Objective To investigate the differential expression of hepatocyte growth factor activator (HGFA) and its inhibitors (HAI-1,HAI-2) during cirrhotic and normal liver regeneration after partial hepatectomy,and to explore the causes of the delayed liver regeneration after partial hepatectomy in cirrhotic rat model.Methods We used 40％ CCl4 subcutaneous injection to establish the cirrhotic rat model,and then performed 70％ liver resection for the experimental group together with no operation for the healthy rats as control group.Rats in each group after 3 hours,6 hours,12 hours,24 hours and 48 hours were randomly sacrificed and specimens were collected.The serum HGFA was detected by enzyme-linked immunosorbent assay (ELISA),and we used RT-PCR to detect the mRNA expressions of HAI-1 and HAI-2 in splenic tissue.Results The serum HGFA level in cirrhotic rats at each time point was all significantly lower than that in the control group (P ＜0.05).The expression of HAI-1 mRNA in cirrhotic rats was sustained at a higher level than that in the control group (P ＜ 0.05),but there was no significant difference on the HAI-2 mRNA expression between the two groups (P ＞ 0.05).Conclusions The synthesis of HGFA during the liver regeneration after partial hepatectomy in cirrhosis rats is lower compared with healthy rats,which may lead to the insufficient activation of HGF precursor,eventually causing the slow liver regeneration.HAI-2 may not be involved in the healing process of liver.

BACKGROUND:Studies have shown that the reason of the slower liver regeneration in individuals of cirrhotic liver after partial hepatectomy compared with healthy liver may be related to the delayed synthesis and secretion of hepatocyte growth factor during liver regeneration, but the cause of this phenomenon is not clear. The hepatocyte growth factor activator inhibitor found in recent years can indirectly inhibit the activation of hepatocyte growth factor, but there is little research to explore the expression of hepatocyte growth factor activator inhibitor in the regeneration process after partial hepatectomy in cirrhotic liver and its relationship with the liver regeneration. OBJECTIVE:To investigate the expression of hepatocyte growth factor activator inhibitors (HAI-1, HAI-2) during cirrhotic and normal liver regeneration after partial hepatectomy through establishing the cirrhotic rat model, and to explore the biological effects of HAI-1, HAI-2 in cirrhotic liver during the liver regeneration after partial hepatectomy. METHODS:We used 40%CCl4 subcutaneous injection to establish the cirrhotic rat model, then we performed 70%liver resection for the experimental group. The rats in the control group only received ordinary water feeding and 70%liver resection. Rats in each group were randomly sacrificed before surgery and at 3 hours, 6 hours, 12 hours, 24 hours and 48 hours after surgery, and samples were col ected. We used RT-PCR technology to detect the expression of HAI-1 mRNA, HAI-2 mRNA in splenic tissue. RESULTS AND CONCLUSION:The expression levels of HAI-1 mRNA of two groups after partial hepatectomy were increased firstly and then decreased. The expression of HAI-1 mRNA in cirrhotic rats was sustained higher than that of the control group (P<0.05), there was no significant difference between the two groups of the expression of HAI-2 mRNA (P>0.05). The expression of HAI-1 mRNA in liver cirrhosis rats after resection was consistently higher than that in healthy rats, which may lead to the insufficient synthesis and secretion of hepatocyte growth factor activator in cirrhotic rats, then hepatocyte growth factor precursor may not be activated enough, eventual y leading to slow liver regeneration. HAI-2 may not be involved in the wound repair process of liver.

A novel method for analysis of three active components curcumin, demethoxycurcumin and bisdemethoxycurcumin in Curcuma longa L. was developed by HPLC coupled with electrochemical detection. Three curcuminoids were well separated on a C18 column and detected with high sensitivity. A mobile phase containing acetonitrile and 10 mM Na2HPO4-H3PO4 (pH 5.0) (50:50, v/v) was used. Good linearity was obtained in the range of 0.208-41.6, 0.197-39.4, and 0.227-114μM for curcumin, demethoxycurcumin and bisdemethoxycurcumin respectively. The limit of detection reached up to 10 ? 8 M, which was lower than that by UV detection. The relative standard deviations (RSDs) ranged from 1.06%to 1.88%for intra-day precision and from 4.30%to 5.79%for inter-day precision, respectively. The proposed method has been applied in real herb sample and recoveries ranging from 86.3%to 111%were obtained.

Objective To study the promoting effects and mechanisms of interleukin-22 on liver regeneration in GCl4-induced liver fibrosis mice after partial hepatectomy.Methods One hundred and fortyfour C57/BL6 mice were randomly divided into four groups:PHX group,CCl4 group,CCl4 + PHX group,and CCl4 + IL22 + PHX group.The blood samples were taken to measure serum ALT and AST levels.ALT /AST was calculated to observe the liver injury at 3 h,6 h,12 h,24 h,48 h and 72 h after hepatectomy.The liver tissue specimens were collected at each time point after hepatectomy.We measured the hepatic lobe to calculate the liver weight ratio and conducted pathological examinations to observe the degree of fibrosis and pathological changes at each time point.The positive expression of proliferating cell nuclear antigen (PCNA) in liver tissue was tested by immunohistochemistry.The level of CyclinD1 and STAT3 (Signal transducer and activator of transcription 3) signaling pathway was detected by Western blot.Results (1) Compared with CCl4 + PHX group,the ALT/AST ratio of CCl4 + IL22 + PHX group was significantly higher at 24 h,48 h and 72 h,and the level of ALB of CCl4 + IL22 + PHX group was obviously increased at 48 h and 72 h (P ＜ 0.05).(2) The liver regeneration was significantly increased in CCl4 + IL22 + PHX group.Compared with CCl4 + PHX group (2.08 ± 0.16,2.77 ± 0.07,2.97 ± 0.14),the liver weight ratio of CCl4 + IL22 + PHX group(2.34 ± 0.07,3.23 ± 0.09,3.55 ± 0.09) dramatically increased at 24 h,48 h and 72 h.Moreover,the pathological sections displayed that the disease was alleviated (P ＜ 0.05).(3) Immunohistochemical assay and western blot revealed that compared with other three groups,the level of PCNA,STAT3 and Cyclin D1 was significantly lower in the CCl4 + PHX group.However,the level of PCNA,STAT3 and Cyclin D1 apparently increased in CCl4 + IL22 + PHX group at 24 h,48 h and 72 h (P ＜ 0.05).Conclusion Interleukin-22 may significantly promote liver regeneration and reduce liver pathological injury in liver fibrosis mice induced by administration of CCl4 after hepatectomy,which plays a positive role in the recovery of liver function.

Objective To explore a reliable method of 70% hepatectomy model in liver fibrosis mice. Methods Sixty-six C57BL6 mice were randomly devided into control group (n=6), the traditional group (n=30, ligation and removal liver lobe) and improved group (n=30, removal of liver lobe after blocking blood flow). Those 60 mice were induced liver fibrosis firstly, then randomly divided into six mice in each group, and were sacrificed at preoperative, 12, 24, 48 and 72 hours after liver resection. Liver tissues and blood samples were collected. The survival rate and incidence of complications were recorded and compared between two groups. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured to observe the liver injury after 70%hepatectomy. The ratio of liver weight to body weight and the expression of proliferating cell nuclear antigen (PCNA) were also measured to observe the difference of liver regeneration between the two groups. Results (1) Compared to the pathological control group, liver fibrosis model was established successfully in both traditional group and improved group, which can be used in 70%hepatectomy. So the follow-up experiment can be undertook timely. (2) Compared to traditional group, the survival rate was improved significantly in improved group (96.67%vs. 73.33%), and the incidence of complications was significantly lower (P<0.05). (3) The ALT and AST levels were higher 12 h and 24 h after operation in traditional group than those of improved group (P<0.05), while ALT and AST levels were increased first 12 h after operation and then decreased in both groups (P<0.05). (4) The liver/body weight ratio showed a decreasing trend 12 h after hepatectomy in two groups. The expression of PCNA increased at the beginning of postoperative, and reached its peak at 48 h (P<0.05). However, there was no significant difference at each time point between the two groups. Conclusion By blocking blood flow to establish 70% hepatectomy model in liver fibrosis mice, we can significantly improve the success rate of the model, and reduce the incidence of complications.

Objective:To investigate the efficacy and safety of nerve decompression surgery through the lateral-rectus approach for sacral plexus nerve injury after sacral fracture fixation.Methods:A retrospective study was conducted to analyze the 10 patients with combined sacral plexus nerve injury after sacral fracture fixation who had been admitted to Department of Orthopedics, Xiangya Hospital between May 2022 and May 2023. There were 2 males and 8 females with an age of 16.5 (15.0, 26.3) years. At the time of injury, the patients had been clearly diagnosed as sacral fracture combined with sacral plexus nerve injury. By the Denis classification of sacral fractures: 7 cases of type Ⅱ and 3 cases of type Ⅲ; sacral plexus nerve injury sites: 1 case of L 4, 8 cases of L 5, 7 cases of S 1, and 2 cases of S 2. All of them were treated with reduction and internal fixation via the posterior approach within 2 weeks after injury, but after surgery their manifestations of sacral plexus nerve injury still persisted which were confirmed by CT, magnetic resonance imaging and neuromuscular electromyography. Therefore, at (4.0±2.3) months after internal fixation, all patients were treated with nerve decompression surgery through the lateral-rectus approach. The operative time, intraoperative bleeding, length of hospitalization, Gibbons nerve damage score and neurological recovery at the last follow-up were recorded. Results:In the 10 patients, the operative time was (112.0±21.5) min, intraoperative bleeding (215.0±91.3) mL, and length of hospitalization 7.0 (6.0, 8.5) d. Intraoperatively, sacral plexus nerve compression was found in 9 cases (6 cases of nerve compression and pulling due to fracture displacement, 3 cases of nerve entrapment due to soft tissue scar adhesion), and 1 case of nerve root avulsion injury. No other intraoperative complications occurred. The 10 patients were followed up for (9.2±2.3) months after surgery. At the last follow-up, the Gibbons score for the 10 patients improved from preoperative 3.0 (3.0, 3.3) points to 1.0 (1.0, 2.0) point, and their British Medical Research Council (BMRC) nerve injury grading was improved from the preoperative grade 0.0 (0.0, 1.3) to grade 3.5 (2.8, 4.0) (1 case of M5, 4 cases of M4, 4 cases of M3, and 1 case of M2).Conclusion:The lateral-rectus approach is effective and safe for exploration and decompression of the sacral plexus nerve in patients combined with sacral plexus nerve injury despite sacral fracture fixation.

Objective:Differences between randomized controlled trial (RCT) results and real world study (RWS) results may not represent a true efficacy-effectiveness gap because efficacy-effectiveness gap estimates may be biased when RWS and RCT differ significantly in study design or when there is bias in RWS result estimation. Secondly, when there is an efficacy- effectiveness gap, it should not treat every patient the same way but assess the real-world factors influencing the intervention's effectiveness and identify the subgroup likely to achieve the desired effect.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:Ten articles were included to discuss how to use the RCT research protocol as a template to develop the corresponding RWS research protocol. Moreover, based on correctly estimating the efficacy-effectiveness gap, evaluate the intervention effect in the patient subgroup to confirm the subgroup that can achieve the expected benefit-risk ratio to bridge the efficacy-effectiveness gap.Conclusion:Using real-world data to simulate key features of randomized controlled clinical trial study design can improve the authenticity and effectiveness of study results and bridge the efficacy-effectiveness gap.

Objective:Randomized controlled trials (RCT) usually have strict implementation criteria. The included subjects' characteristics of the conditions for the intervention implementation are quite different from the actual clinical environment, resulting in discrepancies between the risk-benefit of interventions in actual clinical use and the risk-benefit shown in RCT. Therefore, some methods are needed to enhance the extrapolation of RCT results to evaluate the real effects of drugs in real people and clinical practice settings.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:A total of 12 articles were included. Three methods in the included literature focused on: ①improving the design of traditional RCT to increase population representation; ②combining RCT Data with real-world data (RWD) for analysis;③calibrating RCT results according to real-world patient characteristics.Conclusions:Improving the design of RCT to enhance the population representation can improve the extrapolation of the results of RCT. Combining RCT data with RWD can give full play to the advantages of data from different sources; the results of the RCT were calibrated against real-world population characteristics so that the effects of interventions in real-world patient populations can be predicted.

Objective To compare the difference in risk of drug-induced liver injury(DILI)between Runzao Zhiyang capsules and loratadine tablets.Methods Based on electronic medical records obtained through active drug safety monitoring in China,a retrospective cohort study was conducted to collect clinical data of patients who took oral Runzao Zhiyang capsules or loratadine tablets between January 1,2004,and December 31,2021.After balancing the confounding factors with a 1∶1 propensity score,the logistic regression model was used to analyze the risk of DILI between the two groups.Additionally,the sensitivity analysis of the data before matching and after inverse probability weighting method was conducted.Results A total of 31 636 patients were included,with 26 840 patients taking Runzao Zhiyang capsules orally.After matching there were 4 072 patients in each group,the risk of DILI in the Runzao Zhiyang capsules group was significantly lower than in the loratadine tablets group(0.12％vs.0.83％),OR=0.15(95％CI 0.06 to 0.38).Before matching and after inverse probability weighting,the incidence of DILI in the Runzao Zhiyang capsules group was still lower than that in the loratadine tablets group,and the difference was statistically significant(P＜0.001).Conclusion Runzao Zhiyang capsules have a better safety profile in terms of liver injury compared to the loratadine tablets.The hepatotoxicity of Polygonum multiflorum and its preparations should be scientifically evaluated and rationally treated to ensure medication safety and health.

ObjectiveTo explore the research status and trends of cohort studies on traditional Chinese medicine （TCM） efficacy evaluation from 2017 to 2022 and provide ideas and references for research in this field. MethodsSix databases including Pubmed， Web of Science， Embase， Scopus， Cochrane Library and CNKI were searched from January 1st， 2017 to December 31st， 2022. The total number of annual publications， journals， highly cited literatures， and keywords were quantitatively and visually analyzed by Bibliometrix. ResultsA total of 328 articles were included， which were published in 141 journals. The number of articles published in this field showed an overall upward trend， and retrospective cohort studies （282 papers， 85.98%） accounted for the largest proportion. A total of 151 cohort studies （46.04%） were conducted based on the database and showed an overall upward trend. The subjects were mainly patients with tumors （77 papers， 23.48%）， and cardiovascular and cerebrovascular diseases （64 papers， 19.51%）. The top 3 highly cited literatures mainly explore the association between TCM and survival outcome and quality of life in patients with malignant tumors. Fourteen and twenty-five high-frequency keywords were included in Chinese and English literature respectively， which formed 3 clusters such as research methods， statistical analysis and diseases. ConclusionIt was the current status to focus on retrospective cohort studies and focus on patients with tumors or cardiovascular and cerebrovascular diseases. Using observational database to conduct cohort studies of TCM efficacy evaluation could be the future research direction.