Observation on the Therapeutic Effect of Yiqi Huoxue Huazhuo Therapy on Hepatic Fibrosis in Wilson's Disease / 广州中医药大学学报

Objective To assess the clinical effect of the Yiqi Huoxue Huazhuo therapy(the therapy for replenishing qi,activating blood and resolving turbidity)for the treatment of hepatic fibrosis in Wilson's disease(WD,also known as hepatolenticular degeneration).Methods Using retrospective research method,52 patients with liver fibrosis in WD of qi deficiency and blood stasis type were divided into 24 cases in the control group and 28 cases in the treatment group according to the treatment method.The control group was treated with conventional decopper therapy with western medicines,and the treatment group was treated with Chinese herbal decoction based on Yiqi Huoxue Huazhuo therapy together with conventional decopper therapy.Both groups were treated for a total of 4 weeks.Before and after the treatment,the two groups were observed in the changes of traditional Chinese medicine(TCM)syndrome scores,Unified Wilson's Disease Rating Scale(UWDRS)hepatic symptom scores,serum levels of liver fibrosis indicators of pre-collagen typeⅢ(PCⅢ),hyaluronic acid(HA),collagenⅣ(CⅣ),and laminin(LN),C-X-C motif chemokine ligand 10(CXCL10)level,and the point shear-wave elastography(pSWE)values of hepatic ultrasound based on acoustic radiation force impulse imaging(ARFI).After treatment,the clinical efficacy of the two groups was evaluated.Results(1)After 4 weeks of treatment,the total effective rate of the treatment group was 85.71%(24/28),while that of the control group was 54.17%(13/24),and the intergroup comparison(tested by chi-square test)showed that the therapeutic efficacy of the treatment group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the TCM syndrome scores in both groups were decreased compared with those before treatment(P＜0.01),and the decrease of TCM syndrome scores in the treatment group was significantly superior to that in the control group(P＜0.05).(3)After treatment,the UWDRS liver symptom scores in the two groups were decreased compared with those before treatment(P＜0.01),but the difference was not statistically significant when comparing between the two groups after treatment(P＞0.05).(4)After treatment,serum levels of liver fibrosis indicators of HA,LN,CⅣ and PCⅢ in the treatment group were all decreased compared with those before treatment(P＜0.01),while in the control group only serum LN and PCⅢlevels were decreased(P＜0.05).The intergroup comparison showed that the decrease of serum HA,LN,and PCⅢlevels in the treatment group was superior to that in the control group(P＜0.05 or P＜0.01),while the decrease of serum CⅣlevel tended to be superior to that in the control group,but the difference was not statistically significant(P＞0.05).(5)After treatment,the serum chemokine CXCL10 level in the treatment group was significantly decreased compared with that before treatment(P＜0.01),while the level tended to decrease in the control group,but the difference was not statistically significant(P＞0.05).The intergroup comparison showed that the reduction of serum CXCL10 level in the treatment group was significantly superior to that in the control group(P＜0.05).(6)After treatment,the pSWE values of hepatic ultrasound in the two groups were lower than those before treatment(P＜0.01),and the reduction of pSWE values in treatment group was significantly superior to that of the control group(P＜0.01).Conclusion Yiqi Huoxue Huazhuo therapy can effectively reduce the TCM syndrome scores of WD patients,improve the UWDRS hepatic symptom scores,down-regulate the liver fibrosis indicator level and serum CXCL10 expression level,reduce the pSWE values of hepatic ultrasound,and enhance the clinical efficacy.

Melatonin alleviates CoCrMo particle-induced osteolysis by inhibiting NLRP3 inflammasome activation / 中国组织工程研究

BACKGROUND:Periprosthetic osteolysis is the most common long-term complication of total joint arthroplasty.Many studies suggest that the inflammasome may play an important role during the osteolysis.Melatonin is a rhythm-regulated hormone secreted by the pineal gland with many functions including anti-inflammatory,anti-oxidation,and antitumor,but its effects on osteolysis and inflammasome have yet to be explored. OBJECTIVE:To explore the effect of melatonin on the osteolysis induced by wear particles and the role of melatonin on the activation of NLRP3 inflammasome. METHODS:(1)In vivo test:Fifteen C57BL/6 mice were randomly divided into sham operation group,osteolysis group and melatonin group by random number table method,with 5 mice in each group.The osteolysis model of the osteolysis group and the melatonin group was established by injecting cobalt-chromium-molybdenum(CoCrMo)particles into the sagittal suture of the skull.After injection,the melatonin group was intraperitoneally injected with 50 mg/(kg·d)of melatonin for 14 consecutive days.After drug intervention,the mouse calvarium was collected for micro-CT analysis to observe the micro-structural changes around the sagittal suture.(2)In vitro test:Mouse bone marrow-derived macrophages and THP-1 cells(which had been induced to differentiate into macrophages)were taken and divided into seven groups:normal group,lipopolysaccharide group,lipopolysaccharide+CoCrMo group and melatonin 0.5,1,1.5,2 mmol/L groups(lipopolysaccharide and CoCrMo were added to the melatonin intervention groups).After the intervention for 6 hours,the expression of related proteins(NLRP3,Caspase-1,interleukin-1β,and gasdermin D,gasdermin D-N terminal)in the inflammasome of cell lysate or cell culture supernatant was detected by western blot assay.Cytotoxicity and cell death were observed through lactate dehydrogenase release and live-dead fluorescence staining. RESULTS AND CONCLUSION:(1)In vivo test:Micro-CT scanning 3D reconstruction images showed that the bone mass around the sagittal suture of the skull of mice in the osteolysis group was significantly reduced,and the bone tissue structure was severely damaged.Compared with the osteolysis group,the bone mass around the sagittal suture of the skull in the melatonin group was significantly increased,and the destruction of tissue structure was reduced.(2)In vitro test:For mouse bone marrow-derived macrophages,lipopolysaccharide significantly up-regulated NLRP3 protein expression in cell lysate,and melatonin intervention could reduce NLRP3 protein expression in a dose-dependent manner.CoCrMo particles significantly up-regulated the protein expressions of the gasdermin D-N terminal in cell lysate and Caspase-1 and interleukin-1β in the supernatant of cell culture,while melatonin intervention could reduce the expression of these proteins in a dose-dependent manner.For THP-1 cells,the protein expressions of Caspase-1 and interleukin-1β in the supernatant of cell culture were significantly up-regulated by CoCrMo particles,and the expression of these proteins was decreased dose-dependent by melatonin intervention.Lactate dehydrogenase release and live-dead fluorescence staining showed that CoCrMo particles significantly increased the release of lactate dehydrogenase and cell death in the supernatant of mouse bone marrow-derived macrophage culture,and melatonin intervention could reduce the release of lactate dehydrogenase and cell death.(3)The results show that melatonin can inhibit particle-induced inflammasome activation and pyroptosis to suppress periprosthetic osteolysis.

Teaching methods for the medical integrated courses in "4+4" medical doctor program in Peking Union Medical College: current status and approaches for improvement / 中华医学教育探索杂志

Objective:To investigate the current status of the teaching methods used in the integrated basic and clinical courses and the approaches for improving such teaching methods, and to improve the teaching quality of the integrated basic and clinical courses for "4+4" Medical Doctor Program in Peking Union Medical College.Methods:Students in the Class 2020 of "4+4" Medical Doctor Program who completed the integrated courses from September 2020 to August 2021 were enrolled as subjects. Questionnaire surveys and interviews were performed for the subjects in terms of class hours, integration effect, and self-learning methods. R4.0.0 software was used to perform a statistical analysis of data.Results:The mean weekly class hours of existing modules were (27.59±2.61) hours per week, which was higher than the expectation of students. There was a negative linear correlation between weekly class hours and mean satisfaction score of each module ( r=-0.71, P=0.022). The integration of basic and clinical medical courses had a mean satisfaction score of 2.652. The median preview time for case-based learning/problem-based learning was 30 minutes. Conclusions:In the reform of the integration of basic and clinical medical courses, it is crucial to select and apply proper teaching methods. In order to further improve teaching effect, it is advised to reduce the class hours of theoretical lectures and carefully design and prepare learning materials, and the teaching contents should be organized according to the internal logic of knowledge and the association between clinical knowledge and the knowledge learned during the stage of basic medicine.

Fluoride induced apoptosis and oxidative stress in rat spinal cord nerve cells / 中华地方病学杂志

Objective:To study the effects of fluoride on apoptosis and oxidative stress levels of spinal cord nerve cells in rats.Methods:A total of 54 6-week-old Sprague-Dawley female rats, weighing 150 - 200 g, were selected and fed for 1 week. They were divided into a control group [given deionized water containing 0 mg/L sodium fluoride (NaF)], a low fluoride group (given deionized water containing 50 mg/L NaF), and a high fluoride group (given deionized water containing 100 mg/L NaF) using a random number table method, with 18 rats in each group. All groups received standard feed. After 4, 8, and 12 weeks of fluoride exposure, six rats were selected from each group to observe the occurrence of dental fluorosis, and the motor function of hind limbs in rats was evaluated based on the Basso-Beattie-Bresnahan (BBB) score. Then the rats were anesthetized with 5% chloral hydrate via intraperitoneal injection and euthanized by cardiac puncture. Spinal cord tissue of the rats was collected to detect the activities of oxidative stress factors such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), as well as the contents of malondialdehyde (MDA) and catalase (CAT). After 12 weeks of fluoride exposure, morphologic changes in rat spinal cord neurons were observed using Nissl staining, and apoptosis of spinal cord nerve cells was detected using the TdT mediated dUTP nick end labeling (TUNEL) cell apoptosis detection kit. The Western blotting was used to detect the expression of B-lymphoblastoma-2 (Bcl-2) gene related X protein (Bax), Bcl-2 promoter (Bad), and Bcl-2 protein in rat spinal cord tissue; immunofluorescence staining was used to observe the expression of Bax and Bcl-2 protein in spinal cord neurons.Results:After 12 weeks of fluoride exposure, rats in both the low fluoride and high fluoride groups developed varying degrees of dental fluorosis; the differences of BBB scores of rats in the control, low fluoride, and high fluoride groups were statistically significant ( F = 14.09, P < 0.001). The differences of SOD [(124.04 ± 4.87), (96.66 ± 15.01), (91.12 ± 15.87) U/mg prot] and GSH-Px activitives [(561.92 ± 59.65), (456.83 ± 29.51), (385.07 ± 74.87) U/mg prot], MDA [(9.96 ± 1.50), (16.64 ± 2.05), (20.80 ± 3.37) nmol/mg prot] and CAT contents [(8.97 ± 1.05), (6.39 ± 0.97), (6.42 ± 0.83) nmol/mg prot] among the control, low fluoride, and high fluoride groups were statistically significant ( F = 11.17, 14.19, 30.12, 14.52, P < 0.05). Among them, the SOD, GSH-Px activities, and CAT content in the low fluoride and high fluoride groups were lower than those in the control group, while the MDA content was higher than that in the control group ( P < 0.05). The GSH-Px activity in the high fluoride group was lower than that in the low fluoride group, and MDA content was higher than that in the low fluoride group ( P < 0.05). The intact neuronal structures and clear visible nuclei were seen, and Nissl bodies were uniformly stained in the spinal cord neurons of the control group rats, with more numbers, and no apoptotic cells were observed; the staining of Nissl bodies in the spinal cord neurons of rats was uneven in the low fluoride and high fluoride groups, with fewer numbers, and more apoptotic cells. There were statistically significant differences in the apoptosis rate of spinal cord nerve cells and the expression levels of Bax, Bad, and Bcl-2 protein in the spinal cord tissues of rats in the control, low fluoride, and high fluoride groups ( F = 272.81, 35.53, 17.57, 92.50, P < 0.05). The results of immunofluorescence staining showed that there were statistically significant differences in the fluorescent intensity of Bax and Bcl-2 proteins in the spinal cord neurons of rats in the control, low fluoride, and high fluoride groups ( F = 12.67, 22.14, P < 0.05). Conclusion:Chronic fluorosis induces a decrease in antioxidant enzyme activity, an increase in lipid peroxidation levels, and an increase in neuronal apoptosis in the spinal cord of rats.

Research progress on the effect of fluoride on bone marrow mesenchymal stem cells / 中华地方病学杂志

Fluorine is an important element widely present in nature, and moderate intake can prevent dental caries and promote bone development. However, long-term excessive intake can lead to fluorosis, damaging tissues or organs such as teeth, bones, heart muscle, and blood vessels. Bone marrow mesenchymal stem cells (BMSCs) play an important role in the repair process of bone injury due to their excellent multi-directional differentiation potential. Therefore, studying BMSCs is of great value in the treatment of fluorosis caused by fluoride poisoning. This article summarize the progress on the effect of fluoride on BMSCs, providing new ideas for the study of the pathogenesis and clinical treatment of fluorosis.

Application of double mediastinal drainage tubes in elderly patients with intrathoracic anastomotic leak after thoracoscopic Ivor-Lewis surgery / 中华老年医学杂志

Objective:To investigate the clinical significance of intraoperative prepositioning of dual mediastinal drains in elderly patients developing anastomotic leakage(AL)after a total endoscopic Ivor-Lewis procedure.Methods:This retrospective case-control study analyzed the clinical data of 500 elderly patients who underwent total endoscopic Ivor-Lewis surgery for esophageal or cardia cancer from January 2020 to December 2022.In the control group, one mediastinal drainage tube was placed intraoperatively, while in the study group, two mediastinal drainage tubes were placed.Both groups had a chest tube placed conventionally.The study compared the incidence of anastomotic leak(AL)at 1 month postoperatively, inflammatory indexes in patients with AL, grading of AL, rate of nasal fistula placement, incision infection, anastomotic stenosis, and incidence of hoarseness.Additionally, it compared ICU occupancy, ventilator use, and ICU length of stay between the two groups.Results:The analysis included clinical data from 455 elderly patients.Among the patients who developed AL, the study group had significantly lower peak body temperature[(39.58±1.03)℃ vs.(38.05±0.56)℃, t=4.298, P<0.05], white blood cell count[(18.63±3.35)×10 9/L vs.(14.28±2.78)×10 9/L, t=3.450, P<0.05], and C-reactive protein(CRP)levels[(154.66±41.64)mg/L vs.(122.19±31.29)mg/L, t=2.131, P<0.05]. The study group also had a significantly lower grading of AL and rate of nasal fistula placement(82.4% vs.30.0%, P<0.05). In terms of ICU indicators, the study group had a significantly lower ICU admission rate(64.7% vs.10.0%, P<0.05), shorter period of ventilator use[(6.47±8.15)days vs.(0.90±2.23)days, t=2.62, P<0.05], and shorter ICU stay[(11.70±8.89)days vs.(4.70±6.27)days, t=2.184, P<0.05]. Conclusions:Double mediastinal drainage tubes, have been found to significantly alleviate inflammation, decrease the rate of nasal fistula placement and ICU admission, and shorten the length of ICU stay in elderly patients.Therefore, they are considered safe and deserving of clinical promotion.

Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine：Fibromyalgia Syndrome / 中国实验方剂学杂志

Fibromyalgia syndrome （FMS） is a refractory， chronic non-articular rheumatic disease characterized by widespread pain throughout the body， for which there are no satisfactory therapeutic drugs or options. There are rich Chinese medical therapies， and some non-drug therapies， such as acupuncture， Tai Chi， and Ba-Duan-Jin， have shown satisfactory efficacy and safety and definite advantages of simultaneously adjusting mind and body. FMS is taken as a disease responding specifically to traditional Chinese medicine （TCM） by the National Administration of Traditional Chinese Medicine in 2018. In order to clarify the research progress in FMS and the clinical advantages of TCM/integrated Chinese and Western medicine， the China Academy of Chinese Medicine organized a seminar for nearly 20 experts in Chinese and Western medicine， including rheumatology， psychology， acupuncture and moxibustion， and encephalopathy， with the topic of difficulties in clinical diagnosis and treatment of FMS and advantages of TCM and Western medicine. The recommendations were reached on the difficulties in early diagnosis and solutions of FMS， mitigation of common non-specific symptoms， preferential analgesic therapy， TCM pathogenesis and treatment advantages， and direction of treatment with integrated Chinese and Western medicine. FMS is currently facing the triple dilemma of low early correct diagnosis， poor patient participation， and unsatisfactory benefit from pure Western medicine treatment. To solve the above problems， this paper suggests that rheumatologists should serve as the main diagnostic force of this disease， and they should improve patient participation in treatment decision-making， implement exercise therapy， and fully utilize the holistic and multidimensional features of TCM， which is effective in alleviating pain， improving mood， and decreasing adverse events. In addition， it is suggested that FMS treatment should rely on both TCM and Western medicine and adopt multidisciplinary joint treatment， which is expected to improve the standard of diagnosis and treatment of FMS in China.

Specific DNA barcodes screening, germplasm resource identification, and genetic diversity analysis of Platycodon grandiflorum / 药学学报

Platycodonis Radix is the dry root of Platycodon grandiflorum of Campanulaceae, which has a variety of pharmacological effects and is a commonly used bulk Chinese medicine. In this study, the chloroplast genome sequences of six P. grandiflorum from different producing areas has been sequenced with Illumina HiSeq X Ten platform. The specific DNA barcodes were screened, and the germplasm resources and genetic diversity were analyzed according to the specific barcodes. The total length of the chloroplast genome of 6 P. grandiflorum samples was 172 260-172 275 bp, and all chloroplast genomes showed a typical circular tetrad structure and encoded 141 genes. The comparative genomics analysis and results of amplification efficiency demonstrated that trnG-UCC and ndhG_ndhF were the potential specific DNA barcodes for identification the germplasm resources of P. grandiflorum. A total of 305 P. grandiflorum samples were collected from 15 production areas in 9 provinces, for which the fragments of trnG-UCC and ndhG_ndhF were amplificated and the sequences were analyzed. The results showed that trnG-UCC and ndhG_ndhF have 5 and 11 mutation sites, respectively, and 5 and 7 haplotypes were identified, respectively. The combined analysis of the two sequences formed 13 haplotypes (named Hap1-Hap13), and Hap4 is the main genotype, followed by Hap1. The unique haplotypes possessed by the three producing areas can be used as DNA molecular tags in this area to distinguish from the germplasm resources of P. grandiflorum from other areas. The haplotype diversity, nucleotide diversity and genetic distance were 0.94, 4.79×10-3 and 0.000 0-0.020 3, respectively, suggesting that the genetic diversity was abundant and intraspecific kinship was relatively close. This study laid a foundation for the identification of P. grandiflorum, the protection and utilization of germplasm resources, and molecular breeding.

Study on the Teaching Path of Medical Ethics in Medical Colleges and Universities in Ethnic Areas by Integrating the Consciousness of the Chinese National Community / 中国医学伦理学

From an ethical point of view, the ethical characteristics of the consciousness of the Chinese national community contain an ethical starting point based on "love"; ethical path with "people first" as the core; ethical vision for the purpose of "prosperity". The consciousness of the Chinese national community greatly conforms to the teaching objectives and teaching content of medical ethics. Therefore, medical ethics teaching from the perspective of the Chinese national community should implement the fundamental task of helping students develop good morals and enhance the moral quality of "love"; take the "community of doctor-patient destiny" as the starting point of education and build the concept of "people first"; strengthen the country’s sense of responsibility of "prosperity and strength" and establish the mission of "rooting and maintaining health at the grassroots level", build a strong consciousness of the Chinese national community.

Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine： Threatened Abortion / 中国实验方剂学杂志

Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology， Western medicine obstetrics and gynecology， and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion， the experts concluded that chromosome， endocrine， and immune abnormalities were the key factors for the occurrence of threatened abortion， and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion， TCM has advantages in preventing miscarriages， alleviating clinical symptoms and TCM syndromes， relieving anxiety， regulating reproductive endocrine and immune abnormalities， personalized and diversified treatment， enhancing efficiency and reducing toxicity， and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.

Explore the mechanism of Huangqi Jiedu decoction in the treatment of breast cancer syndrome of Zheng-deficiency and toxic-incandescence based on network pharmacology and molecular docking technology / 中国医师杂志

Objective:To explore the mechanism of Huangqi Jiedu Decoction (HQJD) in the treatment of breast cancer with the syndrome of Zheng deficiency and toxic incandescence by network pharmacology and molecular docking technology.Methods:The main active ingredients and targets of HQJD were screened through the traditional Chinese medicine (TCM) systematic pharmacology database and analysis platform. The relevant targets of breast cancer with the syndrome of Zheng-deficiency, toxic-incandescence were obtained using OMIM, GeneGards and Drugbank databases, and the relevant targets of HQJD for the treatment of breast cancer with the syndrome of Zheng-deficiency and toxic incandescence were obtained by intersection; The Cytoscape 3.9.1 software was used to build the protein protein interaction (PPI) network and the " drug active component target disease" network on the basis of String 11.0 database, and the core active components and core targets of HQJD in treating breast cancer with the syndrome of Zheng-deficiency and toxic-incandescence were inferred according to the topological parameters. gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on core targets using R language; and molecular docking verification on the main active ingredients and core targets were conducted.Results:230 effective targets of active ingredients of HQJD were screened, and 15 467 active ingredients of breast cancer with syndrome of Zheng-deficiency/toxic-incandescence were obtained; 217 intersection targets; GO function enrichment analysis showed that the treatment of HQJD for breast cancer with the syndrome of Zheng-deficiency and toxic-incandescence mainly involved oxidative stress and cytochemical stress; The enrichment analysis of KEGG pathway showed that HQJD treatment of breast cancer with the syndrome of Zheng-deficiency and toxic-incandescence was mainly related to phosphatidylinositol 3-protein kinase B (PI3K-Akt), interleukin-17 (IL-17) and other signal pathways. The molecular docking results showed that the main active ingredients such as β-sitosterol, stigmasterol, luteolin had good binding ability with core targets.Conclusions:HQJD has the characteristics of multi-component, multi target and multi pathway in the treatment of breast cancer with syndrome of Zheng-deficiency and toxic-incandescence, and its main mechanism may be related to PI3K-Akt, IL-17, P53 and other signal pathways.

Screening of specific DNA barcode, identification of germplasm resources, and analysis of genetic diversity of Atractylodes chinenesis / 药学学报

italic>Atractylodes chinensis has important medicinal and economic values. In this study, the chloroplast genome sequences of four A. chinensis samples from different producing areas were sequenced using the Illumina platform. The specific DNA barcodes were screened and the germplasm resources of A. chinensis samples from different producing areas and the genetic diversity of the population were analyzed basing on the specific barcodes. The whole chloroplast genomes of the four A. chinensis samples had a typical cyclic tetrad structure, with 112 genes annotated. The comparative genomics results indicated that ccsA and trnC-GCA_petN were potential specific DNA barcodes for intraspecific identification of A. chinensis. Polymerase chain reaction (PCR) analysis of ccsA and trnC-GCA_petN was performed on 256 samples from 14 areas in 9 provinces, and the amplification efficiency was 100%. Sequence analysis showed that ccsA and trnC-GCA_petN had 11 and 22 variant positions, which could identify 16 and 22 haplotypes, respectively. The combined sequence analysis identified 39 haplotypes, named Hap1-Hap39, of which the most abundant and widely distributed genotype was Hap9. Haplotype diversity (Hd) = 0.896 and nucleotide diversity (Pi) = 0.002 22 indicated high genetic diversity at the species level in A. chinensis. The genetic distances of the haplotypes were 0.000 00-0.004 88, indicating that there were small genetic differences among the haplotypes. The results of phylogenetic tree analysis showed that 39 haplotypes had very close genetic relationship, and formed two obvious branches with other groups of the same genus except Atractylodes macrocephala. This study plays an important role in the identification of the origin of A. chinensis and the protection and breeding of germplasm resources.

Mechanism of active ingredients in Periploca forrestii compound against rheumatoid arthritis based on integrative metabolomics and network pharmacology / 中国中药杂志

In this study, an ultra-performance liquid chromatography-quadrupole time-of-flight high resolution mass spectrometer(UPLC-Q-TOF-HRMS) was used to investigate the effects of the active ingredients in Periploca forrestii compound on spleen metabolism in rats with collagen-induced arthritis(CIA), and its potential anti-inflammatory mechanism was analyzed by network pharmacology. After the model of CIA was successfully established, the spleen tissues of rats were taken 28 days after administration. UPLC-Q-TOF-HRMS chromatograms were collected and analyzed by principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and MetPA. The results showed that as compared with the blank control group, 22 biomarkers in the spleen tissues such as inosine, citicoline, hypoxanthine, and taurine in the model group increased, while 9 biomarkers such as CDP-ethanolamine and phosphorylcholine decreased. As compared with the model group, 21 biomarkers such as inosine, citicoline, CDP-ethanolamine, and phosphorylcholine were reregulated by the active ingredients in P. forrestii. Seventeen metabolic pathways were significantly enriched, including purine metabolism, taurine and hypotaurine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism. Network pharmacology analysis found that purine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism played important roles in the pathological process of rheumatoid arthritis. This study suggests that active ingredients in P. forrestii compound can delay the occurrence and development of inflammatory reaction by improving the spleen metabolic disorder of rats with CIA. The P. forrestii compound has multi-target and multi-pathway anti-inflammatory mechanism. This study is expected to provide a new explanation for the mechanism of active ingredients in P. forrestii compound against rheumatoid arthritis.

Causal links between long-term exposure to NO2 and the risk of cardiovascular hospitalization / 中华流行病学杂志

Objective: To determine the causal association between long-term Nitrogen dioxide (NO2) exposure and the risk of cardiovascular hospitalization. Methods: Based on a sub-cohort of a community-based prospective cohort study, a total of 36 271 participants were recruited from 35 communities randomly selected in Guangzhou in 2015. The annual average exposure of NO2, demographic characteristics, lifestyle factors, and information on the causes of hospitalization was collected. We applied marginal structural Cox models to investigate the effect of NO2 on cardiovascular hospitalization. Demographic and behavioral factors also stratified results. Results: The mean age of participants in the present study was (50.9±17.8) years, and the cardiovascular admission rate was 8.7%, with 203 822 person-years of follow-up. The annual mean NO2 concentration was 48.7 μg/m3 during 2015-2020. For each 10 μg/m3 increase in NO2 concentrations, the HRs (95%CIs) of total cardiovascular hospitalization, cardiovascular hospitalization, and cerebrovascular hospitalization were 1.33 (1.16-1.52), 1.36 (1.16-1.60) and 1.25 (1.00-1.55), respectively. Participants who were never married/married, with secondary education, high exercise frequency, or non-smokers/current smokers may be more susceptible than their counterparts. Conclusion: Long-term exposure to NO2 significantly increased hospitalization risk for cardiovascular disease.

Clinical characteristics of severe pre-eclampsia in a single tertiary referral center of Xiamen City / 中华妇产科杂志

Objective: To explore the key points for preventing and reducing severe pre-eclampsia (SPE) and its severe complications in the tertiary medical referral system of a second-tier city by analyzing the clinical characteristics of SPE. Methods: The clinical data of 341 patients with SPE who terminated pregnancy in Women and Children's Hospital, School of Medicine, Xiamen University, from January 1, 2020 to December 31, 2022 were retrospectively analyzed, and the pre-eclampsia (PE) risk factors, clinical characteristics and severe complications of SPE between the patients referred from primary hospitals (referral group) and the patients received regular prenatal care in the tertiary referral center (central group) were compared, as well as the influence of the referral timing on the maternal and perinatal outcomes. Results: Among the 341 cases of SPE, 92 cases were in the referral group and 249 cases were in the central group. (1) Analysis of PE risk factors: there was no statistical difference in the proportion of risk factors of PE between these two groups [75.0% (69/92) vs 71.9% (179/249); χ2=0.328, P=0.567]. (2) Analysis of clinical features: the gestational ages at the PE early warning factors onset, at the PE first symptom onset and at SPE diagnosed, pregnancy terminated and onset of SPE severe complications in the referral group were significantly earlier than those in the central group (all P<0.05), the proportions of terminating pregnancy before 32 weeks of gestation, between 32 and 34 weeks of gestation, intensive care unit (ICU), neonatal ICU hospitalization and fetal growth restriction in single pregnancies were higher than those in the central group, while the live birth rate was lower than that in the central group (all P<0.05). (3) Analysis of SPE severe complications: the rates of SPE severe complications in the referral group was higher than that in the central group [28.3% (26/92) vs 13.7% (34/249); χ2=9.885, P=0.002]. Among them, the rates of placental abruption [7.6% (7/92) vs 2.8% (7/249); χ2=3.927, P=0.048] and still birth [6.5% (6/92) vs 0.4% (1/249); χ2=9.656, P=0.002] in the referral group were significantly higher than those in the central group. (4) Analysis of referral timings: the timings included referral after onset of SPE severe complications (9.8%, 9/92), referral after SPE diagnosed (63.0%, 58/92), referral after detection of SPE early warning signs (20.7%, 19/92) and referral after detection of PE risk factors (6.5%, 6/92). The gestational ages at SPE diagnosed and pregnancy terminated in group of referral after onset of SPE severe complications and group of referral after SPE diagnosed were significantly earlier than those in group of referral after detection of PE early warning signs and group of referral after detection of PE risk factors (P<0.05). The earlier the referral, the higher the live birth rates (P<0.05). Conclusions: The tertiary referral center of the second-tier city plays an important role in reducing the maternal and perinatal damage of PE. The timing of referral in primary medical institutions is the key point of reducing the occurrence of SPE severe complications and maternal, perinatal damage of PE. It is necessary for medical institutions of all levels in all regions to improve the ability of early identification and early intervention for PE, to enhance the awareness of SPE and its severe complications prevention and control. Primary medical institutions should especially pay attention to raise the consciousness of PE risk factors and early warning signs, and to improve the ability of PE risk factors and early warning signs screening.

Ginsenoside Rg_3 based liposomes target delivery of dihydroartemisinin and paclitaxel for treatment of triple-negative breast cancer / 中国中药杂志

Ginsenoside Rg_3, an active component of traditional Chinese medicine(TCM), was used as the substitute for cholesterol as the membrane material to prepare the ginsenoside Rg_3-based liposomes loaded with dihydroartemisinin and paclitaxel. The effect of the prepared drug-loading liposomes on triple-negative breast cancer in vitro was evaluated. Liposomes were prepared with the thin film hydration method, and the preparation process was optimized by single factor experiments. The physicochemical properties(e.g., particle size, Zeta potential, and stability) of the liposomes were characterized. The release behaviors of drugs in different media(pH 5.0 and pH 7.4) were evaluated. The antitumor activities of the liposomes were determined by CCK-8 on MDA-MB-231 and 4T1 cells. The cell scratch test was carried out to evaluate the effect of the liposomes on the migration of MDA-MB-231 and 4T1 cells. Further, the targeting ability of liposomes and the mechanism of lysosome escape were investigated. Finally, H9c2 cells were used to evaluate the potential cardiotoxicity of the preparation. The liposomes prepared were spheroid, with uniform particle size distribution, the ave-rage particle size of(107.81±0.01) nm, and the Zeta potential of(2.78±0.66) mV. The encapsulation efficiency of dihydroartemisinin and paclitaxel was 57.76%±1.38% and 99.66%±0.07%, respectively, and the total drug loading was 4.46%±0.71%. The accumulated release of dihydroartemisinin and paclitaxel from the liposomes at pH 5.0 was better than that at pH 7.4, and the liposomes could be stored at low temperature for seven days with good stability. Twenty-four hours after administration, the inhibition rates of the ginsenoside Rg_3-based liposomes loaded with dihydroartemisinin(70 μmol·L~(-1)) and paclitaxel on MDA-MB-231 and 4T1 cells were higher than those of the positive control(adriamycin) and free drugs(P<0.01). Compared with free drugs, liposomes inhibited the migration of MDA-MB-231 and 4T1 cells(P<0.05). Liposomes demonstrated active targeting and lysosome escape. In particular, liposomes showed lower toxicity to H9c2 cells than free drugs(P<0.05), which indicated that the preparation had the potential to reduce cardiotoxicity. The findings prove that ginsenoside Rg_3 characterized by the combination of drug and excipient is an ideal substitute for lipids in liposomes and promoted the development of innovative TCM drugs for treating cancer.

Reference values and growth curves of length for weight and head circumference for weight among Chinese newborns / 中华儿科杂志

Objective: To establish the reference values and growth curves of length for weight and head circumference for weight among Chinese newborns in order to provide a reference for the assessment of body proportionality at birth. Methods: A cross-sectional design was applied. A total of 24 375 singleton live birth newborns with gestational ages at birth of 24+0 to 42+6 weeks were recruited from June 2015 to November 2018 from 13 cities including Beijing, Harbin, Xi'an, Shanghai, Nanjing, Wuhan, Guangzhou, Fuzhou, Kunming, Tianjin, Shenyang, Changsha, and Shenzhen, excluding those with maternal or newborn conditions that may impact the establishment of the reference values. The generalized additive model for location, scale, and shape was employed to establish reference values in terms of percentile and growth curves of length for weight and head circumference for weight for male and female newborns. The random forest machine learning method was employed to analyze the importance of variables between the established reference values in this study and the previous published weight/length, body mass index (BMI), ponderal index (PI), weight/head circumference, length/head circumference in the assessment of symmetrical and asymmetrical small for gestational age (SGA) newborns. Results: A total of 24 375 newborns with 13 197 male infants (preterm birth 7 042 infants and term birth 6 155 infants) and 11 178 female infants (preterm birth 5 222 infants and term birth 5 956 infants) were included in this study. The reference values in terms of percentile (P3, P10, P25, P50, P75, P90, P97) and growth curves of length for weight and head circumference for weight were obtained for male and female newborns with gestational ages of 24+0 to 42+6 weeks. The median birth lengths corresponding to the birth weights of 1 500, 2 500, 3 000, and 4 000 g were 40.4, 47.0, 49.3 and 52.1 cm for males and 40.4, 47.0, 49.2, and 51.8 cm for females, respectively; the median birth head circumferences were 28.4, 32.0, 33.2 and 35.2 cm for males and 28.4, 32.0, 33.1, and 35.1 cm for females, respectively. The differences of length for weight between males and females were minimum, with the difference range of -0.3 to 0.3 cm at P50; the differences of head circumference for weight between males and females were minimum, with the difference range of 0 to 0.2 cm at P50. Based on the match between birth length and birth weight for classifying symmetrical and asymmetrical SGA, length for weight and PI contributed the most, accounting for 0.32 and 0.25, respectively; based on the match between birth head circumference and birth weight, head circumference for weight and weight/head circumference contributed the most, accounting for 0.55 and 0.12, respectively; based on the match between birth length or head circumference with birth weight, head circumference for weight and length for weight contributed the most, accounting for 0.26 and 0.21, respectively. Conclusion: The establishment of the new standardized growth reference values and growth curves of length for weight and head circumference for weight among Chinese newborns are useful for clinical practice and scientific research.

Neonatal Glanzmann thrombasthenia: a case report and literature review / 中国新生儿科杂志

Objective:To study the clinical features and genotypes of neonatal Glanzmann thrombasthenia(NGT).Methods:A male neonate with NGT admitted to the Department of Neonatology of our hospital was retrospectively reviewed. CNKI, Wangfang database, VIP, the Chinese Medical Journal Full Text database, PubMed and Embase database were searched using key words '(neonate OR newborn) AND (Glanzmann thrombasthenia)' both in English and Chinese. The clinical features and genotypes of NGT were summarized and analyzed.Results:A male full-term neonate was admitted to our hospital for mass on the forehead and ecchymosis and petechiae on the body within half an hour after birth. He gradually developed subgaleal hemorrhage and severe anemia. Platelet count, mean platelet volume and coagulation functions were normal. The platelet aggregation test indicated decreased platelet aggregation rate induced by arachidonic acid and adenosine diphosphate. Genetic testing revealed two heterozygous mutations in the patient's ITGA2B gene: NM_000419.4: c.886G>A(p.Gly296Arg) and NM_000419.4: c.2855dup(p.Phe953Valfs*83). A total of 42 literature involving 44 patients (our case included) with NGT were retrieved. 33 cases (75.0%) of NGT showed ecchymosis or petechiae on the first day after birth. For 13 cases with detailed information, 5 cases with severe anemia were given erythrocyte and plasma transfusion and platelet transfusion was given in 1 case. 4 cases had homozygous variants and 4 cases showed compound heterozygous variants. 10 cases had follow-up records, including 2 cases without any bleeding and 8 cases with varying degrees of bleeding during follow-up. No deaths were reported.Conclusions:Neonates with ecchymosis and petechiae in the early postnatal period should be suspected of NGT. Blood transfusion is preferred when the indication for transfusion is met.

Study on the application effects of the mode of "Multidisciplinary integration, Doctors & patients co-teaching, Simulated practice" in the teaching of spinal surgery / 中华医学教育探索杂志

Objective:To explore the application effects of the mode of "Multidisciplinary integration, Doctors & patients co-teaching, Simulated practice" in the teaching of spinal surgery.Methods:A total of 64 eight-year program clinical medical students who practiced in Peking Union Medical College Hospital in 2021 were taken as research objects and randomly divided into experimental group ( n=33) and control group ( n=31). The experimental group received the new teaching mode of "Multidisciplinary integration, Doctors & patients co-teaching, Simulated practice", and the control group received regular teaching mode. At the end of teaching, the teaching effects were evaluated from several aspects, including the scores of theoretical examinations, anatomical marks identification tests, and anonymous questionnaires. SPSS 22.0 software was used for paired t-test and two independent-samples t-test. Results:The theoretical test scores [(51.25±6.99) points] and anatomical structure identification scores [(37.56±1.83) points] of the experimental group were higher than those of the control group [(42.46±6.13) points and (30.37±3.46) points], and the differences were statistically significant ( P<0.001). The effective recovery rate of the questionnaire was 100%. The results of the questionnaire showed that the experimental group was significantly higher than the control group in terms of teaching attractiveness, attention, learning interest, learning efficiency, anatomical identification ability, problem-finding and problem-solving ability and overall teaching method satisfaction ( P<0.05). Conclusion:The teaching mode of "Multidisciplinary integration, Doctors & patients co-teaching, Simulated practice" can effectively improve students' theoretical knowledge, learning interest, learning efficiency, operation proficiency and problem-finding and problem-solving ability, which is worth promoting.

Clinical characteristics and prognosis of bacterial liver abscess in patients with diabetes mellitus / 中华传染病杂志

Objective:To compare the clinical characteristics and prognosis of bacterial liver abscess in patients with or without diabetes mellitus (DM), to provide a reference for clinical diagnosis and treatment.Methods:Patients with bacterial liver abscesses hospitalized in Tongren Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to August 2021 were enrolled, and their clinical data were collected. The patients were divided into diabetic and non-diabetic groups for comparison according to whether they had comorbid DM. Statistical analysis was performed by chi-square test or Fisher′s exact test, and multivariate logistic regression analysis.Results:A total of 131 patients with bacterial liver abscesses were included, including 47 cases in the diabetic group and 84 cases in the non-diabetic group. The percentages of platelet count <100×10 9/L, C-reactive protein>10 mg/L, and total bilirubin>17.5 μmol/L were lower in the diabetic group than that in the non-diabetic group, and the differences were all statistically significant ( χ2=3.90, 6.44 and 5.56, respectively, all P<0.05). The percentage of multiple abscesses in the diabetic group was 10.6%(5/47), which was lower than 29.8%(25/84) in the non-diabetic group, and the difference was statistically significant ( χ2=6.24, P=0.012). The positive rate of pus culture for Klebsiella pneumoniae was 64.9%(24/37) in the diabetic group, which was higher than 41.5%(27/65) in the non-diabetic group, with a statistically significant difference ( χ2=5.13, P=0.023). The incidences of pleural effusion and abscesses at other sites in the diabetic group were 29.8%(14/47) and 10.6%(5/47), respectively, which were both higher than 14.3%(12/84) and 1.2%(1/84) in the non-diabetic group, respectively, and the differences were statistically significant ( χ2=4.55, Fisher′s exact test, both P<0.05). The proportion of hospital stays>21 d was 34.0%(16/47) in the diabetic group, which was higher than 16.7%(14/84) in the non-diabetic group, with a statistically significant difference ( χ2=5.15, P=0.023). DM (odds ratio ( OR)=2.654, 95% confidence interval ( CI) 1.020 to 6.907, P=0.046) and abscess maximum diameter>10 cm ( OR=11.045, 95% CI 4.493 to 27.154, P<0.001) were significant risk factors for hospital stay>21 d. Conclusions:Bacterial liver abscesses combined with DM are more common with single abscess, a higher rate of Klebsiella pneumoniae infection, and more likely to develop pleural effusions and abscesses at other sites. Liver abscesses>10 cm in maximum diameter and comorbid DM would prolong hospital stay.