ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

ObjectiveThis paper aims to investigate the differential mechanisms underlying the staged therapeutic effects of Qijia Rougan formula on liver fibrosis using proteomic technology. MethodsThe staged rat model of liver fibrosis was established by subcutaneous injection of carbon tetrachloride （CCl₄） and olive oil. One hundred and four SD rats were randomized into thirteen groups：a normal group，a two-week model group，a four-week model group，a six-week model group，an eight-week model group，a two-week Qijia Rougan formula group，a four-week Qijia Rougan formula group，a six-week Qijia Rougan formula group，an eight-week Qijia Rougan formula group，a two-week compound Biejia Ruangan tablet group，a four-week Compound Biejia Ruangan Tablet group，a six-week Compound Biejia Ruangan Tablet group，and an eight-week compound Biejia Ruangan tablet group. After two weeks of drug intervention，liver tissue and abdominal aortic blood samples were collected from the rats for testing. Hematoxylin-eosin （HE） staining，Masson staining，and Picro Sirius red staining were used to observe pathological damage and collagen fiber deposition in liver tissues. Immunohistochemistry （IHC） was employed to detect the contents of fibrosis markers in liver tissues. The contents of liver function indicators in the serum were measured using a fully automated biochemical analyzer，and the levels of liver fibrosis indicators in the serum were assessed by enzyme-linked immunosorbent assay （ELISA）. Liver tissues from the normal group，each model group，and each Qijia Rougan formula group were subjected to label-free quantitative proteomic analysis to identify differential proteins among the groups，with key proteins validated by Western blot. Finally，bioinformatics analysis was performed on the differential proteins. Results（1） The staged rat model of liver fibrosis constructed with CCl₄ and olive oil showed pathological results at the 2^nd，4^th，6^th，and 8^th weeks of modeling that were consistent with the Metavir standards for the F1，F2，F3，and F4 stages. Compared with those in the normal control group，the protein expressions of α-smooth muscle actin （α-SMA） and Collagen Ⅰ were significantly increased in each stage （P<0.05）. The levels of liver function indicators in the serum，including alanine aminotransferase （ALT），aspartate aminotransferase （AST），alkaline phosphatase （ALP），direct bilirubin （DBIL），and total bilirubin （TBil） in each model group，were significantly elevated in each stage （P<0.01）. The levels of liver fibrosis indicators in the serum，including procollagen Ⅲ peptide （PⅢP），type Ⅳ collagen（Ⅳ-C），hyaluronic acid （HA），and laminin （LN） in each model group，were significantly increased in each stage （P<0.05，P<0.01）. This study successfully established a staged rat model of liver fibrosis. （2） Compared with the model groups at each stage，the administration groups showed a reduction in hepatocyte ballooning degeneration，a more orderly arrangement of hepatocytes，and a decrease of inflammatory cell infiltration. The blue-stained collagen fibers became significantly thinner and finer，with reduced and narrowed fibrous septa. The areas of collagen fibers and Picro Sirius red staining were reduced （P<0.05）. The positive areas of α-SMA and Collagen Ⅰ expression were significantly decreased （P<0.05）. The levels of ALT，AST，ALP，DBIL，and TBil in the rats of the model groups at each stage were significantly reduced （P<0.05，P<0.01）. The levels of PⅢP，Ⅳ-C，HA，and LN in the rats of the model groups at each stage were significantly decreased （P<0.05）. Among these，the improvements in all indicators were most significant in the F3 stage （P<0.01）.（3） The proteomic results show that a total of 165 differential proteins exhibit a callback trend when comparing the model groups at four stages with the normal group，and when comparing the Qijia Rougan formula group with the model group. Western blot analysis reveals that the levels of NAD（P）H：quinone oxidoreductase 1 （NQO1），mitogen-activated protein kinase 1 （MAPK1），arginase 1 （Arg1），and glutathione S-transferase α1 （GSTA1） were consistent with the proteomic results. Bioinformatics results reveal that 165 differentially expressed proteins are enriched in multiple signaling pathways. Notably，signaling pathways such as drug metabolism-cytochrome P450，arginine biosynthesis，and the peroxisome proliferator-activated receptor （PPAR） signaling pathway were found to be closely associated with liver fibrosis，suggesting that the Qijia Rougan formula may exert its staged regulatory effects on liver fibrosis by regulating these pathways. ConclusionThe Qijia Rougan formula may achieve staged regulation of liver fibrosis by regulating drug metabolism-cytochrome P450，arginine biosynthesis，and the PPAR signaling pathway.

Objective::To explore the approach of minimally invasive transthoracic intramyocardial cellular transplantation under echocardiographic guidance to promote ischemic myocardial repair in a preclinical big-animal study.Methods::Female Guangxi Bama miniature pigs (weight: 25–30 kg) were randomly allocated into the sham group, untreated myocardial infarction (MI) group (MI group), the MI and surgical intramyocardial injection (SIM) group (MI-SIM group), and the MI and transthoracic echocardiography-guided percutaneous intramyocardial injection (TTEPIM) group (MI-TTEPIM group) ( n = 4 each) using a lottery method. A swine MI model was established in the 3 groups excluding the sham group, and human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) labeled with the herpes simplex virus type-1 thymidine kinase reporter gene (hiPS-CM TK+) were transplanted by SIM in MI-SIM group and TTEPIM in MI-TTEPIM group. The operation time, postoperative recovery time of animals and volume of blood loss were collected for comparison between MI-SIM group and MI-TTEPIM group. 9-(4-[ 18F] fluoro-3-(hydroxymethyl) butyl) guanine positron emission tomography/computed tomography imaging was performed to track the hiPS-CM TK+in vivo. Cardiac function and morphology were evaluated by echocardiography. Results::The operation time and postoperative recovery time of MI-TTEPIM group were significantly shorter than those of MI-SIM group ((28.3 ± 3.6) min vs. (97.0 ± 6.7) min, P < 0.001; (1.3 ± 0.3) d vs. (7.5 ± 0.9) d, P < 0.001). MI-TTEPIM also showed significantly lesser volume of blood loss during cell transplantation than MI-SIM group ((4.3 ± 0.8) mL vs. (47.0 ± 4.1) mL, P < 0.001). The transplanted cells could be traced more accurately in vivo in MI-TTEPIM than in MI-SIM. The circumferential strain of intervention region in the MI-TTEPIM group (–25.07% ± 0.27%) was significantly higher than that of the MI-SIM (–20.39% ± 0.67%) and MI groups (–19.68% ± 0.67%), respectively ( P < 0.01). Conclusion::A minimally invasive TTEPIM protocol with stem cells for treating the ischemic myocardium was established in this study. Transplantation of hiPS-CM TK+ with this method could promote the recovery of the circumferential strain of the ischemic myocardium. The findings of this study lay a foundation for the clinical transformation of this auxiliary means of treatment in the future.

Objective::To explore the approach of minimally invasive transthoracic intramyocardial cellular transplantation under echocardiographic guidance to promote ischemic myocardial repair in a preclinical big-animal study.Methods::Female Guangxi Bama miniature pigs (weight: 25–30 kg) were randomly allocated into the sham group, untreated myocardial infarction (MI) group (MI group), the MI and surgical intramyocardial injection (SIM) group (MI-SIM group), and the MI and transthoracic echocardiography-guided percutaneous intramyocardial injection (TTEPIM) group (MI-TTEPIM group) ( n = 4 each) using a lottery method. A swine MI model was established in the 3 groups excluding the sham group, and human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) labeled with the herpes simplex virus type-1 thymidine kinase reporter gene (hiPS-CM TK+) were transplanted by SIM in MI-SIM group and TTEPIM in MI-TTEPIM group. The operation time, postoperative recovery time of animals and volume of blood loss were collected for comparison between MI-SIM group and MI-TTEPIM group. 9-(4-[ 18F] fluoro-3-(hydroxymethyl) butyl) guanine positron emission tomography/computed tomography imaging was performed to track the hiPS-CM TK+in vivo. Cardiac function and morphology were evaluated by echocardiography. Results::The operation time and postoperative recovery time of MI-TTEPIM group were significantly shorter than those of MI-SIM group ((28.3 ± 3.6) min vs. (97.0 ± 6.7) min, P < 0.001; (1.3 ± 0.3) d vs. (7.5 ± 0.9) d, P < 0.001). MI-TTEPIM also showed significantly lesser volume of blood loss during cell transplantation than MI-SIM group ((4.3 ± 0.8) mL vs. (47.0 ± 4.1) mL, P < 0.001). The transplanted cells could be traced more accurately in vivo in MI-TTEPIM than in MI-SIM. The circumferential strain of intervention region in the MI-TTEPIM group (–25.07% ± 0.27%) was significantly higher than that of the MI-SIM (–20.39% ± 0.67%) and MI groups (–19.68% ± 0.67%), respectively ( P < 0.01). Conclusion::A minimally invasive TTEPIM protocol with stem cells for treating the ischemic myocardium was established in this study. Transplantation of hiPS-CM TK+ with this method could promote the recovery of the circumferential strain of the ischemic myocardium. The findings of this study lay a foundation for the clinical transformation of this auxiliary means of treatment in the future.

Objective:To analyze the research literature related to end tuberculosis (TB) using bibliometric methods, so as to provide researchers with insights into current research trends and hotspots in this field.Methods:A search was conducted using the Web of Science core collection data base on March 5, 2024. The research was limited to articles and reviews published between 2014 and 2023. The results were visualized with VOSviewer, and an analysis was performed on the involved national, international research cooperation networks and keyword clustering.Results:A total of 1 092 articles related to end TB research were retrieved and screened, with a total citation counts of 14 871 and an average citation counts of 13.62 per article. The United States of America had the highest number of publications (328 articles, 30.04%), while China ranked seventh (100 articles, 9.16%). International scientific collaboration network analysis indicated that countries primarily included the United Kindom, the United States of America, Switzerland, South Africa, the Netherlands, Australia, and India, which had formed close cooperation in the field of end TB research. Keyword clustering analysis suggested that current research hotspots in end TB field included cost analysis related to TB, management of latent TB individuals, strategies for TB prevention and control, key technologies in TB elimination, and TB epidemiology and associated risk factors.Conclusions:Over the past decade, the number of publications and citations in the field of end TB is relatively high. International research collaboration has been extensive, and the research content covers multiple dimensions, including the management and cost analysis of different disease stages, technological innovations, considerations for comprehensive control strategy, and epidemiology.

Objective:To systematically quantify the access to screening and surveillance service of liver cancer in populations in China, especially a series of sub-indicators of the availability.Methods:Following the specific indicators applied by the International Agency for Research on Cancer in the session of availability and use of screening practices in several cancer screening handbooks, information about the access/availability of liver cancer screening and surveillance in population in China were collected; the indicators included local policies and guidelines, procedures most commonly used or recommended, population coverage and participation rate, compliance and related factors, treatment rate, acceptability, equity and others. Systematic review approach was used, combined with searching core literatures/monograph, websites of governments and available program reports, for a systematic analysis on the access to liver cancer screening and surveillance in populations in China.Results:A total of 34 journal articles were included from the systematic review and most of which were about the participation of secondary liver screening or surveillance compliance; additional information were mainly obtained from the other sources. Overall, there were clearly recommended screening and surveillance procedures for liver cancer in the three major cancer screening programs funded by the central government of China. It was estimated that 0.09% of the population aged 35-74 years were covered by liver cancer screening in 2019 in China. The overall participation rates of secondary screening ranged from 37.5% to 62.3% in three major programs, the median compliance rate of surveillance was reported as 26.9% ( Q1, Q3: 23.5%, 41.0%) in the 6 included studies. Two studies reported the factors affecting the participation and compliance. A large-scale multicenter analysis showed that the subject acceptability to alpha fetoprotein test combined with ultrasound screening was as high as 99.3% in high-risk population in urban area. The treatment rate of liver cancer founded by screening, surveillance or follow-up was estimated to be >90% in rural population. No studies of equity were obtained via the systematic review. Conclusions:The public health service programs in China all recommend specific procedures for liver cancer screening in general population and surveillance for high-risk individuals. However, the overall availability needs to be improved, particularly in the indicator of population coverage. Participation rates of screening and compliance rates of surveillance varied among the included programs and the studies, suggesting that the influencing factors need to be further identified. The relatively high subject acceptability suggests the potential demands for screening service. More efforts are needed to address the access to screening and surveillance of liver cancer in populations in China.

Objective To evaluate the technique and clinical results of the modular fluted tapered stems for treating periprosthetic femoral fractures in revision hip arthroplasty.Methods From August 2007 to February 2014,fourteen patients (14hips) with periprosthetic femoral fractures underwent revision hip arthroplasty with modular fluted tapered stem.A retrospective analysis was performed involving all patients who were followed-up more than 2 years.The subjects consisted of 4 males and 10 females with mean age of 73.4±6.6 years (range,62-82 years) at the time of revision.All patients were unilateral with 8 left hips and 6 right hips.The status of primary arthroplasty was bipolar hemiarthroplasty in 3 patients and total hip arthroplasty in 11 patients.Nine cases were with cemented stems,5 cases with uncemented stems.The interval from primary hip arthroplasty to revision surgery ranged from 40 to 163 months,with an average of 120.9±31.9 months.Eight cases with Vancouver type B3 periprosthetic femoral fracture were found preoperatively,6 cases with aseptic loosening and bone deficiency occurred periprosthetic femoral fracture during the operation.Based on the Paprosky classification system for femoral bone deficiency:type ⅢA in 8 hips,type ⅢB in 5 hips,type Ⅳ in 1 hip.Both the femoral and the acetabular components were revised in 9 patients.All femoral fractures were treated with cable fixation,and the cortical allograft struts were used to augment femoral bone stock in 7 patients.The patients were followed up at 6 weeks,3 months,6 months,9 months,12 months and annually thereafter.Harris Hip Score System and radiographic examination was used to evaluate the clinical results,including fracture union,implant stability,bone stock,hip joint function and postoperative complications.Results The mean duration of follow-up was 62.1 ±22.2 months (range,30-96 months).The mean times of fracture union were 6.2±2.5 months (range,3-12 months).The Harris Hip Score improved from 29.6± 10.3 preoperatively to 86.3±4.2 postoperatively (t=-21.6,P=0.00).Thirteen cases (93％,13/14) had the stem subsidence of 4.9±2.5 mm (range,0-9 mm).Thirteen cases (93％,13/14) were presented with femoral bony restoration.Two cases showed incorporation of the allograft in 7 patients.One patient developed deep venous thrombosis of lower limbs,and one suffered from subcutaneous hematomas after surgery.There was no infection,aseptic loosening,dislocation or periprosthetic fracture complications at the followup.Conclusion The short-medium term results of the modular fluted tapered prosthesis applied in periprosthetic femoral fractures are encouraging in revision hip arthroplasty.The present technology can provide reliable primary stability and can tolerate minimal subsidence postoperatively.

OBJECTIVE:To systematically evaluate therapeutic efficacy of local application of gentamicin collagen sponge in the prevention of surgical incision infection,and to provide evidenced-reference for clinical treatment. METHODS:Retrieved from PubMed,EMBase,Cochrane Library,CBM,CJFD,VIP and Wanfang databases,randomized controlled trials (RCTs) about lo-cal application of gentamicin collagen sponge(trial group)vs. routine surgery disposal(control group)in the prevention of surgical incision infection were collected. After data extraction and quality evaluation with modified Jadad scale,Meta-analysis was per-formed by using Rev Man 5.3 statistical software. RESULTS:A total of 16 literatures were included,involving 7752 patients. The results of Meta-analysis showed that the incidence of surgical incision infection in trial group was significantly lower than control group,with statistical significance [OR=0.71,95%CI(0.61,0.84),P<0.001]. The packet statistics showed that the incidence of surgical incision infection in cardiovascular surgery group [OR=0.59,95%CI(0.37,0.96),P=0.03] and skin soft tissue operation group [OR=0.34,95%CI(0.15,0.75),P=0.008] were significantly lower than control group. There was no statistical significance in the incidence of incision infection between digestive system operation group and control group [OR=0.62,95%CI(0.25,1.54), P=0.30]. The incidence of surgical incision infection in≤30 d group was significantly lower than control group[OR=0.58,95%CI (0.41,0.82),P=0.002];there was no statistical significance between more than 30 d group and control group [OR=0.86,95%CI (0.71,1.04),P=0.13]. The incidence of surgical incision infection [OR=0.65,95%CI(0.52,0.82),P<0.001] in gentamicin high-dose group (>100 mg) was significantly lower than control group;there was no statistical significance between gentamicin low-dose group (≤100 mg) and control group [OR=0.96,95%CI(0.72,1.28),P=0.77]. CONCLUSIONS:Local application of gentamicin collagen sponge may have certain effect on the prevention of surgical infection. Different types of surgery,observation time and dose have different prevention effects. It should be used carefully according to clinical practice.

Objective To assess the value of contrast-enhanced ultrasound(US)in differential diagnosis of hyperechoic hepatic lesions when compared to conventional US.Methods Eighty-four hyperechoic liver lesions in 66 patients were examined using both conventional and contrast-enhanced US techniques.Results Receiver operating characteristic analysis revealed a significant improvement in the discrimination of malignant versus benign hyperechoic hepatic lesions (area under the receiver operating characteristic curve,0.867±0.045 at conventional US,0.997±0.003 with contrast-enhanced US(P＜0.0001).For correct diagnoses types of hyperechoic liver lesions,contrast-enhanced US improved from 64.3% to 92.9%,comic)ared with conventional US (P＜0.001).Conclusions Contrast-enhanced US showed a significant improvement in characterization and differentiation of hyperechoic hepatic lesions when compared to conventional US.