Wnt/b-Catenin Promotes the Osteoblastic Potential of BMP9 Through Down-Regulating Cyp26b1 in Mesenchymal Stem Cells

BACKGROUND@#All-trans retinoic acid (ATRA) promotes the osteogenic differentiation induced by bone morphogenetic protein 9 (BMP9), but the intrinsic relationship between BMP9 and ATRA keeps unknown. Herein, we investigated the effect of Cyp26b1, a critical enzyme of ATRA degradation, on the BMP9-induced osteogenic differentiation in mesenchymal stem cells (MSCs), and unveiled possible mechanism through which BMP9 regulates the expression of Cyp26b1. @*METHODS@#ATRA content was detected with ELISA and HPLC–MS/MS. PCR, Western blot, and histochemical staining were used to assay the osteogenic markers. Fetal limbs culture, cranial defect repair model, and micro–computed tomographic were used to evaluate the quality of bone formation. IP and ChIP assay were used to explore possible mechanism. @*RESULTS@#We found that the protein level of Cyp26b1 was increased with age, whereas the ATRA content decreased. The osteogenic markers induced by BMP9 were increased by inhibiting or silencing Cyp26b1 but reduced by exogenous Cyp26b1. The BMP9-induced bone formation was enhanced by inhibiting Cyp26b1. The cranial defect repair was promoted by BMP9, which was strengthened by silencing Cyp26b1 and reduced by exogenous Cyp26b1. Mechanically, Cyp26b1 was reduced by BMP9, which was enhanced by activating Wnt/b-catenin, and reduced by inhibiting this pathway. b-catenin interacts with Smad1/5/9, and both were recruited at the promoter of Cyp26b1. @*CONCLUSIONS@#Our findings suggested the BMP9-induced osteoblastic differentiation was mediated by activating retinoic acid signalling, viadown-regulating Cyp26b1. Meanwhile, Cyp26b1 may be a novel potential therapeutic target for the treatment of bone-related diseases or accelerating bone-tissue engineering.

Correlation between food-specific IgG antibodies and phenotypes of chronic spontaneous urticaria / 中华皮肤科杂志

Objective:To investigate the correlation between food-specific IgG (sIgG) antibodies and phenotypes of chronic spontaneous urticaria (CSU) .Methods:Serum samples were collected from outpatients with active CSU, symptomatic dermographism (SD) , or acute urticaria (AU) , and healthy controls from 5 third-grade class-A hospitals such as the First Hospital of China Medical University between April 2014 and March 2015. Enzyme-linked immunosorbent assay was conducted to detect serum levels of 90 food-sIgG antibodies and total IgE, Western blot analysis to detect levels of 20 allergen-specific IgE antibodies, and chemiluminescent microparticle immunoassay to detect levels of anti-thyroid peroxidase IgG antibodies and anti-thyroglobulin IgG antibodies. Comparisons of normally distributed quantitative data between two groups and among several groups were performed by t test and one-way analysis of variance, respectively; comparisons of non-normally distributed quantitative data between two groups were performed by Mann-Whitney U test; for comparisons of proportions, chi-square test and Fisher′s exact test were used. Results:A total of 248 patients with CSU, 22 with SD, 15 with AU and 13 healthy controls were recruited. The cut-off level for sIgG positivity was 100 U/ml (at least 2+) , and the positive rate of food-sIgG antibodies was slightly higher in the patients with CSU (176/248, 70.97%) , SD (15/22, 68.18%) and AU (11/15) than in the healthy controls (7/13; χ2 = 1.80, P = 0.615) . Among the 248 CSU patients, the proportion of patients with family history of allergic diseases was significantly higher in the sIgG-positive group (71/176, 40.34%) than in the sIgG-negative group (19/72, 26.39%; χ2 = 4.30, P = 0.042) , while no significant difference was observed in the 1-day urticaria activity score (UASday) between the two groups ( Z = 0.18, P = 0.859) . Totally, 177 CSU patients completed 12- to 40-week treatment; their condition could be completely controlled by second-generation H1-antihistamines, and there was no significant difference in the required dosage of second-generation H1-antihistamines between the sIgG-positive group (128 cases) and sIgG-negative group (49 cases; Z = -1.06, P = 0.298) . Conclusions:The prevalence of family history of allergic diseases was relatively high in food-sIgG-positive patients with CSU. However, food-sIgG could not be used as an indicator to reflect the disease activity of CSU and treatment response.

Bushen Anshen acupuncture for perimenopausal insomnia of kidney-yin deficiency: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of Bushen Anshen acupuncture (acupuncture for tonifying kidney and calming spirit ) in treating perimenopausal insomnia (PMI) of kidney-yin deficiency.@*METHODS@#A total of 72 patients with PMI of kidney-yin deficiency were randomized into an observation group (36 cases, 1 case dropped off) and a control group (36 cases, 1 case dropped off). Acupuncture was applied at Baihui (GV 20) and bilateral Shenshu (BL 23), Taixi (KI 3), Anmian (Extra) in the observation group, while sham acupuncture of shallow needling at non-acupoints was applied in the control group. The treatment was required once every other day, 3 times a week for 10 times in the two groups. Before and after treatment, Pittsburgh sleep quality index (PSQI) was used to evaluate the subjective sleep quality, and polysomnography (PSG) was used to monitor the objective sleep quality in the two groups.@*RESULTS@#After treatment, the scores of sleep quality, sleep latency, sleep duration, sleep efficiency, hypnotic, daytime dysfunction and total score of PSQI were decreased compared with those before treatment in the observation group (P<0.01), the scores of sleep duration, sleep efficiency and total score of PSQI were decreased compared with those before treatment in the control group (P<0.05); the scores of sleep quality, sleep latency, sleep efficiency, hypnotic and total score of PSQI in the observation group were lower than those in the control group (P<0.05). After treatment, the sleep time was prolonged, the sleep efficiency was improved, the sleep latency and the awake time after falling asleep were shortened, the arousal awake index was reduced (P<0.01) when PSG indexes were monitored, and the percentage of non-rapid eye movement sleep period 1 (N1%) was decreased while the percentage of non-rapid eye movement sleep period 3 (N3%) was increased (P<0.05) compared with those before treatment in the observation group; there was no statistical difference in the PSG indexes compared with those before treatment in the control group (P>0.05). After treatment, compared with the control group, the sleep time was prolonged, the sleep efficiency was improved, the sleep latency and the awake time after falling asleep were shortened, the arousal awake index and N1% were decreased in the observation group (P<0.01).@*CONCLUSION@#Bushen Anshen acupuncture can effectively improve the subjective and objective sleep quality in PMI patients of kidney-yin deficiency.

To explore the quality markers of Huangqin Qingre Chubi capsule in the treatment of rheumatoid arthritis based on network pharmacology combined with pharmacokinetics and target verification / 药学学报

As an effective prescription for the treatment of rheumatoid arthritis (RA), Huangqin Qingre Chubi capsule (HQC) is still blank in quality control. This study aims to explore quality markers (Q-markers) for HQC in the treatment of RA by integrating network pharmacology and pharmacokinetics. By constructing the visualization network of "pharmacodynamic ingredient-target-pathway", the potential Q-Marker of HQC treatment for RA was preliminatively predicted. A rat model of rheumatic heat obstruction syndrome collagene-induced arthritis (CIA) was established to elucidate the dynamic quantification law of pharmacodynamic components of HQC in the disease state of rats. To establish the inflammatory model of RA synovial fibroblasts (MH7A) induced by tumor necrosis factor-α (TNF-α) in vitro. The effects of active ingredients on protein expression of sphingosin kinase-1 (Sphk1) and p-SphK1 were detected. The network pharmacological results showed that baicalin, geniposide, luteolin, coixol and amygdalin were the important active components of HQC treatment for RA. Quantitative analysis results further verified the measurability of these five components. The expression of Sphk1 and p-SphK1 was significantly inhibited by geniposide and baicalin by Western blotting. The above studies determined that the above 5 components could be used as Q-markers in the treatment of RA by HQC. This experiment was approved by the Experimental Animal Ethics Committee of Anhui University of Chinese Medicine (approval number: AHUCM-rats-2021049). All procedures were conducted in strict accordance with the principles of animal use and care.

Mycoplasma pneumoniae infection and recurrent respiratory tract infection in children / 公共卫生与预防医学

Objective To analyze the risk factors of mycoplasma pneumoniae (MP) infection and recurrent respiratory tract infection (RRTI) in children, and to provide reference for early clinical intervention. Methods A total of 648 RRTI children admitted to our hospital from October 2018 to December 2020 were selected. Serum MP antibody levels were detected by semi-quantitative method. According to whether the children were combined with mycoplasma infection, they were divided into experimental group (MP positive, n=283) and control group (MP negative, n=365). Age, gender, body mass index, nutrient deficiency, preterm birth, anemia, onset season, collective living, antibiotics application were collected from the two groups. Logistic regression was used to analyze the independent risk factors of MP infection in RRTI children. Results Among of 648 RRTI children, 283 (43.67%) had MP infection. There was no statistical significance in MP infection of pneumonia in children of different ages and genders between the two groups (P>0.05).There were statistically significant differences between the two groups in nutrient deficiency, onset season, length of hospital stay, days of fever, group living, application of antibiotics and invasive operation (P<0.05). Logistic regression analysis showed that the onset season, length of hospital stay, group living were independent risk factors for MP infection in RRTI children (P<0.05). Conclusion The risk of MP infection in RRTI children is higher, and the main risk factors are onset season, length of hospital stay, group living and application of antibiotics.

Efficacy and safety of transurethral flexible ureteroscopy combined with single channel minimally invasive percutaneous nephroscopy in the treatment of complex renal calculi / 国际外科学杂志

Objective:To investigate the clinical efficacy and safety of transurethral flexible ureteroscopy combined with single channel minimally invasive percutaneous nephroscopy in the treatment of complex renal calculi.Methods:A total of 72 patients with complex renal calculi admitted to Beijing Friendship Hospital, Capital Medical University from November 2019 to April 2022 were prospective selected, which were randomly divided into study group and control group by the random number table method, with 36 cases in each group. The control group underwent single channel minimally invasive percutaneous nephrolithotomy, while the study group underwent transurethral flexible ureteroscopy combined with single channel minimally invasive percutaneous nephrolithotomy. The perioperative indexes (operation time, postoperative hospital stay, intraoperative blood loss), stone removal effect, renal function indicators [blood urea nitrogen (BUN), serum creatinine (SCr)] and complication rate were compared between the two groups. Measurement data were expressed as mean ± standard deviation ( ± s), and t-test was used for inter-group comparison. The Chi-square test or Fisher exact probability method were used to compare the count data of two groups. Results:The operation time [(101.05±11.34) min vs (107.84±10.28) min] and postoperative hospital stay [(8.54±3.15) d vs (12.36±4.08) d] in the study group were significantly shorter than those in the control group, and the difference were statistically significant ( P<0.05). The amount of intraoperative bleeding was close to that in the control group, but the difference was not statistically significant ( P>0.05). The primary stone clearance rate and summary stone clearance rate in the study group were 91.67% (33/36) and 100.0% (36/36), respectively, which were significantly higher than 69.44% (25/36) and 83.33% (30/36) in the control group, and the differences were statistically significant ( P<0.05). The postoperative BUN and SCr levels in the study group were (5.24±0.31) mmol/L and (90.65±25.57) μmol/L, respectively, the control group was (7.69±0.78) mmol/L and (131.96±37.80) μmol/L, respectively. BUN and SCr levels in the study group were significantly lower than those in the control group, and the differences were statistically significant ( P<0.05). The total incidence of postoperative complications in the study group was significantly lower than that in the control group (5.56% vs 16.67%), and the difference was statistically significant ( P<0.05). Conclusion:Transurethral flexible ureteroscopy combined with single channel minimally invasive percutaneous nephroscopy is an ideal method for the treatment of complex renal calculi, which has good removal effect, less complications and helps to improve renal function.

Repetitive transcranial magnetic stimulation and transcranial direct current stimulation in the treatment of post-stroke depression / 国际脑血管病杂志

Post-stroke depression (PSD) refers to a series of affective disorder syndrome characterized by low mood and lack of interest after stroke, often accompanied by physical symptoms, which is a common complication of stroke. Non-invasive brain stimulation techniques, such as repetitive transcranial magnetic stimulation and transcranial direct current stimulation have been widely used in the treatment of PSD in recent years. This article summarizes the research progress of repetitive transcranial magnetic stimulation and transcranial direct current stimulation in the treatment of PSD.

Chemical constituents in Dolomiaea plants and their pharmacological activities: a review / 中国中药杂志

Dolomiaea plants are perennial herbs in the Asteraceae family with a long medicinal history. They are rich in chemical constituents, mainly including sesquiterpenes, phenylpropanoids, triterpenes, and steroids. The extracts and chemical constituents of Dolomiaea plants have various pharmacological effects, such as anti-inflammatory, antibacterial, antitumor, anti-gastric ulcer, hepatoprotective and choleretic effects. However, there are few reports on Dolomiaea plants. This study systematically reviewed the research progress on the chemical constituents and pharmacological effects of Dolomiaea plants to provide references for the further development and research of Dolomiaea plants.

Acupuncture for delayed sleep-wake phase disorder: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical effect of acupuncture for delayed sleep-wake phase disorder (DSWPD).@*METHODS@#A total of 84 patients with DSWPD were randomized into an observation group (42 cases, 2 cases dropped off) and a control group (42 cases, 3 cases dropped off). On the basis of sleep hygiene education, acupuncture was applied at Shenmai (BL 62), Zhaohai (KI 6), Hegu (LI 4), Taichong (LR 3), Zusanli (ST 36) and Sanyinjiao (SP 6) in the observation group, while placebo acupuncture was applied at the same acupoints in the control group. The treatment lasted for 8 weeks, once every other day, 3 times a week in the 1st to 4th weeks; once every 3 days, 2 times a week in the 5th to 8th weeks. Before and after treatment, the actigraphy (ACT) indexes of objective sleep (total time of stay in bed, total sleep time, sleep efficiency, the number of awakenings and the wake time after falling asleep) and plasma cortisol (CORT) level were observed; before and after treatment and in follow-up of 1, 3 months after treatment, the scores of morningness-eveningness questionnaire (MEQ), insomnia severity index (ISI), fatigue severity scale (FSS) and Epworth sleepiness scale (ESS) were observed in the two groups.@*RESULTS@#Compared before treatment, the total sleep time was prolonged, the sleep efficiency was improved, the number of awakenings was reduced, and the wake time after falling asleep was shortened after treatment in the observation group (P<0.01, P<0.05), and those in the observation group after treatment were superior to the control group (P<0.01, P<0.05). Compared before treatment, the MEQ scores after treatment in both groups and in the follow-up of 1, 3 months after treatment in the observation group were increased (P<0.01), and the MEQ score of each time point after treatment in the observation group was higher than the control group (P<0.01). The scores of ISI, FSS and ESS after treatment, and the scores of ISI、ESS in follow-up of 1, 3 months after treatment in the observation group were decreased compared with those before treatment (P<0.01, P<0.05), and in the observation group, the scores of ISI, FSS and ESS of each time point after treatment were lower than those in the control group (P<0.01, P<0.05). After treatment, the plasma CORT level in the observation group was decreased compared with that before treatment and that in the control group (P<0.01, P<0.05).@*CONCLUSION@#Acupuncture can improve the sleep and wake phase of patients with DSWPD, improve sleep quality and daytime function, and its mechanism may be related to the down-regulation of plasma CORT level.

Qualitative and quantitative study of flavonoids in Notoginseng Radix et Rhizoma based on UPLC-Q-TOF-MS and HPLC-DAD / 中国中药杂志

The flavonoids in Panax notoginseng were qualitatively analyzed by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UPLC-Q-TOF-MS), and the content of three main flavonoids in P. notoginseng of different specifications and grades collected from different habitats was determined by HPLC-DAD. Flavonoids and anthocyanins were analyzed by UPLC-Q-TOF-MS/MS in the positive and negative ion modes, respectively. Twelve flavonoid glycosides and one anthocyanin glycoside in P. notoginseng were identified, but no flavonoid aglycones were detected. Among them, 12 compounds were identified in the underground part of P. notoginseng for the first time and eight compounds were first reported in this plant. Moreover, six and four compounds were identified in the Panax genus and the Araliaceae family for the first time, respectively. A method for simultaneous determination of three flavonoids in P. notoginseng was established by HPLC-DAD. The content of flavonoids in 721 P. notoginseng samples of 124 specifications and grades collected from 20 different habitats was simultaneously determined. Among three flavonoids determined, the content of quercetin-3-O-(2″-β-D-xylosyl)-β-D-galactoside was the highest with the average content in the tested samples of 161.0 μg·g~(-1). The content of compounds quercetin-3-O-hexosyl-hexoside and kaempferol-3-O-pentosyl-hexoside was relatively low, with the average content of 18.5 μg·g~(-1)(calculated as quercetin-3-O-sophoroside) and 49.4 μg·g~(-1)(calculated as kaempferol-3-O-sangbu diglycoside). There were significant differences in flavonoids content of samples from different production area. The content of flavonoids in spring P. notoginseng was significantly lower than that in winter P. notoginseng when the other influencing factors such as production areas, germplasm resources, and cultivation conditions were fixed. As for P. notoginseng of different specifications, the flavonoid content in the part connecting the taproot and the aboveground stem was significantly higher than that in other parts. The results of large-scale data showed that the flavonoid content gradually increased with the increase in the number of heads. There were significant differences between the flavonoid content in most specifications and grades, especially the 20-head P. notoginseng and countless head P. notoginseng, whose content was significantly lower and significantly higher than that of other specifications and grades, respectively. This study provides a scientific basis for the study of the effective components and quality control of P. notoginseng from the perspective of flavonoids.

Rethinking the marketing strategy of anti-tumor drugs by single-arm trials supported / 中华肿瘤杂志

Single-arm trial refers to a clinical trial design that does not set up parallel control group, adopts open design, and does not involve randomization and blind method. These features, on the one hand, speed up the process of clinical trials, significantly shorten the time to market and meet the needs of patients with advanced malignancies, but also lead to the uncertainty of single-arm clinical trials themselves. Recently, the US Food and Drug Administration held a meeting of the oncologic drug advisory committee to discuss six tumor indications that have been accelerated approved, which once again triggered the discussion of single-arm trials. The basis of accelerated approval by single-arm trial is actually a compromise on the level of evidence-based medical evidence requirements after assessing the benefit risk. Therefore, the sponsor should strictly grasp the applicable conditions of single-arm trial in anti-tumor drugs and conduct single-arm trial scientifically. Post-marketing clinical trial should be implement as early as possible to ensure the benefit of patients. Based on the characteristics of single-arm trial, combined with two guidance relevant to single-arm trial issued by National Medical Products Administration recently, this article is supposed to propose and summarize the strategy of single-arm trial supporting the marketing of anti-tumor drugs.

MiR-4484 regulates the expression of integrin α 6 in gastric cancer tissues and its significance / 中华肿瘤杂志

Objective: To investigate the relationship between the expression of integrin α 6 (ITGA6), miR-4484 and the pathologic stage of gastric cancer. Methods: Gastric cancer tissues and normal gastric mucosa tissues adjacent to cancer (>5 cm from tumor margin) of 30 patients with primary gastric cancer who underwent direct surgical resection without adjuvant therapy from June to September 2017 in West China Hospital of Sichuan University were selected. Real-time quantitative polymerase chain reaction (PCR) was used to detect the expression levels of miR-4484 and ITGA6, western blot was used to detect the expression level of ITGA6 protein, dual luciferase reporter gene was used to verify the relationship between ITGA6 and miR-4484. Spearman's correlation analysis was used to determine the relationship between miR-4484 and ITGA6 expression levels in gastric cancer tissues. Results: The expression level of ITGΑ6 in gastric cancer (32.30±13.47) was higher than that in matched normal gastric tissues (24.55±10.25, P=0.015), the area under the receiver operating characteristic (ROC) curve was 0.660 and the diagnostic sensitivity and specificity were 43.3% and 96.7%, respectively. The expression level of miR-4484 in gastric cancer (4.11±2.87) was lower than that of matched normal gastric tissues (5.75±2.80, P=0.029), the area under the ROC curve was 0.690 and the diagnostic sensitivity and specificity were 30.0% and 86.7%, respectively. The expression level of miR-4484 was negatively correlated with ITGA6 in gastric cancer tissues (r=-0.621, P<0.001). The expression level of ITGA6 protein in gastric cancer tissues (0.65±0.19) was higher than that in normal adjacent tissues (0.26±0.12, P<0.001). Compared with ITGA6 3'UTR wild-type+ miR-NC group, ITGA6 3'UTR wild-type+ miRNA mimics group had lower luciferase activity (50.69±5.10, 34.00±1.19, P<0.001), while the luciferase activity of ITGA6 3'UTR wild-type+ ASO miR-4484 group was higher than that of ITGA6 3'UTR wild-type+ miR-NC group (82.44±6.37, 50.69±5.10, P<0.001), indicated that ITGA6 was the direct target gene of miR-4484. The expression levels of miR-4484 in T1, T2, T3 and T4 (4a and 4b) gastric cancer tissues were 9.98±2.24, 5.28±2.03, 2.92±2.04 and 4.11±2.87, respectively, with statistical significance (P<0.001). The expression levels of ITGA6 in N0, N1, N2 and N3 gastric cancer tissues were 29.55±8.32, 21.71±3.75, 24.60±8.79 and 40.69±15.83, respectively, with statistical significance (P=0.022). The expression levels of miR-4484 in N0, N1, N2 and N3 gastric cancer tissues were 5.01±3.52, 5.48±2.76, 5.88±1.83 and 2.30±1.56, respectively, with statistical significance (P=0.032). The expression levels of ITGA6 in M0 and M1 gastric cancer tissues were 26.28±7.66 and 52.08±8.12, respectively, with statistical significance (P<0.001). The expression levels of miR-4484 in M0 and M1 gastric cancer tissues were 4.95±2.74 and 1.34±0.80, respectively, with statistical significance (P<0.001). Conclusions: ITGA6 is upregulated in gastric cancer tissues, while miR-4484 is downregulated in the gastric cancer group, and its expression level is related to the clinicopathological features of gastric cancer. ITGA6 is the direct target gene of miR-4484, implicates that miR-4484 may inhibit the invasion and metastasis of gastric cancer by regulating the expression of ITGA6. Both miR-4484 and ITGA6 may be the new prognostic markers and potential therapeutic targets of gastric cancer.

Factors associated with pathological complete response and construction of scoring system in patients with rectal cancer after neoadjuvant chemoradiotherapy / 中华普通外科杂志

Objective:To identify the clinical factors associated with pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in locally advanced middle and low rectal cancer and establish a scoring system.Methods:In this retrospective analysis the clinical data of patients with locally advanced middle and low rectal cancer treated with nCRT combined with surgery at Union Hospital of Tongji Medical College, Huazhong University of Science and Technology from Jan 2016 to Jan 2020 were studied. Patients were divided into pCR group and non-pCR group. Single factor analysis and Logistic multivariate regression analysis were performed to explore pCR related factors after nCRT, and a pCR prediction scoring system was established.Results:The pCR was achieved in 33 patients (20.8%). Univariate analysis showed that the maximum thickness of the tumor≤25mm before nCRT ( P=0.046), concurrent oxaliplatin-combined intensive chemotherapy ( P=0.013), the NLR≤1.65 before nCRT ( P=0.004) and the serum CEA≤5 ng/ml before nCRT ( P=0.016) were significantly associated with pCR. In multivariate analysis, concurrent oxaliplatin-combined intensive chemotherapy, the NLR before nCRT and serum CEA before nCRT were independent related factors of pCR. The probability of pCR for patients with score of 0, 1, 2, and 3 was 42% (10/24), 30% (19/63), 5% (3/57) and 7% (1/15), respectively. The probability of pCR in patients with score≤1 point was 33% (29/87), and 6% (4/72) for score?1 point ( P?0.001). The area under the curve of the scoring system is 0.729 (95% CI: 0.638-0.820, P?0.001). Conclusions:Concurrent oxaliplatin-combined intensive chemotherapy, NLR≤1.65 before nCRT and serum CEA≤5 ng/ml before nCRT are independent predictors of pCR in locally advanced middle and low rectal cancer and the scoring system constructed in combination with above indicators can effectively predict pCR.

Value of Caprini risk assessment scale and serum D-dimer in early prediction of postoperative deep vein thrombosis of lower extremities in patients with gastrointestinal malignant tumors / 中华普通外科杂志

Objective:To explore the value of Caprini risk assessment scale and serum D-dimer in early prediction of postoperative lower extremities deep vein thrombosis (DVT) in patients with gastrointestinal malignant tumor.Methods:A total of 240 patients with gastrointestinal malignant tumors treated in Union Hospital of Tongji Medical College of Huazhong University of Science and Technology from Jan to Oct 2020 were analyzed retrospectively.Results:Caprini score was 4 in 8 cases, 5-7 in 217 cases, and 8 in 15 cases. Sixty-seven patients developed lower extremity DVT after operation. No patients with Caprini score of 4 had DVT, 57 cases (26.3%) with a score of 5-7 had DVT; 10 cases whose score were ≥8 points (66.7%) developed DVT. There was a higher incidence of lower extremity DVT in patients ≥8 points than those of 5-7 points after surgery ( P<0.01). The postoperative Caprini score of the DVT group was higher than that of the non-DVT group (6.37±1.01 vs. 5.80±0.94, t=4.108, P<0.001). D-dimer on the first day after operation in DVT group (4.08±2.27 vs. 2.01±1.04, t=7.715, P<0.001) and the level of serum D-dimer (2.93±1.81 vs. 2.30±1.21, t=2.631, P<0.001) on day 3 was higher than that in the non-DVT group. According to the ROC curve, the best cut-off value for serum D-dimer to predict lower extremity DVT on the first postoperative day was 2.84 mg/L, the sensitivity was 70.1%, the specificity was 87.3%, and the area under the curve (AUC) was 0.815. The best cut-off value of D-dimer for predicting lower limb DVT on day 3 after surgery was 1.67 mg/L, sensitivity was 85.1%, specificity was 34.7%, and AUC was 0.611. Conclusions:Patients with gastrointestinal malignant tumors have a high incidence of postoperative lower extremity DVT. When the serum D-dimer exceeds 2.84 mg/L on the first postoperative day, the likelihood of postoperative lower extremity DVT is higher.

Advances in the treatment of immune checkpoint inhibitors for esophageal cancer / 中国医师杂志

As a new therapeutic strategy for esophageal cancer, immunotherapy has attracted more and more attention. The completed and ongoing clinical trials of immunotherapy for esophageal cancer confirm the great potential of immune checkpoint inhibitors in esophageal cancer. Future research will focus on the combination of immunotherapy with existing or new therapeutic modalities and the identification of populations likely to benefit from immunotherapy.

Anterior Cingulate Cortex Mediates Hyperalgesia and Anxiety Induced by Chronic Pancreatitis in Rats / 神经科学通报·英文版

Central sensitization is essential in maintaining chronic pain induced by chronic pancreatitis (CP), but cortical modulation of painful CP remains elusive. Here, we examined the role of the anterior cingulate cortex (ACC) in the pathogenesis of abdominal hyperalgesia in a rat model of CP induced by intraductal administration of trinitrobenzene sulfonic acid (TNBS). TNBS treatment resulted in long-term abdominal hyperalgesia and anxiety in rats. Morphological data indicated that painful CP induced a significant increase in FOS-expressing neurons in the nucleus tractus solitarii (NTS) and ACC, and some FOS-expressing neurons in the NTS projected to the ACC. In addition, a larger portion of ascending fibers from the NTS innervated pyramidal neurons, the neural subpopulation primarily expressing FOS under the condition of painful CP, rather than GABAergic neurons within the ACC. CP rats showed increased expression of vesicular glutamate transporter 1, and increased membrane trafficking and phosphorylation of the N-methyl-D-aspartate receptor (NMDAR) subunit NR2B and the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunit GluR1 within the ACC. Microinjection of NMDAR and AMPAR antagonists into the ACC to block excitatory synaptic transmission significantly attenuated abdominal hyperalgesia in CP rats, which was similar to the analgesic effect of endomorphins injected into the ACC. Specifically inhibiting the excitability of ACC pyramidal cells via chemogenetics reduced both hyperalgesia and comorbid anxiety, whereas activating these neurons via optogenetics failed to aggravate hyperalgesia and anxiety in CP rats. Taken together, these findings provide neurocircuit, biochemical, and behavioral evidence for involvement of the ACC in hyperalgesia and anxiety in CP rats, as well as novel insights into the cortical modulation of painful CP, and highlights the ACC as a potential target for neuromodulatory interventions in the treatment of painful CP.

Management and risk factors of anemia in patients with gastric cancer / 中华普通外科杂志

Objective:To review the incidence and treatment status of perioperative anemia in patients with gastric cancer.Methods:The clinicopathological data of gastric cancer patients who underwent surgery at Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from Jan to Dec 2019 were collected. Univariate analysis and multivariate Logistic regression analysis were used to explore the risk factors of preoperative anemia in gastric cancer.Results:A total of 879 patients were included in this study. The incidence of preoperative anemia in patients with gastric cancer was 35.6%. The incidence of postoperative anemia was 63.5%. The proportion of patients with preoperative anemia receiving treatment was 17.3%, and the proportion of patients with postoperative anemia receiving treatment was 17.4%. Univariate analysis showed that age, nutritional risk screening 2002, T stage, M stage, tumor stage and lymph node metastasis were associated with preoperative anemia (all P<0.05). Multivariate Logistic regression analysis showed that age >60 years , nutritional risk screening 2002 ≥3, T 3-4 stage and M 1 stage were independent risk factors for preoperative anemia in patients with gastric cancer (all P<0.05). Conclusions:The incidence of perioperative anemia in patients with gastric cancer is high. At present, the proportion of patients with perioperative anemia receiving treatment is low. High nutritional risk, advanced age, late tumor T stage and distant metastasis are independent risk factors for preoperative anemia in patients with gastric cancer.

Effect of music therapy on motor function recovery in patients with stroke / 国际脑血管病杂志

As a new therapeutic method, music therapy has a good clinical effect on improving the motor dysfunction of patients with stroke. This article reviews the concept, main forms of music therapy and its role in motor function recovery of patients with stroke.

Expression and role of the TRPC family in TGF-β1-induced calcium influx in podocytes / 生理学报

The TRPC family consists of multiple important cationic channels in mammals that participate in a variety of physiological and pathological processes. Our previous studies have shown that transforming growth factor-β1 (TGF-β1) increases the expression of TRPC6 in podocytes, but the roles of other members of the TRPC family in podocytes require further investigation. In this study, we investigated the effect of TGF-β1 on the expression of the TRPC family and the role of the TRPC family in the changes of the intracellular Ca2+ concentration ([Ca2+]i) in podocytes induced by TGF-β1. The model of podocyte injury was established by treatment with TGF-β1 in immortalized glomerular podocytes (MPC5) in vitro. qRT-PCR and Western blot were used to detect the effect of TGF-β1 on the mRNA and protein expression of each TRPC family member. After the expression of each TRPC family member was knocked down by a siRNA-based approach and blocked by SKF96365, respectively, free cytosolic Ca2+ was measured using the fluorescent Ca2+ indicator Fluo-3/AM, and the dynamic change of [Ca2+]i in podocytes was detected by a dynamic high-speed calcium imaging system. The results showed that TGF-β1 increased the protein expression of TRPC1/3/6 in podocytes, but had no effects on the protein expression of TRPC4. The protein expression levels of TRPC5/7 were only affected by 4 ng/mL and 8 ng/mL TGF-β1, respectively. TGF-β1 increased TRPC1/3/6 mRNA levels in podocytes, however had no effects on TRPC4/5/7 mRNA. TGF-β1 significantly increased [Ca2+]i in podocytes. Knockdown of TRPC1/4/5/7 in podocytes had no significant effect on the [Ca2+]i induced by TGF-β1, but TRPC3/6 knockdown significantly decreased the [Ca2+]i. There was no significant difference in the [Ca2+]i between the TRPC6 siRNA-treated group and SKF96365-treated group, but the [Ca2+]i of the TRPC3 siRNA-treated group was significantly higher than that of SKF96365-treated group. These results demonstrate that TGF-β1 increases the expression of the TRPC1/3/6 in podocytes. TGF-β1 increases [Ca2+]i in podocytes, which is dependent on the TRPC3/6 expression. Our results also suggest that the effect of TRPC6 on [Ca2+]i in podocytes may be greater than that of TRPC3.

Considerations on Clinical Development and Regulatory of the Oversea License-in Anti-tumor Drugs / 中国肺癌杂志

With the boom of China's innovative pharmaceutical industry, licensing-in model has gradually become an important research and development model for innovative pharmaceutical companies. The in-licensed drugs at different stages need different research and development (R&D) strategy in China. The pharmaceutical companies take the responsibility to comprehensively collate the oversea clinical data and conduct a detailed analysis of clinical pharmacology, safety, efficacy and ethnic sensitivity. Clinical R&D strategy should be made based on the results of the above data and analysis. We encourage high-quality drugs which fill unmet clinical needs licensed in, and as early as possible, so as to conduct multi-regional clinical trials (MRCTs). The clinical R&D strategy in China is particularly important for the drug's approval. Guidelines published by the National Medical Products Administration (NMPA) and clinical associations should be followed. Communications about clinical R&D strategy with Center of Drug Evaluation (CDE) are encouraged.
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