Objective To observe the chronic hepatotoxicity of the commonly used herbicide mixture in the mice. Methods Low doses herbicide mixture diluted in mice drinking water. The parameters related to hepatic function and ultrastructural changes of the hepatocytes were examined after 18 weeks and 24 weeks of treatment. Results No changes was observed in every parameter after 18 weeks of treatment compared with the control group. After 24-week of treatment, the electron microscope revealed the ultrastructural changes in the hepatocytes, rough endoplasmic reticulum showed dilatation, mitochondria showed matrix muddy with distortion and disappearance of inner crista and the serum transaminase were higher than those in the control group(P

BACKGROUND:At present,the problems such as serious shortage of donor liver organs for transplantation,surgical injury,high incidence of surgical complications,as well as the high costs limit the development of liver transplantation,while the hepatic stem cell(HSC)transplantation provides a new pathway for the treatment of end-stage liver disease.OBJECTIVE:To introduce the source and classification of HSCs,research progress and problems of HSC transplantation for treatment of end-stage liver disease,and the clinical application prospects of HSC transplantation.METHODS:Articles were collected from CNKI and Medline database with the keywords of "hepatic stem cells,liver disease,transplantation" in both Chinese and English from 1999 to 2009.Among 87 articles,30 were included according to inclusion and exclusion criteria.Following reading titles and abstracts,original articles,and articles closely related to HSC transplantation with reliable argument and evidence and general analysis were included.Articles of repetitive studies and poor quality were excluded.RESULTS AND CONCLUSION:The HSC can be divided into liver-derived stem cells and non-liver-derived stem cells.Liver-derived stem cells include hepatic oval cells,mature liver cells and small hepatocyte-like progenitor cell.Non-liver-derived stem cells were mainly derived from embryonic stem cells,bone marrow hematopoietic stem cells and pancreatic stem cells.Currently,the research for the treatment of liver disease by HSC is still in its early stages.There are many difficult issues to be studied and solved in the discovery,separation,purification,comprehensive identification,cultivation,directed differentiation as well as clinical trials.However,as a new source of seed cells,HSC can not only replace the damaged tissue but can stimulate the receptor in tissue regeneration.Hence,compared with the clinical liver transplantation and bio-artificial liver,there are very bright future for the treatment of liver diseases by transplating HSC.

OBJECTIVEThis work investigated mesenchymal stem cells (MSCs) modified with Runt-related transcription factor 2 (Runx2) therapy for bone regeneration in rabbit mandibular distraction osteogenesis.

METHODSForty-eight New Zealand mature white rabbits were randomly divided into three groups after the rabbit model of mandibular distraction osteogenesis was established: reconstruction plasmid modified with Runx2 (group A), plasmid without Runx2 (group B), and the same dose of saline as control (group C). At the fifth day of distraction phase, MSCs with reconstruction plasmid modified with adv-hRunx2-gfp were injected into the distraction gap of group A. MSCs with reconstruction plasmid modified with adv-gfp was injected into the distraction gap of group B, whereas group C was injected with the same dose of saline. At 8 weeks after injection, all animals were sacrificed, and the distracted mandibles were harvested. The general imaging histological observation and three-point bending test were used for evaluation.

RESULTSCT plain scan and histological analysis confirmed that the amount of new bone forming in the distraction gap of group A was significantly higher than those in groups B and C. Dual-energy X ray and three-point bending test results also showed that the bone mineral density, bone mineral content, and maximum load of the distraction gap of group A were significantly higher than those of groups B and C (P<0.01).

CONCLUSIONRunx2-ex vivo gene therapy based on MSCs can effectively promote the bone regeneration in rabbit mandibular distraction osteogenesis and shorten the stationary phase. Therefore, reconstruction of craniofacial fracture would be a valuable strategy

Absorptiometry, Photon ; Animals ; Bone Density ; Bone Regeneration ; physiology ; Core Binding Factor Alpha 1 Subunit ; genetics ; pharmacology ; Genetic Therapy ; Mandible ; physiology ; surgery ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stromal Cells ; Osteogenesis ; genetics ; Osteogenesis, Distraction ; methods ; Plasmids ; Rabbits ; Random Allocation ; Transcription Factors ; genetics ; physiology ; Treatment Outcome

Objective To clarify the role of pentraxin 3 (PTX3) in the development of peripheral arterial disease (PAD) in maintenance hemodialysis (MHD) patients. Methods One hundred and sixteen patients undergone MHD therapy in our center for more than 3 months were enrolled in the study. Clinical data were collected for analysis. Ankle-brachial index (ABI) was used to estimate the presence of PAD. Patients were divided into PAD group (ABI<0.9) and nonestimate the association of PAD with PTX3 as well as other potential risk factors. Results The incidence of PAD was 18.1% (21/116). Plasma level of PTX3 was significantly higher in PAD patients than that in non-PAD patients [(5.55 ±2.63) μg/L vs (2.32 ±1.29)μg/L, P<0.01].Univariate analysis showed ABI values were negatively correlated with plasma PTX3 levels (r =-0.548, P<0.01), high-sensitivity C-reactive protein (hsCRP), age, blood glucose and triglyceride. ROC curve of PAD revealed that area under curve (AUC) of PTX3 was 0.901 (P<0.01). With the cut-off value of PTX3 as 4.06 μg/L, the diagnostic sensitivity and specificity in PAD were 81.0% and 91.5%. ROC curve of PAD showed that AUC of hsCRP was 0.640 (P<0.05). With the cut-off value of hsCRP as 3.33 mg/L, the diagnostic sensitivity and specificity in PAD were 57.1% and 56.8%. Using Logistic regression, plasma PTX3 was found to be associated with PAD (0R=9.755, 95%CI:2.359-19.354, P=0.001). Conclusions The PAD incidence of MHD patients in our center is 18.1%. Plasma PTX3 level is significantly correlated with the presence of PAD in MHD patients. The sensitivity and specificity of PTX3 are higher than those of hsCRP for PAD diagnosis.

Objective:To summarize and evaluate the best evidence for nonpharmacological interventions in patients with post-stroke depression.Methods:Based on the "6S" pyramid model of evidence resources, the Chinese and English databases and websites of relevant professional associations were systematically searched for evidence on nonpharmacological interventions in patients with post-stroke depression, including guidelines, evidence summaries, systematic reviews, and expert consensus. The retrieval time limit was from the establishment of the database to July 31, 2021. The quality of the article was independently evaluated by two researchers, and evidence was extracted and summarized for the article that met the quality standards.Results:A total of 15 articles were included, including 4 guidelines, 1 evidence summary, 9 systematic reviews, and 1 expert consensus. A total of 25 pieces of the best evidence were compiled from five aspects, namely, health education, exercise intervention, psychological intervention, physical intervention and traditional Chinese medicine techniques.Conclusions:Medical and nursing staff should formulate nonpharmacological interventions for post-stroke depression patients according to the specific clinical conditions and patient characteristics, and apply the evidence in clinical practice.

Objective To analyze the influencing factors of frailty in elderly patients with lower extremity osteoarthritis,and to construct and validate the risk assessment model.Methods Convenient sampling method was used to select 535 elderly patients with lower extremity osteoarthritis from tertiary hospitals and community health service centers in Hangzhou from January to September 2022 as the survey subjects including 357 in the modeling group and 178 in the validation group.Univariate and multivariate logistic regression analysis were used to determine the risk factors of frailty,construct a risk assessment model and draw a nomogram.The discrimination and calibration of the model were evaluated by the area under the receiver operating characteristic curve and the Hosmer-Lemeshow test.The Bootstrap method was used for intemal validation of the model,and the time verification method was used for external validation.Results The model variables included the number of affected joints,age-adjusted Charlson comorbidity index,pain,nutritional status,sedentary time,activity of daily living,osteoarthritis index,lower limb muscle strength,and Social Support Rating Scale score.The Hosmer-Lemeshow test results of the model showed that P=0.202,the area under the receiver operating characteristic curve was 0.942,the optimal critical value was 0.392,the sensitivity was 0.914,the specificity was 0.893,and the accuracy rate was 0.902.The internal and external validation showed that the C-statistics were 0.935 and 0.919,respectively,and the calibration curve showed good fitting.Conclusion The risk assessment model has a good degree of discrimination and calibration,which can more intuitively and easily screen elderly patients with lower extremity osteoarthritis at high risk of frailty,and provide references for early monitoring,identification,prevention and control.

Objective:To observe the effect of preoperative application of butorphanol tartrate on postoperative recovery quality in patients undergoing thoracoscopic lobectomy.Methods:A prospective selection was conducted on 96 lung cancer patients who underwent thoracoscopic lobectomy and were admitted to Linyi People′s Hospital from May 2021 to September 2021. They were randomly divided into observation group and control group using a random table number method, with 48 patients in each group. The observation group received intravenous injection of 0.02 mg/kg butorphanol tartrate 15 minutes before anesthesia induction; The control group was given an equal volume of physiological saline. The operation site, operation time, remifentanil dosage during operation, heart rate (HR) and mean arterial pressure (MAP) at each time point of admission (T 0), intubation (T 1), 5 min after intubation (T 2), extubation (T 3), 5 min after extubation (T 4), and 15 min into post-anaesthesia care unit (PACU) (T 5) were recorded; The awakening Restlessness score (RS), Ramsay score, Visual Analogue Scale (VAS) score at T 4 and T 5, the time required from completion to extubation, and postoperative anesthesia related adverse reactions were evaluated. Results:There was no significant difference in the operation site, operation time and remifentanil dosage between the two groups (all P>0.05). Compared with T 0, the HR at T 2, T 3 and T 4, MAP at T 1, T 2, T 3 and T 4 in the two groups decreased significantly (all P<0.05). The HR of the observation group at T 1 and T 3 was significantly lower than that of the control group, and the difference was statistically significant (all P<0.05). The VAS scores of T 4 and T 5 in the observation group were lower than those in the control group after surgery, while the Ramsay score were higher than those in the control group (all P<0.001). The incidence of postoperative restlessness, nausea and vomiting in the observation group was lower than that in the control group ( P<0.05). Conclusions:Administering 0.02 mg/kg butorphanol tartrate 15 minutes before anesthesia induction can improve the quality of recovery in patients undergoing thoracoscopic lobectomy, reduce restlessness and related adverse reactions during recovery.

Coronavirus Disease 2019 (COVID-19) is caused by 2019 novel coronavirus (2019-nCoV). Type I and type III interferons, as important available clinically used broad-spectrum antiviral drugs, have been considered as promising candidate drugs for the treatment and prevention of COVID-19. In early 2020, more than 40 clinical trials, including the World Health Organization (WHO) SOLIDARITY study, have been launched in the world to explore the clinical efficacy and application method of interferons in the treatment of COVID-19. Meanwhile, animal models and human clinical specimens were used in many laboratories to explore the immunologic role and mechanistic function of interferons in COVID-19. However, the conclusion of the studies in the past three years were not consistent and even contradictory albeit numerous data were accumulated by the scientific community, which reflects the complexity of the role and function of interferons in COVID-19. Recently, the results of four large high-quality randomized controlled phase III clinical trials were reported. In this review, we systematically summarize and analyze the complicated and contradictory data from the level of immunopathological mechanism and clinical trials. We clarify that the heterogeneous clinical outcome of 2019-nCoV infection is closely related to the level and production time of interferons and that interferons are protective in the early stage of COVID-19 but may cause immunological damages in the late stage which may exacerbate inflammation. Further high-quality prospective clinical trials that strictly control confounding factors are still warranted to finally elucidate the precise role and clinical application of interferons in COVID-19.