Short-term efficacy of empagliflozin in children with glycogen storage disease type Ⅰb / 中华儿科杂志

Objective: To analyze the short-time efficacy of empagliflozin in the treatment of glycogen storage disease type Ⅰb (GSD Ⅰb). Methods: In this prospective open-label single-arm study, the data of 4 patients were collected from the pediatric department in Peking Union Medical College Hospital from December 2020 to December 2022. All of them were diagnosed by gene sequencing and had neutropenia. These patients received empagliflozin treatment. Their clinical symptoms such as height and weight increase, abdominal pain, diarrhea, oral ulcer, infection times, and drug applications were recorded at 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, and 15 months after treatment to assess the therapeutic effect. The liquid chromatography-tandem mass spectrometry method was used to monitor the changes in 1, 5-anhydroglucitol (1, 5AG) concentration in plasma. At the same time, adverse reactions such as hypoglycemia and urinary tract infection were closely followed up and monitored. Results: The 4 patients with GSD Ⅰb were 15, 14, 4 and 14 years old, respectively at the beginning of empagliflozin treatment, and were followed up for 15, 15, 12 and 6 months, respectively. Maintenance dose range of empagliflozin was 0.24-0.39 mg/(kg·d). The frequency of diarrhea and abdominal pain decreased in cases 2, 3, and 4 at 1, 2 and 3 months of treatment, respectively. Their height and weight increased at different degrees.The absolute count of neutrophils increased from 0.84×109, 0.50×109, 0.48×109, 0.48×109/L to 1.48×109, 3.04×109, 1.10×109, 0.73×109/L, respectively. Granulocyte colony-stimulating factor was gradually reduced in 1 patients and stopped in 3 patient. Plasma 1, 5 AG levels in 2 children were significantly decreased after administration of empagliflozin (from 46.3 mg/L to 9.6 mg/L in case 2, and from 56.1 mg/L to 15.0 mg/L in case 3). All 4 patients had no adverse reactions such as hypoglycemia, abnormal liver or kidney function, or urinary system infection. Conclusion: In short-term observation, empagliflozin can improve the symptoms of GSD Ⅰb oral ulcers, abdominal pain, diarrhea, and recurrent infection, also can alleviate neutropenia and decrease 1, 5AG concentration in plasma, with favorable safety.

Mechanism of blue light-induced ferroptosis in retinal pigment epithelium cells / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the occurrence and possible mechanism of blue light-induced ferroptosis in retinal pigment epithelial cells.METHODS: ARPE-19 cells cultured in vitro were irradiated by 405 nm blue light at 50 mW/cm2 irradiance with different duration and were divided into control, 16.3J/cm2, 32.6J/cm2, and 65.2J/cm2 groups; the 65.2J/cm2 group was defined as the high-level blue light irradiation group and cells were further divided into control, high-level blue light irradiation group and high-level blue light irradiation + ferroptosis inhibitor group. CCK-8 assay was used to detect cell viability, commercial kits were used to detect intracellular glutathione(GSH), ferrous iron and malondialdehyde(MDA)concentration, and Western blot was used to detect the relative expression of glutathione peroxidase 4(GPX4)and xCT proteins in cells.RESULTS: The decrease of ARPE-19 cell viability caused by blue light irradiation was dose-dependent, and the reduction of intracellular GSH concentration, the increase of ferrous iron concentration and MDA concentration were all caused by high-level blue light irradiation(all P<0.05); the ferroptosis inhibitor partially restored cell viability and recovered intracellular GSH, reduced concentrations of MDA and ferrous iron in the blue light irradiation group(all P<0.05). The relative expressions of GPX4 and xCT proteins were significantly decreased in the blue light irradiation group, and such change was alleviated by the ferroptosis inhibitor(P<0.05).CONCLUSION: Blue light irradiation may induce ferroptosis in RPE cells by targeting the xCT and GPX4-associated antioxidant pathways.

Predictive Value of Complete Blood Count and Inflammation Marker on Risk of Recurrence in Children with Henoch-Schönlein Purpura / 中国实验血液学杂志

OBJECTIVE@#To investigate the predictive value of complete blood count (CBC) and inflammation marker on the recurrence risk in children with Henoch-Schönlein purpura (HSP).@*METHODS@#One hundred and thirty-three children with HSP admitted to Cangzhou Central Hospital from February 2017 to March 2019 were enrolled. The clinical data of the children were collected, at the time of admission CBC and C-reactive protein (CRP) were detected. After discharge, the children were followed up for 1 year, the clinical data of children with and without recurrence were compared, and multivariate logistic regression was used to analyze the risk factors affecting HSP recurrence. Receiver operating characteristic (ROC) curve should be drawn and the predictive value of CBC and CRP on HSP recurrence should be analyzed.@*RESULTS@#In the follow-up of 133 children, 8 cases were lost and 39 cases recurred, with a recurrence rate of 31.20% (39/125). The age, skin rash duration, proportion of renal damage at the initial onset, percentage of neutrophils, percentage of lymphocytes, platelet count (PLT), mean platelet volume (MPV) and neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), MPV/PLT ratio (MPR), and CRP level of patients with recurrence were statistically different from those without recurrence (P <0.05). Multivariate logistic regression analysis showed that long skin rash duration, renal damage at the initial onset, increased PLR, high PLT, increased MPV and elevated CRP level were independent risk factors for recurrence in children with HSP (P <0.05). The ROC curve analysis showed that the area under the curve (AUC) of the combination of the four blood and inflammation marker (PLT, MPV, PLR and CPR) in the early prediction of HSP recurrence was 0.898, which was higher than the initial renal damage (AUC=0.687) and persistent skin rash time (AUC=0.708), with a sensitivity of 84.62% and a specificity of 83.72%.@*CONCLUSION@#Observation of CBC and CPR can predict the risk of HSP recurrence early and guide early clinical intervention.

Obesity is positively Associated with Depression in Older Adults: Role of Systemic Inflammation / 生物医学与环境科学（英文）

OBJECTIVE@#We aimed to explore the association between obesity and depression and the role of systemic inflammation in older adults.@*METHODS@#Adults ≥ 65 years old ( n = 1,973) were interviewed at baseline in 2018 and 1,459 were followed up in 2021. General and abdominal obesity were assessed, and serum C-reactive protein (CRP) levels were measured at baseline. Depression status was assessed at baseline and at follow-up. Logistic regression was used to analyze the relationship between obesity and the incidence of depression and worsening of depressive symptoms, as well as the relationship between obesity and CRP levels. The associations of CRP levels with the geriatric depression scale, as well as with its three dimensions, were investigated using multiple linear regressions.@*RESULTS@#General obesity was associated with worsening depression symptoms and incident depression, with an odds ratio ( OR) [95% confidence interval ( CI)] of 1.53 (1.13-2.12) and 1.80 (1.23-2.63), especially among old male subjects, with OR (95% CI) of 2.12 (1.25-3.58) and 2.24 (1.22-4.11), respectively; however, no significant relationship was observed between abdominal obesity and depression. In addition, general obesity was associated with high levels of CRP, with OR (95% CI) of 2.58 (1.75-3.81), especially in subjects free of depression at baseline, with OR (95% CI) of 3.15 (1.97-5.04), and CRP levels were positively correlated with a score of specific dimension (life satisfaction) of depression, P < 0.05.@*CONCLUSION@#General obesity, rather than abdominal obesity, was associated with worsening depressive symptoms and incident depression, which can be partly explained by the systemic inflammatory response, and the impact of obesity on depression should be taken more seriously in the older male population.

The PK bioanalysis method study of c-Met antibody-drug conjugate (RC108) in cynomolgus monkey / 药学学报

Antibody-drug conjugate (ADC) has the characteristics of low toxicity and high efficiency, and plays an important role in cancer treatment. However, due to the complexity of its structure, it brings difficulties in pharmacokinetic (PK) bioanalysis. This study established an analytical method for the detection of ADC (RC108) in cynomolgus monkey plasma by ligand-binding assay (LBA) and liquid chromatography tandem mass spectrometry (LC-MS/MS), which was used to analyze and quantify the total antibody, bound antibody and free drug in cynomolgus monkey plasma. Based on the LBA method, rabbit anti-RC108 Fab and mouse anti-MMAE (monomethyl auristatin E) mAb were pre-coated in 96-well plates as the total antibody and antibody binding reagents, respectively. The samples to be tested were added, and then the detection reagents were added in turn. Goat anti-human IgG (H+L)-HRP, chromogenic solution tetramethylbenzidine (TMB), H2SO4 terminate the reaction, read data at 450 nm/630 nm wavelength of microplate reader; LC-MS/MS analysis method quantifies MMAE concentration, and refer to relevant regulations for methodological validation. The analytical method for quantifying total antibody, bound antibody and free drug of RC108 drug obtained good accuracy and precision, and the selectivity, dilution linearity, hook effect, parallelism and stability were verified. Meet the requirements of biological analysis. Finally, a bioanalytical method for the determination of the concentration of the test substance RC108 (total antibody, conjugated antibody, free MMAE) in cynomolgus monkey plasma with high sensitivity and high throughput was established by LBA and LC-MS/MS method. Subsequent non-clinical research on PK research in cynomolgus monkeys will provide technical support.

Cohort study on different BMI and blood pressure levels in children and adolescents / 中国学校卫生

Objective@#To analyze the relationship between the baseline BMI level and body mass index (BMI) changes of primary and middle school students and the blood pressure level and the risk of elevated blood pressure after 8 years of follow up(also known as the end stage), so as to provide a basis for the prevention and control of blood pressure in children and adolescents.@*Methods@#The physical examination data of 9 748 primary and secondary school students were selected from a cohort study design in Longkou City, Shandong Province for 8 years from 2014 to 2022, and analyzed the association of baseline BMI level and BMI changes with end stage blood pressure level and the risk of elevated blood pressure. Chi square test was used to compare differences between groups, and the generalized linear model and Logistic regression model were used to analyze the effect of baseline BMI level and BMI changes on blood pressure level and elevated blood pressure after 8 year follow up.@*Results@#Among non overweight and obesity group at baseline, the prevalence of high blood pressure was 9.1%. Among the overweight and obesity group, the prevalence of high blood pressure was 12.0%. Under different BMI status at baseline, the incidence of high blood pressure in boys was higher than that in girls. Compared with the BMI Z value≤-1 group, with the increase of BMI Z value, the systolic blood pressure level and the risk of high blood pressure gradually increased; with the BMI change continuously low as the control, sustained high and increased groups showed an increased risk of end stage high blood pressure ( OR=4.00, 2.21, P <0.01), and boys had a greater risk of elevated blood pressure.@*Conclusion@#Children and adolescents with higher baseline BMI level and increased BMI changes are at a higher risk of elevated blood pressure. Therefore, secondary school students should monitor the occurrence and development of blood pressure level in real time, and take comprehensive and effective measures to control the occurrence of elevated blood pressure level in childhood.

The effects and mechanisms of trimethylamine-N-oxide on insulin sensitivity in insulin target cells / 药学学报

Gut microbial metabolite trimethylamine-N-oxide (TMAO) is associated with type 2 diabetes (T2DM). Decreased insulin sensitivity is a significant etiological factor of T2DM. Adipocytes, myocytes, and hepatocytes are the three major target cells for insulin. This study aims to investigate the effects and mechanisms of TMAO on the insulin sensitivity of these target cells. Research results indicate that in different ages of db/db diabetic mice, plasma TMAO levels were increased. TMAO significantly inhibits the insulin signaling pathways in these three major insulin target cells, reduces glucose uptake in 3T3-L1 adipocytes and L6 myocytes and downregulates genes related to gluconeogenesis in primary mouse hepatocytes. Furthermore, in mice with normal insulin sensitivity, elevating plasma TMAO levels to those seen in db/db mice using a minipump results in impaired glucose tolerance and hyperinsulinemia. All animal experiments were carried out with approval of the Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica (Chinese Academy of Medical Sciences and Peking Union Medical College). Mechanistic studies suggest that TMAO exposure increases the levels of endoplasmic reticulum stress-related proteins in these three major insulin target cells. In summary, TMAO directly attenuates insulin sensitivity in insulin target cells, and its mechanism of action may involve enhancing endoplasmic reticulum stress.

Comparison of long-term clinical outcomes between transvaginal mesh and pelvic floor reconstruction with native tissue repair in the treatment of advanced pelvic organ prolapse / 中华妇产科杂志

Objective:To study the long-term clinical effect of transvaginal mesh (TVM) and pelvic floor reconstruction with native tissue repair (NTR) in the treatment of advanced pelvic organ prolapse (POP).Methods:Totally 207 patients with advanced POP who were treated in Hunan Provincial Maternal and Child Health Care Hospital from Jan. 2016 to Sep. 2019 were enrolled. The patient′s pelvic organ prolapse quantification were all at degree Ⅲ or above, and they all complained for different degree of symptoms. They were divided into two groups according to the different surgical methods, TVM group and NTR group. In TVM group, the mesh was implanted through the vagina for pelvic floor reconstruction, while in NTR group, the traditional transvaginal hysterectomy combined with uterosacral ligament suspension and anterior and posterior wall repair, as well as perineal body repair were performed. The median follow-up time was 60 months, during the follow up time, 164 cases (79.2%, 164/207) had completed follow-up, including 76 cases in TVM group and 88 cases in NTR group. The perioperative data and complication rates of the two groups were compared, and the subjective and objective outcomes of the two groups at 1, 3 and 5 years were observed, respectively. The objective efficacy was evaluated by three composite criteria, namely: (1) the distance from the farthest end of the prolapse of the anterior and posterior wall of the vagina to the hymen is ≤0 cm, and the descending distance of the top is ≤1/2 of the total length of the vagina; (2) determine the disappearance of relevant POP symptoms according to “Do you often see or feel vaginal mass prolapse？”; (3) no further operation or pessary treatment was performed due to prolapse. If the above three criteria were met at the same time, the operation is successful; otherwise, it was recurrence. The subjective efficacy was evaluated by the pelvic floor distress inventory-short form 20 (PFDI-20) and pelvic floor impact questionnaire-short form 7 (PFIQ-7).Results:The median follow-up time of the two groups was 60 months (range: 41-82 months). Five years after the operation, the subjective and objective cure rates of TVM group were 89.5% (68/76) and 94.7% (72/76), respectively. The subjective and objective cure rates in NTR group were 80.7% (71/88) and 85.2% (75/88), respectively. There were significant differences in the subjective and objective cure rates between the two groups ( χ2=9.869, P=0.002; χ2=3.969, P=0.046). The recurrence rate of TVM group was 5.3% (4/76), and that of NTR group was 14.8% (13/88). There was a significant difference between the two groups ( P=0.046). The postoperative PFDI-20 and PFIQ-7 scores of the two groups were significantly lower than those before surgery, and there were significant differences of the two groups before and after surgery (all P<0.05). Postoperative mesh exposure in TVM group was 1.3% (1/76). Conclusions:The long-term outcomes between the two groups show that the subjective and objective outcomes of pelvic floor reconstruction in TVM group are significantly higher than those in NTR group, and the recurrence rate is significantly lower than that in NTR group. TVM has certain advantages in the treatment of advanced POP.

China guideline for liver cancer screening (2022, Beijing) / 中华消化外科杂志

In China, the survival rate of liver cancer remains low while the mortality rate is high. Effectively reducing the burden of liver cancer is still a major challenge in the field of public health and chronic disease prevention in the Chinese population. Optimizing screening strategies for liver cancer remains a profound approach to secondary prevention worthy of continuous explora-tion. This guideline was commissioned by the Bureau of Disease Control and Prevention of the National Health Commission. The National Cancer Center of China initiated the guideline develop-ment and convened a multidisciplinary expert panel and working group. Following the World Health Organization Handbook for Guideline Development, this guideline integrated the most up-to-date evidence of liver cancer screening, China′s national conditions, and existing practical experience in liver cancer screening. Evidence-based recommendations on the target population, screening technologies, surveillance strategies, and other key points across the process of liver cancer screening and surveillance management were provided. This guideline would help to standardize the practice of liver cancer screening in China.

Impact of interventional therapy on top of standard drug therapy on left ventricular structure and function in HFrEF patients complicating with middle aortic syndrome caused by Takayasu arteritis / 中华心血管病杂志

Objective: To evaluate the impact of interventional therapy on top of drug therapy on cardiac function and structure in heart failure with reduced ejection fraction (HFrEF) patients complicating with middle aortic syndrome caused by Takayasu arteritis (TA-MAS). Methods: It was a retrospective longitudinal study. The data of patients with TA-MAS and HFrEF, who received interventional therapy on top of drug therapy in Fuwai Hospital from January 2010 to September 2020, were collected and analyzed. Baseline clinical data (including demographic data, basic treatment, etc.) were collected through the electronic medical record system. Changes of indexes such as New York Heart Association (NYHA) classification, N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular end diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI) before and after therapy were analyzed. Results: A total of 10 patients were collected. There were 8 females in this patient cohort, age was (18.4±5.0) years and onset age was (15.3±5.0) years. All 10 patients received standard heart failure medication therapy in addition to hormone and/or immunosuppressive anti-inflammatory therapy, but cardiac function was not improved, so aortic balloon dilatation and/or aortic stenting were performed in these patients. The median follow-up was 3.3(1.3, 5.6) years. On the third day after interventional therapy, the clinical symptoms of the 10 patients were significantly improved, NYHA classfication was restored from preoperative Ⅲ/Ⅳ to Ⅱ at 6 months post intervention(P<0.05). Compared with preoperation, NT-proBNP (P=0.028), LVEDD (P=0.011) and LVMI (P=0.019) were significantly decreased, LVEF was significantly increased (P<0.001) at 6 months after operation. Compared with preoperation, NT-proBNP (P=0.016), LVEDD (P=0.023) and LVMI (P=0.043) remained decreased, LVEF remained increased (P<0.001) at 1 year after operation. Conclusion: Results from short and medium term follow-up show that interventional therapy on top of heart failure drug therpay can effectively improve left cardiac function and attenuate cardiac remodeling in patients with TA-MAS comorbid with HFrEF.

Clinical value of routine contrast esophagram in the diagnosis of anastomotic leakage for three-incision esophagectomy with cervical anastomosis / 中华外科杂志

Objective: To examine the clinical value of routine contrast esophagram (RCE) for the diagnosis of anastomotic leakage (AL) after three-incision esophagectomy with cervical anastomosis. Methods: Clinical data of 1 022 patients with esophageal cancer who underwent McKeown three-incision esophagectomy with cervical anastomosis from January 2015 to December 2019 at Department of Minimally Invasive Esophageal Surgery, Tianjin Medical University Cancer Hospital and Institute were analyzed retrospectively. There were 876 males and 146 females, aging(M(IQR)) 48(16) years (range: 36 to 84 years). There were 253 patients (24.8%) with neoadjuvant therapy, and 817 patients (79.9%) with minimally invasive esophagectomy. According to the diagnosis and treatment habits of the attending surgeons, 333 patients were included in the RCE group, and RCE was performed on the 7th day postoperative, while 689 patients were included in the non-RCE group, and RCE was performed when the patients had suspicious symptoms. Taking clinical symptoms, RCE, CT, endoscopy and other methods as reference to the diagnosis of AL, the sensitivity and specificity were used to analyze and evaluate the efficacy of RCE for the diagnosis of AL. The data were compared by U test or χ² test between groups. Results: The incidence rate of AL after three-incision esophagectomy was 7.34% (75/1 022), including 30 cases in the RCE group and 45 cases in the non-RCE group (9.0%(30/333) vs. 6.5%(45/689), χ²=2.027, P=0.155). The diagnostic time of AL was 9(5) days postoperative (range: 4 to 30 days). Among them, 23 cases showed cervical leakages, 50 cases showed intro-thoracic leakages, and 2 cases both cervical and intro-thoracic leakages. The diagnostic time of patients with intro-thoracic leakages was longer than that of cervical leakages (10(4) days vs. 6(3) days, Z=-2.517, P=0.012). Among the 333 patients in the RCE group, 16 cases of RCE indicated leakages including 11 cases of true positive and 5 cases determined to be false positive, while 317 cases indicated no abnormalities including 19 cases developed leakages. The sensitivity and specificity of RCE to detect AL were 36.7%(11/30) and 98.3%(298/333), respectively. The Youden-index was 0.35, and the diagnostic accuracy was 92.8%(309/333). The positive and negative predictive value were 11/16 and 94.0%(298/317), respectively. Conclusions: Routine contrast esophagram after three-incision esophagectomy with cervical anastomosis has low sensitivity and high specificity in the diagnosis of AL. The diagnostic time of AL is the 9th day after surgery. It is necessary to prolong the observation time clinically, and combine RCE with CT, endoscopy and other inspection methods for diagnosis.

China guideline for liver cancer screening (2022, Beijing) / 临床肝胆病杂志

In China, the survival rate of liver cancer remains low while the mortality rate is high. Effectively reducing the burden of liver cancer is still a major challenge in the field of public health and chronic disease prevention in the Chinese population. Optimizing screening strategies for liver cancer remains a profound approach to secondary prevention worthy of continuous exploration. To address this pressing issue, the Bureau of Disease Control and Prevention of the National Health Commission commissioned this guideline. The National Cancer Center of China initiated the guideline development and convened a multidisciplinary expert panel and working groups. Following the World Health Organization Handbook for Guideline Development, this guideline integrated the most up-to-date evidence of liver cancer screening, China's national conditions, and existing practical experience in liver cancer screening. Evidence-based recommendations on the target population, screening technologies, surveillance strategies, and other key points across the process of liver cancer screening and surveillance management were provided. This guideline would help standardize the practice of liver cancer screening in China.

Phylogenetic and Mutation Points Analysis of Sophora japonica cv. jinhuai Based on DNA Barcoding Sequences / 中国实验方剂学杂志

ObjectiveTo conduct phylogenetic analysis of internal transcribed spacer 2 （ITS2） and chloroplast gene segments including psbA-trnH， rbcL， and matK of Sophora japonica cv. jinhuai resource samples from different geographical sources， and to explore the genetic diversity of S. japonica cv. jinhuai. MethodPolymerase chain reaction （PCR） method was used to amplify the nucleic acid sequences of ITS2， psbA-trnH， rbcL， and matK of S. japonica cv. jinhuai. Neighbor joining （NJ） method was used to construct phylogenetic trees， and Kimura 2-Parameter （K2P） model was used to calculate the genetic distance of different samples. MEGA and BIOEDIT softwares were applied for mutiple alignment and analysis of ITS2， psbA-trnH， rbcL， and matK sequences of S. japonica cv. jinhuai. ResultThe lengths of ITS2 sequence were 278-279 bp. The lengths of psbA-trnH were 289 bp. The lengths of rbcL sequence were 673 bp. The lengths of matK sequences were 786-792 bp. There were 3 mutation points in ITS2 and psbA-trnH， no mutation point in rbcL， and 13 mutation points in matK. The samples of S. japonica cv. jinhuai were clustered into two groups based on the phylogenetic tree constructed by ITS2 sequences. The sample of seedling tree in Baibao was clustered into one group， while the other 25 samples were clustered into another group. For the psbA-trnH sequence， the success rate of PCR amplification of 28 samples of S. japonica cv. jinhuai was 100%. The 28 samples of S. japonica cv. jinhuai were clustered into three groups based on the clustering results of psbA-trnH sequence. The sample of seedling tree in Shaoshui was clustered into one group. The five samples of grafting tree and seedling tree in Miaotou， grafting trees in Jiantang， Wenqiao， and Daxu， and seeding tree in Xianshui were clustered into one group. The other 21 samples were clustered into another group. The 26 samples of S. japonica cv. jinhuai were clustered into two groups based on the phylogenetic tree constructed by matK sequences. The sample of seedling tree in Xianshui was clustered into one group， while the other 25 samples were clustered into another group. The clustering results of the rbcL sequence of S. japonica cv. jinhuai could not distinguish 28 resource samples. The phylogenetic tree constructed by the combined sequence of ITS2+psbA-trnH+rbcL+matK divided S. japonica cv. jinhuai resource samples into 4 groups. The 13 samples of seedling trees in Qiyang， Daoxian， Miaotou， Shaoshui， Shitang， Xianshui， Jiantang， and Xiangli， and grafting trees in Qiyang， Miaotou， Yongsui， Wenqiao， and Yangtang were clustered into one group. The sample of seedling tree in Wenqiao was clustered into one group. The sample of seedling tree in Daxu was clustered into one group. The remaining samples were clustered into another group. ConclusionPhylogenetic and mutation analysis provide the theoretic foundation to investigate the evolution of the resources of S. japonica cv. jinhuai， and evaluate their genuineness. The results of mutation points can be used to identify the related S. japonica cv. jinhuai resources. The findings of this study show that the combination of different gene sequences has an optimal effect on plant identification.

Influence of electroacupuncture on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase signaling pathway in spontaneously hypertensive rats / 中西医结合学报

OBJECTIVE@#To investigate the influence of electroacupuncture (EA) on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase (PI3K/Akt/eNOS) signaling pathway in spontaneously hypertensive rats (SHRs).@*METHODS@#Eight Wistar-Kyoto rats were used as the healthy blood pressure (BP) control (normal group), and 32 SHRs were randomized into model group, EA group, EA plus ghrelin group (EA + G group), and EA plus PF04628935 group (a potent ghrelin receptor blocker; EA + P group) using a random number table. Rats in the normal group and model group did not receive treatment, but were immobilized for 20 min per day, 5 times a week, for 4 continuous weeks. SHRs in the EA group, EA + G group and EA + P group were immobilized and given EA treatment in 20 min sessions, 5 times per week, for 4 weeks. Additionally, 1 h before EA, SHRs in the EA + G group and EA + P group were intraperitoneally injected with ghrelin or PF04628935, respectively, for 4 weeks. The tail-cuff method was used to measure BP. After the 4-week intervention, the rats were sacrificed by cervical dislocation, and pathological morphology of the abdominal aorta was observed using hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of ghrelin, nitric oxide (NO), endothelin-1 (ET-1) and thromboxane A2 (TXA2) in the serum. Isolated thoracic aortic ring experiment was performed to evaluate vasorelaxation. Western blot was used to measure the expression of PI3K, Akt, phosphorylated Akt (p-Akt) and eNOS proteins in the abdominal aorta. Further, quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to measure the relative levels of mRNA expression for PI3K, Akt and eNOS in the abdominal aorta.@*RESULTS@#EA significantly reduced the systolic BP (SBP) and diastolic BP (DBP) (P < 0.05). HE staining showed that EA improved the morphology of the vascular endothelium to some extent. Results of ELISA indicated that higher concentrations of ghrelin and NO, and lower concentrations of ET-1 and TXA2 were presented in the EA group (P < 0.05). The isolated thoracic aortic ring experiment demonstrated that the vasodilation capacity of the thoracic aorta increased in the EA group. Results of Western blot and qRT-PCR showed that EA increased the abundance of PI3K, p-Akt/Akt and eNOS proteins, as well as expression levels of PI3K, Akt and eNOS mRNAs (P < 0.05). In the EA + G group, SBP and DBP decreased (P < 0.05), ghrelin concentrations increased (P < 0.05), and the concentrations of ET-1 and TXA2 decreased (P < 0.05), relative to the EA group. In addition, the levels of PI3K and eNOS proteins, the p-Akt/Akt ratio, and the expression of PI3K, Akt and eNOS mRNAs increased significantly in the EA + G group (P < 0.05), while PF04628935 reversed these effects.@*CONCLUSION@#EA effectively reduced BP and protected the vascular endothelium, and these effects may be linked to promoting the release of ghrelin and activation of the PI3K/Akt/eNOS signaling pathway.

A bibliometric analysis of liver disease research articles published by Chinese mainland authors in Gastroenterology & Hepatology journals indexed in Science Citation Index Expanded / 临床肝胆病杂志

Objective To investigate the articles on liver diseases published by authors from China (excluding Hong Kong, Macao, and Taiwan regions) in Gastroenterology & Hepatology journals indexed in Science Citation Index Expanded (SCIE) in 2016-2020, to analyze the bibliographic and citation data of these articles, and to understand the contribution and impact of Chinese scholars in the field of liver disease research in recent years. Methods The data for bibliometric analysis came from the SCIE database and Journal Citation Reports (JCR). The SCIE database was searched for the journal articles published in JCR Gastroenterology & Hepatology journals in 2016-2020, with a title or abstract containing "Liver", "Hepatocellular", "Hepatitis", "Cirrhosis", or "Hepatic" and a publication type of Article. Clinical guidelines were excluded, and the records with the corresponding author's affiliation containing institutions in China (excluding Hong Kong, Macao, and Taiwan regions) were screened out. R package bibliometrix was used to calculate the frequency of citations of included articles by liver disease studies published by Chinese and global authors in the Gastroenterology & Hepatology journals in 2016-2020, and R package DescTools was used to perform the Cochran-Armitage trend test to observe the change in composition ratio. Results In the Q1 Gastroenterology & Hepatology journals in 2016-2020, liver disease studies published by Chinese authors accounted for 9.5%. In recent years, the proportion of liver disease studies published by Chinese authors in Q1 Gastroenterology & Hepatology journals continues to increase from 6.0% to 12.2% ( P < 0.001). Among the liver disease studies published by Chinese authors in Q1 Gastroenterology & Hepatology journals, 79.7% were funded by National Natural Science Foundation of China, and there was no significant change in the proportion of studies funded by National Natural Science Foundation of China and published by Chinese authors in each partition of Gastroenterology & Hepatology journals in 2016-2020. The frequency of citations of included articles by liver disease studies published by Chinese and global authors in the Gastroenterology & Hepatology journals showed that liver disease studies published by Chinese authors had a high impact in both domestic and international academic communities. Conclusion In recent years, there has been a constant increase in the number of liver disease studies published by Chinese authors in high-impact Gastroenterology & Hepatology journals indexed in SCIE, and most of these studies have been funded by National Natural Science Foundation of China. The liver disease studies published by Chinese authors in Gastroenterology & Hepatology journals have been widely recognized by domestic and international academic communities.

Effect of Kansui Radix stir-fried with vinegar on fecal metabolomics in Walker-256 rats with ascites / 中国中药杂志

Utilizing metabolomics technology, this study explored the change of fecal endogenous metabolites in Walker-256 rats with malignant ascites after the administration with Kansui Radix(KR) stir-fried with vinegar(VKR), sought the potential biomarkers in feces which were related to the treatment of malignant ascites by VKR and revealed the biological mechanism of water-expelling effect of VKR. Ultra-fast liquid chromatography-quadrupole-time-of-flight mass spectrometry(UFLC-Q-TOF-MS) was employed to detect the feces of rats in all groups. Principle component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) were conducted to achieve pattern recognition. Combining t-test and variable importance in the projection(VIP) enabled the screening of potential biomarkers for the malignant ascites. Metabolic pathway analysis was accomplished with MetaboAnalyst. Correlation analysis was finally conducted integrating the sequencing data of gut microbiota to elucidate the mechanism underlying the water-expelling effect of VKR. The results showed that both KR and VKR could restore the abnormal metabolism of model rats to some extent, with VKR being inferior to KR in the regulation. Eleven potential biomarkers were identified to be correlated with the malignant ascites and five metabolic pathways were then enriched. Four kinds of gut microbiota were significantly related to the potential biomarkers. The water-expelling effect of VKR may be associated with the regulation of phenylalanine metabolism, biosynthesis of phenylalanine, tyrosine and tryptophan, tryptophan metabolism, glycerophospholipid metabolism, and glycosylphosphatidylinositol(GPI)-anchor biosynthesis. This study can provide a scientific basis for comprehensive understandings of the interaction between gut microbiota and host which has relation to the water-expelling effect of VKR and guide the reasonable clinical application of VKR.

Chemical ingredient groups B and C in Kansui Radix stir-fried with vinegar affect diversity of gut microbiota in rat model of malignant ascites induced by Walker-256 cells / 中国中药杂志

This study aims to explore the effects of chemical ingredient groups B and C in Kansui Radix stir-fried with vinegar on the diversity of gut microbiota in the rat model of malignant ascites, identify the key differential microbial taxa, and reveal the biological mechanism of water-expelling effect of the two chemical ingredient groups. The rat model of malignant ascites induced by Walker-256 cells was established, and phenolphthalein was used as the positive drug. The rats were orally administrated with corresponding agents for consecutive 7 days. On day 6, fresh feces samples were collected from the rats, and 16 S rDNA high-throughput sequencing and GC-MS were employed to determine the composition of gut microbiota and the content of short-chain fatty acids, respectively. On day 7, serum and intestinal tissue samples were collected for the determination of related indicators. Compared with the control group, the model group showed decreased feces volume and urine volume(P<0.01), increased volume of ascites and levels of Na~+, K~+, and Cl~- in urine(P<0.01), down-regulated mRNA and protein levels of intestinal AQP8(P<0.01), lowered abundance of beneficial Lactobacillus(P<0.01) while risen abundance of potential pathogenic Lachnospiraceae and Anaeroplasma(P<0.01), and reduced content of short-chain fatty acids(P<0.01). Compared with the model group, administration with chemical ingredient groups B and C alleviated all the above indicators(P<0.01). In conclusion, chemical ingredient groups B and C in Kansui Radix stir-fried with vinegar could alleviate the disordered gut microbiota in rats with malignant ascites to expel water through increasing the abundance of beneficial Lactobacillus and reducing the abundance of harmful Lachnospiraceae and Anaeroplasma. This study can provide a reference for the reasonable clinical application of Kansui Radix stir-fried with vinegar.

Mutation analysis of the KRT5 gene in a Chinese pedigree with Dowling-Degos disease / 中华皮肤科杂志

Objective:To investigate mutations in the KRT5 gene in a pedigree with Dowling-Degos disease.Methods:Clinical data were collected from the proband, and a survey was conducted in 12 members in 3 generations of the family. Peripheral blood samples were obtained from the proband, 8 family members and 50 unrelated healthy individuals, genomic DNA was extracted for whole-exome sequencing, and sequencing results were compared with the published sequences of human KRT5, POFUT1 and POGLUT1 genes.Results:There were 3 patients in this family, including the proband, his father and deceased grandmother. The proband and his father clinically presented with reticular pigmentation in the skinfolds, especially the chest and abdomen skinfolds. A novel heterozygous nonsense mutation c.165T>A was identified in exon 1 of the KRT5 gene in the proband and his father, but not in other family members or healthy controls. No abnormality was found in the POFUT1 or POGLUT1 gene in any subjects.Conclusion:A novel heterozygous nonsense mutation c.165T>A was identified in the KRT5 gene, and may contribute to the clinical phenotype of the proband and his father with Dowling-Degos disease.

Serum antibody levels in COVID-19 patients six months after hospital discharge / 上海预防医学

ObjectiveTo investigate the level of serum antibodies in COVID-19 patients six months after discharge， and to provide data to evaluate the duration of IgM， IgG and neutralizing antibody titers in the patients. MethodsEnzyme-linked immunosorbent assay （ELISA） was used to determine the antibody levels of IgM and IgG， and the new coronavirus live virus neutralization test was used to detect the neutralizing antibodies in the plasma of 181 recovered patients. ResultsThe IgG positive rate was 92.27% （167/181） in COVID-19 patients six months after discharge， while the lgM positive rate was 28.18% （51/181）. Six months after hospital discharge， 117 recovered patients （64.64%） were positive for IgG antibodies and negative for IgM antibodies， indicating that they had produced stable antibodies. This result suggested that they had been infected with the new coronavirus （SARS-CoV-2） and were in the recovery stage. The positive detection rate of neutralizing antibodies was as high as 91.71%. ConclusionSix months after infection with SARS-CoV-2， IgG antibodies produced in the patients continue to exist， and the neutralizing antibodies maintain a high and stable level. Results of this study have important guiding significance for future research on the durability of new coronavirus antibodies.

Serum antibody levels in COVID-19 patients six months after hospital discharge / 上海预防医学

ObjectiveTo investigate the level of serum antibodies in COVID-19 patients six months after discharge， and to provide data to evaluate the duration of IgM， IgG and neutralizing antibody titers in the patients. MethodsEnzyme-linked immunosorbent assay （ELISA） was used to determine the antibody levels of IgM and IgG， and the new coronavirus live virus neutralization test was used to detect the neutralizing antibodies in the plasma of 181 recovered patients. ResultsThe IgG positive rate was 92.27% （167/181） in COVID-19 patients six months after discharge， while the lgM positive rate was 28.18% （51/181）. Six months after hospital discharge， 117 recovered patients （64.64%） were positive for IgG antibodies and negative for IgM antibodies， indicating that they had produced stable antibodies. This result suggested that they had been infected with the new coronavirus （SARS-CoV-2） and were in the recovery stage. The positive detection rate of neutralizing antibodies was as high as 91.71%. ConclusionSix months after infection with SARS-CoV-2， IgG antibodies produced in the patients continue to exist， and the neutralizing antibodies maintain a high and stable level. Results of this study have important guiding significance for future research on the durability of new coronavirus antibodies.