Research progress of multimorbidity and its management in the elderly / 中华全科医师杂志

The co-existence of multiple chronic diseases has been increasing in the elderly population, it has become a major challenge globally, and identifying comorbidities patterns can help provide clues for disease prevention and treatment, as well as improving prognosis. This article reviews the identification methods, influencing factors and management strategies of chronic disease comorbidities, to provide a reference for the research and management of comorbidity.

Analysis of 8 Cases of Blau Syndrome/Early-onset Sarcoidosis——Clinical Manifestations, Histopathology Features and Gene Mutation Diversity / 罕见病研究

  Objective  To summarize the clinical manifestations, pathological features and gene mutation diversity of Blau syndrome/early-onset sarcoidosis.  Methods  We collected general data, clinical manifestations, and auxiliary examination results from 8 patients who were diagnosed of Blau syndrome/early-onset sarcoidosis and treated in our hospital from January 2011 to December 2022, and then summarized and analyzed their characteristics and diversity.  Results  Among the 8 patients, 4 were males and 4 were females. The onset age was 3 to 8 months old. Rash was the first symptom in 7 patients(87.5%). 6 patients(75.0%) had papules and erythema.3 cases(37.5%) had arthritis. 2 cases(25.0%) had uveitis and other eye inflammation. 4 cases (50.0%) also showed intermittent fever. 3 cases (37.5%) showed symptoms in nerve and respiratory system, and hypertension respectively. The skin histopathology of 8 patients showed non-caseous granuloma formation. In laboratory detection, CRP and TNF-α were significantly increased before treatment, while IL-6, IL-8, TNF-α and IL-2 receptor(IL-2R) were significantly decreased in 5 patients after glucocorticoid therapy. The results of genetic testing showed that 4 of the 7 patients had p.R334W(c.1000C > T) mutation, 1 had p.H313R(c.938A > G) and p.R471C(c.1411C > T)double mutation, and 1 had p.476_477del (c.1427_1429delcct).  Conclusions  Blau syndrome/early-onset sarcoidosis has significant features in clinical manifestations, histopathology and gene mutation, but it also has diversity.

Clinical Efficacy of Chonglian Oral Liquid on COVID-19 Patients / 中国实验方剂学杂志

ObjectiveTo observe the effect of Chonglian oral liquid on inflammatory and immune markers as well as the clinical outcomes of patients with mild-to-moderate corona virus disease 2019（COVID-19） and comprehensively evaluate its efficacy and safety. MethodA clinical randomized controlled trial （RCT） was conducted， involving 120 confirmed cases of mild-to-moderate COVID-19. The patients were randomly divided into two groups， with 55 cases in the observation group and 56 cases in the control group. According to the updated diagnosis and treatment protocol， the control group received standard western medical treatment， while the observation group received Chonglian oral liquid in addition to standard western medical treatment. Both groups were treated continuously for 10 days. The traditional Chinese medicine （TCM） syndrome scores， syndrome efficacy， fever abatement time， nucleic acid negative conversion time， inflammatory and immune markers， improvement in imaging findings， clinical outcomes， and occurrence of adverse events were compared between the two groups. ResultBoth groups showed a significant decrease in TCM syndrome scores after treatment （P<0.01）. Compared with the control group after treatment， the observation group exhibited a more significant improvement in cough， dry throat， sore throat， fatigue， and muscle pain （P<0.05）. The total effective rate in the observation group was 100% （55/55）， significantly higher than 98.21% （55/56） in the control group （Z=3.707， P<0.01）. The observation group also showed a significantly shorter duration of fever abatement and nucleic acid negative conversion compared with the control group after treatment （P<0.05）. Both groups had a significant increase in lymphocyte count （LYM）， lymphocyte percentage （LYM%）， mature T lymphocytes （CD3+）， and helper/inducer T lymphocytes （CD4+） after treatment （P<0.01）. Compared with the control group after treatment， the observation group showed greater improvement in these markers （P<0.05）. In terms of inflammatory markers， both groups had a significant decrease compared with those before treatment （P<0.01）. The observation group exhibited lower levels of high-sensitivity C-reactive protein （hs-CRP）， interleukin-6 （IL-6）， and procalcitonin （PCT） than the control group after treatment （P<0.05）. There was no statistically significant difference in imaging efficacy evaluation and clinical outcomes between the two groups. No adverse events were reported in either group during the treatment period. ConclusionChonglian oral liquid combined with standard western medical treatment significantly improves clinical symptoms， shortens fever abatement and nucleic acid negative conversion time， regulates immune function， and inhibits inflammatory responses in patients with mild-to-moderate COVID-19， leading to improved clinical efficacy.

Long-term outcome of EVAHEART I implantable ventricular assist device for the treatment of end stage heart failure: clinical 3-year follow-up results of 15 cases / 中华心血管病杂志

Objective: To evaluate the long-term efficacy and safety of the implantable ventricular assist system EVAHEART I in clinical use. Methods: Fifteen consecutive patients with end-stage heart failure who received left ventricular assist device therapy in Fuwai Hospital from January 2018 to December 2021 were enrolled in this study, their clinical data were retrospectively analyzed. Cardiac function, liver and kidney function, New York Heart Association (NYHA) classification, 6-minute walk distance and quality of life were evaluated before implantation and at 1, 6, 12, 24 and 36 months after device implantation. Drive cable infection, hemolysis, cerebrovascular events, mechanical failure, abnormally high-power consumption and abnormal pump flow were recorded during follow up. Results: All 15 patients were male, mean average age was (43.0±7.5) years, including 11 cases of dilated cardiomyopathy, 2 cases of ischemic cardiomyopathy, and 2 cases of valvular heart disease. All patients were hemodynamically stable on more than one intravenous vasoactive drugs, and 3 patients were supported by preoperative intra aortic balloon pump (IABP). Compared with before device implantation, left ventricular end-diastolic dimension (LVEDD) was significantly decreased ((80.93±6.69) mm vs. (63.73±6.31) mm, P<0.05), brain natriuretic peptide (BNP), total bilirubin and creatinine were also significantly decreased ((3 544.85±1 723.77) ng/L vs. (770.80±406.39) ng/L; (21.28±10.51) μmol/L vs. (17.39±7.68) μmol/L; (95.82±34.88) μmol/L vs. (77.32±43.81) μmol/L; P<0.05) at 1 week after device implantation. All patients in this group were in NYHA class Ⅳ before implantation, and 9 patients could recover to NYHA class Ⅲ, 3 to class Ⅱ, and 3 to class Ⅰ at 1 month after operation. All patients recovered to class Ⅰ-Ⅱ at 6 months after operation. The 6-minute walk distance, total quality of life and visual analogue scale were significantly increased and improved at 1 month after implantation compared with those before operation (P<0.05). All patients were implanted with EVAHEART I at speeds between 1 700-1 950 rpm, flow rates between 3.2-4.5 L/min, power consumption of 3-9 W. The 1-year, 2-year, and 3-year survival rates were 100%, 87%, and 80%, respectively. Three patients died of multiple organ failure at 412, 610, and 872 d after surgery, respectively. During long-term device carrying, 3 patients developed drive cable infection on 170, 220, and 475 d after surgery, respectively, and were cured by dressing change. One patient underwent heart transplantation at 155 d after surgery due to bacteremia. Three patients developed transient ischemic attack and 1 patient developed hemorrhagic stroke events, all cured without sequelae. Conclusion: EVAHEART I implantable left heart assist system can effectively treat critically ill patients with end-stage heart failure, can be carried for long-term life and significantly improve the survival rate, with clear clinical efficacy.

Screening of active components and preliminary mechanism exploration of Lycii Fructus for improving osteoporosis based on the zebrafish model / 药学学报

Juvenile zebrafish were used to screen the active components of Lycii Fructus for improving osteoporosis. The screening results were further verified by zebrafish adult osteoporosis model and the action mechanism was explored. Prednisolone was used as the inducer to build osteoporosis models of juvenile and adult zebrafish, and 9 groups of samples of different extracts and chemical parts of Lycii Fructus were given. Alizarin red staining was applied for observing the scale matrix mineralization and bone resorption. The activities of osteoblasts and osteoclasts were detected using alkaline phosphatase (ALP) and tartrate resistant acid phosphatase (TRAP/TRACP) staining. The expressions of bone metabolism-related genes alp, osteoprotectin (opn), osteoblast specific transcription factor (sp7), cathepsin K (ctsk), tracp, and Runt family transcription factor 2b (runx2b) in each group were determined using quantitative polymerase chain reaction. The results showed that all components of Lycii Fructus improved the formation area of the first vertebrae, the staining light density value, and the number of vertebrae joints in juvenile zebrafish and the Lycium barbarum polysaccharide (LBP) treatment group exerted the best effect. In addition, LBP prevented the formation of bone resorption lacunae in zebrafish scales, increased ALP activity, decreased TRAP activity, up-regulated the alp, sp7, and opn genes, and lowered the expressions of ctsk and tracp genes. In conclusion, LBP regulated the activity of osteoblasts and osteoclasts, reduced bone resorption, promoted bone formation and enhanced bone density, which might be the main anti-osteoporosis active fraction of Lycii Fructus. This study provided modern scientific evidence for the scientific connotation of the traditional effect of "strengthening bones and muscles" of Lycii Fructus, provided the reference for the evaluation of the anti-osteoporosis activity of traditional Chinese medicine based on zebrafish adult model, and provided beneficial enlightenment for the bone health needs of the aging society population.

Mechanism of Qilongtian Capsules in treatment of acute lung injury based on network pharmacology prediction and experimental validation / 中国中药杂志

This study aimed to explore the mechanism of Qilongtian Capsules in treating acute lung injury(ALI) based on network pharmacology prediction and in vitro experimental validation. Firstly, UPLC-Q-TOF-MS/MS was used to analyze the main chemical components of Qilongtian Capsules, and related databases were used to obtain its action targets and ALI disease targets. STRING database was used to build a protein-protein interaction(PPI) network. Metascape database was used to conduct enrichment analysis of Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG). AutoDock software was used to perform molecular docking verification on the main active components and key targets. Then, the RAW264.7 cells were stimulated with lipopolysaccharide(LPS) for in vitro experiments. Cell viability was measured by MTT and ROS level was measured by DCFH-DA. NO content was measured by Griess assay, and IL-1β, IL-6, and TNF-α mRNA expression was detected by RT-PCR. The predicted targets were preliminarily verified by investigating the effect of Qilongtian Capsules on downstream cytokines. Eighty-four compounds were identified by UPLC-Q-TOF-MS/MS. Through database retrieval, 44 active components with 589 target genes were screened out. There were 560 ALI disease targets, and 65 intersection targets. PPI network topology analysis revealed 10 core targets related to ALI, including STAT3, JUN, VEGFA, CASP3, and MMP9. KEGG enrichment analysis showed that Qilongtian Capsules mainly exerted an anti-ALI effect by regulating cancer pathway, AGE-RAGE, MAPK, and JAK-STAT signaling pathways. The results of molecular docking showed that the main active components in Qilongtian Capsules, including crenulatin, ginsenoside F_1, ginsenoside Rb_1, ginsenoside Rd, ginsenoside Rg_1, ginsenoside Rg_3, notoginsenoside Fe, notoginsenoside G, notoginsenoside R_1, notoginsenoside R_2, and notoginsenoside R_3, had good binding affinities with the corresponding protein targets STAT3, JUN, VEGFA, CASP3, and MMP9. Cellular experiments showed that Qilongtian Capsules at 0.1, 0.25, and 0.5 mg·mL~(-1) reduced the release of NO, while Qilongtian Capsules at 0.25 and 0.5 mg·mL~(-1) reduced ROS production, down-regulated mRNA expression of IL-1β, IL-6, TNF-α, and inhibited the inflammatory cascade. In summary, Qilongtian Capsules may exert therapeutic effects on ALI through multiple components and targets.

Discussion on the Formation and Prevention Strategies of Chemotherapy Resistance of Malignant Tumor Based on “Yin Fire” Theory / 中医杂志

Chemotherapy is currently the main clinical treatment method for malignant tumors， and chemotherapy resistance is the main factor leading to chemotherapy failure and malignant tumor recurrence and metastasis. The cha-racteristics of malignant tumors formation were regarded as similar to the “Yin Fire” theory， manifested that deficiency of original qi as the foundation of malignant tumors， imbalance of original qi and yin fire as the internal cause of malignant tumor progression， and the internal environment of phlegm-blood stasis-toxicity-deficiency caused by yin fire promoted the formation of chemoresistance. In the treatment of chemoresistance of malignant tumors， traditional Chinese medicine should focus on treating disease before its onset by tonifying the spleen and strengthening the middle， nou-rishing the original qi， and reinforcing healthy qi and anti-cancer； during the treatment， the clinicians should regulate the qi and detoxify to clear yin fire， and improve the internal environment. Summarily， the strategies were adjusting the balance of internal environment of original qi and yin fire， and conducting a comprehensive treatment during the whole process， to provide new ideas for the treatment of chemoresistance of malignant tumors with traditional Chinese medicine.

Age-dependent expression of ion channel genes in rat

Ion channels regulate a large number of cellular functions and their functional role in many diseases makes them potential therapeutic targets. Given their diverse distribution across multiple organs, the roles of ion channels, particularly in age-associated transcriptomic changes in specific organs, are yet to be fully revealed.Using RNA-seq data, we investigated the rat transcriptomic profiles of ion channel genes across 11 organs/tissues and 4 developmental stages in both sexes of Fischer 344 rats and identify tissue-specific and age-dependent changes in ion channel gene expression. Organ-enriched ion channel genes were identified. In particular, the brain showed higher tissue-specificity of ion channel genes, including Gabrd, Gabra6, Gabrg2, Grin2a, and Grin2b. Notably, age-dependent changes in ion channel gene expression were prominently observed in the thymus, including in Aqp1, Clcn4, Hvcn1, Itpr1, Kcng2, Kcnj11, Kcnn3, and Trpm2. Our comprehensive study of ion channel gene expression will serve as a primary resource for biological studies of aging-related diseases caused by abnormal ion channel functions.

Effect of gender difference on antigen induced Sjogren's syndrome model in mice / 中国药理学通报

Aim To study the effect of gender differences in C57BL / 6J mice on antigen induced Sjogren's syndrome(SS)model. Methods The submandibular gland protein of C57BL/6J female and male mice was extracted and mixed with the same amount of Freund's complete adjuvant(FCA)for the first three times, the antigen concentration was adjusted to 2.5 g·L-1, mixed with Freund's incomplete adjuvant(FIA)for the fourth time, and the same-sex mouse antigen was injected into the back of mice for a total of four times to induce the mouse SS model. The mouse SS model was induced by multi-point intradermal injection of antigen on the back of mice for four times,the body weight of female and male mice was measured every week, the general condition was observed, the saliva volume of mice was measured at the sixth week of modeling. After the mice were sacrificed, the pathological changes of submandibular gland and the changes of T and B lymphocyte subsets in spleen were detected, and the differences in SS model preparation between female and male mice were compared. Results The SS model of male and female mice was successfully established, and there was no significant difference in general condition, saliva volume, submandibular gland pathology, plasma cells and memory B cells between male and female SS mice. The success rate of SS model was 75% in female mice and 60% in male mice. Compared with normal mice of the same sex, the weight loss of female SS mice was earlier and more obvious than that of male SS mice; the submandibular gland index of male mice was significantly higher than that of female mice. Compared with normal mice of the same sex, the proportion of Th17 and Treg cells in spleen of female SS mice was more statistically significant than that of male SS mice. Conclusions The success rate of SS modeling in female mice is higher than that in male mice. Compared with male SS mice, female SS mice have more significant SS like manifestations and pathological manifestations, which can provide a reference basis for the selection of gender when establishing SS model.

The expression of RCN3 in colon cancer and its clinical significance / 中国医师杂志

Objective:To analyze the expression and clinical significance of reticulocalbin 3 (RCN3) in colon cancer by bioinformatics database and biological experiments.Methods:Colon cancer HT29 and SW620 cells and colon normal mucosal cells FHC were cultured. The expression of RCN3 in cells was verified by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) and Western blot. The expression data of RCN3 in normal colon tissue and colon cancer tissue were obtained by Ualcan database. The co-expressed gene information of RCN3 from LinkedOmics database was obtained, and the biological processes and related functions of these RCN3 co-expressed genes through were analyzed by gene ontology analysis (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The protein-protein interaction network of RCN3 related coding genes was constructed by using STRING database. Finally, the relationship between the expression of RCN3 and the clinical prognosis of patients with colon cancer was compared and analyzed according to GEPIA, Ualcan and Linked Omics biological database.Results:Western blot and qRT-PCR results showed that the mRNA and protein expression of RCN3 in HT29 and SW620 colon cancer cells was significantly higher than those in FHCcells ( all P<0.05). The analysis of biological database showed that the expression level of RCN3 in colon cancer tissue was higher than that in normal colon tissue ( P<0.05). GO enrichment analysis showed that RCN3 co-expression genes were mainly involved in the composition of extracellular matrix and extracellular domain structure, the binding process of extracellular matrix and multiple receptors, and the biological processes related to tumor development such as cell adhesion, immune response, and angiogenesis through extracellular domain structure. KEGG pathway analysis showed that RCN3 co-expression genes were mainly involved in ECM receptor interaction, cytokine receptor interaction, chemokine signaling pathway, phosphatidylinositol-3-kinase protein kinase B (PI3K-Akt) signaling pathway, phagosome signal, IgA related intestinal immune network signal, these signaling pathways always related to tumor invasion, migration and inflammatory immune response. The protein-protein interaction network analysis showed that the coding protein genes that directly interacted with RCN3 protein that included PRDX6, NOSIP, PCSK6, IMMP1L, PRRG2, FBXO47, FCGRT, FKBP9, PCDHGA12, and PNMAL1, which were mainly involved in the occurrence and development of colorectal cancer, liver cancer, gastric cancer, breast cancer, lung cancer, and ovarian cancer. Survival curve analysis showed that the overall survival rate of colon cancer patients with high expression of RCN3 was significantly lower than that of patients with low expression of RCN3 ( P<0.05). Conclusions:RCN3 is highly expressed in colon cancer tissues and cells, which is closely related to the occurrence, development and prognosis of colon cancer. It can be used as one of the markers for early screening and prognosis prediction of colon cancer.

Establishment of biological reference interval for reverse triiodothyronine by indirect method / 中华核医学与分子影像杂志

Objective:To establish reverse triiodothyronine (rT 3) biological reference interval suitable for laboratory by indirect method. Methods:From April to September 2019, 797 cases (332 males, 465 females, age: 12-95 years) underwent thyroid function, thyroid related antibody and rT 3 tests from hospitalized population in Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine were retrospectively analyzed. The reference individuals with normal thyroid hormone, antibody and without thyroid nodule or goiter were screened as inclusion criteria, and the factors such as acute and chronic diseases or drugs that might affect the values of rT 3 were excluded. Independent sample t test, one-way analysis of variance and least significant difference t test were used to analyze data. The rT 3 reference interval was established by non-parametric sequencing method, and 2.5% and 97.5% percentile values of data distribution were selected as the upper and the lower reference limits. In order to verify the rT 3 reference interval, 20 healthy individuals and 20 inpatients who met the inclusion and exclusion criteria were selected to test rT 3 with a simple random sampling method. Results:A total of 159 reference individuals (66 males, 93 females, age: 23-87 years) were enrolled. The rT 3 values of 23-29( n=4), 30-39( n=18), 40-49( n=29), 50-59( n=43), 60-69( n=40), 70-79( n=19) and over 80( n=6) years old groups were (0.62±0.16), (0.63±0.12), (0.64±0.11), (0.61±0.11), (0.65±0.14), (0.65±0.11) and (0.79±0.10) μg/L, respectively. There was a statistically significant difference in the rT 3 test results among different age groups ( F=2.17, P=0.049). There were statistically significant differences of rT 3 between the individuals over 80 years old and other age groups (all P<0.05), while there were no statistically significant differences among the other groups (all P>0.05). The rT 3 of males and females under 80 years old were (0.62±0.11) and (0.64±0.12) μg/L, respectively, with no significant difference between them ( t=-0.81, P=0.420). The newly established rT 3 reference interval suitable for people above 20 years old and below 80 years old was 0.47-0.92 μg/L, and the lower limit was significantly higher than that of the reference interval in the reagent specification (0.20-0.95 μg/L). The rT 3 range of 20 healthy individuals was 0.57-0.82 μg/L and that of 20 inpatients was 0.48-0.77 μg/L, which were all within the new reference interval. Conclusion:The rT 3 biological reference interval established here has clinical application value, but its applicable range of age still needs to be further improved.

Research status of molecularly imprinted hydrogel drug-loaded contact lenses / 中华实验眼科杂志

Traditional ophthalmic pharmaceutical preparations are mostly eye drops or eye ointments, which have the disadvantages of low efficiency and poor patient compliance in application.Drug-loaded contact lenses can overcome these shortcomings and have attracted much attention.Improving drug loading capacity and enhancing sustained-release performance of drug-loaded contact lenses are the main focus of research and development.In recent years, drug-loaded contact lenses made of molecularly imprinted hydrogel can significantly improve drug loading capacity and sustained-release performance, and have been widely studied.The application status of molecularly imprinted hydrogel drug-loaded contact lenses in the delivery of ophthalmic drugs, as well as the effects of various factors on drug loading capacity and sustained-release performance were reviewed in this article.

Candida Infection-caused Lumbar Vertebral Osteomyelitis:Report of One Case / 中国医学科学院学报

Candida vertebral osteomyelitis,a rare but challenging clinical disease without specific clinical manifestations,is prone to delay in diagnosis,with potential risks of serious complications.Therefore,early diagnosis is the key to improving the cure rate of this disease.A case of invasive candida lumbar osteomyelitis after gastrointestinal surgery is reported in this paper.We analyzed the clinical characteristics of the patient and reviewed the relevant literature,aiming to improve the early diagnosis and treatment of this disease.

Clinical characteristics of human adenovirus infection in hospitalized children with acute respiratory infection in Beijing / 中华儿科杂志

Objective: To compare the clinical characteristics of different types of human adenovirus (HAdV) infection in hospitalized children with acute respiratory infection in Beijing, and to clarify the clinical necessity of adenovirus typing. Methods: In a cross-sectional study, 9 022 respiratory tract specimens collected from hospitalized children with acute respiratory infection from November 2017 to October 2019 in Affiliated Children's Hospital, Capital Institute of Pediatrics were screened for HAdV by direct immunofluorescence (DFA) and (or) nucleic acid detection. Then the Penton base, Hexon and Fiber gene of HAdV were amplified from HAdV positive specimens to confirm their HAdV types by phylogenetic tree construction. Clinical data such as laboratory results and imaging data were analyzed for children with predominate type HAdV infection using t, U, or χ2 test. Results: There were 392 cases (4.34%) positive for HAdV among 9 022 specimens from hospitalized children with acute respiratory infection. Among those 205 cases who were successfully typed, 131 were male and 74 were female, age of 22.6 (6.7, 52.5) months,102 cases (49.76%) were positive for HAdV-3 and 86 cases (41.95%), HAdV-7, respectively, while 17 cases were confirmed as HAdV-1, 2, 4, 6, 14 or 21. In comparison of clinical characteristics between the predominate HAdV type 7 and 3 infection, significant differences were shown in proportions of children with wheezing (10 cases (11.63%) vs. 25 cases (24.51%)), white blood cell count >15 ×109/L (4 cases (4.65%) vs.14 cases (13.73%)), white blood cell count <5×109/L (26 cases (30.23%) vs.11 cases (10.78%)), procalcitonin level>0.5 mg/L (43 cases (50.00%) vs. 29 cases (28.43%)), multilobar infiltration (45 cases (52.33%) vs.38 cases (37.25%)), pleural effusion (23 cases (26.74%) vs. 10 cases (9.80%)), and severe adenovirus pneumonia (7 cases (8.14%) vs. 2 cases (1.96%)) with χ²=5.11, 4.44, 11.16, 9.19, 4.30, 9.25, 3.91 and P=0.024, 0.035, 0.001, 0.002, 0.038, 0.002, 0.048, respectively, and also in length of hospital stay (11 (8, 15) vs. 7 (5, 13) d, Z=3.73, P<0.001). Conclusions: HAdV-3 and 7 were the predominate types of HAdV infection in hospitalized children with acute respiratory tract infection in Beijing. Compared with HAdV-3 infection, HAdV-7 infection caused more obvious inflammatory reaction, more severe pulmonary symptoms, longer length of hospital stay, suggesting the clinical necessity of further typing of HAdVs.

Paeoniflorin besylate relieves mice with antigen-induced experimental Sjogren's syndrome by regulating GRK2-JAK1-STAT1/2 signaling pathway / 中国药理学通报

Aim To observe the effect of CP-25 on the ESS mouse model and establish whether its effect is through regulating the binding of GRK2 to JAK1 and inhibiting the JAK1-STAT1/2-CXCL13 signaling pathway. Method We established ESS mouse model induced by SG protein, established into normal group, model group, CP-25 group with concentration of 35 mg • kg"1, 70 mg • kg"1, and HCQ group with concentration of 80 mg • kg"1. Mouse saliva flow was measured. The infiltration of lymphocyte in SG was observed by HE staining. The expression of p-JAKl, p- STAT1 and p-STAT2 in submandibular gland tissue was detected by Western blot. The level of CXCL13 in SG of mice was tested by IHC. GRK2 and JAK1 binding was determined by immunofluorescence and CO- IP. Results Compared with normal group, the saliva flow rate of ESS mice was low and lymphocytes were significantly infiltrated in the submandibular gland pathological sections. The CXCL13 protein level was highly expressed, which activated the JAK1-STAT1/2 signal. CP-25 significantly increased the salivary flow rate in ESS mice, reduced lymphocyte infiltration, improved pathological abnormalities, and inhibited the expression of JAK1-STAT 1/2 signaling and CXCL13. CP-25 significantly promoted the binding of GRK2 to JAK1. Conclusions CP-25 may inhibit the binding of GRK2 to JAK1, and then inhibit the activation of JAK1-STAT1/2-CXCL13 signaling pathway, improve the abnormal pathological manifestations of lymphocyte infiltration in submandibular gland, and improve the rate of saliva flow. CP-25 plays a therapeutic role in ESS mice.

Prevalence of heart failure in Chinese cognitive impairment patients： a meta-analysis / 上海预防医学

Objective:Heart failure （HF） and cognitive impairment have become serious medical problems in China. This study used meta-analysis to comprehensively evaluate the prevalence of cognitive impairment in patients with HF in China， and provided suggestions for intervention and prevention of cognitive impairment in this population. Methods:A systematic retrieval was conducted by searching relevant literatures regarding cognitive impairment in Chinese HF patients. These reports were published on CNKI， Wanfang， SinoMed， VIP and PubMed， from January 1， 1980 to July 10， 2020. The Agency for Healthcare Research and Quality （AHRQ） criteria and Newcastle-Ottawa Scale were used to evaluate the literature quality of cross-sectional studies and case-control studies， respectively. Stata16.0 was used for combined prevalence and effect value. Results:A total of 20 articles with medium quality were included. Six of them were case-control studies， with a total sample size of 933 people， and healthy people as controls. The Odds Ratios （OR） value of the prevalence of cognitive impairment in patients with HF was 2.77 （95% CI： 2.05-3.74）. 14 articles were cross-sectional studies with a total sample size of 3000. In China， the prevalence of cognitive impairment in patients with HF was 54.3% （95% CI： 0.43-0.65）. Subgroup analysis showed that the prevalence of cognitive impairment was increased with age， and women had a higher prevalence （58.4%） than that in men （48.4%）. The prevalence in studies using the Montreal Cognitive Assessment （MoCA）to evaluate cognitive impairment （63.6%） was higher than those using Mini-mental State Examination （MMSE）（41.7%）. The limitations of this study include the following： only used the relevant literature on cognitive impairment in patients with HF in China； failed to explain the source of heterogeneity， unable to determine the impact of the study area on heterogeneity， and unable to determine the causality of HF and cognitive impairment. Conclusion:The prevalence of cognitive impairment in patients with HF in China is high and significantly affected by age， gender and other factors. Appropriate measures should be taken for prevention and timely intervention.

Associations between urinary bisphenol A concentrations during pregnancy and gestational age / 上海预防医学

Objective We aimed to assess the association between urinary bisphenol A(BPA)concentrations and gestational age in pregnant women. Methods A total of 248 pregnant women were recruited from a maternal and child care hospital in Shanghai. A questionnaire survey was completed to collect socio-demographic information and spot urine samples were collected during pregnancy. Gas chromatography-tandem mass spectrometry(GC-MS/MS)was used to measure BPA concentrations in urine samples. Linear relationship between urinary BPA level and gestational age was assessed by using generalized additive models. Multivariate regression model was used to evaluate associations of prenatal BPA exposure with gestational age. Results BPA was detected in all the urine samples. Median value and geometric mean of urinary BPA levels were 0.85 μg/L and 1.21 μg/L, respectively. Linear relationship between urinary BPA concentration and gestational weeks was confirmed(non-linear P > 0.05). Positive association between urinary BPA level and gestational age was indicated(regression coefficient, β = 0.19;95%CI:0.04-0.35;P = 0.016). However, it was only observed in girls, stratified by sex of newborns(β = 0.18;95%CI:0.03-0.34;P = 0.020). After stratification by trimester, no significant association was found in the second or the third trimesters. Conclusion Pregnant women are extensively exposed to BPA. Urinary BPA exposure during pregnancy may extend gestational age, especially in girls.

Characterization and principal component analysis of functionality-related characteristics of hydroxypropyl methylcellulose type 2208 / 药学学报

Under the guidance of Chinese Pharmacopoeia (2020 edition), the functionality-related characteristics of hydroxypropyl methylcellulose (HPMC) type 2208 from imported A manufacturer, domestic S manufacturer, domestic T manufacturer and different batches of the same manufacturer were characterized. The principal component analysis was used to comprehensively evaluate the functionality-related characteristics. The results were as follows: hydroxypropyl methylcellulose had no significant difference in viscosity and molecular weight distribution between different manufacturers, and there were significant differences in the cumulative particle size distribution of the sample reaches 50% (d50) and 90% (d90), bulk density, tap density and Carr's index. The HPMC from A manufacturer have the biggest inter-batch difference of particle size and their inter-batch difference of polydispersion coefficientis smaller than S manufacturer. Domestic manufactures have the largest inter-batch difference in other functionality-related characteristics. The three principal components were extracted by principal component analysis, and the variance contribution rate reached 89.44%, indicating that the extracted principal components can explain all the data well. By constructing a comprehensive evaluation model, the comprehensive score ranking of all HPMC samples is obtained: S manufacturer > A manufacturer > T manufacturer.

Far-infrared rays enhance mitochondrial biogenesis and GLUT3 expression under low glucose conditions in rat skeletal muscle cells

Far-infrared rays (FIR) are known to have various effects on atoms and molecular structures within cells owing to their radiation and vibration frequencies. The present study examined the effects of FIR on gene expression related to glucose transport through microarray analysis in rat skeletal muscle cells, as well as on mitochondrial biogenesis, at high and low glucose conditions. FIR were emitted from a bio-active material coated fabric (BMCF). L6 cells were treated with 30% BMCF for 24 h in medium containing 25 or 5.5 mM glucose, and changes in the expression of glucose transporter genes were determined. The expression of GLUT3 (Slc2a3) increased 2.0-fold (p < 0.05) under 5.5 mM glucose and 30% BMCF. In addition, mitochondrial oxygen consumption and membrane potential (ΔΨm) increased 1.5- and 3.4-fold (p < 0.05 and p < 0.001), respectively, but no significant change in expression of Pgc-1a, a regulator of mitochondrial biogenesis, was observed in 24 h. To analyze the relationship between GLUT3 expression and mitochondrial biogenesis under FIR, GLUT3 was down-modulated by siRNA for 72 h. As a result, the ΔΨm of the GLUT3 siRNA-treated cells increased 3.0-fold (p < 0.001), whereas that of the control group increased 4.6-fold (p < 0.001). Moreover, Pgc-1a expression increased upon 30% BMCF treatment for 72 h; an effect that was more pronounced in the presence of GLUT3. These results suggest that FIR may hold therapeutic potential for improving glucose metabolism and mitochondrial function in metabolic diseases associated with insufficient glucose supply, such as type 2 diabetes.

Application Value of Abbreviated Comprehensive Geriatric Assessment in Elderly Female Breast Cancer Patients / 中国医学科学院学报

Objective To evaluate the application value of abbreviated comprehensive geriatric assessment(aCGA)in elderly female breast cancer patients. Methods Eight aspects of the traditional CGA were simplified to form the aCGA assessment table,based on which the patients were classified into three grades of A,B and C according to the total scores.This study enrolled the elderly female patients with breast cancer aged 70 years and above who were treated in PUMC Hospital from June 2018 to January 2020.Eastern Cooperative Oncology Group(ECOG)scoring and aCGA grading were performed respectively,and the results of the two methods were compared. Results Of the 162 patients,111(68.5%)were classified by the aGGA method as grade A,43(26.5%)as grade B,and 8(5.0%)as grade C;131(80.9%)cases have concurrent diseases,and the most common complications were hypertension(