Objective To observe the therapeutic effect of ultrasonic microbubble combined with bevacizumab (Avastin) on choroidal neovascularization induced by photocoagulation in rabbits.Methods CNV was induced by photocoagulation with argon laser in 30 rabbits (60 eyes).All of the rabbits underwent fundus fluorecein angiography (FFA) 21 days after photocoagulation;6-8 hours later,3 rabbits were randomly chosen to be executed to having the immunohistochemical examination.Twenty-one days after photocoagulation,27 rabbits were divided randomly into 3 groups:bevacizumb,ultrasonic microbubble+bevacizumb,and control group;each group has 9 rabbits (18 eyes).The rabbits in control group had no interference treatment;while the rats in bevacizumb and ultrasonic microbubble+bevacizumb group underwent injection with bevacizumb or ultrasonic microbubble+bevacizumb respectively.FFA was performed on all of the rabbits 7,14,and 28 days after photocoagulation to observe the inhibition of CNV;immunofluorecence and Western blot were used to detect the expression of VEGF in retina and choroid.Twenty-eight days is the time point to determine the therapeutic efficacy.The expression of VEGF and the results of FFA were the sdandards of the judgement of therapeutic efficacy.Results Proliferaion of CNV to the retinal inner layer and the obvious leakage of fluoresein in the photocoagulation area indicated that the model of CNV was set up successfully.Twenty-eight days after injection,obvious fluorescent leakage was found in the control group,and the average fluorescent leakage in bevacizumab group differed much from the control group(t=16.2952,P<0.05);while the difference between ultrasonic microbubble+bevacizumb group and bevacizumab group was also significant (t=4.7955,P<0.05).At the same time point,the expression of VEGF in bevacizumab group detected by immunofluorecent assay and Western blot differed much from the control group (t=7.0327,9.2596;P<0.05),and the difference of VEGF between ultrasonic microbubble+bevacizumb group and bevacizumab group was significant (t=2.9724,17.1937;P<0.05).this experiment show that ultrasound combined bevacizumab intravitreal injection of the therapeutic effect of CNV superior to other groups(P<0.01).Conclusion Ultrasound microbubble combined with bevacizumab injection may improve the therapeutic effect on CNV by inhibiting the expression of VEGF.

Objective To investigate the operative methods and merits of nasal reconstruction in terms of the aesthetics. Methods The noses of 12 patients were reconstructed with an expanded triangle-shaped forehead flap with unilateral supratrochlear artery, a skin expander was placed obliquely under galea aponeurotica of forehead. Liquid was injected with conventional expansion method. Using the skin and the scars on nasal dorsum and tip as lining, based on intercanthal distance and aesthetic standard, a triangle-shaped forehead myocutaneous flap was designed over the expanded forehead skin tissue and used for a nasal reconstruction. The triangle-shaped flap was trimmed to different layer and reshaped based on aesthetic subunit.Results In twelve post-operative patients with nasal defect, no flap necrosis was found and the appearance of reconstructed noses were almost normal and satisfactory after follow-up for 6 months to 2 years. Conclusion The modified forehead myocutaneous flap according to aesthetic standard is safe and ideal for major nasal reconstruction. Meticulous moulding of triangle-shaped flap, nose interior with good blood supply, and primary insertion of nose stretcher are the key to a satisfactory appearance.

Objective: To investigate the role of miR-19a/b in myocardial ischemia reperfusion injury (R/I) with its clinical significance. Methods: Our research included in 2 parts. Part 1: in H9c2 cells. miR-19a/b expression in H9c2 cells with 10 h hypoxia and 2 h re-oxygenation was detected by real-time PCR, miR-19a/b potential target gene was assessed by luciferase reporter activity assay. Part 2: in natural person. Control group,n=40 healthy subjects and AMI (acute myocardial infarction) group,n=40 relevant patients. Peripheral blood levels of miR-19a/b were detected as Part 1, cTnI were measured by chemiluminescence immune analysis and CK-MB were assessed by immune inhibition method. Results: Part 1: Compared with normal H9c2 cells, miR-19a/b expressions were increased 5.876 times and 2.761 times in H9c2 cells with 10 h hypoxia and 2 h re-oxygenation, bothP<0.01. With respectively transfected miR-19a/b mimic and inhibitor, miR-19a/b expression was up-regulated and down-regulated respectively. miR-19a/b and chromosome-10 deleted phosphatase, tensing homolog gene (PTEN) had the targeting effect. With up-regulated miR-19a/b expression, PTEN level was decreased and with down-regulated miR-19a/b expression, PTEN level was increased. Part 2: Compared with Control group, AMI group had elevated blood level of miR-19a/b,P<0.01. In AMI patients, miR-19a/b was increasing at 0-3 h of chest pain and reaching the peak at 6-12 h; CK-MB enzyme activity and cTnI content were elevating at 2-6 h of onset and reaching the peak at 24 h. Conclusion: miR-19a/b expression was up-regulated by myocardial ischemia reperfusion in H9c2 cells, PTEN was the potential target gene of miR-19a/b. Circulating miR-19a/b might be used as a new non-invasive biological marker for myocardial ischemia R/I diagnosis.

Though Runx2 and Osterix are both key transcription factors in the pathway of osteoblast differentiation, whether Runx2 positively regulates Osterix being unknown. It was showed that Runx2 induced the gene expression of Osterix both in the non-osteoblastic cell lines, either pluripotent or differentiated, and in the osteoblastic cell lines. At the same time, the results also indicated that Runx2 up-regulated the activity of the 3.2 kb human Osterix promoter. Further experiments identified a highly conserved and functional Runx2 binding site "AGTGGTT" within the promoter. Thus the results support the hypothesis that Runx2 is involved in the regulation of the Osterix gene expression. Moreover, the transient transfection and dual-luciferase assay showed Osterix up-regulated the activity of the 2.3 kb type Ⅰ collagen promoter in the non-osteoblastic cells, but Runx2 did not. This difference implies that Osterix, the down stream transcription factor of Runx2 during osteoblast differentiation, is needed to stimulate the osteoblast-specific gene expression of type Ⅰ collagen.

In the context of the new era, paying attention to maternal and child health and advocating prenatal and postnatal care can effectively improve the quality of the birth population. Traditional Chinese medicine has a long history of prenatal and postnatal healthcare with rich content, which is the theoretical basis of modern related services. With the social development and the improvement of people's awareness of prenatal and postnatal healthcare, people have gradually shifted the focus of prenatal and postnatal healthcare to the peri-pregnancy stage at present, namely that couples of childbearing age are guided to prepare for pregnancy under the premise of solving their basic diseases. Infertility is a common and refractory disease for women of childbearing age. Ovulation disorder is one of its common pathological mechanisms. Traditional Chinese medicine believes that kidney deficiency is the main cause and pa-thogenesis of anovulation infertility and blood stasis is an important factor throughout the disease course. In clinical practice, therapies for invigorating kidney and activating blood are safe and reliable to treat anovulatory infertility mainly by adjusting the hypothalamus-pituitary-ovarian axis, improving ovarian function, uterine environment and gamete quality and increasing endometrial volume. Under the guidance of the thought of prenatal and postnatal healthcare, the authors tried to explore the effect of therapies for kidney-tonifying and blood-activating in the treatment of anovulatory infertility in eugenics, with the purpose of providing ideas and basis for subsequent relevant clinical studies and contributing to prenatal and postnatal healthcare services.
Anovulation ; Child ; Eugenics ; Female ; Humans ; Infertility, Female/drug therapy* ; Kidney ; Medicine, Chinese Traditional ; Ovulation ; Pregnancy

This study used network pharmacology and molecular docking to study the mechanism of Bushen Culuan Formula in the treatment of infertility caused by polycystic ovary syndrome(PCOS). The active ingredients and potential drug targets of Bushen Cu-luan Decoction were obtained by searching the Traditional Chinese Medicine System Pharmacology(TCMSP) database, and the targets of PCOS by searching GeneCards. After the drug targets and disease targets were corrected by Uniprot, the intersection genes were obtained. STRING database and Cytoscape 3.7.2 were used for protein-protein interaction(PPI) analysis of the intersection genes. The ClueGO plug-in of Cytoscape 3.7.2 was employed to perform gene ontology(GO) enrichment and KEGG pathway enrichment for the intersection genes. Finally, molecular docking of the key active ingredients with the targets of Bushen Culuan Formula was performed using AutoDockVina and MGLtools. A total of 136 active ingredients and 314 drug targets of the decoction were obtained from TCMSP, and 136 disease targets from GeneCards. Finally, 49 drug-disease intersection genes were obtained. GO enrichment found that the genes were mainly involved in the regulation of muscle cell apoptosis, positive regulation of small molecule metabolism, core promoter binding, RNA polymerase Ⅱ regulation of pri-miRNA transcription, negative regulation of transmembrane transport and other biological functions. The enriched KEGG pathways mainly included MAPK, PI3 K-Akt, p53, and HIF-1 signaling pathways. The results of molecular docking showed that quercetin and PTGS2 can bind stably and interact through amino acid residues THR206, TRP387, ASN382, etc. This study preliminarily reveals the multi-component, multi-target, and multi-pathway mechanism of Bushen Culuan Formula in the treatment of PCOS-related infertility, which provides a basis for further research.
Drugs, Chinese Herbal/pharmacology* ; Female ; Gene Ontology ; Humans ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Polycystic Ovary Syndrome/genetics* ; Signal Transduction

To evaluate the application of outcome indicators in randomized controlled trials(RCTs) concerning the treatment of tension-type headache(TTH) with traditional Chinese medicine(TCM) in recent five years, so as to provide a basis for the study of core outcome set(COS) for TCM intervention in TTH. The RCTs on TCM treatment of TTH in recent five years were systematically retrieved from CNKI, Wanfang, VIP, CBM, EMbase, PubMed, Cochrane Library, Web of Science, ClinicalTrials.gov and China Clinical Trial Registry. After literature screening, data extraction and evaluation of the risk of bias, the outcome indicators in the included RCTs were subjected to qualitative analysis. The preliminary search yielded 19 042 articles, and 10 983 were left after the elimination of duplication. Finally, 52 RCTs(48 in Chinese and 4 in English) were included for qualitative analysis. The outcome indicators of RCTs included in this study were classified into seven domains: TCM syndrome, symptom and sign, physical and chemical detection, quality of life, long-term prognosis, economic evaluation, and safety event. The findings demonstrated that headache characteristic index in the symptom and sign domain was the index with the highest reporting frequency and reporting rate. Seventeen RCTs used TCM syndrome score as the outcome indicator. Further analysis revealed that there existed such problems in research design as non-distinction between primary and secondary outcome indicators, great difference in the adopted measurement tools for outcome indicators, and the neglect of measurement time of outcome indicators. Moreover, the syndrome indicators reflecting TCM advantages, objective evaluation indicators, safety and health-economic indicators were lacking. These limitations have affected the quality and reliability of RCTs on TTH treatment with TCM. It is suggested that the efficacy and characteristics of TCM should be combined into current clinical research, and the COS in RCTs regarding TCM treatment of TTH should be established according to internationally recognized standard procedures.
Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Quality of Life ; Randomized Controlled Trials as Topic ; Reproducibility of Results ; Tension-Type Headache/drug therapy*

This study aims to systematically evaluate the clinical efficacy and safety of Toutongning Capsules in the treatment of tension-type headache(TTH), so as to provide a corresponding basis for clinical treatment. Eight commonly used medical research databases and two clinical trial registration systems were retrieved with the time interval from the establishment of the database or system to November 2020. The randomized controlled trials of Toutongning Capsules in the treatment of TTH were screened out according to the pre-set criteria. The quality of the included papers was evaluated by the bias risk assessment tool in Cochrane Reviewers Handbook 6.1 and the data were statistically analyzed by RevMan v5.4 provided by Cochrane collaboration. A total of 13 studies were included and the quality of methodology was generally low. Meta-analysis showed that Toutongning Capsules assisted with western medicine therapy can effectively reduce the pain intensity(MD_(VAS)=-1.94,95%CI[-2.50,-1.38],P<0.000 01;MD_(NRS)=-0.83,95%CI[-0.86,-0.80],P<0.000 01), headache duration(SMD=-0.98,95%CI[-1.17,-0.79],P<0.000 01), headache frequency(MD=-1.01,95%CI[-1.16,-0.85],P<0.000 01), headache index(MD=-11.13,95%CI[-12.10,-10.16],P<0.000 01), anxiety and depression scale score(MD_(HAMA)=-4.02,95%CI[-6.58,-1.46],P=0.002;MD_(HAMD)=-2.67,95%CI[-4.04,-1.29],P=0.000 1), while Toutongning Capsules as monotherapy only reduced the headache score(MD=-2.24,95%CI[-2.97,-1.51],P<0.000 01). The available clinical studies demonstrate that Toutongning Capsules combined with western medicine in the treatment of TTH can improve the related outcome indicators, but the clinical safety and efficacy of Toutongning Capsules alone remain unclear. Due to the small number and low quality of the included studies, large-sample, multi-center, high-quality and strictly designed randomized controlled trials are still needed to verify the clinical efficacy in the future.
Capsules ; Databases, Factual ; Drugs, Chinese Herbal ; Humans ; Tension-Type Headache/drug therapy* ; Treatment Outcome

The efficacy of gastrodin as a Chinese herbal medicine extract in the treatment of tension-type headache has been confirmed. This paper systematically reviewed the efficacy and safety of gastrodin in the treatment of tension-type headache, aiming to provide a new choice for the treatment of this disease. In this study, four Chinese databases, four English databases and two trial registries were searched from the date of establishment to September 2020. The related randomized controlled trials(RCTs) were screened out according to the predetermined criteria. The bias risk assessment tool developed by Cochrane collaboration was used to evaluate the quality of the reports. RevMan 5.4.1 was used for Meta-analysis, and GRADE system for the evidence-based evaluation on the quality of outcome indicators. A total of 177 articles were retrieved and 8 articles were finally included for analysis, with a total sample size of 1 091 cases, which included 565 cases in the treatment group and 526 cases in the control group. The overall quality of included stu-dies was not high. The results of Meta-analysis are as follows:(1)In terms of headache frequency, gastrodin group was better than wes-tern medicine group(MD=-2.90, 95%CI[-3.76,-2.03], P<0.000 01).(2)In terms of number of abnormal blood vessels in TCD, gastrodin group was better than western medicine group(MD=-88.96, 95%CI[-102.36,-75.55], P<0.000 01).(3)In terms of effective rate, gastrodin group was better than western medicine group(RR=1.47, 95%CI[1.29, 1.68], P<0.000 01). The results of subgroup analysis are as follows:(1)Effective rate based on age, for the patients upper age limit 40-46 years old, gastro-din group was better than western medicine group(RR=1.69, 95%CI[1.50, 1.90], P<0.000 01); for the patients upper age limit 55-60 years old, gastrodin group was better than western medicine group(RR=1.27, 95%CI[1.16, 1.38], P<0.000 01).(2)Effective rate based on dosage form, both the gastrodin capsules and injection groups were better than western medicine group(RR_(capsules)=1.42, 95%CI[1.08, 1.88], P=0.01; RR_(injection)=1.50, 95%CI[1.26, 1.77], P<0.000 01). GRADE evaluation showed that the above outcomes had low quality of evidence. Only one article detailed the occurrence of adverse reactions and thus the present study cannot make a positive conclusion on the safety of gastrodin in the treatment of tension-type headache. The small number and low quality of the included reports affected the reliability of the results. In the future, more high-quality randomized controlled trails are needed to improve the evaluation on the efficacy and safety of gastrodin in the treatment of tension-type headache.
Adult ; Benzyl Alcohols/therapeutic use* ; Drugs, Chinese Herbal/adverse effects* ; Glucosides ; Humans ; Middle Aged ; Reproducibility of Results ; Tension-Type Headache

Danggui Buxuetang， derived from Clarifying Doubts about Damage from Internal and External Causes （Volume 2）： Treatise on Heat Injury to Stomach Qi（《内外伤辨惑论卷中·暑伤胃气论》） by LI Dongyuan in the Jin and Yuan dynasties， is a classic and famous formula for tonifying qi and generating blood that has been inherited and promoted by successive generations of medical practitioners and has been included in the "Catalogue of Ancient Classical Prescriptions （First Batch）" published by the National Administration of Traditional Chinese Medicine in 2018. The paper analyzed the historical origin， composition， dosage， processing， preparation， decocting， and taking methods， efficacy， and application of the classic formula Danggui Buxuetang by consulting ancient and modern literature and combining the key information examination principles of ancient classic prescriptions. A total of 604 pieces of information on relevant ancient literature were collected， including 186 ancient Chinese medical books， of which 40 （five in the Jin and Yuan dynasties， 19 in the Ming Dynasty， and 16 in the Qing Dynasty） had detailed records of composition， processing， and dosage. Danggui Buxuetang is mainly comprised of Astragali Radix and Angelicae Sinensis Radix. According to the ancient and modern dose conversion， there are 37.3-38.1 g of Astragali Radix and 7.5-7.6 g of Angelicae Sinensis Radix in the formula. Astragali Radix is preferably fried with honey and Angelicae Sinensis Radix with wine. Astragali Radix and Angelicae Sinensis Radix are decocted with 600 mL of water to 300 mL， and taken warm before meals. The main effect of this formula are described in ancient books as blood deficiency and fever， with symptoms of muscle fever， dryness and heat， irritability and thirst， red eyes and face， sleeplessness in daytime and night， and surging and feeble pulse which is weak under hard pressing， and it is a famous formula for replenishing qi and generating blood. Modern research shows that Danggui Buxuetang is commonly used in the treatment of various kinds of anemia， diabetic nephropathy， tumors， and cardiovascular and cerebrovascular diseases. The above research results can provide a reference for the subsequent development and research on the classic formula Danggui Buxuetang.