Objective The aim of this study was to investigate the molecular regulatory mechanism of cancer susceptibility candidate 15(CASC15),a long-stranded non-coding RNA(lncRNA),in hepatocellular carcinoma(HCC).Methods Bioinformat-ics methods were used to predict the expression of target genes and analyze the relationship between the expression of target genes and the survival time of patients;Hepatocellular carcinoma tissues and adjacent tissues from patients with HCC were collected;CCK-8,Tr-answell,and flow cytometry experiments were used to detect proliferation,invasion,migration and apoptosis of SMMC7721 cells and Huh-7 cells;The dual-luciferase assay was used to detect the targeting relationship between miR-144-3p and CASC15,as well as leucine rich repeat containing protein 1(LRRC1);RT-qPCR and Western blot were used to detect mRNA and protein expression of target genes;Immunofluorescence was used for protein localization of target genes;Replicate experiment was performed to verify the effect of CASC15/miR-144-3p/LRRC1 on the progression of HCC.In vivo experiment was performed to verify the effect of CASC15 on HCC progression.Results TCGA database and RT-qPCR assay showed high expression of CASC15,low expression of miR-144-3p,and high expression of LRRC1 in HCC tissues and cells(P<0.05).The results of cell function experiments on proliferation,inva-sion and migration showed that CASC15 and LRRC1 played a promoting role in tumor development,while miR-144-3p had an inhibi-tory effect,consistent with the results of apoptosis experiments(P<0.05).Cell function experiments showed that CASC15 inhibited miR-144-3p function,miR-144-3p inhibited LRRC1,and CASC15 bound to miR-144-3p,leading to the upregulation of LRRC1.The replicate experimental results indicated that CASC15 promoted LRRC1 expression through inhibiting miR-144-3p,thereby pro-moting HCC cell proliferation,invasion and migration,and inhibiting apoptosis.Conclusion CASC15 may promote HCC progression by regulating the miR-144-3p/LRRC1 axis.

Objective To investigate effects of ligustilide(LIG)on proliferation,apoptosis,angiogenic mimicry and Ras homolog gene family member A(RhoA)/Rho associated coiled coil containing protein kinase 1(ROCK)signaling pathway in esophageal cancer cells.Methods Esophageal cancer cell line EC-109 was treated with LIG at concentrations of 0,12.5,25,50,100,and 200 μmol/L to detect cell activity,and the suitable concentration was selected for subsequent experiments.EC-109 cells were grouped into the control group,the LIG low,medium and high concentration groups(LIG-L,LIG-M and LIG-H groups),and the LIG-H+RhoA activator Naciclassine group(LIG-H+Naciclassine group).Edu was applied to detect cell proliferation,and flow cytometry was applied to detect cell apoptosis.Angiogenetic mimicry was observed.Western blot assay was applied to detect expression levels of proteins related to cell proliferation and apoptosis,and RhoA,ROCK proteins.Nude mouse tumor transplantation experiment was applied to verify the effect of LIG on the growth of esophageal cancer tumors.Immunohistochemistry was applied to detect expression levels of angiogenesis related factors(VEGF),RhoA and ROCK proteins in transplanted tumors.Results Compared with the control group,the vascular mimicry tubular structure of EC-109 cells decreased sequentially in the LIG-L group,the LIG-M group and the LIG-H group.The positive rate of Edu,the expression levels of Cyclin D1,Ki67,Bcl-2,RhoA and ROCK reduced in turn.P21,cell apoptosis rate,the expression of Bax and Caspase-3 increased in sequence(P＜0.05).Naciclasine,RhoA activator,partially reversed the effect of LIG on cell proliferation,apoptosis and vasculogenic mimicry of esophageal cancer cells.Nude mouse transplantation tumor experiment showed that compared with the control group,the growth rate of transplanted tumor showed down,tumor volume decreased and the expression levels of RhoA,ROCK and VEGF decreased in the LIG group(P＜0.05).Conclusion Ligustilide inhibits the proliferation and angiogenic mimicry of esophageal cancer cells by inhibiting RhoA/ROCK signaling pathway,and promotes the apoptosis of esophageal cancer cells.

Objective:To explore the clinical effect of a self-designed wound measurement grid on the design of lobulated perforator flap.Methods:From January 2019 to December 2022, soft tissue defects in limbs of 9 patients were reconstructed by lobulated perforator flaps in the Department of Orthopaedics and Traumatology of Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine. The patients were 7 males and 2 females aged 21-55 years old with 40.3 years old in average. There were 6 upper limb defects and 3 lower limb defects. Self-designed wound measuring grids were applied to guide the design and excision of lobulated perforator flaps during surgery. Five patients were treated by lobulated perforator flap pedicled with the descending branch of lateral circumflex femoral artery and 4 by perforator flaps pedicled with dorsal interosseous artery. The areas of soft tissue defect were 4.0 cm×1.5 cm-26.0 cm×8.0 cm, and the sizes of the flaps were 4.5 cm×1.8 cm-22.0 cm×10.0 cm. After surgery, the blood supply of flaps, flap survival and wound healing were monitored. Flap survival, donor site recovery and limb function were observed at outpatient clinic over the postoperative follow-up, and the limb function was evaluated by the Evaluation Standard of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association and Lower Extremity Measure(LEM).Results:In this study, a total of 17 of 18 lobes of the lobulated perforator flaps survived after surgery. One flap had venous occlusion and after exploration and further treatment, a necrosis occurred in 1 lobe of the lobulated flap and then a free flap transfer was performed again. All the wounds achieved stage-I healing. Postoperative follow-up lasted for 3-18 months with 8.6 months in average. All flaps had good colour and texture, satisfactory appearance and only linear scars remained in the donor sites, without pain and scar contracture. The reconstructed upper extremity defect were evaluated according to the Evaluation Standard of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, with 4 patients were in excellent and 2 in good. The reconstructed lower extremity defects were evaluated according to the LEM, and 2 patients were in excellent and 1 in good.Conclusion:The self-designed wound measurement grid was successfully applied in the design of lobed perforator flaps. It can accurately measure a wound surface and quickly extract a wound profile, and it is more convenient and intuitive to guide the design of flaps. It has a good effect in clinical application and further clinical trials are required.

Objective:To investigate the surgical method and clinical effect in the repair of thumb tip defect with radial thenar fasciocutaneous flap.Methods:From March, 2016 to January, 2019, 15 patients with thumb tip defect were treated by radial thenar fasciocutaneous flap. There were 6 defects in left thumb and 9 in right thumb. All the thumbtip defects had the exposure of digital bone, and some had defects of digital bone itself. The size of defects ranged from 1.0 cm×2.0 cm to 1.5 cm×3.0 cm, and the size of the flaps ranged from 1.2 cm×2.5 cm to 1.8 cm×4.0 cm. All of the donor sites were directly closed. The patients entered follow-up by outpatient visit, telephone calls or WeChat reviews to evaluate the quality of the flaps and the clinical effects of the surgery.Results:All flaps survived with good quality. All the donor sites achieved primary healing. The follow-ups lasted for 6 to 18 months with an average of 10.5 months. At the final follow-up review, the appearance of flaps was satisfactory in natural colour, flexible and wear-resistant. There were various degrees of sensation recovery of the flaps, with TPD from 6 mm to 12 mm. The sensation around the donor site was close to normal. Function of the thumbs was evaluated according to the total active movement (TAM) evaluation system. Twelve thumbs were graded excellent and 3 in good.Conclusion:The radial thenar fasciocutaneous flap achieved satisfactory clinical effect in the repair of thumb tip defect. The texture of the flaps is close to the recipient site and the damage to the donor site is minimal.

Model informed precision dosing (MIPD) is a new concept to guide precision dosing for individual patient by modeling and simulation based on the available information about the individual patient, medications and the disease. Compared to the empirical dosing, MIPD could improve the efficacy, safety, economics and adherence of the pharmacotherapy according to the individual's pathophysiology, genotyping and disease progression. This consensus report provides a brief account of the concept, methodology and implementation of MIPD as well as clinical decision supporting systems for MIPD. The status and future advancing of MIPD was also discussed to facilitate the appropriate application and development of MIPD in China.

Objective: Comparing the benefit of Abidor, lopinavir/ritonavir and recombinant interferon α-2b triple combination antiviral therapy and lopinavir/ritonavir and interferon dual combination antiviral therapy to hospitalized novel coronavirus pneumonia 2019 in Zhejiang province. Methods: A multi-center prospective study was carried out to compare the effect of triple combination antiviral therapy with dual combination antiviral therapy in 15 medical institutions of Zhejiang Province. All patients were treated with recombinant interferon α-2b (5 million U, 2 times/d) aerosol inhalation. 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir / ritonavir (2 tablets, 1 time/12 h) as the triple combination antiviral treatment group. 41 patients were treated with lopinavir / ritonavir (2 tablets, 1 time/12 h) as the dual combination antiviral treatment group. The patients who received triple combination antiviral therapy were divided into three groups: within 48 hours, 3-5 days and > 5 days after the symptom onset. To explore the therapeutic effects of triple combination antiviral drugs and dual combination antiviral drugs, as well as triple combination antiviral drugs with different antiviral initiate time. SPSS17.0 software was used to analyze the data. Results: The time of virus nucleic acid turning negative was (12.2 ± 4.7) days in the triple combination antiviral drug group, which was shorter than that in the dual combination antiviral drug group [(15.0 ± 5.0) days] (t = 6.159, P < 0.01 ). The length of hospital stay [12 (9, 17) d] in the triple combination antiviral drug group was also shorter than that in the dual combination antiviral drug group [15 (10, 18) d] (H = 2.073, P < 0.05). Comparing the antiviral treatment which was started within 48 hours, 3-5 days and > 5 days after the symptom onset of triple combination antiviral drug group, the time from the symptom onset to the negative of viral shedding was 13 (10,16.8), 17 (13,22) and 21 (18-24) days respectively (Z = 32.983, P < 0.01), and the time from antiviral therapy to the negative of viral shedding was (11.8±3.9) , (13.5±5.1) and (11.2±4.3) d. The differences among the three groups were statistically significant (Z=32.983 and 6.722, P<0.01 or<0.05). Conclusions The triple combination antiviral therapy of Abidor, Lopinavir/Litonavir and recombinant interferon α-2b showed shorter viral shedding time and hospitalization time compared with the dual combination antiviral therapy. The earlier the time to initiate triple antiviral treatment, the shorter the time of virus shedding.

Objective: To explore the effect of circ_0005075 on the proliferation and invasion of liver cancer cells and its underlying mechanism. Methods:Atotal of 35 cases of cancer tissues and corresponding para-cancerous tissues from liver cancer patients, who underwent surgical resection in Tangshan Workers’Hospital from March 2015 to March 2018, were collected for this study. qPCR was used to detect the expression levels of circ_0005075 and miR-335 in liver cancer tissues, para-cancerous tissues, liver cancer cell lines (HCCC9810, HepG2, HLE and hepatic epithelial THLE-3 cells). Dual luciferase reporter gene assay was used to verify the targeting relationship among circ 0005075, mir-335 and CCND1. By using liposome-mediated method, Sh-circ_0005075, miR-335 mimics, miR335 mimics+pcDNA-CCND1, sh-circ_0005075+pcDNA-CCND1, pcDNA-circ_0005075+miR-335 mimics, sh-CCND1+pcDNA-circ_ 0005075 were transfected into HCCC9810 cells, respectively. The effects of circ_0005075/miR-335/CCND1 molecular axis on the proliferation and invasion of HCCC9810 cells were detected by MTT and Transwell methods. Results: circ_0005075 was highly expressed in liver cancer tissues and cell lines (P<0.01) ,and the highest expression in HCCC9810 cells (P<0.05). Dual luciferase reporter gene results showed that circ_0005075 negatively regulated miR-335 (P<0.05), and CCND1 was a target gene of miR-335 (P<0.05). Further experiments proved that knockdown of circ_0005075 or overexpression of miR-335 could inhibit the proliferation and invasion of HCCC9810 cells by regulating CCND1（P<0.05 or P<0.01） . Conclusion: Circ_0005075 upregulates the expression level of CCND1 by sponging miR-335, thereby promoting the proliferation and invasion of HCCC9810 cells.

With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.

Objective To analyze humanized nursing and postoperative function of early stage training under arthroscopic rotator cuff injury minimally invasive surgery in patients with application value. Methods A total of 104 routine under arthroscopy of minimally invasive surgery in patients with rotator cuff injury by double-blind controls (usual care) and observation group (phase humanized nursing and early function training). With preoperative and postoperative week 5, 10, 15 weeks, 20 weeks of observation point in time, compared two groups of Constant Murley shoulder joint assessment of the indicators (pain, muscle strength, joint mobility, daily life) score, compared two groups of Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD) score. Results Preoperative, two groups of patients with pain, muscle strength, (range of motion, ROM), comparison between daily life score group were no significant differences (P> 0.05). Observation group of 10, 15, 20 weeks postoperatively pain scores were (4.32±0.17), (2.20±0.39), (1.01±0.24) points, which were higher than (4.61±0.21), (3.36±0.38), (1.76±0.14) points of the control group, and there were significant differences (t=7.74, 15.36, 19.47, P<0.01). All the observation time point strength postoperative observation group were (11.53±1.40)-(22.01± 0.31)points, which werehigher than (9.16 ± 1.06)- (17.14 ± 1.01) points of control group, and there were significant differences (t=8.97- 33.24,P<0.01). Each time point ROM postoperative observation group were (74.96±4.39)-(150.01±2.34) points which were higher than (69.01±2.63)-(120.15±2.36)points of control group, and there were significant differences(t=8.38-64.79,P<0.01). The observation group of 10 -20 weeks daily life score were (13.05±1.21)-(17.10±0.75) points higher than (10.65±1.31)-(13.42±1.04) points of control group, and there were significant differences(t=9.70- 20.70,P <0.01). HAMA and HAMD score after the intervention of observation group were (10.25±1.60), (12.02±1.84) points which were lower than (12.01 ± 2.78), (14.95 ± 2.11) points of the control group, and there were significant differences (t=3.25, 6.19, P< 0.01). Conclusions Humanized nursing and functional training for early stage in patients with rotator cuff injury under the arthroscope minimally invasive surgery; has the following functions: improve patients'psychological status, the positive application of treatment and rehabilitation; pain relief, and functional training smoothly; the early functional training to increase muscle strength and joint motion and improve everyday life.

Objective To get a controllable acetabulum component inclination angle during the total hip arthroplasty(THA) with the lateral position,a new method using a self-made instrument was introduced.Methods Totally 80 consecutive patients undergoing THA at the lateral position were enrolled.Forty acetabular components were assembled using a new method with a self-made instrument referring to the 42 degrees' angle drawn on the wall(group A),while another 40 acetabular cups were implanted free-handedly(group B).The postoperative inclination angle was evaluated on the anterior-posterior pelvic radiographs.Results The average inclination angle was 43.3° ± 3.7°(34.7°～49.1°) in group A and 40.3 ± 4.5o(32.8°～50.7°) in group B.Moreover,40/40 of group A and 38/40 of group B were in the Lewinnek's inclination safe zone(P＞0.05),without significant differences between the two groups.Conclusion It is practical and reliable to decide the acetabular component orientation using the lateral position instrument and reference angle on the wall.