Objective To explore the effects of Ginkgolide B on the expression of hypoxia inducible factor 1 α (HIF-1α) and P I3K/Akt pathway in the hippocampus of developing rats after pentylenetetrazol(PTZ)-induced status epilepticus,and to investigate the correlation between HIF-1α expression and PI3K/Akt pathway.Methods Ninety-six SD rats aged 21 days were randomly divided into normal saline group(group NS),status epilepticus group (group P),GKB treatment groups (group G+P),GKB +wortmannin treated group (group G+P+W),wortmannin treated group(group P+W).The brain tissue were harvested from the rats at 4 and 8 hours after the inducement,but in the group G+P at 1 h,4 h,8 h,24 h.Immunohistochemistry and Western blot were used respectively to detect HIF-1α and p-Akt protein expression.Results (1) For the group G+P,there were statistical differences in the expression levels of p-Akt protein between 1 h,4 h,8 h and 24 h(P＜0.01),The p-Akt protein reached the peak level at 4 hours (0.85±0.03),there were statistical differences in the expression levels of HIF-1α protein between 1 h,4 h,8 h and 24 h(P＜0.01),the HIF-1α expression reached the peak level at 8 hours(1.00±0.13).(2) The expression of HIF-1α in all the groups at 8 hours time point:the expression levels of HIF-1α in the group P and group G+P were significantly higher than those in the group NS (P＜0.01) and the expression levels of HIF1α in the group G+P were higher than those in the group P(P＜0.01).Using wortmannin,the PI3K/Akt specific inhibitor,HIF-1α protein expression in the group G+P+W and P+W was significantly decreased when compared with the group G+P and P (P＜0.01).(3)The expression of p-Akt in all the groups at 4 hours time point:the expression levels of p-Akt in the group P and group G+P were significantly higher than those in the group NS (P＜0.01) and the expression levels of p-Akt in the group G+P were higher than those in the group P (P＜ 0.01).Using wortmannin,p-Akt protein expression in the group G+P+W and P+W was significantly decreased when compared with the group G+P and P (P＜0.01).Conclusion GKB can activate PI3K/Akt signaling pathway,and the pathway is involved in regulating the expression of HIF-1α.

Objective To observe the efficacy and side effects of exemestane in postmenopausal breast cancer patients with bone metastasis.Methods One hundred and ten postmenopausal breast cancer patients with bone metastasis were treated with exemestane 25 mg.Results In the evaluable data from 110 patients,the complete remission(CR)was encountered in 7 cases,partial remission(PR)in 28 cases,with a total response rate of 31.8％ ;Thirty nine patients had stabled diseases for more than 24 weeks.It produced a clinical benefit (CR + PR + SD)over 24 weeks in 74 cases(67.3％).Diseases progressed in 12 of the cases(10.9％).The patients with positive ER and PR status had a higher chance to be benefited from the treatment than those with negative receptor status.The clinical efficacy was not correlated with treatment history,pathological subtypes and bone,liver,lung and lymph node metastasis(x2 =0.045,0.078,0.200,P ＞ 0.05).No severe adverse effects were observed.Conclusion Exemestane is effective to treat bone metastasis of breast cancer with minor adverse reactions and good tolerability.

A female patient aged 3 years and 1 month developed poikilodermatous patches on the right forearm at the age of 6 months, which spread to bilateral cheeks, buttocks and limbs at the age of 1 year and 4 months. Skin examination showed multiple brown and off-white poikilodermatous patches on the bilateral cheeks, buttocks and limbs, which were intermingled with normal skin and did not merge with each other. The trunk and oral mucosa were not involved. The fifth toenail of the right foot was thickened. Blood routine examination showed that the neutrophil count fluctuated between 1.70 × 10 9/L and 9.32 × 10 9/L. Histopathological examination of the brown patches on the left upper limb showed hyperpigmentation in the basal layer of the epidermis, and a few melanophages around the dermal vessels. Next-generation sequencing of peripheral blood genomic DNA revealed two compound heterozygous mutations c.798A>G in exon 7 and c.479delT in exon 3 of the USB1 gene in the child, which were inherited from her father and mother respectively. Neither of the two mutations was identified in 100 unrelated healthy controls. The patient was diagnosed with poikiloderma with neutropenia.

Objective:To study the application effect of scenario simulation teaching combined with mini-clinical evaluation exercise (Mini-CEX) in the standardized residency training of general surgery.Methods:The study included in 62 trainees who had standardized residency training in the Department of General Surgery of the Affiliated Hospital of Xuzhou Medical University From July 2019 to July 2020. The subjects were randomly divided into traditional teaching group (control group) and scenario simulation teaching combined with Mini-CEX teaching group (experimental group), with 31 students in each group. The scores of the entrance examination, Mini-CEX scores and the evaluation of teaching effect were compared between the two groups. SPSS 21.0 was used to perform t test on the test scores, Mini-CEX scores and teaching effective evaluation scores of the two groups. Results:①The theoretical scores of the experimental group [(82.48 ± 6.02) points] were significantly higher than those of the control group [(77.32±6.25) points], with significant differences ( t=3.31, P<0.01). The clinical practice scores of the experimental group [(88.96 ± 2.93) points] were significantly higher than those of the control group [(80.87±5.41) points], with significant differences ( t=7.33, P<0.01). ②Mini-CEX scores of the experimental group were higher than those of the control group ( P<0.01). ③Through the teaching questionnaire, the scores of the experimental group were higher than those of the control group ( P<0.01). Conclusion:Scenario simulation teaching combined with Mini-CEX has achieved good results in the standardized residency training of general surgery, which could be used as a new clinical teaching mode.

Objective:To investigate the clinical efficacy of da Vinci Xi surgical system assisted programmed six-hole method anterior resection of rectal cancer.Methods:The retrospec-tive cohort study was conducted. The clinicopathological data of 102 patients with middle and low rectal cancer who were admitted to the Affiliated Hospital of Xuzhou Medical University from August 2020 to June 2021 were collected. There were 62 males and 40 females, aged (53±12)years. Of the 102 patients, 51 cases undergoing da Vinci Xi surgical system assisted programmed six-hole method anterior resection of rectal cancer were divided into the robotic group and 51 cases undergoing laparoscopic anterior resection of rectal cancer were divided into the laparoscopic group. Observa-tion indicators: (1) treatment; (2) postoperative pathological examination; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Repeated measurement data were analyzed using the repeated ANOVA. Results:(1) Treatment. All patients of the two groups under-went radical resection of rectal cancer successfully, and none of patient with intraoperative blood transfusion, conversion to open surgery, and death within 30 days after surgery. The operation time, volume of intraoperative blood loss, number of lymph nodes dissected, time to postoperative first flatus, time to postoperative first liquid food intake, time to postoperative catheter removal, cases with postoperative pain grading as grade 1, grade 2, grade 3, grade 4, cost of treatment were (170±12)minutes, (73±50)mL, 23±6, (35.1±9.4)hours, (2.1±0.8)days, (2.9±2.7)days, 13, 15, 17, 6, (7.1±4.5) ten thousand yuan in patients of the robotic group, versus (153±22)minutes, (119±66) mL, 15±4, (40.7±1.9)hours, (2.9±0.4)days, (5.3±2.1)days, 6, 7, 26, 12, (6.7±1.6) ten thousand yuan in patients of the laparoscopic group, showing significant differences in the above indicators between the two groups ( t=6.79, -4.46,20.09, -3.01, -5.54, -16.69, Z=-2.87, t=4.22, P<0.05). (2) Postoperative patho-logical examination. The tumor diameter, length of specimen resected, distance of upper resection margin to tumor, distance of lower resection margin to tumor, cases with mesorectal specimens as integrity and mostly integrity, cases with tumor differentiation as high differentiation, moderate differentiation, low differentiation, cases with postoperative TNM staging as stage Ⅰ, stage Ⅱ, stage Ⅲ were (3.8±1.1)cm, (18.7±3.2)cm, (11.8±3.6)cm, (2.7±0.8)cm, 48, 3, 4, 41, 6, 6, 17, 28 in patients of the robotic group, versus (3.7±1.0)cm, (18.3±2.8)cm, (10.2±2.7)cm, (2.5±0.6)cm, 46, 5, 6, 39, 6, 5,20, 26 in patients of the laparoscopic group, showing no significant difference in the above indicators between the two groups ( t=1.72, 1.29, 1.64, 1.11, χ2=0.14, Z=-0.42, -0.26, P>0.05). Cases with positive circumferential margin and cases with destruction of mesentery was 0 and 0 in patients of the robotic group, versus 1 and 1 in patients of the laparoscopic group, showing no significant difference in the above indicators between the two groups ( P>0.05). (3) Follow-up. All patients in the two groups were followed up for 12 months after surgery and none of patient had postoperative local recurrence and distant metastasis of tumors. The anal incontinence score, low anterior resection syndrome score, international prostate symptom score, night urination score, international index of erectile score, female sexual function index score in patients of the robotic group were 0, 12.25±1.08, 4.43±0.33, 0.49±0.09, 24.07±2.75, 65.84±1.79 before surgery and 1.34±0.11, 18.11±3.54, 4.03±0.26, 1.08±0.28, 22.63±2.03, 38.57±6.13 at postoperative 12 months, respectively. The above indicators in patients of the laparoscopic group were 0, 12.60±1.11, 4.56±0.36, 0.46±0.07, 23.11±2.77, 66.31±1.73 before surgery and 1.99±1.33,20.85±6.19, 6.43±1.78, 2.27±0.23, 21.00±2.73, 27.62±8.20 at postoperative 12 months, respectively. There were significant differences in the above indicators between the two groups ( P<0.05). Conclusions:The oncological effects of da Vinci Xi surgical system assisted programmed six-hole method anterior resection of rectal cancer and lapa-roscopic anterior resection of rectal cancer are comparable. However, robotic surgery is superior to laparoscopic surgery in terms of intraoperative bleeding, lymph node dissection, gastrointestinal function recovery, and pelvic autonomic nerve protection.

Objective: The purpose of this study is to investigate the anti-diabetic effects of linarin, a flavonoid extracted from Chrysanthemi Indici Flos (CIF), and its potential mechanisms. Methods: The effects of linarin on cell viability and glucose consumption in HepG2 cells were measured. Meanwhile, monosodium glutamate (MSG) mouse model was constructed to monitor the changes of insulin tolerance, glucose tolerance, triglyceride and cholesterol. The protein expression levels of p-AMPK, p-ACC, PEPCK and p-GS were detected by Western blot. Results: Linarin could increase the relative glucose consumption of HepG2 cells, improve insulin tolerance and glucose tolerance, and decrease the levels of triglyceride and cholesterol of MSG mice. Simultaneously, the expression levels of p-AMPK and p-ACC in HepG2 cells and the liver tissue of MSG mice were increased, while the expression levels of PEPCK and p-GS were decreased after treatment with linarin. Conclusion: Insulin resistance could be ameliorated by linarin in type 2 diabetes, and its mechanism may be related to AMPK signaling pathway.

Objective     To assess the clinical value of preoperative localization coupled with computed tomography (CT) three-dimensional reconstruction in pulmonary nodule-centered uniportal thoracoscopic combined subsegmental/segmental resection. Methods     The clinical data of 30 patients of combined subsegmental/segmental resection in our hospital from December 2019 to October 2021 were retrospectively collected. There were 19 males and 11 females with the mean age of 56.4 (32.0-71.0) years. The pulmonary nodules were located by CT-guided injection of glue before operation. The three-dimensional reconstruction image and operation planning were carried out by Mimics 21.0 software. Results    The operations were all successfully performed, and there was no conversion to open thoracotomy or lobectomy. The mean tumor diameter was 11.6±3.5 mm, the mean distance between the nodule and the visceral pleura was 13.6±5.6 mm, the mean width of the actual cutting edge was 25.0±6.5 mm, the mean operation time was 110.2±23.8 min, the mean number of lymph node dissection stations was 6.5±2.4, the mean amount of intraoperative bleeding was 50.8±20.3 mL, the mean retention time of thoracic catheter was 3.2±1.1 d, and the mean postoperative hospital stay was 4.5± 1.7 d. There was 1 patient of subcutaneous emphysema, 1 patient of atrial fibrillation and 1 patient of blood in sputum. Conclusion     Preoperative CT-guided injection of medical glue combined with CT three-dimensional reconstruction of pulmonary bronchus and blood vessels is safe and feasible in pulmonary nodule-centered uniportal thoracoscopic  combined subsegmental/segmental resection, which ensures the surgical margin and reserves lung tissues.

ObjectiveTo evaluate the effect of Tripterygium wilfordii polyglycoside tablets （TWPT） combined with conventional synthetic disease-modifying antirheumatic drugs （csDMARDs） including methotrexate （MTX） and/or leflunomide （LEF） on autoantibodies in rheumatoid arthritis （RA） patients. MethodPubMed， EMBASE， Web of Science， Cochrane Library， China National Knowledge Infrastructure （CNKI）， VIP， Wanfang Data， and China Biomedical Literature Service System （SinoMed） were searched for randomized controlled trials （RCTs） of TWPT combined with MTX and/or LEF in the treatment of RA patients from database inception to December 1， 2021. Primary outcome indicators included rheumatoid factor （RF） and anti-citrullinated protein antibody （ACPA）， and secondary outcome indicators included immunoglobulin （IgA， IgG， and IgM） and adverse drug events （ADE）. ResultThirty-one RCTs， involving 2 643 adult patients， were included， including 20 RCTs of TWPT combined with MTX， 10 of TWPT combined with LEF， and one of TWPT combined with MTX and TWPT. The follow-up time ranged from two weeks to 13 months. Compared with csDMARDs alone， TWPT combined with other drugs significantly improved serum RF of RA patients ［SMD=-2.45， 95% CI ［-2.97， -1.93］， P<0.000 01］， anti-CCP ［SMD=-1.41， 95% CI （-2.35， -0.48）， P=0.003］， IgM ［SMD=-1.90， 95% CI （-3.03， -0.76）， P=0.001］， and IgA ［SMD=-1.18， 95% CI （-2.23， -0.12）， P=0.03］. There were no significant effects on IgG ［SMD=-1.02， 95% CI （-2.04， 0.01）， P=0.05］ and ADE ［RR=0.87， 95% CI （0.66， 1.15）， P=0.32］. ConclusionThe results of this study show that compared with csDMARDs alone， TWPT combined with csDMARDs can effectively improve the levels of autoantibodies in RA patients without increasing the incidence of ADE. However， due to the limited quality and quantity of the included RCTs， the relevant conclusions are only used as a reference for the clinical diagnosis and treatment of RA， and more high-quality studies are still needed to further confirm their efficacy.

ObjectiveTo observe the intervention effect of Ruyi Zhenbao pills （RYZBP） on central pain after thalamic stroke in mice and explore the underlying mechanism. MethodThe central post-stroke pain syndrome （CPSP） model was induced by stereotactic injection of type Ⅳ collagenase into the hypothalamus in mice. The mice were divided into a sham group， a model group， low-， medium-， and high-dose RYZBP groups （0.65， 1.3， 2.6 g·kg^-1）， and a pregabalin group （0.075 g·kg^-1）. Seven days after modeling， the mice in the groups with drug intervention were administered with corresponding drugs by gavage according to the body mass， once per day for 25 days， while those in the sham group and the model group received an equal volume of normal saline. During this period， mechanical pain and cold pain were detected at different time points， and the apoptotic state of brain tissue cells was detected by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL）. The 36 classical broad-spectrum inflammatory factors were quantitatively analyzed by liquid-phase chip technology， and differential molecules were screened out and verified by Western blot and enzyme-linked immunosorbent assay （ELISA）. ResultCompared with sham operation group, mechanical pain threshold and cold sensitive pain threshold in model group were significantly changed （P<0.01）. TUNEL results showed that apoptosis of brain cells was obvious. Western blot and ELISA results showed that the expressions of interleukin-1α (IL-1α) and chemokine ligand 5 (CCL5) increased in hypothalamus tissue and serum， while the expressions of Ang-2, granulocyte-colony-stimulating factor (G-CSF) and IL-4 decreased significantly （P<0.01）. Compared with model group， RYZBW dose groups significantly increased mechanical pain threshold， decreased cold sensitivity pain threshold， decreased hypothalamus cell apoptosis ratio （P<0.01）， decreased the expression of IL-1α and CCL5 in hypothalamus tissue and serum， while the expression of ANG-2， G-CSF and IL-4 were significantly increased （P<0.05）. ConclusionRYZBP can relieve hyperalgesia in CPSP mice， and its mechanism is related to the regulation of the expression of pro-/anti-inflammatory factors IL-1α， CCL5， IL-4， G-CSF， and Ang-2.

ObjectiveTo observe the anti-swelling and analgesic effects of Jianpi Tongluo prescription （JPTL） and to explore its mechanism initially. MethodA total of 120 ICR mice were divided into normal group， model group， JPTL low-， medium- and high-dose groups （5， 10， 20 g·kg^-1） and positive drug （celecoxib， 0.03 g·kg^-1） group， with 10 in each group （po，once a day）. Complete freund's adjuvant （CFA） was used to induce the model of chronic inflammatory pain， and xylene-induced ear swelling test， hot plate test and acetic acid writhing test were performed to observe the anti-swelling and analgesic effects of different doses of JPTL in these four acute and chronic models. Further， enzyme-linked immunosorbent assay （ELISA） was used to detect the expressions of prostaglandin E₂ （PGE₂）， interleukin-1β （IL-1β）， interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in serum and inflammatory paw of mice with chronic inflammatory pain， and the expressions of aquaporin 1 （AQP1）， aquaporin 3 （AQP3）， cyclooxygenase 1 （COX1）， cyclooxygenase 2 （COX2） and mitogen-activated protein kinases （MAPKs） in inflammatory paw were detected by Western blot， to explore the preliminary mechanism of JPTL. ResultCompared with the conditions in the normal group， there was a significant increase in the ear swelling of xylene-induced model mice， a shortened paw withdrawal latency in the hot plate test （P<0.01）. Compared with the model group， JPTL remarkably increased the inhibition rate of xylene-induced ear swelling （P<0.05， P<0.01）， prolonged the latency period of writhing caused by acetic acid and reduced the number of writhing （P<0.05， P<0.01）. Compared with normal group, the degree of feet swelling in chronic inflammatory pain mice was significantly increased， the threshold of mechanical pain was decreased and the threshold of cold pain was increased （P<0.05， P<0.01）， the protein contents of AQP1 and AQP3 in inflammatory feet were increased， and the contents of IL-1β， IL-6， TNF-α， PGE₂ and COX2 in inflammatory feet were increased in serum and/or inflammatory feet. The protein expression levels of p-p38 MAPK， p-JNK and p-ERK in inflammatory feet were increased （P<0.01）. Compared with the model group， JPTL relieved paw swelling of mice with chronic inflammatory pain， elevated mechanical withdrawal threshold while decreased cold withdrawal threshold， with analgesia lasting for 4 h and the optimal time point for analgesia being 2 h after administration （P<0.05， P<0.01）. Moreover， JPTL down-regulated AQP1， AQP3， COX2， p-p38 MAPK， p-JNK and p-ERK in inflammatory paw of mice with chronic inflammatory pain and reduced IL-1β， IL-6， TNF-α， and PGE₂ in serum and/or inflammatory paw， but it had no significant effect on COX1 （P<0.05， P<0.01）. ConclusionJPTL has anti-swelling and analgesic effects， and its mechanism is related to inhibiting the production of cytokines and inflammatory mediators via the down-regulation of MAPKs signaling pathway， which provides an experimental basis for the clinical application of JPTL.