ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia（FD） and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats（7 days old） were randomly divided into the normal group（n=12） and the modeling group（n=48）， and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared， the rats in the modeling group were randomly divided into the model group， the low-dose and high-dose groups of Xingpi capsules（0.135， 0.54 g·kg^-1） and the domperidone group（3 mg·kg^-1）， with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water， and rats in the rest of the groups were gavaged with the corresponding medicinal solution， once a day for 7 d. The general survival condition of the rats was observed， and the water intake and food intake of the rats were measured， the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment， the pathological damage of the rat duodenum was examined by hematoxylin-eosin（HE） staining， and the expressions of colonic tight junction protein（Occludin） and zonula occludens protein-1（ZO-1） were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group， and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration， and Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses were carried out. The transcriptomic results were validated by Western blot， immunofluorescence， and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group， the general survival condition of rats in the model group was poorer， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly reduced（P<0.05）， inflammatory infiltration was seen in duodenal pathology， and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced（P<0.01）. Compared with the model group， the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly increased（P<0.05）， the duodenal pathology showed a decrease in inflammatory infiltration， and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased（P<0.01）. Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） through the key genes such as Slc5a1， Abhd6. The validation results showed that compared with the normal group， the phosphorylation levels of PI3K and Akt proteins， the protein expression level of interleukin（IL）-1β， and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3， Slc5a9 and other key genes were significantly increased（P<0.01）. Compared with the model group， the phosphorylation levels of PI3K and Akt， the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3 and Slc5a9 were significantly reduced（P<0.05）. Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein， and linarionoside A， valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats， its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum， and E-nerolidol， Z-nerolidol， linarionoside A， valerosidatum and senkirkine may be its key active ingredients.

ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia（FD） and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats（7 days old） were randomly divided into the normal group（n=12） and the modeling group（n=48）， and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared， the rats in the modeling group were randomly divided into the model group， the low-dose and high-dose groups of Xingpi capsules（0.135， 0.54 g·kg^-1） and the domperidone group（3 mg·kg^-1）， with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water， and rats in the rest of the groups were gavaged with the corresponding medicinal solution， once a day for 7 d. The general survival condition of the rats was observed， and the water intake and food intake of the rats were measured， the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment， the pathological damage of the rat duodenum was examined by hematoxylin-eosin（HE） staining， and the expressions of colonic tight junction protein（Occludin） and zonula occludens protein-1（ZO-1） were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group， and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration， and Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses were carried out. The transcriptomic results were validated by Western blot， immunofluorescence， and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group， the general survival condition of rats in the model group was poorer， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly reduced（P<0.05）， inflammatory infiltration was seen in duodenal pathology， and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced（P<0.01）. Compared with the model group， the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly increased（P<0.05）， the duodenal pathology showed a decrease in inflammatory infiltration， and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased（P<0.01）. Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） through the key genes such as Slc5a1， Abhd6. The validation results showed that compared with the normal group， the phosphorylation levels of PI3K and Akt proteins， the protein expression level of interleukin（IL）-1β， and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3， Slc5a9 and other key genes were significantly increased（P<0.01）. Compared with the model group， the phosphorylation levels of PI3K and Akt， the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3 and Slc5a9 were significantly reduced（P<0.05）. Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein， and linarionoside A， valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats， its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum， and E-nerolidol， Z-nerolidol， linarionoside A， valerosidatum and senkirkine may be its key active ingredients.

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Osteoporosis （OP） is a skeletal metabolic disease characterized by bone loss and destruction of bone microstructure. Changes in estrogen levels are not the only pathogenic factors for the occurrence and development of OP. MicroRNA （miRNA） plays an important regulatory role in cells. The complementary sequences of miRNA and targeted mRNA combine to inhibit the expression of targeted mRNA through post-transcriptional regulation， forming a complex regulatory network. Research suggests that miRNA is closely related to the occurrence and development of various diseases， including inflammatory diseases， metabolic diseases， and cancer. Targeted mRNA participates in post-transcriptional gene expression regulation in OP， mainly regulating the balance among bone construction， bone resorption， and osteoblast differentiation. Therefore， miRNA-based gene therapy is a rapidly developing disease treatment strategy. Traditional Chinese medicine can improve bone metabolism by intervening in miRNA differential expression to target and regulate osteogenic/osteoclast differentiation. This article summarized the targeting effects of miRNAs in physiological and developmental processes such as bone cell proliferation， differentiation， survival， and apoptosis， reviewed and classified their mechanisms of action and targets， and sorted out the current treatment methods of traditional Chinese medicine for preventing and treating OP and drugs that exert bone protective functions through miRNAs. This review is expected to provide theoretical reference and research guidance for future research on OP treatment by regulating miRNA.

Objective:To explore the influence of deep learning reconstruction algorithm combined with low-dose CT on image quality and bone mineral density measurement and the application value in opportunistic osteoporosis screening.Methods:A total of 119 patients (aged ≥40 years) who underwent a combined chest and upper abdominal low-dose scan were prospectively included. All the images were reconstructed using filtered back projection(FBP) alogrithm, hybrid model-based adaptive statistical iterative reconstruction (ASIR-V) 50% and three levels of deep learning reconstruction algorithm respectively. Bone mineral density (BMD) values for different reconstruction conditions were measured and compared using asynchronous quantitative CT software. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of descending aorta, liver and spleen were calculated, and the image noise was the standard deviation of anterior abdominal wall fat and the image quality was objectively evaluated by using the five-point subjective evaluation method. The objective and subjective image quality of different body parts with different reconstruction method was compared.Results:There was no statistical difference in BMD with different reconstruction method ( P > 0.05). Compared with ASIR-V 50%, the SNRs of high level deep learning image reconstruction (DLIR-H)in descending aorta, latissimus dorsi, liver and spleen were increased by 103.88%, 125.09% and 136.13% respectively, and the image noise was decreased by 55.98%. Both the CNR and subjective scores (except the ability to display lung lesions) of DLIR-H were better than those of DLIR-L and ASIR-V 50% ( χ2 =158.31-275.35, P<0.001). Conclusions:The deep learning algorithm does not affect the accuracy of bone mineral density measurement, and the image quality is better than that of ASIR-V 5%. Deep learning algorithm combined with low-dose CT can be used for opportunistic osteoporosis screening.

Objective:To compare the efficacy between deep continuous irrigation combined with vacuum sealing drainage (VSD) and routine dressing change in treating multidrug-resistant bacterial infections at the surgical wound site in patients with major vascular injury.Methods:A retrospective cohort study was conducted to analyze the clinical data of 28 patients with surgical wound infections by multidrug-resistant bacteria after major vascular injury treated at the First Affiliated Hospital of Henan University of Science and Technology from March 2015 to December 2021. There were 15 males and 13 females, aged 15-65 years [(41.8±12.9)years]. All patients received vascular graft surgery after major vascular injury. Postoperative microbiological culture indicated that the wound infections were caused by Carbapenem-resistant organisms (CRO) or vancomycin- resistant Enterococci (VRE), with no available sensitive antibiotics for treatment. The patients received surgical debridement every five days after vascular graft surgery and were divided into two groups to receive the subsequent treatments including a routine dressing change (routine dressing group, 14 patients) or a deep continuous irrigation combined with VSD (irrigation combined with VSD group, 14 patients). On the first day post-operation and then every 3 days, inflammatory indicators [white blood cell count, neutrophils, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and procalcitonin] were observed in the two groups (repeat tests when a patient′s condition changed). Microbiological cultures were applied with patient samples every 5 days to observe the wound and infection control. Comparisons were made between the two groups regarding the duration to normal levels of inflammatory indicators, duration to negative CRO or VRE cultures, visual analogue score (VAS) before and at 1, 2 and 3 hours after changing the irrigation fluid (changing the dressing), conditions of wound skin grafting or flap repair, and incidences of anastomotic fistula.Results:All patients were followed up for 12-24 months [(14.3±2.4)months], during which no wound redness, rupture, purulent discharge or infection recurrence was noted. The duration to normal levels was (9.4±2.4)days for white blood cells, (9.6±2.8)days for neutrophils, (9.8±3.1)days for CRP, (12.2±3.6)days for ESR, and (7.6±1.9)days for procalcitonin in the irrigation combined with VSD group, significantly shorter than those in the routine dressing group [(15.2±3.1)days, (13.6±3.4)days, (14.2±3.9)days, (19.9±3.3)days, and (12.9±4.1)days, respectively] (all P<0.01). The duration to negative CRO or VRE cultures was (13.9±3.1)days in the irrigation combined with VSD group, significantly shorter than that in the routine dressing group [(19.2±6.9)days] ( P<0.05). The VAS before and at 1, 2 and 3 hours after changing the irrigation fluid was (4.2±0.7)points, (4.1±0.9)points, (4.2±0.9)points and (4.1±0.8)points in the irrigation combined with VSD group, respectively, and was (4.3±0.6)points, (6.9±0.7)points, (5.4±0.9)points and (4.5±0.9)points in the routine dressing group, respectively. The VAS score in the irrigation combined with VSD group was significantly lower than that in the routine dressing group at 1 hour and 2 hours after changing the irrigation fluid (all P<0.01), while no significant differences were found before and at 3 hours after changing the irrigation fluid (all P>0.05). After infection control, 5 patients (35.7%) in the irrigation combined with VSD group required skin grafting or flap repair at the wound site, lower than 11 patients (78.6%) in the routine dressing group ( P<0.01). The incidence of anastomotic fistula was 7.1% (1/14) in the irrigation combined with VSD group, lower than 42.9% (6/14) in the routine dressing group ( P<0.05). Conclusion:When multidrug-resistant bacterial infections occur at the surgical wound site after major vascular injury, deep continuous irrigation combined with VSD performs better than routine dressing change in controlling infection as well as in reducing pain, rate of wound skin grafting or flap repair and incidence of anastomotic fistula, without reliance on antibiotics.

Objective To investigate the association between baseline IgM level and treatment response to ursodeoxycholic acid (UDCA) in patients with primary biliary cholangitis (PBC). Methods A retrospective analysis was performed for the clinical data of 637 PBC patients who were diagnosed and treated with UDCA for the first time in The Fifth Medical Center of Chinese PLA General Hospital from January 2010 to January 2020. The PBC patients were divided into UDCA complete response group with 436 patients and UDCA poor response group with 201 patients, and baseline clinical data were compared between the two groups. According to the optimal cut-off value of IgM determined by the area under the ROC curve (AUC) of baseline indices in predicting the risk of poor treatment response, the patients were divided into IgM ≥1.5×ULN group and IgM < 1.5×ULN group, and baseline parameters, treatment response, and prognostic model score were compared between groups. The t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. The Cochran-Mantel-Haenszel test was used for subgroup analysis, and forest plots were plotted for related risk values. Results Compared with the UDCA complete response group, the UDCA poor response group had significantly higher proportion of patients with liver cirrhosis, levels of total bilirubin, aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bile acid, total cholesterol (TC), IgA, and IgM, and positive rate of anti-Gp210 antibody at baseline ( χ 2 =4.596, Z =-9.932, -8.931, -8.361, -7.836, -4.694, -3.242, and -2.115, χ 2 =15.931, all P < 0.05). The UDCA poor response group had significantly higher Mayo Risk Score, Globe score, and UK-PBC risk score than the UDCA complete response group ( t =4.092, Z =-10.910 and -11.646, all P < 0.001). Compared with the normal IgM group, the elevated IgM group had significantly higher levels of AST, ALP, TC, IgA, and IgG and a significantly higher positive rate of anti-Gp210 antibody ( Z =-3.774, -5.063, -4.344, -2.051, and -6.144, χ 2 =25.180, all P < 0.05). IgM had an AUC of 0.552 in predicting poor treatment response. Compared with the IgM < 1.5×ULN group, the IgM ≥1.5×ULN group had significantly higher levels of AST, ALP, TC, and IgG, a significantly higher positive rate of anti-Gp210 antibody, and a significantly higher poor UDCA response rate ( Z =-4.193, -5.044, -3.250, and -5.465, χ 2 =25.204 and 8.948, all P < 0.05). IgM ≥1.5×ULN had an odds ratio of 1.416 (95% confidence interval [ CI ]: 1.129-1.776, P =0.003) in predicting poor response. The subgroup analysis showed that for patients without liver cirrhosis, IgM ≥1.5×ULN had an odds ratio of 1.821 (95% CI : 1.224-2.711, P =0.003) in predicting poor response. Conclusion Baseline IgM level has an important value in predicting UDCA response. IgM level should be closely monitored during treatment in PBC patients with a high baseline IgM level, and second-line drugs should be given in time if the abnormality persists.

Objective:To explore the diagnostic accuracy of muscle ultrasound and plasma monocyte chemoattractant protein-1 (MCP-1) for ICU-acquired weakness (ICU-AW) in patients with sepsis.Methods:A prospective observational study was conducted. Patients with sepsis admitted to the intensive care unit (ICU) of Henan Provincial People's Hospital from April 2021 to October 2021 were enrolled. The demographic data were collected. The enrolled patients were evaluated with Medical Research Council (MRC) score every day until discharged from ICU. During this period, patients with total MRC score < 48 (for two consecutive times and a time interval of 24 hours) were divided into ICU-AW group, those with total MRC score ≥ 48 were served as non-ICU-AW group. On the 1st, 4th and 7th day following admission into ICU, ultrasound was used to measure the muscle linear thickness of the rectus femoris (RF-MLT), the cross sectional area of the rectus femoris (RF-CSA) and the muscle linear thickness of the vastus intermedius muscle (VI-MLT). And meanwhile, the plasmas samples of patients were collected to measure MCP-1 concentration by enzyme-linked immunosorbent assay (ELISA). The difference of each index was compared between the ICU-AW group and the non-ICU-AW group. The risk factors of ICU-AW in patients with sepsis were analyzed by binary Logistic regression. Besides, receiver operator characteristic curve (ROC curve) was plotted, the diagnostic value of ultrasound parameters and plasma MCP-1 level for ICU-AW in patients with sepsis was analyzed.Results:A total of 99 septic patients were enrolled, with 68 patients in the ICU-AW group and 31 patients in the non-ICU-AW group. Compared with the patients in the ICU-AW group, the patients in the non-ICU-AW group tended to be older, and had higher sequential organ failure assessment (SOFA) score, higher acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, higher rates of septic shock, higher blood lactic acid and lower Glasgow coma score (GCS). Binary Logistic regression analysis showed that APACHEⅡ score and septic shock were the risk factors of ICU-AW for septic patients [odds ratio ( OR) and 95% confidence interval (95% CI) were 1.310 (1.138-1.509) and 0.232 (0.072-0.746), respectively, both P < 0.05]. The RF-MLT, RF-CSA and VI-MLT on the 1st, 4th and 7th ICU day was falling over time. Compared with the patients in the ICU-AW group, the patients in the non-ICU-AW group had smaller RF-MLT on the 7th day [cm: 0.32 (0.22, 0.47) vs. 0.45 (0.34, 0.63), P < 0.05] and higher 7-day RF-CSA atrophy rate [25.85% (10.37%, 34.28%) vs. 11.65% (2.28%, 22.41%), P < 0.05]. According to ROC curve analysis, 7-day RF-MLT had diagnostic value for ICU-AW of septic patients. Area under ROC curve (AUC) was 0.688 (95% CI was 0.526-0.849); when the cut-off value was 0.41 cm, the sensitivity and the specificity were 66.7% and 68.4%. The levels of plasma MCP-1 in the ICU-AW group were significantly higher than those in the non-ICU-AW group on the 1st, 4th and 7th day. ROC curve analysis showed that the plasma MCP-1 levels on the 1st, 4th and 7th day played a significant role to diagnose ICU-AW for septic patients, the AUC and 95% CI were 0.732 (0.629-0.836), 0.865 (0.777-0.953), 0.891 (0.795-0.986), respectively. When the cut-off values were 206.3, 410.9, 239.5 ng/L, the sensitivity was 87.1%, 64.0%, 82.4%, and the specificity was 54.4%, 96.1%, 86.2%, respectively. Conclusion:The muscle mass parameters on the 7th day of bedside ultrasound and plasma MCP-1 levels had certain diagnostic values for ICU-AW in patients with sepsis.

OBJECTIVE To op timize the i ntegrated technology of producing area processing and decoction pieces processing of Curcuma longa （hereinafter refer to “integrated technology ”）. METHODS The content of ethanol-soluble extract in C. longa was determined by hot leaching method ；the contents of curcumin ，demethoxycurcumin and bisdemethoxycurcumin were determined by high performance liquid chromatography. On the basis of identification of producing area processing technology ， Using overall desirability （OD） value of the contents of ethanol-soluble extract ， curcumin， demethoxycurcumin and bisdemethoxycurcumin as evaluation indexes ，moisture content ，slice thickness and drying temperature as factors ，the integrated technology of C. longa was optimized by single factor tests combined with central composite design-response surface method ，and the validation tests were conducted. At the same time ，prepared product was compared with traditional decoction pieces prepared according to 2020 edition of Chinese Pharmacopoeia （part Ⅰ）. RESULTS The best integrated technology was that the fresh C. longa was boiled in boiling water for 5 min，dried at 50 ℃ to 40％ water content ，cut into 2 mm thin slices ，and dried at 50 ℃ until moisture content not exceeding 15.0％. After validation ，The deviation between the average OD value （0.811 3，RSD＝2.13％） and the predicted value （0.848 1）of the contents of ethanol-soluble extract ，curcumin，demethoxycurcumin and bisdemethoxycurcumin was 4.34％. OD value of the contents of ethanol-soluble extract ，curcumin，demethoxycurcumin and bisdemethoxycurcumin in decoction pieces prepared by integrated technology were all higher than those prepared by traditional technology. CONCLUSIONS The process optimized in this study is simple ，stable and feasible.

Methotrexate (MTX) is a widely used immunosuppressive drug. Large-dose of MTX is used for the treatment of cancer while low-dose is used for the treatment of rheumatoid arthritis (RA). This study aimed to explore the effect of MTX on the urinary proteome of rats. MTX was given to rats orally to construct an MTX intragastric administration rat model. The urine of the rats were collected within 10 hours after giving MTX, and the urine proteins of the rats were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). A total of 31 differential proteins were identified, of which 7 proteins were related to the effect MTX and the symptom of RA. The biological processes of some rats reflected the effect of MTX on the body's glutathione metabolism and the JAK/STAT signaling pathway, which indicated that urine proteins have the ability to reflect the effects of MTX on the body of rats. The spectrum of the differential proteins of each single rat showed that different individuals respond to the drug quite differently.
Rats ; Animals ; Methotrexate/metabolism* ; Proteome ; Chromatography, Liquid/methods* ; Tandem Mass Spectrometry/methods* ; Arthritis, Rheumatoid/drug therapy*