Objective To discuss the evaluation basis of the clinical rational use of Dahuang Zhechong Capsule and to establish its rationality evaluation criterion to promote the sensible use of Dahuang Zhechong Capsule.Methods The rationality evaluation criterion for Dahuang Zhechong Capsule was formulated by referring to the package insert,treatment guidelines,and other literature.According to the criterion,270 outpatient prescriptions using Dahuang Zhechong Capsule in Xiyuan Hospital,China Academy of Chinese Medical Sciences were reviewed from January to June 2020.The indication,usage and dosage,drug combination,and repeated administration were analyzed.The pharmaceutical intervention was performed to address the problems found in the prescription reviews,and 328 outpatient prescriptions using Dahuang Zhechong Capsule in October 2020 were reevaluated.Results The irrational use rate of Dahuang Zhechong Capsule from January to June 2020 was 42.22％(114 cases),including 108(40％)cases of inappropriate indications,five(1.85％)cases of improper usage and dosage,and one(0.37％)case of inappropriate administration route.However,the pharmaceutical intervention in October 2020 remarkably reduced the irrational use rate of Dahuang Zhechong Capsule(4.27％,14 cases),all of which were inappropriate indications.Conclusion Dahuang Zhechong Capsule is being used irrationally;therefore,establishing an evaluation criterion is required.The specific situation of irrational drug use can be identified by prescription review according to its rationality evaluation criterion to manage its clinical use better and promote its rational use.

Objective To investigate the associations of reproductive health indicators with lung function and chronic obstructive pulmonary disease(COPD)among women aged 40 years and above.Methods From Jul to Sep,2021,female subjects aged 40 years and above were randomly selected from the Shanghai Suburban Adult Cohort and Biobank for COPD screening.A questionnaire was used to obtain information on demographic characteristics and reproductive health indicators.Linear regression was used to analyze the effects of reproductive health indicators on forced vital capacity(FVC)and forced expiratory volume in the first second(FEV1).Logistic regression was also used to analyze the effects of reproductive health factors on FVC as a percentage of the predicted value(FVC%Pred)and FEV1%Pred as well as on COPD.Results A total of 1876 women aged 40 years and above were enrolled with mean age of(62.1±8.2)years old,among them,78.1%were menopausal,and 40.9%had been pregnant≥3 times.Multivariate analysis showed that FVC and FEV1 decreased in postmenopausal women,but menopause was not associated with a decrease in their percentage of predicted values.Pregnancies≥3 times was a risk factor for COPD(for 3 times,OR=4.92,95%CI:1.48-19.95,P<0.05;for≥4 times,OR=9.06,95%CI:2.32-41.57,P<0.01),while pregnancies of 2 times did not increase the risk of COPD.Conclusion In women aged 40 years and above,menopause is associated with poorer FVC and FEV1,and excessive pregnancy(≥3 times)is a risk factor for COPD.

Objective Mobile artificial lumbar complex(MALC)which suitable for reconstruction after subtotal lumbar resection in goats was developed,and to test stability of the complex and postoperative lumbar segmental motor function.Methods Eighteen male boer goats aged from 1 to 2 years old(weighted from 35 to 45 kg)were selected and divided into con-trol group,fusion group and non-fusion group,with 6 goats in each group.According to preoperative CT scans and MRI exami-nations of lumbar,the goat MALC was designed and performed by 3D printed for non-fusion group.Operation was performed on three groups respectively,and only vertebral body and disc were exposed in control group.In fusion group,L4 part of vertebral body and the upper and lower complete disc tissues were removed,and the lumbar spine bone plate fixation was performed with titanium mesh bone grafting.In non-fusion group,vertebral body and disc were removed in the same way,and MALC was im-planted.AP and lateral X-rays of lumbar vertebrae in goat were taken at 6 months after surgery,in order to understand whether the plant was dislocated,displaced and fractured.Biomechanical tests were performed on the specimens by mechanical instru-ment to measure range of motion(ROM)of L2,3,L,4,L4,5intervertebral space and the overall ROM of L2-5 lumbar vertebrae.Results MALC of lumbar vertebra was designed by 3D printing,and its component artificial vertebrae and upper and lower ar-tificial end plates were manufactured.The semi-spherical structure was fabricated by precision lathe using high-crosslinked polyethylene material,and the prosthesis was assembled.Postoperative AP and lateral X-rays of lumbar vertebra at 6 months showed the implant position of implant and MALC were good without displacement and dislocation.In vitro biomechanical test of lumbar vertebrae specimens:(1)There were no statistical significance in ROM of lumbar intervertebral space flexion and extension,lateral flexion and rotation on L.4 and L4,5,between non-fusion group and control group(P＞0.05),while ROM of fu-sion group was significantly reduced compared with the other two groups(P＜0.05).There were no significant difference in ROM of L2.3 intervertebral flexion and extension,lateral flexion and rotation between non-fusion group and control group(P＞0.05),while fusion group was significantly increased compared with the other two groups(P＜0.001).(2)There was no signifi-cant difference in overall lumbar ROM of L2-5(P＞0.05).Conclusion The individual MALC could restore intervertebral height of lumbar vertebra while maintaining the stability of lumbar vertebra and re-establishing motor function of lumbar space.

Objective To evaluate the effect of manual massage on complications after endoscopic foam sclerotherapy injection for the treatment of internal hemorrhoids.Methods Consecutive 113 patients with grade Ⅰinternal hemorrhoids were prospectively enrolled and completed endoscopic foam sclerotherapy.The patients were randomly divided into a massage group(n=65)and a control group(n=68).Massage group performed manual perianal massage,Visual analogue scale(VAS)was used to evaluate perianal pain.The postoperative bleeding,short-term and long-term efficacy were also compared.Results The median VAS of 24 h postoperation was 1.0(0.0,3.0)in massage group,which was significantly lower than 2.0(1.0,4.0)in control group,the difference was statistically significant(P=0.014).The no bleeding rate of one week postoperation was 84.6％in massage group,which was significantly higher than 64.7％in control group,the difference was statistically significant(P=0.009).After 12 weeks,6 months and 12 months of follow-up,there were no significant differences in cure rate and remission rate between the two groups(P＞0.05).Conclusion Manual massage after endoscopic sclerosing agent injection is beneficial to relieve postoperative pain of grade Ⅰ internal hemorrhoids and reduce bleeding.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

OBJECTIVE: To screen for aberrantly expressed genes in osteosarcoma cells and investigate the role of RHPN2 in regulating the proliferation, apoptosis, migration and tumorigenic abilities of osteosarcoma cells. METHODS: We used GEO2R to analyze the differential gene expression profile between osteosarcoma cells and normal cells in the GSE70414 dataset. RTqPCR and Western blotting were performed to detect RHPN2 expression in osteosarcoma cell lines MG-63, 143B and SAOS2. Two RHPN2-shRNA and a control NC-shRNA were designed to silence the expression of RHPN2 in 143B cells, and CCK8 assay, colony-forming assay, annexin V-FITC/PI staining and scratch assays were carried out to examine the changes in proliferation, apoptosis and migration of the cells. We also established nude mouse models bearing osteosarcoma xenografts derived 143B cells and RHPN2-shRNA-transfected 143B cells, and assessed the effect of RHPN2 silencing on osteosarcoma cell tumorigenesis using HE staining. Kaplan-Meier survival curves were used to analyze the correlation between RHPN2 expression and survival outcomes of patients with osteosarcoma. RESULTS: RHPN2 expression was significantly upregulated in osteosarcoma cell lines MG-63, 143B and SAOS2 (P < 0.01). Silencing of RHPN2 significantly inhibited the proliferation and migration of 143B cells in vitro, promoted cell apoptosis (P < 0.01), and suppressed tumorigenic capacity of the cells in nude mice. A high expression of RHPN2 was significantly correlated with a poor prognosis of patients with osteosarcoma (P < 0.05). CONCLUSION RHPN2 is highly expressed in osteosarcoma cells to promote cell proliferation and migration and inhibits cell apoptosis. A high expression of RHPN2 is associated with a poorer prognosis of the patients with osteosarcoma.
Adaptor Proteins, Signal Transducing/metabolism* ; Animals ; Apoptosis ; Bone Neoplasms/metabolism* ; Carcinogenesis ; Cell Line, Tumor ; Cell Movement/physiology* ; Cell Proliferation/physiology* ; Humans ; Immediate-Early Proteins ; Mice ; Mice, Nude ; Osteosarcoma/metabolism* ; RNA, Small Interfering/genetics*

In order to increase the stability and solubility of essential oil in Jieyu Anshen Formula, this study was to prepare the essential oil into liposomes. In this experiment, the method for the determination of encapsulation efficiency of liposomes was established by ultraviolet spectrophotometer and dextran gel column. The encapsulation efficiency and particle size of liposomes were used as evaluation indexes for single factor investigation and Box-Behnken design-response surface method was used to optimize the design. Then the optimal formulation of volatile oil liposome was characterized using methyleugenol, elemin, β-asarone and α-asarone as index components. Finally, the in vitro transdermal properties of liposomes were studied by modified Franz diffusion cell. The results showed that the concentration of lecithin, the mass ratio of lecithin to volatile oil, and the stirring speed were the three most significant factors affecting the liposome preparation. The optimum formulation of volatile oil liposome was as follows: the concentration of lecithin was 7 g·L~(-1); mass ratio of lecithin to volatile oil was 5∶1; and the stirring speed was 330 r·min~(-1). Under such conditions, the prepared liposomes had blue emulsion light, good fluidity, half translucent, with particle size of(102.6±0.35) nm, Zeta potential of(-17.8±0.306) mV, permeability of(1.67±1.01)%, and stable property if liposome was stored at 4 ℃. 24 h after percutaneous administration, the cumulative osmotic capacity per unit time was(30.485 2±1.238 9),(34.794 8±0.928 3),(26.677 1±1.171 7),(3.066 2±0.175 3) μg·cm~(-2)respectively for methyleugenol, elemin, β-asarone and α-asarone. In vitro transdermal behaviors of methyleugenol, elemin, β-asarone and α-asarone in liposomes were all consistent with Higuchi equation. The prepared volatile oil liposomes met the relevant quality requirements, providing a reference for further research on preparation of multi-component Chinese medicine essential oil liposomes.
Administration, Cutaneous ; Drugs, Chinese Herbal ; analysis ; Liposomes ; Oils, Volatile ; analysis ; Particle Size ; Solubility

To detect the concentration of triptolide in skin and joint after percutaneous administration,an HPLC-MS/MS method and skin and joint micro-dialysis( MD) method of triptolide were established in this study. The separation was achieved on triple quadrupole( AB QTRAP4500) and phenomenex-C18( 4. 6 mm×150 mm,5 μm,luna) column with acetonitrile-water with 0. 1% formic acid( 65 ∶35) as the mobile phase at a flow rate of 0. 7 m L·min-1. An electrospray ionization( ESI) source was applied and operated in the positive multiple reaction monitoring( MRM) mode. The fragment ion for triptolide was m/z 361. 1→145. 0. The effects of different perfusion [Ringer's,PBS( p H 7. 4),30% ethanol saline]drug concentrations and flow rates on the recovery rate,as well as the relationship between the recovery rate and the loss rate were determined by incremental( dialysis) and reduction( retrodialysis) methods.The reduction method was applied in the in vivo study to investigate and determine the stability of the probe recovery rate in 10 h. The results of HPLC-MS/MS detection method conformed to the requirements of biological samples. The perfusion fluid was 30% ethanol saline. The recovery rate of skin and joint probes in vitro of triptolide increased within the flow rate of 0. 5-2. 5 μL·min-1. In order to increase the timeliness of data and the accuracy,the flow rate was determined to be 1 μL·min-1,and the sample interval was determined to be 0. 5 h. The recovery rate of triptolide in skin and joint probes in vitro and the loss rate were stable and equal despite of change of triptolide concentration within 10-200 μg·L-1. This indicated that the effect of drug concentration on the MD probe recovery rate was small,and the recovery rate could be replaced by the loss rate. The loss rate in vivo using MD method was measured at 10 h,indicating that the transfer rate of triptolide was stable within 10 h. The established method of triptolide in MD and HPLC-MS/MS can be applied to investigate the kinetic in skin and joint after percutaneous administration of triptolide.
Chromatography, High Pressure Liquid ; Diterpenes ; pharmacokinetics ; Epoxy Compounds ; pharmacokinetics ; Humans ; Joints ; metabolism ; Phenanthrenes ; pharmacokinetics ; Reproducibility of Results ; Skin ; metabolism ; Tandem Mass Spectrometry

Objective Head and neck cancer radiotherapy patients often appear a series of oral complications including mucositis, xerostomia, pain, dysphagia.The purpose of this study was to investigate whether personalization customized positioning oral stent was able to push normal tissue off the high dose target area and maintain accurate repeatable stable positions, thus protecting the normal tissue during radiotherapy of the nasopharyngeal carcinoma patients.Methods 15 newly diagnosed nasopharyngeal carcinoma patients were collected from March to August 2016 in Department of Radiation Oncology, Nanjing General Hospital of Nanjing Military Region and randomly divided into trial group and control group.Two groups of patients were treated with intensity modulated radiation therapy (IMRT).Trial group patients wear personalization customized oral positioning stents during radiotherapy while the control group did not wear.After radiotherapy, we compared the exposure doses of clinical target area(CTV) and normal oral tissue in two groups.ResultsThe left parotid gland radiotherapy doses of the trail group and the control group were 2223.557±294.549 cGy and 2900.563±374.660 cGy, the difference was statistically significant(t=3.847, P=0.002);the right parotid gland radiotherapy doses of the trail group and control group were 2284.957±256.673 cGy and 2994.670±339.264 cGy, the difference was statistically significant(t=4.512, P=0.001).The mean exposure doses of CTV in two groups were no statistically significant difference (6142.829±135.986 cGy vs 173.306±6221.825 cGy, t=0.971, P=0.349.Conclusion During the intensity modulated radiation therapy, patients with personalization customized oral positioning stents can keep the mandible in a precise repeatable stable position.And it can reduce the exposure dose of bilateral parotid without affect the radiotherapy effect of the clinical target area.

BACKGROUND:The connection between high-level central nervous system and spinal cord and peripheral nerve under injury level is blocked by traumatic spinal cord injury,and the whole function of the body is thereby influenced.The loss of motor function and feeling both severely affect the patient's life quality in views of physiology,psychology,function and social economics.RNA interference is an effective method to silence target genes,which provides a new treatment strategy for spinal cord injury.OBJECTIVE:To explore the application status of RNA interference in spinal cord injury.METHODS:PubMed and CNKI databases were retrieved using the keywords of "RNA interference,RNAi,spinal cord injury" in English and Chinese,respectively.The articles addressing the application of RNA interference in spinal cord injury were collected and reviewed.RESULTS AND CONCLUSION:Totally 44 articles were enrolled.It is urgent to find a new way to treat spinal cord injury.Compared with the traditional gene silencing technology,RNA interference owing to high specificity,high efficiency,high stability and high penetrability is considered to be a new direction for the studies on the pathogenesis and treatment of spinal cord injury.