The purpose of this paper is to explore the decoction and dosing methods of rhubarb root and rhizome in classical prescriptions and to provide a reference basis for the clinical use of rhubarb root and rhizome. By collating the relevant classical prescriptions of rhubarb root and rhizome in Shanghan Lun and Jingui Yaolüe, the relationship between its decoction and dosing methods and the syndrome was analyzed. The decoction of rhubarb root and rhizome in classical prescriptions can be divided into three categories: simultaneous decoction, decoction later, and other methods (impregnation in Mafei decoction, decoction with water from the well spring first taken in the morning, and pills). If it enters the blood level or wants to slow down, rhubarb root and rhizome should be decocted at the same time with other drugs. If it enters the qi level and wants to speed up, rhubarb root and rhizome should be decocted later. If it wants to upwardly move, rhubarb root and rhizome should be immersed in Mafei decoction. If it wants to suppress liver yang, rhubarb root and rhizome should be decocted with water from the well spring first taken in the morning. If the disease is prolonged, rhubarb root and rhizome should be taken in pill form. The dosing methods of rhubarb root and rhizome can be divided into five categories: draught, twice, three times, before meals, and unspecified. For acute and serious illnesses with excess of pathogenic qi and adequate vital qi, we choose draught. For gastrointestinal diseases, we choose to take the medicine twice. For achieving a moderate and long-lasting effect, we choose to take the medicine three times. If the disease is located in the lower part of the heart and abdomen, we choose to take it before meals. The use of rhubarb root and rhizome in clinical practice requires the selection of the appropriate decoction and dosing methods according to the location of the disease, the severity of the disease, the patient′s constitution, and the condition after taking the medicine.

BACKGROUND:During healing process of chronic wounds,excessive production of reactive oxygen species can impair the function of L929 fibroblasts,thereby delaying wound repair.Therefore,protecting fibroblasts from oxidative stress is important to promote wound healing. OBJECTIVE:To assess the protective effects of carboxymethyl chitosan-oxidized chondroitin sulfate/platelet-rich plasma(CMC-OCS/PRP)hydrogel on L929 cells under H2O2 stimulation. METHODS:CMC-OCS/PRP hydrogels were prepared,and the micromorphology,degradation performance,scavenging ability of H2O2 and hydroxyl radical and biocompatibility of the hydrogels were characterized.L929 cells with good growth state were taken and cultured in five groups.The control group was cultured conventionally.H2O2 was added to the H2O2 group.Carboxymethyl chitosan-oxidized chondroitin sulfate hydrogel extract+H2O2 was added to the CMC-OCS group.Platelet-rich plasma gel extract+H2O2 was added to the PRP group.The CMC-OCS/PRP group was treated with carboxymethyl chitosan-oxidized chondroitin sulfate/platelet-rich plasma hydrogel extract+H2O2.Each group was treated with hydrogel extract for 6 hours,and then H2O2 for 24 hours.After culture,the levels of active oxygen and malondialdehyde,apoptosis and expression of collagen fiber I protein were detected.In the presence of H2O2,the above hydrogel extracts were directly or indirectly co-cultured with L929 fibroblasts for 36 hours,respectively.Migration ability of the cells was detected by scratch test and Transwell chamber test. RESULTS AND CONCLUSION:(1)CMC-OCS/PRP hydrogels had uniform and interrelated porous structure and good degradation ability,could effectively remove H2O2 and hydroxyl radicals in vitro,and had good biocompatibility.(2)Compared with the control group,the apoptosis rate,reactive oxygen species,and malondialdehyde levels were increased(P<0.05);the spread area of cells was decreased(P<0.05),and the expression of collagen fiber I protein had no significant changes(P>0.05)in the H2O2 group.Compared with the H2O2 group,reactive oxygen species level was decreased in the CMC-OCS group(P<0.05),malondialdehyde level was decreased(P<0.05),and cell spread area was increased(P<0.05)in the PRP group,CMC-OCS group,and CMC-OCS/PRP group;apoptosis rate was decreased in the CMC-OCS/PRP group(P<0.05),and collagen fiber I protein expression was increased in the PRP group,CMC-OCS group,and CMC-OCS/PRP group(P<0.05).(3)Compared with the control group,the number of cell migration was decreased(P<0.05),and the migration area had no significant change(P>0.05)in the H2O2 group.Compared with the H2O2 group,the number and area of cell migration were increased in the PRP group,CMC-OCS group,and CMC-OCS/PRP group(P<0.05),and the increase was most significant in the CMC-OCS/PRP group.(4)Under oxidative stress,CMC-OCS/PRP hydrogel can improve the migration ability of fibroblasts,resist cell apoptosis,and preserve cell extension function.

Probiotics have shown excellent application prospects in preventing and treating many diseases. However, their sensitivity to the harsh environment in vivo always leads to a massive loss of viability and insufficient therapeutic effect. Fortunately, modified probiotics have emerged and provide multiple possibilities for their use in various diseases. Modification not only endows probiotics with extra capacity to resist severe environments but also gives them exogenous characteristics, such as prolonged retention time and improved therapeutic effects. Modified probiotics could combine with other therapies, which has opened up new avenues to enhance the efficacy of probiotic-based therapy. In this review, we have summarized the current physicochemical and biological modification strategies of probiotics. In addition, the progress of research on probiotic-based combination therapy has also been extensively reviewed, which contributes to the enhanced delivery of probiotics or other active constituents and provides new ideas for disease treatment, bioimaging, and diagnosis.

Psoriasis is a chronic inflammatory skin disease, and its pathogenesis is largely modulated by abnormal angiogenesis. Previous research has indicated that AlkB homolog 5 (ALKBH5), an important demethylase affecting N⁶-methyladenosine (m⁶A) modification, plays a role in regulating angiogenesis in cardiovascular and eye diseases. Our present study found that ALKBH5 was upregulated and co-localized with cluster of differentiation 31 (CD31) in the skin of IMQ group compared with control group. ALKBH5-deficient mice decreased IMQ-induced psoriatic dermatitis and exhibited histological improvements, including decreased epidermal thickness, hyperkeratosis, numbers of dermal capillary vessels and inflammatory cell infiltration. ALKBH5-KO mice alleviated angiogenesis in psoriatic lesions by downregulating the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Additionally, the expression of ALKBH5 was significantly upregulated in IL-17A-induced human umbilical vein endothelial cells (HUVECs), which further promoted the expression of angiogenesis-related cytokines and endothelial cell proliferation. Cell proliferation and angiogenesis were suppressed in ALKBH5 knockdown group, whereas ALKBH5 overexpression promoted these processes. The regulation of angiogenesis in HUVECs by ALKBH5 was facilitated through the AKT-mTOR pathway. Collectively, ALKBH5 plays a pivotal role in psoriatic dermatitis and angiogenesis, which may offer a new potential targets for treating psoriasis.
Animals ; Psoriasis/chemically induced* ; Mice ; Humans ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; AlkB Homolog 5, RNA Demethylase/genetics* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Cell Proliferation ; Mice, Knockout ; Disease Models, Animal ; Signal Transduction ; Male ; Skin/blood supply* ; Mice, Inbred C57BL ; Angiogenesis

Objective:To investigate the correlation between non-Hodgkin lymphoma (NHL) and chronic hepatitis B virus (HBV) infection by using the method of two-sample bidirectional Mendelian randomization (MR) analysis.Methods:Genetic variation data for NHL came from the Finnish database (FinnGen) Consortium 2021 public genome-wide association study (GWAS) dataset including 1 088 patients with NHL and 299 952 control subjects. The GWAS dataset for chronic HBV infection was derived from GWAS analysis published in 2021, including 145 NHL patients and 351 740 control subjects. NHL was used as an exposure factor, single nucleotide polymorphism (SNP) significantly associated with NHL was used as an instrumental variable (IV), chronic HBV infection was used as an outcome variable. The two-sample MR analysis was performed by using inverse-variance weighted (IVW) method. Chronic HBV infection was taken as an exposure factor, SNP significantly associated with chronic HBV infection was taken as IV, and NHL was taken as outcome variable, and then reverse two-sample MR analysis was performed. The IVW method used the inverse variance of each IV as the weight to fit, and the ratio method was used to measure SNP one by one and make weighted regression analysis, so as to obtain the overall estimate. MR-Egger regression and the weighted median (WME) method were also used to supplement the IVW method. In sensitivity analysis, leave-one-out sensitivity analysis was used to evaluate the impact of a single SNP. Cochran Q test was used to analyze the heterogeneity of the selected IV. MR-Egger regression was used to measure the average horizontal pleiotropy of IV, and the P-value of directivity was calculated. The MR-pleiotropy residual sum and outlier (MR-PRESSO) Global Test was used to exclude possible horizontal pleiotropic outliers and reduce bias. Results:In the leave-one-out sensitivity analysis, SNP with significant effects on causal associations was excluded. In forward MR analysis, IVs were 10 SNPs associated with NHL; the IVW method indicated that there was no causal association between NHL and chronic HBV infection ( OR = 0.979, 95% CI: 0.925-1.036, P = 0.465). MR-Egger regression ( OR = 0.992, 95% CI: 0.926-1.062, P = 0.825) and WME method ( OR = 0.992, 95% CI: 0.934-1.055, P = 0.805) were used as supplementary methods to obtain the consistent results. In sensitivity analysis, Cochran Q test showed no heterogeneity among IVs (IVW method: P = 0.271, MR-Egger regression: P = 0.239). Horizontal pleiotropy was not found in the MR-Egger regression (intercept was -0.01, P = 0.778) and the MR-PRESSO Global Test ( P > 0.05), suggesting robust results. In the reverse MR analysis, IVs were 8 SNPs associated with NHL; the IVW method ( OR = 1.117, 95% CI: 0.942-1.324, P = 0.202) also found no significant causal relationship between chronic HBV infection and NHL; MR-Egger regression ( OR = 0.777, 95% CI: 0.450-1.343, P = 0.401) and WME method ( OR = 1.120, 95% CI: 0.887-1.415, P = 0.351) also showed similar risk estimates. Sensitivity analysis also suggested the consistency and reliability of the results. Cochran Q test showed no heterogeneity among IVs (IVW method: P = 0.775, MR-Egger regression: P = 0.903). Horizontal pleiotropy was not found by MR-Egger regression (intercept was 0.102, P = 0.548) and MR-PRESSO Global Test ( P > 0.05). Conclusions:MR analysis suggests no causal relationship between NHL and chronic HBV infection.

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 search, evaluate and summarize the best research evidence of perioperative intestinal management in patients with cervical spinal cord injury, so as to provide evidence-based basis for clinical nursing practice.Methods:Literature on perioperative intestinal management of cervical spinal cord injury were systematically searched in databases, domestic and foreign relevant guidlines network and professional associations, such as UpToDate, Cochrane Library, PubMed, China National Knowledge Infrastructure, Wanfang Database, etc. The search period was from the establishment of the databases to October 1, 2023. The quality of the included literature was evaluated and the evidence was extracted and summarized.Results:Finally, 9 articles were included, including 2 guidelines, 2 expert consensuses, 1 randomized controlled trials, and 4 observational studies. Twenty-five pieces of evidence were summarized across six aspects: assessment, diet management, physical activity, physical therapy, drug therapy, prevention and management of intestinal complications.Conclusions:The best evidence of perioperative intestinal management in patients with cervical spinal cord injury summarized in this study can provide reference for clinical nursing practice.

Objective:To construct a prediction model for neurogenic shock in patients with traumatic cervical spinal cord injury and validate its effectiveness.Methods:A retrospective case-control study was conducted on the clinical data of 381 patients with traumatic cervical spinal cord injury admitted to the Third Hospital of Shanxi Medical University from January 2017 to December 2022, including 311 males and 70 females, aged 12-86 years [(55.1±12.9)years]. A total of 121 patients (31.8%) were complicated with neurogenic shock. The patients were randomly divided into training set ( n=267) and validation set ( n=114) with a ratio of 7∶3. The training set was divided into neurogenic shock group ( n=81) and non-neurogenic shock group ( n=186) according to whether they were complicated with neurogenic shock. The general data, clinical data, laboratory indicators and imaging data of the patients were collected. Univariate analysis was used to determine differences in the aforementioned indicators between the neurogenic shock group and non-neurogenic shock group in the training set. Multivariate Logistic regression analysis was conducted to screen the predictors for neurogenic shock in patients with traumatic cervical spinal cord injury, and regression equation was constructed. A nomogram prediction model based on the regression equation was plotted with R programming language. Receiver operating characteristic (ROC) curves of the training set and validation set were plotted, when the area under the curve (AUC) was calculated to determine the discriminability of the model. The calibration of the model was assessed with calibration curves. The clinical applicability of the model was evaluated by the decision curve analysis (DCA). Results:The univariate analysis showed that there were statistically significant differences in the American Spinal Injury Association (ASIA) grade, tracheal intubation, serum albumin concentration within 24 hours on admission, intramedullary lesion length (IMLL), maximum spinal cord compression (MSCC), increased signal intensity (ISI), and highest damaged segment between the neurogenic shock group and non-neurogenic shock group in the training set ( P<0.05). The multivariate Logistic regression analysis revealed that AISA grade (grade C vs. grade A: OR=0.13, 95% CI 0.03, 0.59, P<0.01; grade D vs.grade A: OR=0.04, 95% CI 0.01, 0.28, P<0.01), serum albumin concentration within 24 hours on admission ( OR=0.75, 95% CI 0.65, 0.86, P<0.01), IMLL ( OR=2.71, 95% CI 1.68, 4.38, P<0.01), ISI (grade 2 vs.grade 0: OR=5.62, 95% CI 1.07, 29.48, P<0.05), and highest damaged segment ( OR=0.49, 95% CI 0.29, 0.83, P<0.01) were predictors for neurogenic shock in patients with traumatic cervical spinal cord injury. Based on the 5 forementioned variables, the regression equation was constructed as follows: Logit[ P/(1- P)]=10.99-1.06×＂AISA grade＂-0.29×＂serum albumin concentration within 24 hours on admission＂+1.04×＂IMLL＂+0.89×＂ISI＂-0.74×＂highest damaged segment＂. In the prediction model constructed based on the equation, the AUC values of the training set and validation set were 0.97 (95% CI 0.97, 0.99) and 0.95 (95% CI 0.91, 0.99). Calibration curves of the training set and validation set demonstrated the prediction curve roughly overlapped with the reference curve and the mean absolute errors of the two sets were 0.013 and 0.050. DCA results showed that the net benefit rate of patients was greater than 0 when the threshold probability ranged from 0% to 97% for the training set and from 0% to 100% for the validation set. Conclusion:The prediction model based on the AISA grade, serum albumin concentration within 24 hours on admission, IMLL, ISI, and highest damaged segment demonstrates good discriminability, calibration and clinical applicability in predicting neurogenic shock in patients with traumatic cervical spinal cord injury.

BACKGROUND:Diabetic wounds have complicated conditions such as infection,ischemia,peripheral neuropathy,and vascular disease.Ordinary hydrogel dressings with single structure and function cannot meet the needs of diabetic wound healing. OBJECTIVE:To explore the effect of a hydrogel loaded with platelet-rich plasma on wound healing of full-thickness skin defects in diabetic rats. METHODS:The blood of SD rats was extracted to prepare platelet-rich plasma.Carboxymethyl chitosan/oxychondroitin sulfate hydrogel and carboxymethyl chitosan/oxychondroitin sulfate hydrogel loaded with platelet-rich plasma were prepared separately.Streptozotocin was used to induce diabetes model in adult male SD rats.A round full-thickness skin wound with a diameter of 2 cm was made on the back of diabetic rats.The rats were randomly divided into four groups(n=10 per group).The blank group was applied with gauze on the wound.The hydrogel group,platelet-rich plasma group,and composite hydrogel group were respectively applied with the corresponding hydrogel,platelet-rich plasma and hydrogel loaded with platelet-rich plasma.The wound healing was observed within 20 days after treatment. RESULTS AND CONCLUSION:(1)On day 20 after treatment,the wound healing rate of the hydrogel group,platelet-rich plasma group and composite hydrogel group was significantly higher than that of the blank group(P<0.05).The wound healing rate of the composite hydrogel group was significantly higher than that of the platelet-rich plasma group(P<0.05).(2)The results of hematoxylin-eosin staining on day 5 after treatment showed that compared with the blank group,hydrogel group and platelet-rich plasma group,there were a large number of inflammatory cell infiltration,new granulation tissue and capillary formation in the wound tissue of the composite hydrogel group.(3)On day 5 after treatment,the results of immunohistochemical staining and western blot assay showed that the expression levels of tumor necrosis factor α and interleukin 1β in wound tissue in the composite hydrogel group were significantly lower than those in the blank group,hydrogel group and platelet-rich plasma group(P<0.05).(4)Masson staining results on day 15 after treatment showed that compared with the blank group,hydrogel group and platelet-rich plasma group,there were more collagen fibers in the wound tissue of the composite hydrogel group,which were orderly,evenly distributed and dense.(5)CD31 immunofluorescence staining showed that on day 15 after treatment,the expression of CD31 in wound tissue of the composite hydrogel group was significantly higher than that of the blank group,hydrogel group and platelet-rich plasma group(P<0.05).(6)These results suggest that the hydrogel loaded with platelet-rich plasma can promote the healing of full-thickness skin defect wounds in diabetic rats by promoting granulation tissue,collagen fiber and angiogenesis,and reducing the inflammatory response.