Analysis of therapeutic mechanism of Liushen Wan against colitis-associated colorectal cancer based on network pharmacology and validation in mice / 南方医科大学学报

OBJECTIVE@#To explore the therapeutic mechanism of Liushen Wan (LSW) against colitis-associated colorectal cancer (CAC) by network pharmacology.@*METHODS@#TCMSP, BATMAN-TCM, CNKI, PubMed, Genecards, OMIM, and TTD databases were used to obtain the related targets of LSW and CAC. The common targets of LSW and CAC were obtained using Venny online website. The PPI network was constructed using Cytoscape 3.8.2 to screen the core targets of LSW in the treatment of CAC. GO and KEGG enrichment analysis were conducted using DAVID database. The therapeutic effect of LSW on CAC was evaluated in a C57BL/6J mouse model of AOM/DSS-induced CAC by observing the changes in body weight, disease activity index, colon length, and size and number of the tumor. HE staining and RT-qPCR were used to analyze the effect of LSW on inflammatory mediators. Immunohistochemistry and TUNEL staining were used to evaluate the effect of LSW on the proliferation and apoptosis of AOM/DSS-treated colon tumor cells. Immunohistochemistry and Western blotting were used to detect the effects of LSW on the expression of TLR4 proteins in CAC mice.@*RESULTS@#Network pharmacology analysis identified 69 common targets of LSW and CAC, and 33 hub targets were screened in the PPI network. KEGG pathway enrichment analysis suggested that the effect of LSW on CAC was mediated by the Toll-like receptor signaling pathway. In the mouse model of AOM/DSS-induced CAC, LSW significantly inhibited colitis-associated tumorigenesis, reduced tumor number and tumor load (P < 0.05), obviously improved histopathological changes in the colon, downregulated the mRNA levels of proinflammatory cytokines, and inhibited the proliferation (P < 0.01) and promoted apoptosis of colon tumor cells (P < 0.001). LSW also significantly decreased TLR4 protein expression in the colon tissue (P < 0.05).@*CONCLUSION@#LSW can inhibit CAC in mice possibly by regulating the expression of TLR4 to reduce intestinal inflammation, inhibit colon tumor cell proliferation and promote their apoptosis.

Analysis of the clinical characteristics and therapeutic effect of refractory juvenile dermatomyositis to tofacitinib / 中华儿科杂志

Objective: To elucidate the clinical features of patients with refractory juvenile dermatomyositis (JDM), and to explore the efficacy and safety of tofacitinib in the treatment of refractory JDM. Methods: A total of 75 JDM patients admitted to the Department of Rheumatology and Immunology in Shenzhen Children's Hospital from January 2012 to January 2021 were retrospectively analyzed, and to analyze the clinical manifestations, efficacy and safety of tofacitinib in the treatment of refractory JDM. Patients were divided into refractory group with using of glucocorticoids in combination with two or more anti-rheumatic drugs for treatment, and the presence of disease activity or steroid dependence after a one-year follow-up. The non-refractory group is defined as clinical symptoms disappeared, laboratory indicators were normal, and clinical remission was achieved after initial treatment, and the clinical manifestations and laboratory indexes of the two groups were compared. The Mann-Whitney U test, Fisher's precision probability test was used for intergroup comparison. Binary Logistic multivariate regression analysis was used to identify risk factors for refractory JDM. Results: Among the 75 children with JDM, 41 were males and 34 were females with a age of onset of 5.3 (2.3, 7.8) years. The refractory group consisted of 27 cases with a age of onset of 4.4 (1.5, 6.8) years, while the non-refractory group consisted of 48 cases with a age of onset of 5.9 (2.5, 8.0) years. Compared with 48 cases in the non-refractory group, the proportion of interstitial lesions and calcinosis in the refractory group was higher than that in the non-refractory group (6 cases (22%) vs. 2 cases (4%), 8 cases (30%) vs. 4 cases (8%), both P<0.05). Binary Logistic regression analysis showed that observation group were more likely to be associated with to interstitial lung disease (OR=6.57, 95%CI 1.22-35.31, P=0.028) and calcinosis (OR=4.63, 95%CI 1.24-17.25, P=0.022). Among the 27 patients in the refractory group, 22 cases were treated with tofacitinib, after treatment with tofacitinib, 15 of 19 cases (86%) children with rashes showed improvement, and 6 cases (27%) with myositis evaluation table score less than 48 score both were improved, 3 of 6 cases (27%) had calcinosis were relieved, and 2 cases (9%) had glucocorticoid-dependence children were successfully weaned off. During the tofacitinib treatment, there was no increase in recurrent infection, blood lipids, liver enzymes, and creatinine were all normal in the 22 cases. Conclusions: Children with JDM with calcinosis and interstitial lung disease are more likely to develop refractory JDM. Tofacitinib is safe and effective for refractory JDM.

Therapeutic efficacy of hematopoietic stem cell transplantation for Wiskott-Aldrich syndrome in 60 children / 中华儿科杂志

Objective: To evaluate the therapeutic efficacy of hematopoietic stem cell transplantation (HSCT) for Wiskott-Aldrich syndrome (WAS), and to analyze the factors related to the outcomes. Methods: The clinical data of 60 children with WAS received HSCT in Shanghai Children's Medical Center from January 2006 to December 2020 were retrospectively analyzed. All cases were treated with a myeloablative conditioning regimen with busulfan and cyclophosphamide, and a graft-versus-host disease (GVHD) prevention regimen based on cyclosporine and methotrexate. Implantation, GVHD, transplant-related complications, immune reconstitution and survival rate were observed. Survival analysis was performed by Kaplan-Meier method, and Log-Rank method was used for univariate comparison. Results: The 60 male patients had main clinical features as infection and bleeding. The age at diagnosis was 0.4 (0.3, 0.8) years, and the age at transplantation was 1.1 (0.6, 2.1) years. There were 20 cases of human leukocyte antigen matched transplantation and 40 mismatched transplantation; 35 patients received peripheral blood HSCT, and 25 cord blood HSCT. All cases were fully implanted. The incidence of acute GVHD (aGVHD) was 48% (29/60) and only 2 (7%) developed aGVHD of grade Ⅲ; the incidence of chronic GVHD (cGVHD) was 23% (13/56), and all cases were limited. The incidence of CMV and EBV infection was 35% (21/60) and 33% (20/60) respectively; and 7 patients developed CMV retinitis. The incidence of sinus obstruction syndrome was 8% (5/60), of whom 2 patients died. There were 7 cases (12%) of autoimmune hemocytopenia after transplantation. Natural killer cells were the earliest to recover after transplantation, and B cells and CD4+T cells returned to normal at about 180 days post HSCT. The 5-year overall survival rate (OS) of this group was 93% (95%CI 86%-99%), and the event free survial rate (EFS) was 87% (95%CI 78%-95%). EFS of non-CMV reactivation group is higher than that of CMV reactivation group (95% (37/39) vs.71% (15/21), χ2=5.22, P=0.022). Conclusions: The therapeutic efficacy of HSCT for WAS is satisfying, and the early application of HSCT in typical cases can achieve better outcome. CMV infection is the main factor affecting disease-free survival rate, which can be improved by strengthening the management of complications.

Anemoside B4 regulates fatty acid metabolism reprogramming in mice with colitis-associated cancer / 中国中药杂志

The study aimed to investigate the effect of anemoside B4(B4) on fatty acid metabolism in mice with colitis-associated cancer(CAC). The CAC model was established by azoxymethane(AOM)/dextran sodium sulfate(DSS) in mice. Mice were randomly divided into a normal group, a model group, and low-, medium-, and high-dose anemoside B4 groups. After the experiment, the length of the mouse colon and the size of the tumor were measured, and the pathological alterations in the mouse colon were observed using hematoxylin-eosin(HE) staining. The slices of the colon tumor were obtained for spatial metabolome analysis to analyze the distribution of fatty acid metabolism-related substances in the tumor. The mRNA levels of SREBP-1, FAS, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 were determined by real-time quantitative PCR(RT-qPCR). The results revealed that the model group showed decreased body weight(P<0.05) and colon length(P<0.001), increased number of tumors, and increased pathological score(P<0.01). Spatial metabolome analysis revealed that the content of fatty acids and their derivatives, carnitine, and phospholipid in the colon tumor was increased. RT-qPCR results indicated that fatty acid de novo synthesis and β-oxidation-related genes, such as SREBP-1, FASN, ACCα, SCD-1, ACOX, UCP-2, and CPT-1 mRNA expression levels increased considerably(P<0.05, P<0.001). After anemoside B4 administration, the colon length increased(P<0.01), and the number of tumors decreased in the high-dose anemoside B4 group(P<0.05). Additionally, spatial metabolome analysis showed that anemoside B4 could decrease the content of fatty acids and their derivatives, carnitine, and phospholipids in colon tumors. Meanwhile, anemoside B4 could also down-regulate the expression of FASN, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 in the colon(P<0.05, P<0.01, P<0.001). The findings of this study show that anemoside B4 may inhibit CAC via regulating fatty acid metabolism reprogramming.

UPLC-Q-TOF-MS metabolomic study on improvement of acute myocardial ischemia in rats by Dalbergia cochinchinensis heartwood / 中国中药杂志

This paper aimed to study the effect of Dalbergia cochinchinensis heartwood on plasma endogenous metabolites in rats with ligation of the left anterior descending coronary artery, and to analyze the mechanism of D. cochinchinensis heartwood in improving acute myocardial ischemic injury. The stability and consistency of the components in the D. cochinchinensis heartwood were verified by the establishment of fingerprint, and 30 male SD rats were randomly divided into a sham group, a model group, and a D. cochinchinensis heartwood(6 g·kg~(-1)) group, with 10 rats in each group. The sham group only opened the chest without ligation, while the other groups established the model of ligation. Ten days after administration, the hearts were taken for hematoxylin-eosin(HE) staining, and the content of heart injury indexes in the plasma creatine kinase isoenzyme(CK-MB) and lactate dehydrogenase(LDH), energy metabolism-related index glucose(Glu) content, and vascular endothelial function index nitric oxide(NO) was determined. The endogenous metabolites were detected by ultra-high-performance liquid chromatography-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS). The results showed that the D. cochinchinensis heartwood reduced the content of CK-MB and LDH in the plasma of rats to relieve myocardial injury, reduced the content of Glu in the plasma, improved myocardial energy metabolism, increased the content of NO, cured the vascular endothelial injury, and promoted vasodilation. D. cochinchinensis heartwood improved the increase of intercellular space, myocardial inflammatory cell infiltration, and myofilament rupture caused by ligation of the left anterior descending coronary artery. The metabolomic study showed that the content of 26 metabolites in the plasma of rats in the model group increased significantly, while the content of 27 metabolites decreased significantly. Twenty metabolites were significantly adjusted after the administration of D. cochinchinensis heartwood. D. cochinchinensis heartwood can significantly adjust the metabolic abnormality in rats with ligation of the left anterior descending coronary artery, and its mechanism may be related to the regulation of cardiac energy metabolism, NO production, and inflammation. The results provide a corresponding basis for further explaining the effect of D. cochinchinensis on the acute myocardial injury.

Genomic structure of varicella-zoster virus and its vaccine application status / 中华预防医学杂志

With the determination of the whole genome sequence of varicella-zoster virus (VZV) virus, the successful breakthrough of infectious cloning technology of VZV, and the emergence of effective preventive vaccines, which have been proven to be effective and safe, varicella has become a disease preventable by specific immunity. This article will review the genomic structure, epidemiological characteristics, and research application progress of varicella vaccine and herpes zoster vaccine of varicella zoster virus to provide reference for primary prevention of the disease.

Progress on biliary flora and primary intrahepatic stone formation / 公共卫生与预防医学

Primary intrahepatic stone （PIS）is one of the intractable diseases in hepatobiliary surgery and an important cause of death from benign biliary tract diseases, and it has a high prevalence in the Yangtze River basin and southeastern coastal areas of China. At present, the mechanism of PIS occurrence has not been fully elucidated, but the role of biliary flora in the formation of PIS has been recognized by more and more studies. This article reviews the research progress of biliary flora in the formation of PIS with a view to strengthening the clinical understanding of mechanism of PIS, increasing the attention to the detection of biliary flora, and providing a reference for the prevention and treatment of PIS and the improvement of prognosis.

Inhibitory effect of chikusetsusaponin IVa on proliferation of triple negative breast cancer cells / 药学学报

Chikusetsusaponin IVa (CsIVa) is a natural active monomer of triterpene saponins in the Chinese herbal medicine of Panax japonicus, which has anti-inflammatory, anti-tumor and other effects. However, its function and mechanism in triple negative breast cancer (TNBC) remain unclear. This study investigated the inhibitory effect and mechanisms of CsIVa on the proliferation of triple negative breast cancer cell line MDA-MB-231. In this study, we found that CsIVa could significantly inhibit the proliferation of MDA-MB-231 cells and eliminate its potential toxic effect on normal breast cells (MCF-10A). The transcriptome sequencing results showed that the inhibition of proliferation of MDA-MB-231 cells by CsIVa was closely related to cell cycle and the pathway regulating cell cycle. Further studies confirmed that CsIVa blocked the cell cycle in G2/M phase by down-regulating the expression of cyclin dependent kinase 1 (CDK1), cyclin B1 and up-regulating the expression of cyclin dependent kinase inhibitor 1A (p21). Moreover, CsIVa can block cell cycle through inhibiting PI3K/AKT signal pathway. In conclusion, CsIVa regulates the expression of cell cycle related proteins (p21, CDK1, cyclin B1) via inhibiting the activity of PI3K/AKT signaling pathway, blocks TNBC cell cycle, and thus exerts its anti-tumor activity.

Diagnosis and treatment of intrahepatic biliary cystadenoma / 中华肝胆外科杂志

Objective:To study the clinical features of intrahepatic biliary cystadenoma (BCA), with the aim to improve its treatment results.Methods:The clinical data and follow-up results of 86 patients with BCA treated at our department from March 2010 to January 2021 were retrospectively analyzed. Of 86 patients, there were 15 males and 71 females, with age of (48.4±13.1) years old. According to the surgical procedures carried out, 44 patients were divided into the minimally invasive group and 42 into the open group. Clinical data including imaging data, blood biochemistry, and tumor markers were collected. The follow-up data of these patients was collected in outpatient clinics or by telephone review.Results:Of 86 patients, 19(22.1%) patients had a monocystic lesion while 67(77.9%) patients had a multicystic lesion, 64 patients (74.4%) had intracapsular segregation, and 12(14.0%) patients had solid structures. Eighty-six patients with BCA were misdiagnosed as hepatic cysts in 9 patients (10.4%), hepatic echinococcosis in 2 patients (2.3%), biliary hamartoma in 1 patient (1.2%), and hepatic hemangioma in 1 patient (1.2%) before surgery. The tumor size [(6.5±3.2) vs. (9.0±4.0) cm], operative time [115(88, 185) vs. 195(160, 254) min], intraoperative blood loss [50(20, 162) vs. 300(200, 600) ml], and postoperative hospital stay [4(3, 6) vs. 8(7, 10) d] were significantly lower in the minimally invasive group than the open group. The differences were statistically significant ( P<0.05). In the 73 patients with complete follow-up, (median follow-up 63.5 months), 4 patients had developed tumor recurrence. Conclusion:Intrahepatic bile duct cystadenoma lacks specific clinical manifestations, and has a high rate of misdiagnosis and mistreatment. Early radical hepatectomy improved clinical outcomes.

Value of dynamic monitoring of absolute value and function of peripheral blood lymphocyte subsets in predicting the risk of early viral infection after kidney transplantation / 器官移植

Objective To investigate the predictive and diagnostic value of absolute value and function of different lymphocyte subsets in evaluating the risk of early viral infection after kidney transplantation. Methods Ninety-five kidney transplant recipients were enrolled in this prospective observational cohort study, and divided into the stable group (n=77) and infection group (n=18) according to postoperative immune status. Peripheral blood samples were collected for flow cytometry before operation, and 2 weeks, 1 month, 2 months and 6 months after operation. The dynamic changes of the absolute values of CD4+T cells, CD8+T cells and natural killer (NK) cells were compared between two groups. The function of lymphocyte subsets in two groups was evaluated by detecting the proportion of interferon (IFN)-γ+CD4+T cells, IFN-γ+CD8+T cells and IFN-γ+NK cells. The value of the absolute values and function of lymphocyte subsets in predicting and diagnosing viral infection in the early stage after kidney transplantation was evaluated. Results During viral infection, the absolute values of CD4+T cells, CD8+T cells and NK cells in the infection group were at a relatively low level. At 2 months after operation, the absolute values of CD4+T cells and NK cells in the infection group were lower than those in the stable group. At 6 months after operation, the absolute values of CD4+T cells and CD8+T cells in the infection group were significantly lower compared with those in the stable group (all P < 0.05). During viral infection, the proportion of IFN-γ+CD4+T cells, IFN-γ+CD8+T cells and IFN-γ+NK cells in the infection group were all at a relatively low level, especially that of IFN-γ+CD8+T cells decreased most significantly. At postoperative 2 months, the proportion of IFN-γ+CD8+T cells and IFN-γ+NK cells in the infection group was significantly higher than those in the stable group. At 6 months after operation, the proportion of IFN-γ+CD4+T cells and IFN-γ+CD8+T cells in the infection group was significantly higher than those in the stable group (all P < 0.05). Logistic regression analysis showed that the increasing proportion of IFN-γ+CD8+T cells and IFN-γ+NK cells was correlated with the increasing risk of viral infection at 2 months after operation (both P < 0.05). The receiver operating characteristic (ROC) curve demonstrated that the diagnostic value of absolute values of lymphocyte subsets combined with IFN-γ secretion function for viral infection in the immunocompromised recipients was significantly higher than that of absolute values of lymphocyte subsets alone (P < 0.05). Conclusions Dynamic monitoring of the changes of absolute values and function of lymphocyte subsets provides critical reference value for the prediction, diagnosis and medication guidance of viral infection.

Effects of transient receptor potential vanilloid type 4-specific activator on human vascular endothelial cell functions and blood supply of rat perforator flap and its mechanism / 中华烧伤杂志

Objective: To analyze the effects of transient receptor potential vanilloid type 4 (TRPV4) activation on the function and endothelial-to-mesenchymal transition (EndMT) of human umbilical vein endothelial cells (HUVECs), as well as to explore the effects of TRPV4 activation on blood perfusion and survival of rat perforator flap and the mechanism. Methods: The experimental research methods were used. The 3rd to 6th passages of HUVECs were used for experiments and divided into 0.5 μmol/L 4α-phorbol 12, 13-didecanoate (4αPDD) group, 1.0 μmol/L 4αPDD group, 3.0 μmol/L 4αPDD group, 10.0 μmol/L 4αPDD group, and phosphate buffer solution (PBS) group, which were cultivated in corresponding final molarity of 4αPDD and PBS, respectively. The cell proliferation activity at 6 and 12 h of culture was detected using cell counting kit-8 (CCK-8). Another batch of cells was acquired and divided into PBS group, 1 μmol/L 4αPDD group, and 3 μmol/L 4αPDD group, which were treated similarly as described before and then detected for cell proliferation activity at 6, 12, 24, and 48 h of culture. The residual scratch area of cells at post scratch hour (PSH) 12, 24, and 48 was detected by scratch test, and the percentage of the residual scratch area was calculated. The number of migrated cells at 24 and 48 h of culture was detected by Transwell experiment. The tube-formation assay was used to measure the number of tubular structures at 4 and 8 h of culture. The protein expressions of E-cadherin, N-cadherin, Slug, and Snail at 24 h of culture were detected by Western blotting. All the sample numbers in each group at each time point in vitro experiments were 3. A total of 36 male Sprague-Dawley rats aged 8 to 10 weeks were divided into delayed flap group, 4αPDD group, and normal saline group according to the random number table, with 12 rats in each group, and iliolumbar artery perforator flap models on the back were constructed. The flap surgical delay procedure was only performed in the rats in delayed flap group one week before the flap transfer surgery. Neither rats in 4αPDD group nor normal saline group had flap surgical delay; instead, they were intraperitoneally injected with 4αPDD and an equivalent mass of normal saline, respectively, at 10 min before, 24 h after, and 48 h after the surgery. The general state of flap was observed on post surgery day (PSD) 0 (immediately), 1, 4, and 7. The flap survival rates were assessed on PSD 7. The flap blood perfusion was detected by laser speckle contrast imaging technique on PSD 1, 4, and 7. The microvascular density in the flap's choke vessel zone was detected by immunohistochemical staining. All the sample numbers in each group at each time point in vivo experiments were 12. Data were statistically analyzed with analysis of variance for factorial design, analysis of variance for repeated measurement, one-way analysis of variance, least significant difference t test, and Bonferroni correction. Results: At 6 and 12 h of culture, there were no statistically significant differences in cell proliferation activity in the overall comparison among PBS group, 0.5 μmol/L 4αPDD group, 1.0 μmol/L 4αPDD group, 3.0 μmol/L 4αPDD group, and 10.0 μmol/L 4αPDD group (P>0.05). At 6, 12, 24, and 48 h of culture, there were no statistically significant differences in cell proliferation activity in the overall comparison among PBS group, 1 μmol/L 4αPDD group, and 3 μmol/L 4αPDD group (P>0.05). At PSH 12, the percentages of the residual scratch area of cells in 1 μmol/L 4αPDD group and 3 μmol/L 4αPDD group were close to that in PBS group (P>0.05). At PSH 24 and 48, compared with those in PBS group, the percentages of the residual scratch area of cells in 3 μmol/L 4αPDD group were significantly decreased (with t values of 2.83 and 2.79, respectively, P<0.05), while the percentages of the residual scratch area of cells in 1 μmol/L 4αPDD group showed no significant differences (P>0.05). At 24 h of culture, the number of migrated cells in 1 μmol/L 4αPDD group and 3 μmol/L 4αPDD group were close to that in PBS group (P>0.05). At 48 h of culture, the number of migrated cells in 1 μmol/L 4αPDD group and 3 μmol/L 4αPDD groups were significantly greater than that in PBS group (with t values of 6.20 and 9.59, respectively, P<0.01). At 4 h of culture, the numbers of tubular structures of cells in 1 μmol/L 4αPDD group and 3 μmol/L 4αPDD group were significantly greater than that in PBS group (with t values of 4.68 and 4.95, respectively, P<0.05 or <0.01). At 8 h of culture, the numbers of tubular structures of cells in 1 μmol/L 4αPDD and 3 μmol/L 4αPDD groups were similar to that in PBS group (P>0.05). At 24 h of culture, compared with those in PBS group, the protein expression level of E-cadherin of cells in 3 μmol/L 4αPDD group was significantly decreased (t=5.13, P<0.01), whereas there was no statistically significant difference in the protein expression level of E-cadherin of cells in 1 μmol/L 4αPDD group (P>0.05); the protein expression level of N-cadherin of cells in 3 μmol/L 4αPDD group was significantly increased (t=4.93, P<0.01), whereas there was no statistically significant difference in the protein expression level of N-cadherin of cells in 1 μmol/L 4αPDD group (P>0.05); the protein expression levels of Slug of cells in 1 μmol/L 4αPDD group and 3 μmol/L 4αPDD group were significantly increased (with t values of 3.85 and 6.52, respectively, P<0.05 or P<0.01); and the protein expression level of Snail of cells in 3 μmol/L 4αPDD group was significantly increased (t=4.08, P<0.05), whereas there was no statistically significant difference in the protein expression level of Snail of cells in 1 μmol/L 4αPDD group (P>0.05). There were no statistically significant differences in the protein expression levels of E-cadherin, N-cadherin, Slug, or Snail of cells between 1 μmol/L 4αPDD group and 3 μmol/L 4αPDD group (P>0.05). The general condition of flaps of rats in the three groups was good on PSD 0. On PSD 1, the flaps of rats in the three groups were basically similar, with bruising and swelling at the distal end. On PSD 4, the swelling of flaps of rats in the three groups subsided, and the distal end turned dark brown and necrosis occurred, with the area of necrosis in flaps of rats in normal saline group being larger than the areas in 4αPDD group and delayed flap group. On PSD 7, the necrotic areas of flaps of rats in the 3 groups were fairly stable, with the area of necrosis at the distal end of flap of rats in delayed flap group being the smallest. On PSD 7, the flap survival rates of rats in 4αPDD group ((80±13)%) and delayed flap group ((87±9)%) were similar (P>0.05), and both were significantly higher than (70±11)% in normal saline group (with t values of 2.24 and 3.65, respectively, P<0.05 or P<0.01). On PSD 1, the overall blood perfusion signals of rats in the 3 groups were basically the same, and the blood perfusion signals in the choke vessel zone were relatively strong, with a certain degree of underperfusion at the distal end. On PSD 4, the boundary between the surviving and necrotic areas of flaps of rats in the 3 groups became evident, and the blood perfusion signals in the choke vessel zone were improved, with the normal saline group's distal hypoperfused area of flap being larger than the areas in delayed flap group and 4αPDD group. On PSD 7, the blood perfusion signals of overall flap of rats had generally stabilized in the 3 groups, with the intensity of blood perfusion signal in the choke vessel zone and overall flap of rats in delayed flap group and 4αPDD group being significantly greater than that in normal saline group. On PSD 7, the microvascular density in the choke vessel zone of flap of rats in 4αPDD group and delayed flap group were similar (P>0.05), and both were significantly higher than that in normal saline group (with t values of 4.11 and 5.38, respectively, P<0.01). Conclusions: After activation, TRPV4 may promote the migration and tubular formation of human vascular endothelial cells via the EndMT pathway, leading to the enhanced blood perfusion of perforator flap and microvascular density in the choke vessel zone, and therefore increase the flap survival rate.

Clinical application of expanded internal mammary artery perforator flap combined with vascular supercharge in reconstruction of faciocervical scar / 中华烧伤杂志

Objective: To summarize the clinical experience of expanded internal mammary artery perforator (IMAP) flap combined with vascular supercharge in reconstruction of faciocervical scar. Methods: The retrospective observational study was conducted. From September 2012 to May 2021, 23 patients with postburn or posttraumatic faciocervical scars who met the inclusion criteria were admitted to Shanghai Ninth People's Hospital of Shanghai Jiao Tong University School of Medicine, including 18 males and 5 females, aged from 11 to 58 years, all of whom were reconstructed with expanded IMAP flaps. At the first stage, one or two skin and soft tissue expander (s) with appropriate rated capacity were implanted in the anterior chest area according to the location and size of the scars. The IMAP, thoracic branch of supraclavicular artery, and lateral thoracic artery were preserved during the operation. The skin and soft tissue expanders were inflated with normal saline after the operation. The flaps were transferred during the second stage. The dominant IMAP was determined preoperatively using color Doppler ultrasound (CDU) blood flow detector. The faciocervical scars were removed, forming wounds with areas of 9 cm×7 cm-28 cm×12 cm, and the perforators of superficial temporal artery and vein or facial artery and vein were preserved during the operation. The flaps were designed according to the area and size of the wounds after scar resection with the dominant IMAP as the pedicle. Single-pedicle IMAP flaps were used to repair small and medium-sized wounds. For larger defects, the blood perfusion areas of vessels in the anterior chest were evaluated by indocyanine green angiography (ICGA). In situations where the IMAP was insufficient to nourish the entire flap, double-pedicle flaps were designed by using the thoracic branch of supraclavicular artery or lateral thoracic artery for supercharging. Pedicled or free flap transfer was selected according to the distance between the donor areas and recipient areas. After transplantation of flaps, ICGA was conducted again to evaluate blood perfusion of the flaps. The donor sites of flaps were all closed by suturing directly. Statistics were recorded, including the number, rated capacity, normal saline injection volume, and expansion period of skin and soft tissue expanders, the location of the dominant IMAP, the total number of the flaps used, the number of flaps with different types of vascular pedicles, the flap area, the flap survival after the second stage surgery, the occurrence of common complications in the donor and recipient areas, and the condition of follow-up. Results: Totally 25 skin and soft tissue expanders were used in this group of patients, with rated capacity of 200-500 mL, normal saline injection volume of 855-2 055 mL, and expansion period of 4-16 months. The dominant IMAP was detected in the second intercostal space (20 sides) or the third intercostal space (5 sides) before surgery. A total of 25 expanded flaps were excised, including 2 pedicled IMAP flaps, 11 free IMAP flaps, 4 pedicled thoracic branch of supraclavicular artery+free IMAP flaps, and 8 free IMAP+lateral thoracic artery flaps, with flap areas of 10 cm×8 cm-30 cm×14 cm. After the second stage surgery, tip necrosis of flaps in three patients occurred, which healed after routine dressing changes; one patient developed arterial embolism and local torsion on the vascular pedicle at the anastomosis of IMAP and facial artery, and the blood supply recovered after thrombectomy and vascular re-anastomosis. Fourteen patients underwent flap thinning surgery in 1 month to 6 months after the second stage surgery. The follow-up for 4 months to 9 years showed that all patients had improved appearances of flaps and functions of face and neck and linear scar in the donor sites of flaps, and one female patient had obvious nipple displacement and bilateral breast asymmetry. Conclusions: The expanded IMAP flap is matched in color and texture with that of the face and neck, and its incision causes little damage to the chest donor sites. When combined with vascular supercharge, a double-pedicle flap can be designed flexibly to further enhance the blood supply and expand the flap incision area, which is a good choice for reconstruction of large faciocervical scar.

Application of intravenous immunoglobulin G in children with rheumatic diseases / 中华实用儿科临床杂志

The indications for the application of intravenous immunoglobulin G (IVIG) mainly include the replacement therapy of antibody deficiency diseases and immunomodulatory therapy with a high dose of IVIG.IVIG is extensively used in children with rheumatic diseases due to its immunomodulatory effects.However, most of them are " off-label drugs". In the treatment of pediatric rheumatic diseases, IVIG can benefit Kawasaki disease and primary immune thrombocytopenia, and may be beneficial in treating Sj?gren′s syndrome, dermatomyositis and systemic lupus erythematosus.However, for the patients with Stevens-Johnson syndrome, antineutrophil cyctoplasmic antibody (ANCA) asso-ciated vasculitis and systemic scleroderma, there is not much chance to obtain benefits.In the treatment of rheumatic diseases in children, the application of IVIG needs to be further standardized.

Herbal Textual Research on Zingiberis Rhizoma Recens in Famous Classical Formulas and Its Quality Evaluation / 中国实验方剂学杂志

ObjectiveTo provide references for the selection of Zingiberis Rhizoma Recens on the research of famous classical formulas and the reasonable uses for medicines and foods through herbal textural research and quality analysis of Zingiberis Rhizoma Recens from main producing areas in China. MethodBy consulting the ancient and modern literature， the name， origin， producing areas， harvest time， processing methods of Zingiberis Rhizoma Recens were summarized. According to the 2020 edition of Chinese Pharmacopoeia， the contents of 6-gingerol， 8-gingerol， 10-gingerol， and volatile oil in Zingiberis Rhizoma Recens samples were determined. ResultHerbal textural research indicated that medicinal Zingiberis Rhizoma Recens originated from the fresh rhizome of Zingiber officinale. Before Tang dynasty， Zingiberis Rhizoma Recens produced in Sichuan was the best. In the Song dynasty， Zingiberis Rhizoma Recens produced in Sichuan， Zhejiang， and Anhui was of excellent quality. The cultivation of Zingiberis Rhizoma Recens in Shandong developed during the Ming and Qing dynasties. From ancient times to the present， the harvest period extended from the autumnal equinox to the winter solstice. Quality evaluation standards of Zingiberis Rhizoma Recens were essentially the same in ancient and present documents， as those with little gluten or gluten-free and strong pungency were preferred. After determination， the contents of 6-gingerol， 8-gingerol， and 10-gingerol in 44 samples were qualified in 27 samples， with a qualified rate of 61.4%. Among them， 17 samples were unqualified in the total contents of 8-gingerol and 10-gingerol. Among these qualified samples， the content of 6-gingerol ranged from 0.067% to 0.255%， and the total contents of 8-gingerol and 10-gingerol ranged from 0.040% to 0.131%. The content of volatile oil in 36 samples were qualified in 33 samples， with a qualified rate of 91.7%. Among the qualified samples， the content of volatile oil ranged from 0.175% to 0.410%. ConclusionZingiberis Rhizoma Recens has been used as medicines and foods since ancient times， and the genuine producing areas are consistent in ancient and present times， while the quality of the products， especially the medicinal Zingiberis Rhizoma Recens， should be monitored. Medicinal Zingiberis Rhizoma Recens planted in Leshan city of Sichuan province contains high contents of effective components， followed by Qujing and Wenshan cities of Yunnan province. Zingiberis Rhizoma Recens planted in Shandong and other places is mostly edible.

Mechanism of Tibetan medicine Pterocephalus hookeri extract in treatment of rheumatoid arthritis based on serum metabonomics / 中国中药杂志

Ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF/MS) was used to investigate the effect of Pterocephalus hookeri on serum metabolism of adjuvant arthritis(AA) model rats induced by complete Freund's adjuvant. After the AA model was properly induced, the serum of rats was collected 30 days after treatment. UPLC-Q-TOF-MS chromatograms were collected and analyzed by principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA). The results revealed that compared with the control group, the model group showed increased content of 12 biomarkers in the serum(P<0.05) and reduced content of the other nine biomarkers(P<0.05). P. hookeri extract could recover the above-mentioned 19 biomarkers to a certain range. Pathway enrichment showed that these markers mainly involved eight metabolic pathways, including valine, leucine, and isoleucine degradation, arachidonic acid metabolism, arginine and proline metabolism, glycerol phospholipid metabolism, primary bile acid biosynthesis, bile acid biosynthesis, tryptophan metabolism, and unsaturated fatty acid biosynthesis. The findings of this study demonstrate that P. hookeri extract can regulate metabolic disorders and promote the regression of metabolic phenotype to the normal level to exert the therapeutic effect on AA rats. This study is expected to provide a certain scientific basis for the biological research on the treatment of rheumatoid arthritis by P. hookeri.

Clinical efficacy observation of acupoint thread-embedding in treating obese patients with food addiction / 针灸推拿医学（英文版）

Objective: To observe the effects of acupoint thread-embedding therapy and low-carbohydrate diet therapy on obese patients with food addiction. Methods: Sixty-five eligible patients were randomized into a thread-embedding group of 33 cases and a diet group of 32 cases to respectively receive 12-week treatment. Before treatment, after treatment and at 6-month follow-up, the two groups were observed and compared in terms of body mass (BM), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), body mass index (BMI), body fat rate (BFR), basal metabolic rate (BMR) and Yale food addiction scale version 2.0 (YFAS 2.0). Results: At the end of treatment, there were no significant differences in the general efficacy, and the improvements in BM, BMI, WC, HC, WHR and BFR between the thread-embedding group and diet group (all P>0.05). At follow-up, the thread-embedding group showed more significant improvements in all the aforementioned indicators compared with the diet group except HC (all P<0.05). At the end of treatment and follow-up, BMR and YFSA 2.0 had more significant improvements in the thread-embedding group than in the diet group (all P<0.05). Conclusion: Acupoint thread-embedding therapy can produce significant efficacy in treating obese patients with food addiction; it can improve the food addiction state and work better in maintaining the efficacy compared with low-carbohydrate diet therapy.

Genotype analysis of thalassemia in children with thalassemia in Wuzhou / 公共卫生与预防医学

Objective To investigate the prevalence and genotype of thalassemia in high-risk children with thalassemia in Wuzhou, and to provide a reference for formulating strategies for the prevention and treatment of thalassemia and for reducing the incidence of thalassemia. Methods Four deletions and 3 point mutations of alpha-thalassemia and 17 point mutations of beta-thalassemia were detected and analyzed by GAP-PCR and PCR combined with reverse dot blot hybridization in children at a high risk for thalassemia in Wuzhou from 2010 to 2018. Results There were 1,421 positive cases in the first screening, and 871 cases were confirmed through genotyping, with a positive rate of 61.29%, including4 deletion types and 14 mutation types. There were 452 cases (51.89%) of α-thalassemia, 337 cases (38.69%) of β-thalassemia and 82 cases (9.41%) of combination of α-thalassemia and β-thalassemia. The common genotypes of α-thalassemia in children in Wuzhou were: --SEA/αα, --SEA/-α3.7, -α3.7/αα, --SEA/αCS αCS, αWSα/αα, --SEA/-α4.2, -α4.2/αα, and αCSα/αα. CD41-42, CD17, -28 and CD71-72 were the most common heterozygotes, while CD41-42/-28, CD41-42/IVS-2-654, and CD41-42/ CD71-72 were the most common double heterozygotes in children with β-thalassemia in Wuzhou. The most common homozygous genotypes were CD41-42 / CD41-42 and -28/-28. Conclusion In order to control thalassemia it is critical to increase investment in large-scale screening of carriers of the thalassemia mutant gene, and to prevent the birth of children with severe thalassemia.

Role of myeloid-derived suppressor cell in respiratory tract infections / 中华微生物学和免疫学杂志

Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells that are generated from the blockade differentiation of myeloid cells during pathological conditions. MDSC are regulatory immune cells with a potent immunosuppressive function, and play an important role in the development of various diseases including tumor, autoimmune diseases and trauma. Interestingly, emerging evidence shows that respiratory tract infections by viruses, bacteria and fungi can cause MDSC expansion and activation. MDSC levels are closely related to the symptoms of diseases caused by respiratory pathogens. Further investigation on the role and molecular mechanism of MDSC expansion and activation in respiratory tract infections will contribute to the development of novel strategies for the prevention and treatment of diseases caused by respiratory pathogens. Here, we summarized the role of MDSC in respiratory viral, bacterial and fungal infections and the relevant molecular mechanisms, aiming to provide a reference for further investigating the role of MDSC in respiratory tract infections.

Trans-base and trans-vault low-velocity penetrating brain injury: A retrospective comparative study of characteristics, treatment, and outcomes / 中华创伤杂志(英文版)

PURPOSE@#Low-velocity penetrating brain injury (LVPBI) caused by foreign bodies can pose life-threatening emergencies. Their complexity and lack of validated classification data have prevented standardization of clinical management. We aimed to compare the trans-base and trans-vault phenotypes of LVPBI to help provide guidance for clinical decision-making of such injury type.@*METHODS@#A retrospective study on LVPBI patients managed at our institution from November 2013 to March 2020 was conducted. We included LVPBI patients admitted for the first time for surgery, and excluded those with multiple injuries, gunshot wounds, pregnancy, severe blunt head trauma, etc. Patients were categorized into trans-base and trans-vault LVPBI groups based on the penetration pathway. Discharged patients were followed up by outpatient visit or telephone. The data were entered into the Electronic Medical Record system by clinicians, and subsequently derived by researchers. The demography and injury characteristics, treatment protocols, complications, and outcomes were analyzed and compared between the two groups. A t-test was used for analysis of normally distributed data, and a Mann-Whitney U test for non-parametric data. A generalized linear model was further established to determine whether the factors length of stay and performance scale score were influenced by each factor.@*RESULTS@#A total of 27 LVPBI patients were included in this analysis, comprised of 13 (48.1%) trans-base cases and 14 (51.9%) trans-vault cases. Statistical analyses suggested that trans-base LVPBI was correlated with deeper wounds; while the trans-vault phenotype was correlated with injury by metal foreign bodies. There was no difference in Glasgow Coma Scale score and the risk of intracranial hemorrhage between the two groups. Surgical approaches in the trans-base LVPBI group included subfrontal (n = 5, 38.5%), subtemporal (n = 5, 38.5%), lateral fissure (n = 2, 15.4%), and distal lateral (n = 1, 7.7%). All patients in the trans-vault group underwent a brain convex approach using the foreign body as reference (n = 14, 100%). Moreover, the two groups differed in application prerequisites for intracranial pressure monitoring and vessel-related treatment. Trans-base LVPBI was associated with higher rates of cranial nerve and major vessel injuries; in contrast, trans-vault LVPBI was associated with lower functional outcome scores.@*CONCLUSION@#Our findings suggest that trans-base and trans-vault LVPBIs differ in terms of characteristics, treatment, and outcomes. Further understanding of these differences may help guide clinical decisions and contribute to a better management of LVPBIs.

Study on effect of anemoside B4 in improving COPD rats by regulating IL-12/STAT4 and IL-4/STAT6 signaling pathways / 中国中药杂志

To study the effect of anemoside B4 on rats with chronic obstructive pulmonary disease (COPD).Seventy-two SD male rats were randomly divided into blank group and model group.The method of exposure to cigarette smoke and combined with lipopolysaccharide (LPS) was used to replicate the rat model of COPD.After the model was maintained for 5 weeks,the rats were randomly divided into model group,dexamethasone group (0.81 mg·kg~(-1)) and anemoside B4 low,medium and high (2,4,8 mg·kg~(-1)) dose groups,a group of 12 animals were administered,and then the administration was started.The administration was maintained until the28th day,and the pulmonary function parameters of rats were measured by an animal pulmonary function instrument.After testing the rat lung function parameters,immediately draw rat alveolar lavage fluid (BALF),and use high-throughput protein chip technology to determined the expression levels of inflammatory cytokines in rat BALF.HE staining was used to observe the general pathological changes of rat lung and tracheal tissue.Masson staining was used to observe the collagen deposition in rat lung tissue.Real-time q PCR method was used to determine the mRNA expression level of related genes in rat lung tissue.Western blot method was used to determine the expression levels of related proteins in rat lung tissues.According to the findings,compared with the model group,the dexamethasone group and the anemoside B4 drug groups had different degrees of increase in the lung function parameters of rats (P<0.01,P<0.05),improved the expression level of inflammatory cytokines in the BALF of rats to varying degrees (P<0.01,P<0.05),and improved the pathological structure of rat lung tissue to varying degrees.Relative mRNA expressions of matrix metalloproteinase 2 (MMP-2),matrix metalloproteinase 12 (MMP-12),matrix metalloproteinase inhibitor 1 (TIMP-1),interleukin-6 (IL-6),and transforming growth factor-β1 (TGF-β1) were significantly reduced (P<0.01);whereas relative mRNA expressions of matrix metalloproteinase 9(MMP-9) and matrix metalloproteinase inhibitor 2 (TIMP-2) were increased significantly (P<0.01).The mRNA and protein expression levels of T-box transcription factor (T-bet),interleukin-12 (IL-12) and signal transducer and activator of transcription 4(STAT4) reduced to varying degrees (P<0.01,P<0.05).The mRNA of transcription factor GATA3 (binding protein-3),interleukin-4 (IL-4) and signal transducer and activator of transcription 6 (STAT6) in rat lung tissues and the protein expression levels of IL-4 and STAT6 were increased to varying degrees (P<0.01,P<0.05).In conclusion,anemoside B4 has a certain protective effect on COPD rats caused by cigarette smoke exposure and combined with LPS.The mechanism of action may be related to the regulation of IL-12/STAT4 and IL-4/STAT6 signaling pathways.