AIM: To investigate the effect and the mechanism of apolipoprotein (a) [apo (a) ] on proliferation of vascular smooth muscle cells ( VSMCs). METHODS: All VSMCs used in experiments were serial subcultured from primary cells and were identified by immunohistochemistry staining of a - actin. Cell growth assay was observed as cell counting and MTT assay. Western blotting was also employed to detect the related mechanism. RESULTS: All cells used in experiments were confirmed as VSMCs. Although apo (a) enhanced VSMCs proliferation, this effect was attenuated by anti -integrin α_vβ_3, LM609.Use these reagents alone had no effect on VSMCs growth. The results of Western blotting demonstrated that focal adhesion kinase (FAK) was activated by apo (a) and the expression of total or phosphorylated transforming growth factor β_1 (TGF -β_1) was also decreased. However, these effects described above were all blocked by LM609.CONCLUSION: Apolipoprotein (a) enhances VSMCs proliferation and this effect is mediated by integrin α_vβ_3, which activates FAK and attenuates TGF - β_1 and phospho -TGF - β_1 expression.

Objective To investigate the association between plasma lipoprotein (a) [LP (a)] concentra-tion and in-stent restenosis after coronary stent implantation. Methods 152 patients with successful elective coro-nary stont implantation and percutancous transluminal coronary angioplasty (PICA) undergoing foUow-up angiogra-phy were retrospectively analyzed. These patients were divided into restenosis group( n = 29) and no-restenosis group (n = 123 ). The serum LP (a) levels of all patients were also investigated. The general clinical data were analyzed. Multivariate logistic regression was used for statistical analysis. Results We compared the serum Lap (a) levels, smoking and diabet in the two groups, and there was a statisticaLly significant difference between the restenosis group and no-restenosis group(P<0.05). Multivariate logistic regression showed that the elevation of Lap (a) level re-mained as an independent predictor of restenosis (RR =2. 648,95% CI 1. 066-6. 575,P <0. 05). Other risk fac-tors,such as smoking(P =0.023) ,diabet(P =0. 036) and the type of stent(P = 0.011 ) were also correlated with restenosis. Conclusions High plasma LP (a) concentration is an independent predictor of stent restenosis after stent implantation.

Objective To investigate the molecular genetic characteristics and clinical characteristics of severe combined immunodeficiency(SCID)in children caused by a novel mutation of interleukin 2 receptor gamma IL-2RG gene.Methods The clinical data,laboratory results and genetic testing data of a child with SCID admitted to the Department of Children's Hematology of Northwest Women and Children's Hospital were analyzed.Results A two-month-old male infant was admitted to the hospital for treatment due to recurrent infections after birth.The child's blood routine results showed that the total number of white blood cells was normal,but lymphocytes were decreased.The lymphocyte subpopulation results showed a significant decrease in the proportion of total T(CD3+),helper T(CD3+CD4+),killer T(CD3+CD8+),and NK(CD3-CD16+CD56+)lymphocytes,while the proportion of B(CD3-CD19+)lymphocytes were increased.The immunoglobulin levels showed a significant decrease in IgG,and IgM and IgA were below the lower detection limit.The patient's cytokine levels did not significantly increase during infection.In the last three generations of the mother's family,9 males died of infection within one year after birth.The whole exome sequencing results of the core family revealed a semi zygous new missense mutation[c.675 C＞A,p.S225R(p.Ser225Arg)]in the IL-2RG gene on the X chromosome(chrX:70329160)of the patient,and the mother was a carrier.Based on the above evidence,the child was diagnosed with X-SCID.Subsequently,intravenous immunoglobulin was injected monthly,and routine antibiotics and antiviral drugs were taken to prevent infection,preparing for hematopoietic stem cell transplantation.Because the child was vaccinated with BCG after birth,the child developed disseminated BCG disease at the age of 6 months.After treatment,hematopoietic stem cell transplantation was performed.Conclusion The immune function of the X-SCID patient was severely compromised,which endangered the patient's life,and vaccination with live vaccines may lead to severe infections.This study found that the c.675 C＞A mutation of the IL-2RG gene was a novel pathogenic variation of the genetic cause of X-SCID,expanding the mutation spectrum of the X-SCID pathogenic gene IL-2RG.

Objective To observe the clinical efficacy of Tongfengke Granules combined with external treatment of TCM in acute gouty arthritis(AGA)with damp-heat accumulation type.Methods A total of 96 patients with AGA were divided into the experimental group and the control group according to random number table method,with 48 patients in each group.The control group received meloxicam treatment.On this basis,the experimental group was treated with Tongfengke Granules(1 bag at a time,three times a day,orally)combined with external therapy of TCM(once a day),and mobile continuing care.The treatment for both groups lasted for 2 weeks.The clinical efficacy of both groups was observed.Before and after the treatment,pain visual analogue scale(VAS),TCM syndrome scores,major symptom scores,and levels of serum uric acid(UA),interleukin-6(IL-6),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),platelet/lymphocyte ratio(PLR),as well as engagement in self-care ability scale(ESCA),general self-efficacy scale(GSES),negative psychological condition[self-rating depression scale(SDS),self-rating anxiety scale(SAS)]were measured.The adverse reactions in both groups were monitored.Results Totally 45 and 47 patients in the experimental group and control group were finally included respectively in the analysis.The total effective rate of the experimental group was 75.6%(34/45),while that of the control group was 63.8%(30/47),with statistical significance(P<0.05).Compared with before treatment,the VAS score and TCM syndrome score in the experimental group decreased significantly(P<0.05);after treatment,the VAS score and TCM syndrome score of the experimental group were lower than those of the control group(P<0.05).Compared with before treatment,the joint pain,joint tenderness,joint swelling,and joint mobility limitation scores in both groups were significantly decreased after treatment(P<0.05,P<0.01);after treatment,the scores of joint pain,joint tenderness,and joint swelling in the experimental group were lower than those in the control group(P<0.01).Compared with before treatment,the levels of UA,ESR,CRP and PLR in both groups decreased significantly after treatment(P<0.01);after treatment,the levels of UA,ESR,CRP and PLR in the experimental group were lower than those in the control group(P<0.05,P<0.01).Compared with before treatment,the experimental group showed significant improvement in ESCA,GSES and SAS after treatment(P<0.05,P<0.01),while the control group showed significant improvement in ESCA(P<0.01);after treatment,the ESCA and GSES of the experimental group were better than those of the control group(P<0.05,P<0.01).There was no statistical significance in safety indicators and incidence of adverse reactions between the two groups(P>0.05).Conclusion Tongfengke Granules combined with external treatment of TCM can significantly improve the clinical efficacy of AGA,reduces UA levels,significantly improves inflammatory response,and has anti-inflammatory,anti-inflammatory,and analgesic effects.

Objective To systematically review the present status of oral Chinese patent medicines(CPMs)for treating functional dyspepsia(FD),explore the formation rules of CPMs,and reveal the potential problems by referring to the methods and procedures of Scoping review.Methods First,we screened all CPMs from the domestic-related drug catalogs which are generally accepted and own the force of law,then we sorted the CPMs based on the drug instructions while carrying out Chinese and English database document retrieval to review the clinical studies.Descriptive analysis of the basic feature and clinical research evidence of CPMs was performed combined with visual charts.Results This study included 42 CPMs for treating FD.Among the formulas of CPMs,Tangerine peel,Radices saussureae,Poria cocos,Glycyrrhiza,Atractylodes macrocephala,and Six Divine Qu appeared frequently.In addition,96 studies involving 21 CPMs were included,among which Zhizhu Kuanzhong Capsule,Liuwei Anxiao capsule,and Dalitong granules had more clinical literature.By analyzing the included 96 clinical studies,we found that the combination of Chinese and Western medicine was the main intervention,and the effective rate,clinical symptom score,and adverse reactions were the main outcomes that were concerned.In addition,8 studies had off-label use of diseases,involving the Wuling capsule to treat the FD whether the disease was accompanied by depression and anxiety symptoms or not,and Zhizhu Kuanzhong Capsule to treat the FD with anxiety and depression.Although the Wuling capsule and Zhizhu Kuanzhong capsule were off-label used in clinical practice,there was no beyond the scope of the guideline.Conclusion The qi-regulating drug,spleen-strengthening drug and digestant drugs are the usual Chinese medicines used for treating adult FD.In recent years,research on CPMs for treating adult FD has increased rapidly.But there is insufficient reflection of CPMs treatment characteristics,ambiguous differences from the primary and secondary outcomes,multiple composite outcomes,and not explicit information on FD or its symptoms in drug package insert,which needs to be improved in the future.

Objective To establish a stable rat model of non-obese polycystic ovary syndrome(PCOS)with clinical characteristics.Methods Dehydroepiandrosterone(DHEA)was used to establish a PCOS rat model by subcutaneous injection.Three-week-old female SD rats were divided into a normal group,6 mg/kg DHEA model group,and 60 mg/kg DHEA model group.The model groups were subcutaneously injected with the corresponding dose of DHEA daily,while the normal group was subcutaneously injected with glycerol daily for 21 consecutive days.The model was evaluated with ovarian histopathology as the gold standard to determine the optimal dosage of DHEA to induce a PCOS rat model.On this basis,the optimal DHEA modeling dose was selected,and stop and continue modeling groups were set up to observe the model for 28 days and evaluate its maintenance.The stop modeling group was no longer given DHEA,and the continued modeling group was subcutaneously injected with 60 mg/kg DHEA every 48 h.The evaluation indicators included body mass,estrous cycle,fasting blood glucose,serum insulin,histopathologic morphology of the ovaries,and serum sex hormone levels.Results(1)Compared with the normal group,the 6 mg/kg and 60 mg/kg DHEA model groups showed no significant difference in body mass,and their estrous cycles were irregular.There were more cystically dilated large follicles in the ovaries;fewer mature follicles;reduced layers of granulosa cells,which were arranged in a sparse and disorganized manner;and fewer lutea in the 6 mg/kg and 60 mg/kg DHEA model groups than the normal group.Furthermore,serum T and E2 levels were significantly higher in the 60 mg/kg DHEA model group(P＜0.05)than the normal group.(2)The stop modeling group(A2 group)resumed regular estrous cycles after 2 weeks,various growth follicles and corpora lutea were observed in the ovarian tissues,the number of cystic follicles was reduced,the number of granulosa cell layers increased,mature follicles were visible,oocyte morphology was locally intact,and the levels of E2 and AMH were reduced compared with the normal group(A1 group)(P＜0.05).(3)The continue model group(B2 group)was in the late stage of estrous cycle for a long period,and there were more large follicles with cystic dilatation,fewer mature follicles,fewer layers of granulosa cells with a sparse and disordered arrangement,and significantly fewer corpus lutea in the ovaries compared with the normal group(B1 group).The levels of serum LH,LH/FSH,and T were elevated(P＜0.05).Conclusions Subcutaneous injection of 60 mg/kg DHEA for 21 consecutive days can be used to successfully construct a non-obese PCOS rat model that possesses clinical characteristics.Subcutaneous injection of 60 mg/kg DHEA every 48 hours maintains the stability of the model.

ObjectiveTo establish the clinical comprehensive evaluation index system for Chinese patent medicine（CPM） based on Evidence and Value：Impact on DEcisionMaking（EVIDEM） framework， so as to promote the scientific， systematic and standardized implementation of clinical comprehensive evaluation of CPM. MethodThe clinical comprehensive evaluation index system was determined through literature review， semi-structured interview and Delphi method， and the weights of each index were clarified by analytic hierarchy process（AHP）. ResultThe recovery rates of both rounds of expert consultation were 100%， and the authority coefficient of experts was 0.90 and 0.905， respectively. Kendall's coordination coefficients（W） of the second- and third-level indicators in the first-round consultation were 0.320 and 0.283（P<0.001）， and in the second round were 0.411 and 0.351， respectively（P<0.001）. The finally constructed clinical comprehensive evaluation index system for CPM included 6 first-level indicators， 13 second-level indicators and 28 third-level indicators. Among the first-level indicators， the weights of effectiveness， safety， economy， innovation， suitability and accessibility were 37.34%， 32.68%， 11.85%， 5.87%， 5.79% and 6.47%， respectively. ConclusionThis study has constructed a universal clinical comprehensive evaluation index system for CPM， and the domain and criteria are introduced and interpreted in detail， which can provide reference and information for carrying out the clinical comprehensive evaluation of CPM， but it needs to be refined and improved in combination with the clinical practice of CPM for specialized diseases.

To understand the development status and provide the basis for the construction and development of health technology assessment （HTA） institutions/organizations in China， this paper systematically reviewed the status of international HTA institutions/organizations and the HTA institutions/organizations in western developed countries and some Asian countries. This study was based on the results of the second round of global survey on HTA conducted by the World Health Organization （WHO） in 2020/2021. The websites of WHO， International HTA Database （INAHTA）， international HTA institutions/organizations， and the HTA institutions/organizations in different countries were searched. After data extraction and classification， we summarized the status of 9 international HTA institutions/organizations （including Decide： Health Decision Hub， Health Technology Assessment International， HTAsiaLink， International Network of Agencies for Health Technology Assessment， European Network for Health Technology Assessment， Health Technology Assessment Network of the Americas， International Society for Pharmacoeconomics and Outcomes Research， Southern African Health Technology Assessment Society， International Information Network on New and Emerging Health Technologies）， 11 HTA institutions/organizations in western developed countries and Asian countries （including Canada， France， Germany， the United Kingdom， Australia， the United States， Japan， Malaysia， South Korea， Singapore， and Thailand）， and 6 HTA organizations/teams in China. The use of HTA varies greatly because of different medical and health systems among different countries， and thus the role of HTA in health decision-making varies among different countries. The international HTA institutions/organizations have greatly strengthened the communication between HTA institutions/organizations and the pharmaceutical industry and facilitated the promotion and practice of evidence-based health decision-making.

ObjectiveThis study performed a scoping review to comprehensively analyze and report the information on the instructions of Chinese patent medicines and clinical research evidence for the treatment of respiratory diseases in children. MethodChinese patent medicines against respiratory diseases in children were obtained by searching the three major drug catalogues. The Chinese and English databases were searched for relevant literature，followed by data statistics and visualized analysis. ResultAfter screening and analysis，52 Chinese patent medicines were included，involving nine dosage forms. The main drugs were Scutellariae Radix，Armeniacae Semen Amarum，Forsythiae Fructus，etc. The main functions included clearing heat and releasing exterior syndrome，and relieving cough and dissipating phlegm. The indications mainly included common cold with wind-heat syndrome and cough in children. Adverse drug reactions and contraindications were only specified in 19.23% （10/52） of Chinese patent medicines，and the rest only displayed "unclear". A total of 279 articles were included，including 277 articles from Chinese Core Periodicals and two articles from SCIE. In terms of research type，those articles included 253 randomized controlled trials （RCTs，with six dosage form/dose comparisons involved），11 retrospective analyses based on Hospital Information System （HIS） data，one case series，13 systematic reviews/Meta-analyses （with two network Meta-analyses involved），and one economic evaluation article. Among them，72.76% （203/279） of the articles were published in the Core Journals of Chinese Science and Technology. Only 33 Chinese patent medicines were involved，and Xiaoer Feire Kechuan Oral Liquid was the top 1 under investigation，accounting for 15.71% （44/280）. The indicated diseases were mainly infantile pneumonia，bronchitis，respiratory tract infection，cough，asthma，and other western medicine diseases. Xiaoer Chiqiao Qingre Granules and Xiaoer Dingchuan Oral Liquid were used off-label. The sample size was concentrated in 51-150 cases，accounting for 67.17% （178/265）. The interventions in the experimental group were mainly Chinese patent medicine + western medicine + basic treatment or Chinese patent medicine + western medicine. The main outcomes were the effective rate and the improvement of clinical symptoms. The adverse reactions were mainly gastrointestinal reactions，drug-induced skin symptoms，etc.，and two studies have shown that drug doses were associated with adverse reactions. ConclusionIn research years，the research on Chinese patent medicines in the treatment of respiratory diseases in children has advanced rapidly. However，there are still some problems that need to be resolved in the future，such as incomplete information on drug content in the instruction，concentrated drugs to be studied，limited indications，failure to highlight the characteristics of traditional Chinese medicine （TCM） syndromes，unstandardized research design，and an incomplete reflection of Chinese patent medicine.

ObjectiveTo systematically review the clinical experience of four sessions of Masters of Traditional Chinese Medicine and two sessions of National Famous Chinese Medicine Practitioners in treating ulcerative colitis （UC）. Data mining and analysis were conducted to clarify the diagnosis and treatment ideas and characteristics of prescription used by these famous doctors in treating UC. MethodsRelevant literature on the treatment of UC by renowned doctors was retrieved from the establishment of the database until March 31， 2023. The literature was collected from databases such as China National Knowledge Infrastructure （CNKI）， Wanfang Data Knowledge Service Platform， Chinese Science and Technology Periodicals Database， and China Biomedical Literature Database. The data mining techniques including frequency analysis， association rules， and cluster analysis were conducted using the Ancient and Modern Medical Case Cloud Platform V2.3.5. ResultsA total of 157 literatures were included in this study， including 115 clinical case data. The study found that UC can be categorized into 14 types of syndrome patterns for treatment， including large intestine dampness-heat syndrome （75，65.22%）， syndrome of dampness stagnancy due to spleen deficiency （23， 20.00%）， spleen-kidney yang deficiency syndrome （21， 18.26%）. The main affected organs were the spleen （85， 73.91%） and large intestine （75， 65.22%）， and they were closely related to liver （24， 20.87%） and the kidney （21， 18.26%）. The predominant pathogenic factors were dampness （83， 72.17%） ， heat （80， 69.57%） and qi deficiency （65， 56.52%）. The treatment involved 30 kinds of treatment methods， including heat-clearing and dampness-draining method （75， 65.22%）， pleen-tonifying and qi-boosting method （25，21.74%） and spleen-invigorating and dampness-transforming method （23， 20.00%）. The medication involved 187 ingredients， with the most commonly used being heat-clearing herbs （37， 19.79%） and tonifying herbs （27， 14.44%）. The tastes of the herbs were mostly sweet （85， 45.45%） ， bitter （80， 42.78%） ， and pungent （71， 37.97%）. The association rules revealed 16 high-frequency combinations mainly composed of Huanglian （黄连）， Baishao （白芍） and Gancao （甘草） along with Baizhu （白术）， Fuling （茯苓）， Muxiang （木香） and Danggui （当归）. ConclusionFamous doctors are skilled in diagnosing and treating UC based on the differentiation of the zang-fu organs and qi-blood. The key pathological mechanism is “spleen deficiency as the root， and large intestine damp-heat as the manifestation”. The core treatment approach is “heat-clearing， spleen-tonifying， and dampness-draining”， with the inclusion of “regulating qi and blood， and balancing cold and heat”.