Expressions of STMN1, BubR1, bcl-2 and Bad in patients with esophageal squamous cell carcinoma and their relationship with chemotherapy effect of paclitaxel-containing regimen / 肿瘤研究与临床

Objective:To investigate the correlation between the expression levels of STMN1, BubR1, bcl-2 and Bad and the chemotherapy effect of paclitaxel-containing regimen in patients with esophageal squamous cell carcinoma (ESCC).Methods:The clinical data of ESCC patients who received paclitaxel-containing chemotherapy at Fenyang Hospital Affiliated to Shanxi Medical University from September 2016 to June 2021 were retrospectively analyzed. Among them, 59 cases received maintenance chemotherapy and 27 cases received surgery after 3 courses of neoadjuvant chemotherapy. The expression levels of STMN1, BubR1, bcl-2 and Bad in tumor tissues before chemotherapy were detected by immunohistochemistry. The imaging efficacy after 3 courses of chemotherapy and pathological efficacy after neoadjuvant chemotherapy were evaluated. The imaging efficacy, pathological efficacy and progression-free survival (PFS) were compared between the high expression group and the low expression group of each protein.Results:The proportion of patients with stage Ⅳ (46.3%, 19/41), the proportion of patients with low differentiation (22%, 9/41) and the incidence of lymph node metastasis (95.1%, 39/41) in STMN1 high expression group were higher than those in STMN1 low expression group (17.8%, 8/45; 4.4%, 2/45; 64.4%, 29/45), and the differences were statistically significant (all P < 0.05). The proportion of patients with stage Ⅳ in Bad high expression group was lower than that in Bad low expression group, and the difference was statistically significant ( P < 0.05). In the evaluation of imaging efficacy, the chemotherapy sensitivity rates in STMN1 and BubR1 high expression groups (29.3%, 12/41; 37.9%, 22/58) were lower than those in STMN1 and BubR1 low expression groups (75.6%, 34/45; 85.7%, 24/28), and the chemotherapy sensitivity rate of patients in Bad high expression group (65.9%, 27/41) was higher than that in Bad low expression group (42.2%, 19/45), and the difference was statistically significant (all P < 0.05). There was no statistical correlation between bcl-2 expression and chemotherapy sensitivity rate ( P > 0.05). In the evaluation of pathological efficacy, the proportion of patients with tumor regression grade (TRG) score 0-1 after neoadjuvant therapy in STMN1 high expression group (27.3%, 3/11) was lower than that in STMN1 low expression group (75.0%, 12/16), and the difference was statistically significant ( P = 0.022). There were no statistical differences in the proportions of patients with TRG score 0-1 after neoadjuvant therapy between high and low expression groups of BubR1, bcl-2 and Bad (all P > 0.05). The PFS rate was 15.2% (9/59) for patients received maintenance chemotherapy, and the median PFS time was 6 months. Kaplan-Meier analysis showed that PFS in STMN1 low expression group was better than that in STMN1 low expression group ( χ2 = 12.90, P < 0.001). PFS in BubR1 low expression group was better than that in BubR1 high expression ( χ2 =12.04, P < 0.001). PFS in Bad high expression group was better than that in Bad low expression group ( χ2 =9.69, P = 0.004). There was no statistical difference in PFS between high and low bcl-2 expression groups ( χ2 =1.43, P = 0.320). Conclusions:ESCC patients with low expression of STMN1, low expression of BubR1 and high expression of Bad have better chemotherapy effect after receiving paclitaxel-containing regimen, but there is no correlation between bcl-2 expression and chemotherapy efficacy.

Anti-inflammatory sesquiterpene polyol esters from the stem and branch of Tripterygium wilfordii / 中国天然药物

The stem and branch extract of Tripterygium wilfordii (Celastraceae) afforded seven new dihydroagarofuran sesquiterpene polyesters [tripterysines A-G (1-7)] and eight known ones (8-15). The chemical structures of these new compounds were established based on combinational analysis of HR-ESI-MS and NMR techniques. The absolute configurations of tripterysines A-C (1-3) and E-G (5-7) were determined by X-ray crystallographic analysis and circular dichroism spectra. All the compounds were screened for their inhibitory effect on inflammation through determining their inhibitory effect on nitric oxide production in LPS-induced RAW 264.7 cells and the secretion of inflammatory cytokines TNF-α and IL-6 in LPS-induced BV2 macrophages. Compound 9 exhibited significant inhibitory activity on NO production with an IC50 value of 8.77 μmol·L-1. Moreover, compound 7 showed the strongest inhibitory effect with the secretion of IL-6 at 27.36%.

Antibiotic articular cement spacer for shoulder infection in the elderly / 中华创伤骨科杂志

Objective:To investigate the therapeutic effects of antibiotic articular cement spacer on shoulder joint infection in the elderly patients during stage-one operation.Methods:The data of 3 patients were analyzed retrospectively who had been treated at Department of Orthopaedics, The Sixth People's Hospital Affiliated to Shanghai Jiao Tong University for shoulder infection from May 2018 to December 2019. They were one man and 2 women with an average age of 65.3 years (from 64 to 67 years). One case of infection followed shoulder puncture, another proximal humeral fracture and another shoulder prosthesis replacement. All the 3 patients underwent radical debridement and implantation of antibiotic shoulder cement spacer in stage-one operation but no stage-two operation. The therapeutic effects were evaluated by American Shoulder and Elbow Surgeons (ASES) scoring, Quick Disabilities of the Arm, Shoulder, and Hand (Quick-DASH) scoring, Visual Analog Scale (VAS), and range of shoulder motion.Results:The 3 patients were followed up for 18 to 28 months (mean, 22.7 months). There was no recurrence of infection and the spacers were in good position. The microorganisms detected were Bifidobacterium brevis in one case and methicillin-resistant Staphylococcus aureus in 2 cases. At the final follow-up, the ASES scores averaged 54.4 (from 46.3 to 60.0), Quick-DASH scores 45.1 (from 40.8 to 50.0), VAS scores 2.3 (from 2 to 3), ranges of elevation 65.7 °, ranges of abduction 43.8° and ranges of external rotation 21.7°.Conclusion:For the elderly patients with shoulder infection, implantation of antibiotic shoulder cement spacer after radical debridement can well control infection, relieve pain and improve shoulder functions, sparing them secondary operation.

Establishment and validation of a nomogram prediction model for early preoperative diagnosis of hepatocellular carcinoma with microvascular invasion / 中华肝胆外科杂志

Objective:To establish a convenient preoperative nomogram prediction model for early diagnosis of hepatocellular carcinoma (HCC)with microvascular invasion (MVI), and to evaluate the model through internal and external validations for use informulating reasonable and individualized treatment strategies for patients with early-staged HCC.Methods:The clinical data of 294 patients who underwent hepatectomy at the General Hospital of Ningxia Medical University from January 2017 to December 2020 were retrospectively collected and analyzed. Based on the different admission times, they were divided into the training group ( n=231) and the validation group ( n=63). Based on the results from previous published literatures and our relevant clinical experience, risk factors including γ-glutamyltranspeptidase (GGT), platelet-lymphocyte ratio (PLR), fibrinogen albumin ratio (FAR), lymphocyte monocyte count ratio (LMR) and ALT-platelet ratio (APRI) were subjected to multi-factor logistic regression analysis to determine independent risk factors of HCC with MVI, and a nomogram prediction model was then constructed. The validation group was applied to the model for validation. Results:Of 294 patients who were enrolled in this study, there were 231 patients in the training cohort, with an average age of (55.1±10.9) years. In the training group, 95 patients were MVI positive and 136 patients were MVI negative. In the validation group, 38 patients were MVI positive and 25 patients were MVI negative. Logistic regression analysis showed that FAR>0.06, GGT>50 U/L, APRI>0.16, tumor diameter>5 cm, LMR>3.57 and PLR>98.75 were independent risk factors ( P<0.05), and a nomogram prediction model was established. The correction curve of the nomogram showed that the actual prediction result was close to the ideal result of the prediction model. The internal validated results showed the C-indexes to be between 0.71 and 0.90, and the prediction model had good discrimination. DCA curve was used to evaluate the clinical net benefit of the predictive model. When the net benefit rate was above zero, the threshold of the prediction model was 4%-77%, indicating that the prediction model had good clinical practicability. Conclusion:The established nomogram prediction model based on preoperative clinical indexes of GGT, APRI, LMR, PLR, FAR and diameter of tumor could be used to predict early diagnosis of HCC with MVI. The nomogram has good clinical application values.

Influence of endoplasmic reticulum stress in degeneration of cochlear hair cells in type 2 diabetic mice / 吉林大学学报(医学版)

Objective:To investigate the influence of endoplasmic reticulum stress (ERS) in the degeneration of cochlear hair cells in the type 2diabetic mice, and to clarify its mechanism.Methods:Twenty clean Kun Ming male mice aged one month were selected and randomly divided into control group and model group (n=10) .The mice in model group were injected with STZ (40 mg·kg-1) to establish the type 2diabetic models.The fasting blood glucose levels of the mice were measured through collecting the vena caudalis blood of the mice.Auditory brain stem response (ABR) was used to detect the ABR threshold of the mice.Otoacoustic emission (OAE) test was used to detect the OAE threshold of mice.The defect rate of mouse cochlear outer hair cells was calculated by the mouse cochlear spreading technique.The expression levels of GRP78, caspase-12, p-ERK and Nrf2proteins were detected by Western blotting method.Results:Compared with control group, the fasting blood glucose levels of the mice in model group at the 7th and the 14th days had no significant differences (P＞0.05) , but the levels were increased significantly at the 21th, 28th and 35th days and the level reached the highest value at the 35th day.The ABR thresholds of the mice in model group at 8, 12, and 24kHZ were increased significantly compared with control group (P＜0.05) .Under the stimulation of low frequency, there was no significant change in the OAE threshold of the mice in model grouop compared with control group.The OAE thresholds of the mice in model group were increased significantly under the medium frequency and high frequency stimulation compared with control group (P＜0.05) .The defects of the cochlear hair cells were mainly concentrated on the bottom of gyrus of the mice, and the defects in middle temporal gyrus and parietal gyrus were less.Compared with control group, the defect rate in the bottom of gyrus of the mice in model group was increased significantly (P＜0.05) ;the defect rates in the middle temporal gyrus and parietal gyrus were increased, but there was no significant difference (P＞0.05) .The expression levels of p-ERK and Nrf2in the cochlear hair cells of the mice in model group were lower than those in control group (P＜0.05) , and the expression levels of GRP78and caspase-12were higher than those in control group (P＜0.05) .Conclusion:ERS can result in the increase of defect rate of cochlear outer hair cells and ABR brainstem hearing threshold of the diabetic mice and decrease the expression levels of p-ERK and Nrf2proteins, suggesting that ERS can promote the degenerative lesions of cochlear hair cells in the type 2diabetic mice.

Discussion on the Development Direction of Drug Circulation Enterprises under "Two Invoice System" / 中国药房

OBJECTIVE: To provide suggestions for the development of drug circulation enterprises under "two invoice system".METHODS: By analyzing the negative effects of "multi invoice system" on drug circulation enterprises and positive effects of "two invoice system" on drug circulation enterprises, the development direction of drug circulation enterprises was investigated under "two invoice system".RESULTS & CONCLUSIONS: The "multi invoice system" formulates the high drug price, causes high drug circulation cost and is difficult to check drug quality. The "two invoice system" standardizes the order of drug circulation field, saves medical drug source, reduce drug price and kept capital chain stable. Under "two invoice system", drug circulation enterprises should actively adapt to the transformation of medical and pharmaceutical market, and reconstruct the chain of drug circulation. The integration of medical circulation network should be established between the relevant departments and various subjects. Drug circulation subjects should promote the check of ticket, account and goods, standardize the date of back account, implement reform stably.

Therapeutic effect of arterial thrombolysis for acute cerebral infarction：analysis of related factors / 介入放射学杂志

Objective To investigate the relationship between the residual forward blood flow and the therapeutic outcome in patients with acute cerebral infarction after arterial thrombolysis treatment. Methods During the period from January 2009 to December 2013 at authors’ hospital, a total of 40 patients with acute anterior circle cerebral infarction were treated with arterial thrombolysis. The clinical data were retrospectively analyzed. The patients were divided into group A (n=23) when residual forward blood flow and/or collateral circulation were presented, and group B (n=17) if no residual forward blood flow and/or collateral circulation were detected. The NIHSS scores and hemorrhagic transformation state were determined 14 days after the thrombolysis treatment, and the results were compared between the two groups. Results In group A, 21 cases (91.3%) showed complete or partial re- canalization of the infracted vessels, and asymptomatic hemorrhagic transformation was seen in one case. The pre-treatment NIHSS score was 12.69 ± 3.88 and the post-treatment NIHSS score was 6.05 ± 3.25. In group B, complete or partial re-canalization of the infracted vessels was seen in 15 cases (88.2%), asymptomatic hemorrhagic transformation was found in one case and symptomatic hemorrhagic transformation occurred in one case, who died of massive cerebral hemorrhage seven hours after the thrombolysis treatment. The pre-treatment NIHSS score was 13.51 ± 4.19 and the post-treatment NIHSS score was 8.68 ± 5.16. The differences between the two groups were statistically significant (P < 0.05). The obvious effect rate in group A and group B was 68.1% and 43.8% respectively, and the effective rate in group A and group B was 86.3% and 56.3% respectively, indicating that the clinical outcome of group A was much better than that of group B. Conclusion The therapeutic effect of arterial thrombolysis for acute cerebral infarction patients is not only closely related to the time window but also to the residual forward blood flow. The more the residual forward blood flow there is, the better the therapeutic result with less risk of hemorrhagic transformation will be.

HGF depress the production of α-SMA and extracellular matrix induced by TGF-β1 in fibroblasts of the flexor tendon sheath / 中华显微外科杂志

Objective To examine the effectiveness of HGF in blocking TGF-β1 induced α-SMA and extracellular matrix production in fibroblasts of the flexor tendon sheath. Methods Seven adult male New Zealand white rabbits (3.75-4.00 kg) were used for this study. Both of their front feet were sterilised and the middle digit flexor digitorum profundus tendon equivalents were identified and isolated. These specimens were used to establish primary cell cultures. Sheath fibroblasts were obtained from rabbit flexor tendons. After the cells reached confluence, cells were detached with trypsin/ethylenediamine tetra-acetic acid. All experiments were performed using the cells at the third passage. At 70% confluence the medium was supplemented with 5 ng/ml of TGF-β1 along with increasing doses of HGF (10-40 ng/ml). After 72 hours incubation, the productions of α-SMA were assayed by Western-Blot. The productions of collagen Ⅰ and fibronectin in supernatants culture were examined using ELISA. Results Evaluation of protein expression revealed that TGF-β1 markedly induced α-SMA expression in cultured rabbit flexor tendon sheath fibroblasts. TGF-β1 treated fibroblasts expressed 1.8-fold more protein compared to non-treated fibroblasts (P ＜ 0.05). However, simultaneous incubation of HGF significantly abrogated TGF-β1 induced α-SMA expression in a dose-dependent manner (P＜ 0.05). Treatment with TGF-β1 significantly stimulated collagen Ⅰ and fibronectin production in flexor tendon sheath fibroblasts (P ＜ 0.01). Remarkably, the addition of HGF reduced productions of all components induced by TGF-β1 in a dose-dependent manner (P ＜ 0.05). Conclusion HGF antagonizes TGF-β1 induced α-SMA, collagen Ⅰ, and fibronectin production in flexor tendon sheath fibroblasts. The findings provide a cellular and molecular basis for HGF's acting as a therapeutic agent for adhesions in flexor tendons.

Dose-response relationship between nerve growth factor and angiogenesis of regenerative sciatic nerve / 中国组织工程研究

BACKGROUND: Effect of nerve growth factor(NGF)on angiogenesis of regenerative perpheral nerve is still researched up to now.OBJECTIVE:To evaluate the dose-response relationship and mechanism of NGF on angiogenesis of regenerative sciatic nerve in rats.DESIGN:Randomized controlled animal study.SEFFING:Department of Neurology,the 324 Hospital of Chinese PLA;the Third Laboratory,Institute of Battle Surgery,Daping Hospital of the Third Military Medical University of Chinese PLA.MATERIALS:A total of 32 healthy adult Wistar rats weighing 200-250 g and of both genders were selected in this study.Silica gel conduit was provided by Shanghai Xinya Medical Rubber-goods Factory and NGF was provided by Sigma Company,USA.METHODS:The experiment was carried out in the Third Laboratory,Institute of Battle Surgery,Daping Hospital Affiliated to the Third Military Medical University of Chinese PLA from August 2003 to February 2005.Experimental grouping:All rats were randomly divided into 4 groups,including saline group,50,100 and 500 ng NGF groups with 8 rats in each group.Experimental intervention:Sciatic nerves were cut to establish defect of 10 mm in length,and then the defect was bridged with silica gel conduit in the left latter limb.After the bridging,rats in the saline group were perfused with 5 μL saline,and rats in the NGF groups were perfused with 2.5,5 and 25μL NGF(20 mg/L),respectively.Experimental evaluation:On the 30th day,immunohistochemical technique was used to detect the expressions of CD34,vWf,vascular endothelial growth factor(VEGF)and trkA in newborn vascular endothelial cells of regenerative sciatic nerve;meanwhile,their forms were performed with quantitative analysis.MAIN OUTCOME MEASURES:Pathological and immunohistochemical changes of nerve regeneration of rats in each group.RESULTS:All 32 rats were involved in the final analysis,①Results of pathological sections of nerve regeneration in rats:Distal end of sciatic nerve was completely bridged at 30 days after operation and thickness of sciatic nerve in silica gel conduit lined in 500 ng NGF group＞50 and 100 ng NGF group＞saline group.Numbers of fiber and regularity of arrangement of sciatic nerve were superior in NGF groups to those in saline group,In addition,angiogenesis was obviously observed at 30 days after operation.②Results of immunohistochemical staining:There were significant differences among three NGF groups as compared with saline group in the expressions of four antigens (P＜0.05).Expressions of four antigens were increased in 500 ng NGF group as compared with those in 100 and 50 ng NGF groups(CD34:94.2±6.4,74.2±10.9,77.0±11,0;vWf:116.2±20.0,72.0±13.1,68.0±9.7;TrkA:105.4±10.6,57.8±11.5,58.8±6.5;VEGF:89.0±3.0,48 6±7.4,35.2±2.9;P＜0.05 or P＜0.01).CONCLUSION: NGF can promote angiogenesis of the regenerative peripheral nerves and show a dose-response relationship,while its mechanism may be related to promoting expressions of TrkA and VEGF.

Effects of TGF-?1 on production of a-SMA and extracellular matrix in flexor tendon sheath fibroblasts / 中国矫形外科杂志

[Objective]To examine the effects of TGF-?1 on the production of ?-SMA and extracellular matrix in flexor tendon sheath fibroblasts. [Methods]Sheath fibroblasts were obtained from rabbit flexor tendons.Cell culture was supplemented with 5ng/ml of TGF-?1.After 48 hours incubation,the production of a-SMA was assayed by Western-Blot.The productions of collagen I and fibronectin in supernatants culture were examined using ELISA.[Results]Treatment with TGF-?1 significantly stimulated a-SMA production in flexor tendon sheath fibroblasts (P

Biological differences between healing and normal medial collateral ligament fibroblasts / 中国矫形外科杂志

[Objective]To examine the difference of proliferation and ?-smooth muscle actin(?-SMA) expression between healing and normal medial collateral ligament(MCL) fibroblasts.[Method]Ten adult,male,Sprague-Dawley rats weighing between 350 and 375 g were used in this study.Normal and healing MCL were cut into small pieces in aseptic conditions,and then placed and cultured in culture chamber.Fibroblasts were passaged with 0.25% trypsin.After 24 and 48 hours incubation,MTT was used to measure the cell proliferation.The production of ?-SMA was measured by Western Blot.[Result]After 24 and 48 hours incubation,healing fib roblasts showed absorbency values of 0.49?0.080 and 0.53?0.07 respectively.II was found that healing fibroblasts proliferated faster than normal fibroblasts(P