma was explored. Scanning electron microscopy (SEM) and dynamic light scattering (DLS) were used to characterize the morphological differences of Rhubarb single decoction, Coptis single decoction and Rhubarb and Coptis co-decoction. An in vitro antibacterial model (E. coli, E. faecium and B. subtilis) was established to evaluate the damage effect of the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma on enterobacteria. Ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the changes of chemical components of single decoctions and co-decoctions. The co-decoction of Rhei Radix et Rhizoma and Coptidis Rhizoma was turbid after decocting. The spherical particles of 300-400 nm were observed under SEM, and the co-decoction was more uniform and stable than that of single decoction. The interaction between supramolecules formed after the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma and enterobacteria was significantly different from that of single decoction. In the process of interaction between supramolecules and enterobacteria, the spherical state was maintained, and the medicinal ingredients in Coptidis Rhizoma or Rhei Radix et Rhizoma were blocked, which could effectively alleviate the damage to enterobacteria. This study provided a reference for subsequent studies on the regulation of intestinal flora homeostasis by the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma.

Mechanism of Fufang Congrong Yizhi Capsules in treatment of mild cognitive impairment based on network pharmacology / 中国药理学通报

Aim To predict the mechanism of Fufang Congrong Yizhi Capsules (FCYC) in the treatment of mild cognitive impairment (MCI) by network pharmacology method, and further validate it in combination with cellular experiments. Methods TCMSP, Gene-Cards, OMIM and TTD databases, Chinese Pharmacopoeia and related literature were used to screen the active ingredients of FCYC and the targets of MCI treatment. The TCM-compound-target-disease network and PPI of intersection targets were constructed, and the GO and KEGG analysis were performed by the Ehamb bioinformation platform. GO and KEGG analysis were performed through Yihanbo biological information platform. Cell model of MCI was established by PC-12 injury induced by Aβ

Resveratrol inhibits autophagy and promotes apoptosis in uveal melanoma cells via miR-512-3P/DUSPl axis / 中国药理学通报

Aim To investigate the regulatory role and mechanism of resveratrol in inhibiting autophagy and promoting apoptosis in choroidal melanoma cells. Methods Choroidal melanoma cells (MUM2B) were divided into control and experimental groups, and treated with different concentrations of resveratrol (0, 10, 20,40,60,80 μmol ·L

The Harm of Shame to Self and Its Way out from the Perspective of Bioethics / 中国医学伦理学

Psychological research results confirmed that the negative impact of shame on self often causes psychological diseases, and shame does not always related to ethical value. People with serious sense of shame will lead to negative evaluation and overall negation to themselves, and the sense of shame accompanied by great pain will cause great harm to individuals. To realize the sublimation of shame, the ethical orientation of its self cognitive schema and evaluation method must be changed, from the orientation of "transforming self and reaching perfection" to the position of "caring for self and accepting imperfect self" . To tap the positive value of shame, individuals must avoid hurting themselves and then care for themselves. "The principle of not harming life" and "do not denying people’s ethical subject status" are the bottom line of the ethical value of shame.

Establishment and application of a prospective follow-up research method for acute infectious diseases in Shanghai community residents / 上海预防医学

ObjectiveTo present the exploration and application of a prospective follow-up research method for acute infectious disease surveillance based on natural community populations， using COVID-19 infection as an example， and to provide a reference for improving the infectious disease surveillance and early warning system. MethodsA multi-stage probability proportional sampling method was employed to sample residents from all communities of 16 administrative districts in Shanghai， with households as the units. A cohort for acute infectious diseases based on natural community populations was established. The baseline survey was conducted for all cohort subjects， and COVID-19 antigen test kits were distributed. From December 21， 2022 to September 30， 2023， prospective follow-up monitoring of COVID-19 antigen and nucleic acid was carried out on the study subjects on a weekly basis. The baseline characteristics and follow-up information of the cohort subjects were described. ResultsThe cohort for acute infectious diseases included a total of 12 881 subjects， comprising 6 098 males （47.3%） and 6 783 females （52.7%）. The baseline survey revealed that 35.2% （4 540/12 881） of the subjects had a history of COVID-19 infection. During the follow-up period from December 21， 2022 to September 30， 2023， the average incidence density in the cohort was 0.61/person-year， with a higher incidence density in females （0.63/person-year） compared to males （0.59/person-year）. Individuals aged 60 and above （0.64/person-year） and those with underlying health conditions （0.67/person-year） had a higher incidence density. Healthcare workers showed a notably higher incidence density （0.84/person-year） than that in other occupational groups. As of September 30， 2023， a total of 340 subjects in the cohort experienced secondary infections， with a median interval of 170 days between the first and second infections. ConclusionThis study applies cohort study method to acute infectious disease surveillance， providing crucial data support for estimating infection rates and forecasting alerts for acute infectious diseases in the community. This method can be promoted and applied as a new approach for acute infectious disease surveillance.

Prediction of the Impact of CYP2C19 Polymorphism on Drug-Drug Interaction between Voriconazole and Tacrolimus Using Physiologically-Based Pharmacokinetic Modelling

Abstract Voriconazole increases tacrolimus blood concentration significantly when coadministrated. The recommendation of reducing tacrolimus to 1/3 in voriconazole package insert seems not to be satisfactory in clinical practice. In vitro studies demonstrated that the magnitude of inhibition depends on the concentration of voriconazole, while voriconazole exposure is determined by the genotype status of CYP2C19. CYP2C19 gene polymorphism challenges the management of drug-drug interactions(DDIs) between voriconazole and tacrolimus. This work aimed to predict the impact of CYP2C19 polymorphism on the DDIs by using physiologically based pharmacokinetics (PBPK) models. The precision of the developed voriconazole and tacrolimus models was reasonable by evaluating the pharmacokinetic parameters fold error, such as AUC0-24, Cmax and tmax. Voriconazole increased tacrolimus concentration immediately in all population. The simulated duration of DDIs disappearance after voriconazole withdrawal were 146h, 90h and 66h in poor metabolizers (PMs), intermediate metabolizers (IMs) and extensive metabolizers(EMs), respectively. The developed and optimized PBPK models in this study can be applied to assit the dose adjustment for tacrolimus with and without voriconazole.

Study on the time-point distribution characteristics of the occurrence of laryngopharyngeal reflux / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the characteristics of the time-point distribution of the occurrence of laryngopharyngeal reflux (LPR) by 24-hour multichannel intraluminal impedance-pH monitoring (24 h MII-pH) and to provide guidance for the development of individualized anti-reflux strategies for LPR patients. Methods: We conducted a retrospective analysis of 24 h MII-pH data from 408 patients [339 males and 69 females, aged 23-84 (55.08±11.08) years] attending the Department of Otorhinolaryngology Head and Neck Surgery at the Sixth Medical Center of the PLA General Hospital from January 2013 to March 2020. The number of gas acid/weak-acid reflux, mixed gas-liquid acid/weak-acid reflux, liquid acid/weak-acid reflux and alkaline reflux events at different time points were recorded and statistically analyzed through SPSS 26.0 software. Results: A total of 408 patients were included. Based on the 24 h MII-pH, the total positive rate of LPR was 77.45% (316/408). The type of positive gaseous weak-acid reflux was significantly higher than the remaining types of LPR (χ2=297.12,P<0.001). Except the gaseous weak-acid reflux, the occurrence of the remaining types of LPR showed a tendency to increase after meals, especially after dinner. Liquid acid reflux events occurred mainly between after dinner and the following morning, and 47.11% (57/121) of them occurred within 3 h after dinner. There was a significant positive association between Reflux Symptom Index scores and gaseous weak-acid reflux(r=0.127,P<0.01), liquid acid reflux(r=0.205,P<0.01) and liquid weak-acid reflux(r=0.103,P<0.05)events. Conclusions: With the exception of gaseous weak-acid reflux events, the occurrence of the remaining types of LPR events has a tendency to increase after meals, especially after dinner. Gaseous weak-acid reflux events accounts for the largest proportion of all types of LPR events, but the pathogenic mechanisms of gaseous weak-acid reflux are needed to further investigate.

Research progress on prevention and local intervention of oral mucositis in patients with hematopoietic stem cell transplantation / 中华口腔医学杂志

Oral mucositis (OM) is a common complication during hematopoietic stem cell transplantation. When OM occurs, with the destruction of oral mucosal barrier function, the formation of oral bacterial environment is accelerated, which has a negative impact on the life quality and clinical outcomes of patients. OM can be prevented by keeping the oral cavity clean, using the mouthwash properly, and limiting the delivery of cytotoxic drugs to oral tissues. This review describes the research progress on the prevention and local intervention of OM in patients with hematopoietic stem cell transplantation, in order to provide ideas for the selection of clinical intervention and management strategies on OM, and to provide references for exploring effective management methods for OM.

Effect of Qigongwan on Quality of Oocytes and Embryonic Development Potential in Patients with PCOS Infertility with Phlegm-dampness Syndrome / 中国实验方剂学杂志

ObjectiveTo observe the regulation of Qigongwan on the expression of proliferation and apoptosis-related factors programmed cell death 4 （PDCD4） and proliferating cell nuclear antigen （PCNA） in ovarian granulosa cells （GCs） in patients with polycystie ovarian syndrome （PCOS） infertility with phlegm-dampness syndrome， and to explore the effect of Qigongwan on the quality of oocytes and embryonic development potential. MethodSixty-six patients with PCOS with phlegm-dampness syndrome who underwent in vitro fertilization and embryo transfer （IVF-ET） were randomly selected and divided into an observation group （Qigongwan + western medicine） and a control group （western medicine）， with 33 patients in each group. Antagonist regimen was used to promote ovulation in the two groups. The observation group was given Qigongwan one cycle before IVF based on the treatment of conventional western medicine， while the control group was not given Chinese medicine. The improvement of phlegm and dampness syndrome， the dosage and the number of days of using gonadotropins （Gn）， the levels of luteinizing hormone （LH）， estradiol （E2）， and progesterone （P） on the day of human chorionic gonadotropin（HCG） injection， the 2PN fertilization rate， and the high-quality embryo rate of patients in the two groups were compared. Real-time polymerase chain reaction （Real-time PCR） and Western blot technology were used to detect the expression of PCNA and PDCD4 in GCs. ResultAs compared with groups before treatment， the score of phlegm-dampness syndrome in both groups was significantly lower （P<0.01）. The score of phlegm and dampness syndrome in the observation group was significantly lower than that of the control group （P<0.01）. As compared with the control group， the levels of LH， E2， and P in the observation group was higher， but only the difference in the level of E2 was statistically significant （P<0.01）. The 2PN fertilization rate ［82.25% （556/676） vs 69.92% （365/522）， χ2=25.172， P<0.01］ and high-quality embryo rate ［44.19% （190/430） vs 34.23% （102/298）， χ2=7.266， P<0.01］ in the observation group were significantly higher than that of the control group （P<0.01）. As compared with the control group， the mRNA and protein expression of PDCD4 in ovarian GCs was down-regulated in the observation group and that of PCNA was up-regulated （P<0.05）. ConclusionBy down-regulating the expression of PDCD4 and up-regulating the expression of PCNA， Qigongwan may interfere with follicle development， adjust hormone levels， improve the symptomatic manifestations of patients with PCOS with phlegm-dampness syndrome， inhibit the apoptosis of GCs， and promote growth， thus improving the quality of oocytes and embryonic development potential.

Placebo Response among Different Types of Sham Acupuncture for Low Back Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials / 中国结合医学杂志

BACKGROUND@#Low back pain (LBP) is a prevalent and debilitating condition that poses a significant burden on healthcare systems. Acupuncture has been proposed as a promising intervention for LBP, but the evidence supporting its specific effect is insufficient, and the use of sham acupuncture as a control in clinical trials presents challenges due to variations in sham acupuncture techniques and the magnitude of the placebo effect.@*OBJECTIVE@#To investigate the magnitude of the placebo response of sham acupuncture in trials of acupuncture for nonspecific LBP, and to assess whether different types of sham acupuncture are associated with different responses.@*METHODS@#Four databases including PubMed, EMBASE, MEDLINE, and the Cochrane Library were searched through April 15, 2023, and randomized controlled trials (RCTs) were included if they randomized patients with LBP to receive acupuncture or sham acupuncture intervention. The main outcomes included the placebo response in pain intensity, back-specific function and quality of life. Placebo response was defined as the change in these outcome measures from baseline to the end of treatment. Random-effects models were used to synthesize the results, standardized mean differences (SMDs, Hedges'g) were applied to estimate the effect size.@*RESULTS@#A total of 18 RCTs with 3,321 patients were included. Sham acupuncture showed a noteworthy pooled placebo response in pain intensity in patients with LBP [SMD -1.43, 95% confidence interval (CI) -1.95 to -0.91, I2=89%]. A significant placebo response was also shown in back-specific functional status (SMD -0.49, 95% CI -0.70 to -0.29, I2=73%), but not in quality of life (SMD 0.34, 95% CI -0.20 to 0.88, I2=84%). Trials in which the sham acupuncture penetrated the skin or performed with regular needles had a significantly higher placebo response in pain intensity reduction, but other factors such as the location of sham acupuncture did not have a significant impact on the placebo response.@*CONCLUSIONS@#Sham acupuncture is associated with a large placebo response in pain intensity among patients with LBP. Researchers should also be aware that the types of sham acupuncture applied may potentially impact the evaluation of the efficacy of acupuncture. Nonetheless, considering the nature of placebo response, the effect of other contextual factors cannot be ruled out in this study. (PROSPERO registration No. CRD42022304416).

Correlation analysis between imaging classification of varus knee osteoarthritis and axis angle of tibiofemoral and patellofemoral joints / 中国骨伤

OBJECTIVE@#To explore correlation between imaging classification of knee osteoarthritis (KOA) and axis angle of tibiofemoral and patellofemoral joints.@*METHODS@#A retrospective analysis of 739 middle-aged and elderly patients with KOA (1 026 knee joints) who underwent vertical X-ray examination of both lower limbs and lateral knee joints from September 2018 to December 2020. Among them, 63 patients with K-L 0 grade (95 knee joints), 100 patients with K-L 1 grade (130 knee joints), 161 patients with K-L 2 grade (226 knee joints), 187 patients with K-L 3 grade (256 knee joints), and 228 patients of K-L 4 grade (319 knee joints). According to relative position of knee joint center and line between hip joint center and ankle joint center, the affected knee was divided into varus group(844 knees joints) and valgus group (182 knees joints). According to Install-Salvati method, the affected knee was divided into three groups, such as high patella (patella height>1.2 mm, 347 knees joints), median patella (patella height ranged from 0.8 to 1.2 mm, 561 knees joints), and low patella (patella height<0.8 mm, 118 knees joints). Lower femur angle, upper tibia angle, femoral neck shaft angle, femoral tibial angle, joint gap angle, hip-knee-ankle angle, patella-femoral angle and patella height among different groups were observed and compared.@*RESULTS@#(1) In varus KOA group, there were statistical differnces in hip-knee-ankle angle, tibiofemoral angle, lower femoral angle, upper tibial angle, joint space angle, and femoral neck shaft angle of patients with different K-L grades (P<0.05). Hip-knee-ankle angle, tibiofemoral angle, lower femoral angle, upper tibial angle, joint space angle and K-L grade were significantly positively correlated at 0.01(P<0.05);femoral neck shaft angle and K-L grade showed negative correlation at 0.01(P<0.05). (2) In valgus KOA group, hip-knee-ankle angle, there were statistical differences in tibiofemoral angle, inferior femoral angle, superior tibial angle, joint space angle, and femoral neck shaft angle of patients with different K-L grades(P<0.05). Hip-knee-ankle angle, tibiofemoral angle, lower femoral angle, upper tibial angle, and femoral neck shaft angle showed negative correlation with K-L grades at level of 0.01 (P<0.05);joint gap angle and K-L grades showed significantly positive correlation at level of 0.01(P<0.05). (3) In high patella group, there were statistically differences in patellar height and patellar femoral angle of different K-L grades(P<0.05);there were no statistical difference in patella height and patellar femoral angle of different K-L grades in median patella group. There was no significant difference in patella heightin low patella group with different K-L grades(P>0.05), and there was statistical difference in patellofemoral angle(P<0.05). Patellar height and patella-femoral angle of high patella group were significantly positively correlated with K-L grades at the level of 0.01 (P<0.05);patella height and patella-femoral angle were not correlated with K-L grades in median patella group(P>0.05). There was no correlation between height of patella and K-L grade in low patella group (P>0.05). There was significant negative correlation between patella-femoral angle and K-L grade at level of 0.05 (P<0.05).@*CONCLUSION@#Inferior femoral angle, tibiofemoral angle, joint gap angle, hip-knee-ankle angle, femoral neck shaft angle and high patella are related to K-L classification of varus KOA, which could be used for early diagnosis and provide objective data for efficacy analysis of conservative treatment.

Dachengqi decoction reduces inflammatory response and promotes recovery of gastrointestinal function in patients with mild acute pancreatitis by regulating the intestinal microbiota / 中华危重病急救医学

Objective:To explore the therapeutic effect and mechanism of Dachengqi decoction on patients with mild acute pancreatitis (MAP).Methods:A parallel randomized controlled trial was conducted. Sixty-eight patients with acute pancreatitis (AP) admitted to Shanghai Traditional Chinese Medicine (TCM)-Integrated Hospital from March 2018 to February 2021 were enrolled. Referring to the condition on admission of the patients and whether they agreed to receive the Dachengqi decoction or not, they were divided into conventional treatment group and Dachengqi decoction group according to the principle of 1∶1 equal randomness. Meanwhile, 20 healthy volunteers were recruited as controls. Both groups of patients were treated with octreotide, fasting, gastrointestinal decompression, antipyretic and analgesic, anti-inflammatory, inhibition of gastric acid and pancreatic juice secretion, maintenance of electrolyte balance and other western conventional medicine. The patients in the Dachengqi decoction group received Dachengqi decoction orally on the basis of routine treatment, 100 mL each time, twice a day, for seven consecutive days. The inflammation parameters [white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6)] before and after treatment and the recovery time of gastrointestinal function (first exhaust time, time to recover bowel sounds, first defecation time) of patients were recorded. 16S rRNA gene sequencing of stool samples was recorded, and normalized data were obtained after quality control and other related processing. The data were subjected to diversity analysis (Alpha diversity and Beta diversity) and linear discriminant analysis effect size analysis (LEfSe analysis) to observe changes in the gut microbiota of MAP patients. Spearman rank correlation coefficient was used to analyze the correlation between inflammatory indexes and microorganisms at the intestinal genus level. Blood, urine, stool samples, renal function, and electrocardiogram (ECG) during treatment of MAP patients were detected to assess the safety of the treatment.Results:Of the 68 patients with AP, 16 were excluded from moderate-severe AP, 4 were not collected or voluntarily abandoned treatment. Finally, 48 patients with MAP were enrolled, 24 in the conventional treatment group and 24 in the Dachengqi decoction group. The inflammation parameters levels at 7 days of treatment in both groups were significantly lower than those before treatment. CRP, PCT and IL-6 levels in the Dachengqi decoction group were significantly lower than those in the conventional treatment group [CRP (mg/L): 8.50 (3.50, 13.00) vs. 16.00 (9.25, 29.75), PCT (μg/L): 0.06 (0.03, 0.08) vs. 0.09 (0.05, 0.11), IL-6 (ng/L): 6.36 (3.96, 10.79) vs. 13.24 (6.69, 18.87), all P < 0.05]. The first exhaust time, time to recover bowel sounds and first defecation time in the Dachengqi decoction group were significantly shorter than those in the conventional treatment group [first exhaust time (days): 1.62±0.65 vs. 2.80±0.65, time to recover bowel sounds (days): 1.13±0.58 vs. 2.31±0.76, first defecation time (days): 3.12±0.75 vs. 4.39±0.76, all P < 0.05]. The analysis of intestinal microflora diversity showed that both the diversity and abundance of microbial communities were the highest in the healthy control group and the lowest in the conventional treatment group. In addition, the coincidence degree of microbial communities in healthy controls and MAP patients was small, while the coincidence degree of MAP patients among different treatment methods was relatively large. LEfSe analysis showed that Dachengqi decoction reduced the relative abundance of Escherichia coli-Shigella and Clostridium erysipelae, and increased the relative abundance of three beneficial bacteria, namely Lactobacillus, Rombutzia and Brutella. In the intestines of MAP patients, Lactobacillus mucilaginus and Lactobacillus conjunctus were significantly enriched. Correlation analysis showed that positive correlations between Escherichia coli- Shigella and the four inflammatory indicators including WBC, CRP, PCT, IL-6 were statistically significant ( r value was 0.31, 0.41, 0.57, 0.43, respectively, all P < 0.05). There was no significant correlation between other bacteria and inflammatory indicators. During the treatment, there was no obvious abnormality in blood, urine and feces, renal function and ECG of MAP patients. Conclusions:Dachengqi decoction could reduce inflammatory responses and promote recovery of intestinal microecological balance and gastrointestinal function in patients with MAP by regulating the composition of intestinal flora. No significant adverse effects were observed during the treatment period.

The effects of natural polysaccharide supramolecular hydrogel on bacteriostatic activity and biofilm clearance of berberine / 药学学报

Taking berberine (BBR) as an example, to study whether the supramolecular hydrogel formed by berberine and lotus root starch (Nelumbo nucifera Gaertn; LRS), a natural polysaccharide, affects the inhibition to Staphylococcus aureus and the ability of biofilm clearance. The chemical structure and rheological properties of BBR@LRS gel were characterized by infrared spectroscopy and rheometer. The in vitro release of supramolecular hydrogel was observed at pH = 1.2 and pH = 7.4. Broth dilution method and biofilm clearence experiment were used to observe the bacteriostasis and biofilm clearance respectively. Cytotoxicity test and in vitro hemolysis test were used to evaluate the biosafety preliminarily. The results showed that the LRS polysaccharide hydrogel could encapsulate BBR, and there was an interaction between them. The BBR@LRS gel had good rheological properties and biosafety, and played a role in solubility enhancement and slow release of BBR, which was stronger than BBR in inhibiting the growth of Staphylococcus aureus and clearing biofilm. This study provides reference for the effect of natural polysaccharide supramolecular hydrogels on biological functions of active components of traditional Chinese medicine.

Effect of Chorionicity， Gestational Age at Birth and Birth Weight Discordance on Neonatal Outcomes in Twin Pregnancies / 中山大学学报(医学科学版)

ObjectiveTo investigate the effect of chorionicity， gestational age at birth and birth weight discordance on neonatal outcomes in twin pregnancies. MethodsWe conducted a population-based retrospective study of monochorionic diamniotic （MCDA） twin pregnancies and dichorionic diamniotic （DCDA） twin pregnancies who were admitted in the First Affiliated Hospital， Sun Yat-sen University from January 2015 to December 2020. A total of 1504 live-born twins were included， with 386 cases in MCDA group and 1118 cases in DCDA groups， respectively. The comparison of neonatal outcomes between MCDA and DCDA twins was performed using t-test， Wilcoxon rank sum test， Chi-square test or Fisher’s exact test. Logistic regression was performed to evaluate the effects of chorionicity， gestational age at birth， birth weight discordance and sex on neonatal outcomes. There were 168 live-born twins affected by inter-twin birth weight discordance≥25%， with 96 cases in MCDA group and 72 cases in DCDA groups， respectively. Logistic regression was performed to evaluate the effects of chorionicity， gestational age at birth， birth weight light or heavy （small twin or large twin） of the twin and sex on neonatal outcomes. ResultsAmong the 1 504 newborns， gestational age at birth was lower in MCDA group compared with DCDA group （P = 0.000）， and the degree of birth weight discordance was higher in MCDA group than that of the DCDA group （P = 0.001）. Birth asphyxia， respiratory distress syndrome （RDS）， bronchopulmonary dysplasia （BPD）， and sepsis were more frequency in MCDA group compared with DCDA group （P = 0.000， P = 0.000， P = 0.000， P = 0.000）. Low gestational age at birth was an independent risk factor for birth asphyxia， RDS， BPD， sepsis， necrotizing enterocolitis （NEC）≥stageⅡ， acute kidney injury （AKI）， retinopathy of prematurity （ROP）， and neonatal death respectively （P = 0.000， P = 0.000， P = 0.000， P = 0.000， P = 0.011， P = 0.000， P = 0.000， P = 0.000）. High degree of birth weight discordance was an independent risk factor for birth asphyxia， RDS， BPD， sepsis and ROP respectively （P = 0.045， P = 0.000， P = 0.000， P = 0.004， P = 0.017 ）. Chorionicity was not an independent risk factor for neonatal morbidity and death （P > 0.05）. Among the 168 twins with birth weight discordance ≥25%， low gestational age at birth was an independent risk factor for birth asphyxia， RDS， BPD， sepsis and ROP， respectively （P = 0.000， P = 0.000， P = 0.000， P = 0.000， P = 0.000）； small twin was an independent risk factor for birth asphyxia and BPD， respectively （ P = 0.013， P = 0.001）； chorionicity was not an independent risk factor for neonatal morbidity （P > 0.05）. ConclusionChorionicity was not an independent risk factor for adverse neonatal outcome in twin births. Low gestational age at birth and high degree of birth weight discordance were independent risk factor for adverse neonatal outcome in twin births. Small twins had increased risk of adverse neonatal outcome in twins with birth weight discordance ≥25%.

Safflor yellow injection combined with anti-vascular endothelial growth factor drugs in the treatment of non-ischemic central retinal vein occlusion / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the efficacy and safety of safflor yellow injection combined with anti-vascular endothelial growth factor(VEGF)drug in the treatment of non-ischemic central retinal vein occlusion(CRVO).METHODS: A total of 91 patients(91 eyes)with non-ischemic CRVO complicated with macular edema who were treated in the Affiliated Eye Hospital of Nanchang University from April 2017 to December 2021 were selected. They were randomly divided into observation group, with 47 cases(47 eyes)treated with safflor yellow injection combined with intravitreal injections of ranibizumab, and control group with 44 cases(44 eyes)who were treated with intravitreal injections of ranibizumab. Followed-up for 11mo, the best corrected visual acuity(BCVA)and macular central retinal thickness(CRT)of the two groups were observed and the cases of complete absorption of retinal hemorrhage, the times of anti-VEGF drug injections, the cases of ischemic CRVO, and the occurrence of systemic or ocular complications were recorded.RESULTS: At 1, 2, 3, 5, 7, 9 and 11mo after treatment, the BCVA and CRT in both groups were significantly improved compared with those before treatment, and BCVA and CRT in the observation group were superior to the control group at 3, 5, 7, 9 and 11mo after treatment(all P&#x003C;0.05). At 5, 7, 9 and 11mo after treatment, the complete absorption rate of retinal hemorrhage in the observation group was higher than that in the control group(P&#x003C;0.05). During the follow-up period, the anti-VEGF drug injection in the observation group was significantly less than that in the control group(4.83±1.05 vs. 5.75±1.01, P&#x003C;0.05), and the incidence of ischemic CRVO was significantly lower than that in the control group(21% vs. 86%, P&#x003C;0.05), and there were no treatment-related systemic and ocular complications in both groups.CONCLUSION: Safflor yellow injection combined with anti-VEGF drugs is a safe and effective method for the treatment of non-ischemic CRVO, which can significantly improve vision and reduce CRT. It can increase the complete absorption rate of retinal hemorrhage, reduce the times of anti-VEGF drug injections and the incidence of ischemic CRVO compared with monotherapy of anti-VEGF drug.

Expression and localization of vascular endothelial growth factor-B in diencephalon and brainstem related tissues of the Yak’s brain / 解剖学报

Objective To explore the expression and distribution characteristics of vascular endothelial growth factor-B(VEGF-B) in diencephalon and brainstem of Yak’s brain tissues, and to investigate the associations between its expression and hypoxia adaptation. Methods Five healthy yaks were selected, and the brain tissues were divided and collected according to the gross anatomical structure of the brain, including pituitary, thalamus, hypothalamus, oblongata and pons. The characteristics of expression and location of VEGF-B in different regions of Yak’s brain tissues were detected by Real-time PCR, Western blotting and immunohistochemical techniques. Results The results showed that the highest expression level of VEGF-B mRNA of yak brain tissue was in the pituitary, and the content was significantly higher than that found in other parts of the brain(P<0. 05). Following the expressions were in the hypothalamus, thalamus and medulla oblongata, while the lowest expression level was in pons. The expression level of VEGF-B protein in Yak’s brain tissue was similar to the mRNA expression level except that the thalamus was higher than that of hypothalamus. The result of immunohistochemistry showed that VEGF-B protein-positive substances were mainly distributed in the cytoplasm of various types of cells. Among them, the positive staining of VEGF-B was mainly concentrated in eosinophils of pituitary. The positive staining of VEGF-B was mainly concentrated in pleomorphic cells of thalamus and hypothalamus. The distribution of VEGF-B protein-positive substances were mainly focused in nerve cell body of medulla oblongata and pons. Conclusion VEGF-B protein is expressed in both diencephalon and brainstem of yak, which may be closely related to its functions of anti-apoptosis, "survival factor" and angiogenesis. However, the specific mechanism of its neuroprotective effect on Yak brain under hypoxic environment needs to be further studied. The difference of expression in different regions may be related to the tissue specificity and function in different regions of the brain.

Impairment of superovulation on the establishment of pregnancy in mice / 解剖学报

Objective To explore whether superovulation impairs the process of pregnancy establishment in mice by changing the intrauterine environment. Methods The implantation and pregnancy of superovulated and normal mice were compared. The superovulated mice were subjected to unilateral tubal ligation on day 0. 5 and blastocysts were transplanted to the other uterine horn on day 2. 5. The number of implantation sites of bilateral uterine horn was compared. The differences between preimplantation uteri of superovulated and normal pseudopregnancy mice were compared by tissue sections and high-throughput sequencing. Bioinformatics analysis was performed on the differentially expressed genes in two groups. Results Compared with the control group, the pregnancy rate of mice in the superovulation group decreased significantly. The number of implantation sites in the superovulation group was higher than the control. There was no significant difference in the pregnancy rate of the uterine horn between the control side and the transplanted side of the superovulated mice. The endometrium was thinned and the number of glands was reduced in superovulated pseudopregnancy mice. The gene expression patterns of preimplantation uterus in superovulation pseudopregnancy and normal pseudopregnancy mice were different. There were 1097 significantly differentially expressed genes, including 752 up-regulated genes and 345 down-regulated genes. Bioinformatics analysis showed that differentially expressed genes are mainly involved in biological processes, such as decidualization, response to progesterone, positive regulation of angiogenesis. They were mainly enriched in FoxO signaling pathway, cell cycle pathway and steroid biosynthesis pathway. Conclusion Superovulation impaired the process of establishing pregnancy and altered the gene expression patterns of biomarker of uterine receptivity in mice.

Effects of treadmill exercise on learning and memory of the vascular dementia rats and its mechanism / 解剖学报

Objective To observe the effects of 4-week low intensity treadmill exercise on the learning and memory, amino acid levels and the protein expression of protein kinase A ( PKA) , cyclic adenosine monophosphate response element binding protein( CREB) and brain-derived neurotrophic factor(BDNF) in the prefrontal cortex (PFC) of the vascular dementia (VD) rats. Methods Thirty-nine SD rats were randomly allocated to 3 groups, sham group (sham, n= 13) , vascular dementia group (VD, n= 13) and vascular dementia treaded with exercise group (VD + EX, n= 13). Chronic cerebral ischemia model in VD group and VD+EX group rats were established by permanent ligation of bilateral, then VD+EX group rats were submitted to 4-week low intensity treadmill exercise. After exercise, spatial learning and memory ability were evaluated by Moms water maze test ( MWM ) , glutamic ( Glu ) and gamma-aminobutyric acid (GABA) levels in the PFC were measured by high performance liquid chromatography( HPLC) ; the protein expression of PKA, CREB and BDNF in the PFC of rats were detected by Western blotting. Results The result of the MWM showed the average escape latency of rats in the VD group on the 1 -5 days was significantly higer than sham group, the time to first find the original platform was significantly prolonged and the platform crossings decreased significantly ( P 0. 05 ) between the two groups. Conclusion Four-week low-intensity running exercise improves the learning and memory ability of VD rats through enhancing the Glu level and activating PKA-CREB-BDNF signaling in the PFC of rats.

Role of TGF-β/Smad signaling pathway in pulmonary fibrosis after rheumatoid arthritis in mice / 中国药理学通报

Aim To investigate the role of TGF-β/Smad signaling pathway in rheumatoid arthritis (RA) - associated postinterstitial pulmonary fibrosis in mice. Methods The mouse model of RA was constructed by subcutaneous administration of complete Freund's adjuvant (CFA) and chicken II collagen (Col-II) to the tail root of mice. The blank group was given the same amount of distilled water, and the control group was given the same amount of glacial acetic acid (solvent). The degree of toe swelling (joint swelling degree and arthritis index) was monitored to evaluate the mouse modeling. The pathological changes of mouse lung tissues were observed by HE and Masson staining. The expression of TGF-β in lung tissues were observed by immunohistochemical staining. The level of hydroxyproline in lung tissues was measured by chemiluminescence method. The expressions of Smad2, Smad3 and phosphorylated p-Smad2 and phosphorylated p-Smad3 in lung tissues were detected by Western blot. Results Compared with blank group and solvent group, the joint swelling and arthritis index of model group significantly increased. Twenty-one days after administration, HE staining showed inflammatory changes in lung interstitium of the model group, Masson staining showed collagen fiber deposition and obvious fibrosis in lung interstitium of the model group, and immunohistochemical staining showed that the expression of TGF-β in cytoplasm of lung interstitial cells of the model group increased, which was brown and yellow. Meanwhile, hydroxyproline was significantly raised in lung tissue homogenate of the model group. Further WB analysis showed that compared with blank group and solvent group, the expression of p-Smad2 and pSmad3 in lung tissues of the model group was significantly up-regulated (P < 0. 05, P < 0. 01). Conclusions RA can give rise to pulmonary fibrosis, and the expressions of p-Smad2 and p-Smad3 are up-regulated, which is be pivotal in pulmonary fibrosis and RA-related post-interstitial pulmonary fibrosis.

Dichloroacetate and vitamin C synergistically suppress proliferation, migration and invasion of glioma U87 and U251 cells / 中国药理学通报

Aim To investigate the effects of dichloroacetate(DCA)combined with vitamin C(VC)on the malignant behavior of glioma U87 and U251 cells, and to explore the potential mechanism. Methods U87 and U251 cells were treated with different concentrations of DCA alone or in combination with 5 mmol·L-1 VC. The proliferation rate of each group was detected by CCK-8 method and the cooperative index was calculated. U87 and U251 cells were treated with DMSO, 15 mmol·L-1 DCA, 5 mmol·L-1 VC and their combination. The changes of clonal formation, reactive oxygen species content, apoptosis, cell cycle, migration and invasion were detected via in vitro experiments, while the proliferation of U251 cells in vivo in each group was detected by subcutaneous tumor-forming model. Western blot was used to detect the expression levels and degradation rates of BCL2A1 and CDC25A in each group of cells after network pharmacological analysis of DCA and VC targets and their value in glioma, and the expression levels of CDK4, CDK6, cytochrome C, caspase-7 and cleaved-caspase-7 were detected. Results The combined index of 15 mmol·L-1 DCA and 5 mmol·L-1 VC was the highest. Compared with the control and single drug groups, the clonal formation, migration and invasion ability of cells in combination group in vitro significantly decreased, the proliferation rate in vivo also decreased, and the content of reactive oxygen species, apoptosis rate and G1 phase arrest rate significantly increased. BCL2A1 and CDC25A proteins were important targets of DCA and VC in glioma. Compared with the control and single-drug groups, the expression levels of BCL2A1, CDC25A, CDK4, and CDK6 in the combination group were significantly reduced, and the expression levels of cytochrome C and cleaved-caspase-7 markedly increased, and the protein degradation rates of BCL2A1 and CDC25A significantly increased in the combination group. Conclusions VC can cooperate with DCA to promote the degradation of BCL2A1 and CDC25A, and inhibit the malignant behavior of glioma cells.