Anti-cutaneous squamous cell carcinoma effect and mechanism of dihydrochromone-spliced polycyclic pyrrole-spiroepoxidole compound 3m / 中国药房

OBJECTIVE To study the effect and mechanism of dihydrochromone-spliced polycyclic pyrrole-spiroepoxidole compound 3m on cutaneous squamous cell carcinoma. METHODS Using human cutaneous squamous cell carcinoma A431 and Colo-16 cells as research subjects， CCK-8 assay was used to detect the effects of different concentrations of 3m （5， 10， 20， 40， 80 μmol/L） on the proliferation of A431 and Colo-16 cells after 24， 48 and 72 hours； the median inhibitory concentration （IC50） was calculated at 48 h of treatment. A431 and Colo-16 cells were divided into control group， 3m low-concentration and high- concentration groups （15， 30 μmol/L）. After treated with relevant drugs or culture medium for 48 h， the morphological changes of cells in each group were observed by inverted microscope. Clone formation rate， migration rate and number of cell invasions， cell cycle distribution and apoptosis rate were detected. The phosphorylation， or expression of Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3） signaling pathway related proteins [JAK2， STAT3， B-cell lymphocyte-2 （Bcl-2）， Bcl-2- associated X protein （Bax）]， and their mRNA expression in cells were detected. RESULTS 3m could significantly inhibit the proliferation of A431 and Colo-16 cells after treated for 24， 48， 72 h （P＜0.01）， and IC50 of them were 20.36， 23.72 μmol/L， respectively. After 48 hours of treatment， compared with control group， A431 and Colo-16 cells arranged sparsely and loosely connected in 3m low-concentration and high-concentration groups. The clone formation rate， migration rate， number of cell invasions， mRNA expressions of JAK2， STAT3 and Bcl-2， the phosphorylation of JAK2 and STAT3， protein expression of Bcl-2 were significantly decreased/weakened （P＜0.01）. Proportion of cell cycle in G2 phase， apoptosis rate， protein and mRNA expression of Bax were increased significantly （P＜0.01）； and all the above effects were in dose-dependent manner. CONCLUSIONS 3m can inhibit the proliferation， clone formation， migration and invasion abilities of cutaneous squamous cell carcinoma A431 and Colo-16 cells in a dose-dependent manner， the mechanism of which may be associated with inhibiting the activity of JAK2/STAT3 signaling pathway， and inducing cell apoptosis.

Short-term exposure to gossypol causes reversible reproductive toxicity and nephrotoxicity in mice / 南方医科大学学报

OBJECTIVE@#To study the toxic effects of short-term exposure to gossypol on the testis and kidney in mice and whether these effects are reversible.@*METHODS@#Twenty 7 to 8-week-old male mice were randomized into blank control group, solvent control group, gossypol treatment group and drug withdrawal group. In the former 3 groups, the mice were subjected to daily intragastric administration of 0.3 mL of purified water, 1% sodium carboxymethylcellulose solution, and 30 mg/mL gossypol solution for 14 days, respectively; In the drug withdrawal group, the mice were treated with gossypol solution in the same manner for 14 days followed by treatment with purified water for another 14 days. After the last administration, the mice were euthanized and tissue samples were collected. The testicular tissue was weighed and observed microscopically with HE and PAS staining; the kidney tissue was stained with HE and examined for mitochondrial ATPase activity.@*RESULTS@#Compared with those in the control group, the mice with gossypol exposure showed reduced testicular seminiferous epithelial cells with rounded seminiferous tubules, enlarged space between the seminiferous tubules, interstitium atrophy of the testis, and incomplete differentiation of the spermatogonia. The gossypol-treated mice also presented with complete, non-elongated spermatids, a large number of cells in the state of round spermatids, and negativity for acrosome PAS reaction; diffuse renal mesangial cell hyperplasia, increased mesangial matrix, and adhesion of the mesangium to the wall of the renal capsule were observed, with significantly shrinkage or even absence of the lumens of the renal capsules and reduced kidney mitochondrial ATPase activity. Compared with the gossypol-treated mice, the mice in the drug withdrawal group showed obvious recovery of morphologies of the testis and the kidney, acrosome PAS reaction and mitochondrial ATPase activity.@*CONCLUSIONS@#Shortterm treatment with gossypol can cause reproductive toxicity and nephrotoxicity in mice, but these toxic effects can be reversed after drug withdrawal.

Acute inferior myocardial infarction combined with papillary muscle rupture: A case report / 中南大学学报(医学版)

The incidence of acute myocardial infarction (AMI) is increasing. Acute papillary muscle rupture is one of the serious and rare mechanical complications of AMI, which occurs mostly in inferior and posterior myocardial infarction. A patient with acute inferior myocardial infarction developed pulmonary edema and refractory shock, followed by cardiac arrest. After cardiopulmonary resuscitation (CPR), revascularization of criminal vessels was carried out by emergency percutaneous transluminal coronary angioplasty (PTCA) under the support of intra-aortic balloon pump (IABP) and extra corporeal membrane oxygenation (ECMO). Although the patient was given a chance for surgery, his family gave up treatment due to unsuccessful brain resuscitation. It reminds that mechanical complications such as acute papillary muscle rupture, valvular dysfunction and rupture of the heart should be highly suspected when cardiogenic pulmonary edema and cardiogenic shock are difficult to correct in acute inferior myocardial infarction. Echocardiogram and surgery should be put forward when revascularization of criminal vessels is available.

Research on the reform of position setting and performance evaluation in medical research institutes under the background of institute integration / 中华医学科研管理杂志

Objective:To explore the collaborative innovation development mechanism of hospitals and research institutes, fully integrate the institute personnel with hospitals, and conduct classified management and performance appraisal, promoting the integrated development of hospitals and research institutes.Methods:The idea of personnel classification, the establishment of an integrated research team, and technical team groupings and service directions were determined through key informant interviews, research ability and technical strength surveys, and other research methods; The performance appraisal scheme of research teams were established by using literature analysis and optimization and Delphi expert investigation; The platform team assessment programs were established by qualitative research methods.Results:Built a position setting framework for research institutes, formed hospital-institute integrated research teams around the hospital's clinical advantageous disciplines with researchers and clinical staff, set up platform teams based on existing equipment and technicians′ specialties, established a performance appraisal scheme for research teams based on Science and Technology Evaluation Metrics(STEM), determined a full-dimensional comprehensive performance evaluation scheme for the technology platforms based on service volume and quality.Conclusions:This study formulated a set of position setting and performance evaluation schemes that fit with the current situation of municipal research institutes, and explored a new scientific research cooperation mechanism of resource sharing, team co-construction, and technology sharing, which can provide a certain reference value for the reform of other medical research institutes.

Analysis of peripheral blood lymphocyte status in low-level-viremia patients with chronic hepatitis B virus infection after nucleos(t)ide analogue treatment / 中华微生物学和免疫学杂志

Objective:To evaluate the status of T, B and NK lymphocytes in peripheral blood of patients with chronic hepatitis B virus(HBV) infection and low-level viremia after nucleos(t)ide analogue (NA) treatment and to provide ideas for solving low-level viremia.Methods:This retrospective study involved 344 patients with chronic HBV infection who had been treated with NAs. They were divided into two groups: low-level viremia group (LLV group) and complete virological response group (CVR group). Clinical data including basic information, biochemistry and coagulation test results, HBV DNA, peripheral blood lymphocyte counts, PD1 and CD28 expression by T lymphocytes, and perforin and granzyme B expression by NK lymphocytes were collected and compared between the two groups. Propensity matching analysis was performed to verify the accuracy of the results.Results:Among the 344 cases, 162 were in the LLV group and 182 in the CVR group. There were no significant differences in disease diagnosis, alanine aminotransferase (ALT), aspartate aminotransferase (AST) or albumin (ALB) level between the two groups ( P>0.05), but the differences in gender and age were statistically significant ( P<0.05). The differences in the counts and percentages of peripheral blood CD3 +, CD4 + and CD8 + T lymphocyte and CD4 + /CD8 + ratios between the two groups were not statistically significant ( P>0.05), but the expression of PD1 and CD28 by peripheral blood CD3 +, CD4 + and CD8 + T lymphocytes was higher in the LLV group than in the CVR group ( P<0.05). The count of peripheral blood CD19 + B lymphocytes in the LLV group was higher than that in the CVR group ( P>0.05), and the percentage of peripheral blood CD19 + B lymphocytes was also higher in the LLV group ( P<0.05). The count of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of perforin in the LLV group were lower than those in the CVR group ( P>0.05). The percentage of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of granzyme B in the LLV group were lower than those in the CVR group ( P<0.05). After propensity score matching, 108 cases in the LLV group and 108 cases in the CVR group showed no significant differences in basic information ( P>0.05); the percentage of CD4 + T lymphocytes and CD4 + /CD8 + ratio in peripheral blood T lymphocyte subsets were higher in the LLV group than in the CVR group, while the percentage of CD8 + lymphocytes was lower in the LLV group ( P<0.05); the expression of PD1 and CD28 by CD3 +, CD4 + and CD8 + T lymphocytes remained higher in the LLV group ( P<0.05); the differences in the counts and percentages of peripheral blood CD19 + B lymphocytes as well as CD16 + CD56 + NK lymphocytes between the two groups were not statistically significant ( P>0.05); no significant difference in the expression of perforin by CD16 + CD56 + NK lymphocytes was found between the two groups ( P>0.05), and the expression of granzyme B remained lower in the LLV group ( P<0.05). Conclusions:Abnormal number and function of T lymphocytes and decreased function of NK lymphocytes might be related to the development of LLV in patients with chronic HBV infection after treatment. Therefore, in addition to adjusting NAs, targeting of T and NK lymphocytes might also be a feasible measure for future LLV treatment.

Clinical characteristics of hospitalized premenopausal patients with hyperuricemia / 中华全科医师杂志

Objective:To analyze the clinical characteristics of hospitalized premenopausal patients with hyperuricemia.Methods:The medical records of premenopausal women with hyperuricemia (serum uric acid ≥360 μmol/L during hospitalization) admitted in Peking Union Medical College Hospital from 2013 to 2018 were reviewed and the clinical data were analyzed.Results:A total of 2 099 patients were enrolled. Only 14.01% (294 cases) of the patients were concerned about hyperuricemia by physicians. Autoimmune diseases (32.11%, 674 cases), nephrotic disease (19.29%, 405 cases) and endocrine system diseases (9.72%, 204 cases) are the main reasons for hospitalization, while 6.34%(133 cases) of patients were in gestation. In terms of the etiology, renal diseases (49.35%, 1 035 cases), specific drug use (49.26%, 1 034 cases) were the main causes of secondary hyperuricemia in premenopausal women, followed by metabolic diseases (10.62%, 233 cases). There was no significant difference in serum uric acid level among premenopausal women of different ages ( H=4.47, P=0.107), but the etiology of hyperuricemia among patients of different ages had significant differences. The proportion of hyperuricemia in patients with cancer and metabolic syndrome,secondary to use of diuretics and anti-tuberculosis drugs had differences among different age groups ( χ2=90.96,52.89,19.26 and 6.41, P<0.05). Conclusion:Hyperuricemia is not uncommon in premenopausal women. There are many secondary factors leading to hyperuricemia in premenopausal women, among which drugs and renal lesions are the main causes. In addition, the secondary factors in women with hyperuricemia has differences among different age groups.

Effect of chronic restraint stress on the phenotypic transition of hippocampal astrocytes and depression-like behavior in mice / 解剖学报

Objective To explore the effect of chronic restraint stress (CRS) on the phenotypic transition of hippocampal astrocytes and depression-like behavior in mice. Methods Forty eight male C57BL/6 mice were randomly divided into control groups (control), model groups (CRS) and fluoxetine(FLX) drug intervention groups (CRS+FLX), 16 for each group. The mice of the CRS group were subjected to 3 weeks chronic restraint stress. The mice of CRS + FLX group were treated with fluoxetine by intraperitoneal injection 30 minutes before restraint stress from the day 8 to day 21.

Effects of transient receptor potential vanilloid 4 inhibitor HC067047 on anxiety-like behavior in mice induced by lipopolysaccharide / 解剖学报

Objective To investigate the effect of transient receptor potential vanilloid 4 (TRPV4) inhibitor HC067047 on anxiety-like behavior in mice induced by lipopolysaccharide (LPS). Methods Totally 48 male C57BL/6 mice were randomly divided into control group (NS), model group (LPS) and drug intervention group (HC + LPS). Anxiety mouse model was established by intraperitoneal injection of 0.83 mg/kg LPS. The HC + LPS group was intraperitoneally injected with HC067047 (10 mg/kg) 30 minutes before LPS injection, and the NS group and LPS group were injected with equal volume of normal saline. Open field test and social interaction experiments were used to detect anxiety-like behaviors in each group of mice; Immunohistochemical chemistry and Western blotting were used to detect the expression of TRPV4, inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) in the hippocampus. Results Immunohistochemical and Western blotting experiments showed that, compared with the NS group, the expression of TRPV4 in the hippocampus of the LPS group was significantly up-regulated (P<0.0001); In the open field test, compared with the NS group, the total distance (P < 0.0001), the distance in the central area (P<0.01) and the time of in the central area mice in the LPS group reduced significantly (P< 0.01). HC067047 intervention reversed the activities of LPS model mice total distance (P < 0.05), the distance of activities in the central area (P < 0.001) and the time of in the central area (P < 0.01); In the social interaction test, compared with the NS group, the interaction time the unfamiliar mice reduced significantly in LPS group (P<0.01), which was reversed by HC067047 treatment (P< 0.01); Western blotting detection revealed that the expression of hippocampal iNOS (P<0.05), nNOS (P < 0.001), and eNOS (P < 0.001) in the LPS group were significantly higher than the NS group, which reduced remarkably by HC067047 treatment (iNOS P < 0.05, nNOS P < 0.01 and eNOS P < 0.01). Conclusion Inhibiting the expression of TRPV4 can improve the anxiety-like behavior, and this process may be related to anti-oxidative stress.

Dexmedetomidine improving complete Freund's adjuvant-induced anxiety-like and depression-like behaviour by promoting the expression of brain-derived neurotrophic factor-tyrosin kinase receptor B in mice hippocampus / 解剖学报

Objective To study the effect of dexmedetomidine (DEX), an α2- adrenoceptor agonist, on the pain-related anxiety-like and depression-like behaviour induced by complete Freund' s adjuvant (CFA) injection and its possible regulatory mechanism. Methods Thirty-six ICR female mice were randomly divided into normal saline (NS) group, CFA group and DEX + CFA group, n = 12 for each group. Chronic inflammatory pain model was established by subcutaneous injection of 10 μl CFA into the right hind limb of mice. DEX + CFA group mice were injected intraperitoneally with 0.025 mg/kg DEX 30 minutes before nociceptive behavior test, and once a day for 7 days. Von-frey fiber was used to evaluate the threshold of mechanical pain in mice, n = 12 for each group. The anxiety-like behavior of mice were detected by open field test, n = 12 for each group. Sucrose preference, tail suspension test and forced swimming test were used to detected the depression-like behavior of mice, n = 12 for each group. The expression of adrenergic receptor β2 (ADRB2), Brain-derived neurotrophic factor (BDNF), tyrosine kinase B receptor (TrkB), and glutamate receptors 1 (GluR1) and GluR2 were detected by Western blotting, n = 8 for each group. Immunohistochemical staining was used to detect the expression of recombinant doublecortin(DCX), which is a marker of newborn neurons in the hippocampus, n = 4 for each group. Results Compared with the NS group, the mechanical threshold of mice on the 1st, 3rd and 7th day after CFA injection decreased significantly (P 0.05). Compared with the NS group, the time spent in the inner ares (P<0.01), number of entering the central grid area (P<0.01) and distance travelled in the inner area (P<0.01) of CFA group mice reduced significantly, while the time (P<0.01), numbers (P < 0.05) and distance (P < 0.05) of DEX + CFA group mice entering the central grid area enhanced significantly. The result of depression-like behavior tests showed that the sucrose preference percentage (P < 0.05) reduced significantly in CFA group when compared with NS group, and the immobility time increased significantly in tail suspension test (P<0.01) and forced swimming test (P< 0.001) in CFA mice when compared with NS group, while DEX intervention could significantly increase the sucrose preference scores (P<0.05) and decreased the immobility time in tail suspension test (P<0.05) and forced swimming test (P<0.05). The result of Western blotting showed that compared with the NS group, the levels of ADRB2 (P<0.0010), BDNF (P < 0.001), TrkB (P < 0.01), GluR1 (P < 0.001) and GluR2 (P < 0.001) in the hippocampus of CFA group were significantly decreased, while DEX intervention could significantly increase the expression of ADRB2 (P<0.05), BDNF (P < 0.001), TrkB (P < 0.001), GluR1 (P < 0.001) and GluR2 (P < 0.001). Immunohistochemical result showed that compared with the NS group, the average absorbance (AA) of DCX decreased significantly in hippocampus of CFA group (P<0.05), but increased significantly in DEX+CFA group (P < 0.05). Conclusion Dexmedetomidine may promote hippocampal neurogenesis through upregulated the expression of BDNF-TrkB, thus improving CFA-induced anxiety-like and depression-like behaviors in mice.

Diagnosis status and genetic characteristics analysis of Fanconi anemia in China / 中华儿科杂志

Objective: To analyze the clinical and molecular diagnostic status of Fanconi anemia (FA) in China. Methods: The General situation, clinical manifestations and chromosome breakage test and genetic test results of 107 pediatric FA cases registered in the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) and the Chinese Children Blood and Marrow Transplantation Registry Group (CCBMTRG) from August 2009 to January 2022 were analyzed retrospectively. Children with FANCA gene variants were divided into mild and severe groups based on the type of variant, and Wilcoxon-test was used to compare the phenotypic differences between groups. Results: Of the 176 registered FA patients, 69 (39.2%) cases were excluded due to lack of definitive genetic diagnosis results, and the remaining 107 children from 15 hospitals were included in the study, including 70 males and 37 females. The age at transplantation treatment were 6 (4, 9) years. The enrolled children were involved in 10 pathogenic genes, including 89 cases of FANCA gene, 7 cases of FANCG gene, 3 cases of FANCB gene, 2 cases of FANCE gene and 1 case each of FANCC, FANCD1, FANCD2, FANCF, FANCJ, and FANCN gene. Compound heterozygous or homozygous of loss-of-function variants account for 69.2% (72/104). Loss-of-function variants account for 79.2% (141/178) in FANCA gene variants, and 20.8% (37/178) were large exon deletions. Fifty-five children (51.4%) had chromosome breakage test records, with a positive rate of 81.8% (45/55). There were 172 congenital malformations in 80 children.Café-au-Lait spots (16.3%, 28/172), thumb deformities (16.3%,28/172), polydactyly (13.9%, 24/172), and short stature (12.2%, 21/172) were the most common congenital malformations in Chinese children with FA. No significant difference was found in the number of congenital malformations between children with severe (50 cases) and mild FANCA variants (26 cases) (Z=-1.33, P=0.185). Conclusions: FANCA gene is the main pathogenic gene in children with FA, where the detection of its exon deletion should be strengthened clinically. There were no phenotypic differences among children with different types of FANCA variants. Chromosome break test is helpful to determine the pathogenicity of variants, but its accuracy needs to be improved.

Establishment and validation of a preoperative nomogram model for predicting the risk of hepatocellular carcinoma with microvascular invasion / 中华外科杂志

Objective: To establish and validate a nomogram model for predicting the risk of microvascular invasion(MVI) in hepatocellular carcinoma. Methods: The clinical data of 210 patients with hepatocellular carcinoma who underwent hepatectomy at Department of Hepatobiliary and Pancreatic Surgery,the Affiliated Hospital of Qingdao University from January 2013 to October 2021 were retrospectively analyzed. There were 169 males and 41 females, aged(M(IQR)) 57(12)years(range:30 to 80 years). The patients were divided into model group(the first 170 cases) and validation group(the last 40 cases) according to visit time. Based on the clinical data of the model group,rank-sum test and multivariate Logistic regression analysis were used to screen out the independent related factors of MVI. R software was used to establish a nomogram model to predict the preoperative MVI risk of hepatocellular carcinoma,and the validation group data were used for external validation. Results: Based on the modeling group data,the receiver operating characteristic curve was used to determine that cut-off value of DeRitis ratio,γ-glutamyltransferase(GGT) concentration,the inverse number of activated peripheral blood T cell ratio (-aPBTLR) and the maximum tumor diameter for predicting MVI, which was 0.95((area under curve, AUC)=0.634, 95%CI: 0.549 to 0.719), 38.2 U/L(AUC=0.604, 95%CI: 0.518 to 0.689),-6.05%(AUC=0.660, 95%CI: 0.578 to 0.742),4 cm(AUC=0.618, 95%CI: 0.533 to 0.703), respectively. Univariate and multivariate Logistic regression analysis showed that DeRitis≥0.95,GGT concentration ≥38.2 U/L,-aPBTLR>-6.05% and the maximum tumor diameter ≥4 cm were independent related factors for MVI in hepatocellular carcinoma patients(all P<0.05). The nomogram prediction model based on the above four factors established by R software has good prediction efficiency. The C-index was 0.758 and 0.751 in the model group and the validation group,respectively. Decision curve analysis and clinical impact curve showed that the nomogram model had good clinical benefits. Conclusions: DeRitis ratio,serum GGT concentration,-aPBTLR and the maximum tumor diameter are valuable factors for preoperative prediction of hepatocellular carcinoma with MVI. A relatively reliable nomogram prediction model could be established on them.

Investigation on knowledge, attitude and practice on e-cigarette use among college students in Guiyang City / 预防医学

Objective @#To investigate the knowledge, attitude and practice on e-cigarette use among college students in Guiyang City, so as to provide insights into tobacco control health education among colleges and universities. Methods College students were sampled from full-time colleges and universities in Guiyang City using a multi-stage stratified cluster sampling method from March to May in 2022. Students' knowledge, attitude and practice on e-cigarette use were collected using a questionnaire designed based on the 2019 China National Youth Tobacco Survey Questionnaire, and factors affecting the attempt to use e-cigarette were identified using a multivariable logistic regression model. @* Methods@# College students were sampled from full-time colleges and universities in Guiyang City using a multi-stage stratified cluster sampling method from March to May in 2022. Students' knowledge, attitude and practice on e-cigarette use were collected using a questionnaire designed based on the 2019 China National Youth Tobacco Survey Questionnaire, and factors affecting the attempt to use e-cigarette were identified using a multivariable logistic regression model. @* Results @#Totally 2 800 questionnaires were recovered, including 2 694 valid questionnaires, with an effective recovery rate of 96.21%. The respondents included 687 males (25.50%) and 2 007 females (74.50%). The total score of knowledge on e-cigarette use was (2.95±1.02) points, and there were low proportions of knowing that e-cigarettes contained hazardous substances, including nicotine and tar (59.06%) and knowing that e-cigarette use may cause diseases (53.27%). The total score of attitudes towards e-cigarette use was (5.09±2.36) points, and 93.50% of respondents did not use e-cigarettes given by companions. There were 132 students with attempts to use e-cigarettes (4.90%), and there were 29 current e-cigarette users (1.08%). Multivariable logistic regression analysis identified age of 20 years and lower (OR=0.438, 95%CI: 0.267-0.719), living in rural areas (OR=0.458, 95%CI: 0.264-0.794), thinking that e-cigarettes are addictive (OR=0.449, 95%CI: 0.217-0.928), and thinking that e-cigarette smoking is harmful (OR=0.263, 95%CI: 0.131-0.527) as factors protecting from e-cigarette use, and monthly living expenses of more than 2 000 Yuan (OR=2.995, 95%CI: 1.135-7.902), cigarette smoking (OR=19.826, 95%CI: 11.385-34.527), and using companions' e-cigarettes (OR=9.141, 95%CI: 5.534-15.101) and thinking that people around me support my use of e-cigarettes (OR=2.673, 95%CI: 1.426-5.013) were risk factors for e-cigarette use among college students. @* Conclusions @#There is a low awareness rate of e-cigarette use among college students in Guiyang City, and the majority oppose e-cigarette use, with a low proportion of attempt to use e-cigarettes. Age, source of students, monthly living expenses, e-cigarette smoking, knowledge on e-cigarette use and use of companions' e-cigarettes may affect the attempt to use e-cigarettes.

The therapeutic efficacy of compound lidocaine cream on psoriasis / 药学学报

Psoriasis is a non-infectious chronic inflammatory skin disease. It′s acknowledged that interleukin (IL)-17 signaling pathway dominantly drives the development of psoriasis. Recently, the role of neuro-immune axis in psoriasis has attracted widespread attention. Lidocaine, a local anesthetic, has ability to block the conduction of nerve impulses, while its therapeutic efficacy on psoriasis remains to be confirmed. Here, we evaluated the therapeutic efficacy of topical application of compound lidocaine cream (LIDO) on imiquimod (IMQ)-induced mouse psoriasis model. Animal welfare and experimental procedures follow the regulations of the Ethics Committee of China Pharmaceutical University. The psoriasis area and severity index (PASI) scoring was used to evaluate the severity of psoriasis-like symptoms. Hematoxylin-eosin staining was used to examine histopathological changes and epidermal thickness was measured. Ki67 immunofluorescence staining was used to evaluate the proliferation of keratinocytes. The relative mRNA expression of inflammatory cytokines (including Il17, Il22, Il23 and Il36) in skin was measured by real-time quantitative PCR. Results show that IMQ-induced increases in the PASI score, epidermal thickness, number of Ki67+ cells and the mRNA expression of inflammatory cytokines are significantly alleviated by topical application of LIDO, whose therapeutic efficacy is also better than that of the positive control drug calcipotriol. Our study suggests that LIDO could be used for psoriasis treatment.

Production of limonene and its derivative in Saccharomyces cerevisiae via metabolic engineering / 生物工程学报

Limonene and its derivative perillic acid are widely used in food, cosmetics, health products, medicine and other industries as important bioactive natural products. However, inefficient plant extraction and high energy-consuming chemical synthesis hamper the industrial production of limonene and perillic acid. In this study, limonene synthase from Mentha spicata was expressed in Saccharomyces cerevisiae by peroxisome compartmentalization, and the yield of limonene was 0.038 mg/L. The genes involved in limonene synthesis, ERG10, ERG13, tHMGR, ERG12, ERG8, IDI1, MVD1, ERG20ww and tLS, were step-wise expressed via modular engineering to study their effects on limonene yield. The yield of limonene increased to 1.14 mg/L by increasing the precursor module. Using the plasmid with high copy number to express the above key genes, the yield of limonene significantly increased up to 86.74 mg/L, which was 4 337 times higher than that of the original strain. Using the limonene-producing strain as the starting strain, the production of perillic acid was successfully achieved by expressing cytochrome P450 enzyme gene from Salvia miltiorrhiza, and the yield reached 4.42 mg/L. The results may facilitate the construction of cell factory with high yield of monoterpene products by S. cerevisiae.

Relationship between pancreatic fibrotic markers and glycated hemoglobin levels in patients with type 3c diabetes mellitus secondary to chronic pancreatitis / 中华胰腺病杂志

Objective:To investigate the relationship between pancreatic fibrotic marker transforming growth factor-β(TGF-β) and platelet derived growth factor-BB(PDGF-BB) and serum glycated hemoglobin (HbA1c) levels in patients with type 3c diabetes mellitus secondary to chronic pancreatitis(CP-T3cDM).Methods:The clinical data of 39 patients with CP-T3cDM admitted to the Department of Gastroenterology of the First Affiliated Hospital of Naval Medical University between February 2018 and August 2020 were collected, and the patients' age, gender, body mass index, duration of chronic pancreatitis and diabetes mellitus, smoking history, alcohol consumption history, serum HbA1c level at admission, degree of pancreatic atrophy, morphology of the main pancreatic duct, and treatment of diabetes mellitus were recorded. Serum TGF-β and PDGF-BB were detected by ELISA. Patients were divided into high and low level group according to the median TGF-β and PDGF-BB levels, respectively. Clinical characteristics of patients were compared between the TGF-β and PDGF-BB high and low level group. The correlation between TGF-β, PDGF-BB and HbA1c was analyzed by Spearman's correlation analysis.Results:A total of 39 CP-T3cDM patients were included; 35 were male and 4 were female. The age of first onset of chronic pancreatitis was (42±14) years old, and the duration of diabetes mellitus was 24(4, 36) months. The serum HbA1c level was (7.8±1.6)%, and the serum TGF-β and PDGF-BB levels were 20.5(10.5, 43.1) and 647.5(276.9, 1349.2)pg/ml, respectively. The serum HbA1c levels of patients in the high-level group of serum TGF-β and PDGF-BB were significantly higher than those in the corresponding low-level group [8.6%(7.4%, 9.9%) vs 6.7%(6.2%, 7.8%) and 8.6%(7.4%, 9.6%) vs 6.7%(6.1%, 7.8%), respectively] , and the difference was statistically different (both P value <0.01), while none of other indicators showed statistically significant differences between both groups. The correlation analysis showed that the levels of TGF-β and PDGF-BB were significantly positively correlated with HbA1c level ( r=0.45, 0.53, both P value <0.01). Conclusions:Increased pancreatic fibrosis in patients with CP-T3cDM was an important factor contributing to elevated blood glucose level. Patients with higher serum pancreatic fibrotic factors exhibited a significant increase in HbA1c level.

Effects of ultrasound-guided nerve block combined with dexmedetomidine on postoperative oxidative stress in patients with hip fracture and diabetes / 中国医师进修杂志

Objective:To explore the effect of ultrasound-guided nerve block combined with dexmedetomidine (DEX) on postoperative oxidative stress in patients with hip fracture and diabetes.Methods:From March 2017 to December 2019, 78 patients with diabetes who underwent hip fracture surgery were enrolled and divided into two groups by random number table method, with 39 cases in each group. After the operation, the control group was treated with ultrasound-guided femoral nerve combined with lateral femoral cutaneous nerve block with 0.375% ropivacaine, and the study group was treated with ultrasound-guided femoral nerve combined with lateral femoral cutaneous nerve block with 0.375% ropivacaine and DEX 0.5 μg/kg. Patients in both groups were received patient controlling intravenous analgesia (PCIA) after the operation, and visual analogue scoring (VAS) was used to evaluate the resting pain score of the patients at 4 h (T 1), 8 h (T 2), 16 h (T 3), 24 h (T 4), 36 h (T 5) and 48 h after operation (T 6). The levels of serum superoxide dismutase (SOD), malondialdehyde (MDA), 8-hydroxydeoxyuridine (8-OHdG), at T 1 and T 6 were compared between the two groups. The management system of continuous glucose monitoring system (CGMS) was used to calculate the mean amplitude of glycemic excursions(MAGE), largest amplitude of glycemic excursions (LAGE), absolute means of daily differences (MODD) of the patients during 48 h after operation, and the correlation between the blood glucose fluctuation indicators and the oxidative stress of the study group were compared. Results:The scores of VAS in the study group at T 1-T 6 were lower than those in the control group , the difference were statistically significant ( P<0.05). At T 6, the level of serum SOD in the study group was higher than that in the control group: (79.58 ± 13.55) kU/L vs. (64.16 ± 11.95) kU/L; the level of serum MDA and 8-OhdG in the study group were higher than those in the control group: (4.36 ± 0.81) μmol/L vs. (5.64 ± 0.94) μmol/L, (1.06 ± 0.19) μg/L vs.(1.42 ± 0.22) μg/L, the differences were statistically significant ( P<0.05). The levels of MAGE, LAGE, MODD in the study group were lower than those in the control group: (2.42 ± 0.47) mmol/L vs. (5.19 ± 0.96) mmol/L, (3.47 ± 0.64) mmol/L vs. (7.61 ± 1.32) mmol/L, (1.21 ± 0.27) mmol/L vs. (2.74 ± 0.46) mmol/L, the differences were statistically significant ( P<0.05). The correlation analysis showed that the blood glucose fluctuation indicators MAGE, LAGE and MODD of the study group were negatively correlated with SOD, and were positively correlated with MDA, 8-OHdG ( P<0.05). Conclusions:The use of ultrasound-guided nerve block combined with dexmedetomidine (DEX) for patients with hip fracture and diabetes can improve the analgesic effect, reduce oxidative stress of the patients, and improve the blood glucose fluctuation indicators.

A Single-Center Analysis of the Use of G-CSF Combined with Plerixafor to Mobilize Peripheral Blood Hematopoietic Stem Cell from Healthy Related Donors in Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To study the effect and safety of G-CSF combined with Plerixafor on the mobilization of peripheral blood hematopoietic stem cells from healthy related donors of allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#It was analyzed retrospectively that the data of peripheral blood hematopoietic stem cells from 33 (observation group) related donors mobilized by G-CSF plus Plerixafor in Hebei Yanda Lu Daopei Hospital from April 2019 to April 2021. Bone marrow and peripheral blood hematopoietic stem cells (PBSCs) of these donors were respectively collected on the fourth and fifth day of G-CSF-induced mobilization. Following the administration of Plerixafor on the night of the fifth day, PBSCs were collected on the sixth day once again. 46 donors using "G-CSF only" mobilization method in the same period were randomly selected as the control and respectively analyzed the differences of CD34+ cell counts on the fifth and the sixth day in two groups. And the donors' adverse reaction to Plerixafor in the form of questionnaire was also observed. Then it was compared that the patients who underwent allo-HSCT in "G-CSF+Plerixafor" group and "G-CSF only" group in terms of acute GVHD at grade I-IV or III-IV, CMV reactivation and EBV reactivation.@*RESULTS@#CD34+ cells count (M±Q) among PBSCs collected on the fifth and the sixth day in the observation group were (1.71±1.02)×106/kg and (4.23±2.33)×106/kg, respectively. CD34+ cell counts on the sixth day was significantly higher than that of the fifth day (P<0.001); While the counterparts in the control group were (2.47±1.60)×106/kg and (1.87±1.37)×106/kg, respectively. By statistical analysis, CD34+ cell counts on the sixth day was significantly less than that of the fifth day (P<0.001). The adverse reaction to Plerixafor for the donors in the study were all grade 1 or 2 (mild or moderate) according to CTCAE 5.0 and disappeared in a short time. The patients who underwent allo-HSCT in the "G-CSF+Plerixafor" group and "G-CSF only" group were not statistically significant in terms of acute GVHD at grade I-IV or III-IV, CMV reactivation and EBV reactivation (P>0.1).@*CONCLUSION@#The cell mobilization program of G-CSF combined with Plerixafor is safe and effective for being applied to allo-HSCT. The addition of Plerixafor can significantly increase the number of CD34 postive cells in the PBSC collection. Key words　　; ;

Research progress on TRPV3 channel / 药学学报

Transient receptor potential vanilloid 3 (TRPV3) is a non-selective cation channel, located on cell membranes. TRPV3 is extensively expressed in various organs such as skin, brain, dorsal root ganglia, heart and colon. It's reported that TRPV3 involves in many physiological processes including sensation, skin barrier formation, hair growth and vasodilatation, and pathological processes like pruritus, cutaneous inflammatory disease and cancer. TRPV3 can respond to innoxious warm stimulation (≥ 33 ‍℃‍), endogenous substances (e.‍g., farnesylpyrophosphate) and exogenous small molecules (e.g., carvacrol, camphor and 2-APB). Recently, several natural or synthetic small molecules (e.g., osthole, 74a and dyclonine) have been shown to suppress TRPV3 activity, accompanying with therapeutic efficacy in animal models of diseases, which suggests the potential of TRPV3 as drug target. This paper reviews the research progress on the structure, physiological functions, related diseases and modulators of the TRPV3 channel to provide theoretical references for the future study on TRPV3 channel.

Coactivator p300-induced H3K27 acetylation mediates lipopolysaccharide-induced inflammatory mediator synthesis / 南方医科大学学报

OBJECTIVE@#To investigate the role of acetylated modification induced by coactivator p300 in lipopolysaccharide (LPS)- induced inflammatory mediator synthesis and its molecular mechanism.@*METHODS@#Agilent SurePrint G3 Mouse Gene Expression V2 microarray chip and Western blotting were used to screen the molecules whose expression levels in mouse macrophages (RAW246.7) were correlated with the stimulation intensity of LPS. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (chip-qPCR) were used to verify the binding of the molecules to the promoters of IL-6 and TNF-α genes. The effects of transfection of RAW246.7 cells with overexpression or interfering plasmids on IL-6 and TNF-α synthesis were evaluated with ELISA, and the binding level of the target molecules and acetylation level of H3K27 in the promoter region of IL-6 and TNF-α genes were analyzed by chromatin immunoprecipitation sequencing technique (chip-seq).@*RESULTS@#Gene microarray chip data and Western blotting both confirmed a strong correlation of p300 expression with the stimulation intensity of LPS. Immunocoprecipitation confirmed the binding between p300 and c-myb. The results of EMSA demonstrated that c-myb (P < 0.05), but not p300, could directly bind to the promoter region of IL-6 and TNF-α genes; p300 could bind to the promoters only in the presence of c-myb (P < 0.05). The expressions of p65, p300 and c-myb did not show interactions. Both p300 overexpression and LPS stimulation could increase the level of promoter-binding p300 and H3K27 acetylation level, thus promoting p65 binding and inflammatory gene transcription; such effects were obviously suppressed by interference of c-myb expression (P < 0.05). Interference of p65 resulted in inhibition of p65 binding to the promoters and gene transcription (P < 0.05) without affecting p300 binding or H3K27 acetylation level.@*CONCLUSION@#LPS can stimulate the synthesis of p300, whose binding to the promoter region of inflammatory genes via c-myb facilitates the cohesion of p65 by inducing H3K27 acetylation, thus promoting the expression of the inflammatory genes.

Extracorporeal shock waves promote the repair of injured muscle tissue by regulating insulin-like growth factor-1 and phosphorylated protein kinase B levels / 中华物理医学与康复杂志

Objective:To determine whether or not shock wave therapy promotes the repair of muscle injury by regulating insulin-like growth factor-1 (IGF-1) and/or the phosphorylation of protein kinase B (p-Akt).Methods:Sixty-six adult male Sprague-Dawley rats were randomly divided into a normal group, a model group and a treatment group. A custom-made striker was used to induce blunt contusion in the gastrocnemius muscles of the rats of the model and treatment groups. The normal and model groups were then not given any therapeutic intervention. Twenty-four hours later, the treatment group underwent 500-impulse shockwave treatment at 0.14mJ/mm 2 and 10Hz. That was repeated 4 days later. The injured muscle was sampled on the 1st, 3rd, 5th, and 7th day after modeling. Hematoxylin and eosin staining was applied to observe the arrangement of muscle fibers, and the expressions of myostatin, myogenic differentiation antigen 1 (MYOD1), IGF-1 and p-AKTs473 were detected by immunohistochemistry and western blotting. Results:(1) The staining showed that in the model group the space between the muscle cells was larger than in the normal group. In the treatment group there were more newly-formed mononuclear or multinucleated muscle tubes. The regeneration of skeletal muscle in the treatment group was superior to that in the model group at the same time points. (2) The average myostatin expression of the model group increased significantly compared with the normal group at all the time points, while that of the treatment group had decreased significantly compared with the model group. Moreover, no significant differences were found on the 7th day between the treatment and normal groups. (3) Western blotting showed that the expression of MyoD1 in the model group was significantly higher than that in the normal group on days 1 and 3, and the expression of MyoD1 in the treatment group was significantly higher than in the model group. The expression levels of IGF-1 and P-AKTS473 in the model group were higher than those in the normal group at the same time point, and the expression levels in the treatment group were significantly higher than those in the model group.Conclusion:Extracorporeal shock wave therapy can promote the regeneration and repair of skeletal muscle by regulating IGF-1 and p-AKT levels.