Experimental study of curcumol inhibiting vascular endothelial growth factor-induced neovascularization / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To study the role and mechanism of curcumol in neovascularization induced by vascular endothelial growth factor(VEGF).METHODS: Human umbilical vein endothelial cells were cultured in vitro and treated with 50ng/mL VEGF and curcumol at different concentrations. Cell proliferation was detected by CCK-8 and EdU assay, the migration ability of cells was analyzed by Transwell assay, the angiogenesis ability of endothelial cells was analyzed by tube formation assay, and the change of Akt/mTORC1 signal pathway was detected by Western blot.RESULTS: CCK-8 results showed that the OD450 value of cells in 400 and 800 μmol/L curcumol+VEGF group was significantly lower than that in VEGF group(all P<0.01). EdU results showed that the rate of cell proliferation in 400 μmol/L curcumol+VEGF group was significantly lower than that in VEGF group(P<0.001). Transwell assay and the formation assay results showed that the number of migratory cells in 400 μmol/L curcumol+VEGF group was decreased, and the number and length of tube branches were also reduced compared with VEGF group(all P<0.001). Western blot results showed that curcumol significantly inhibited the expression of p-Akt and p-S6, which were downstream targets of Akt/mTORC1 pathway in cells.CONCLUSION: Curcumol can inhibit VEGF-induced cell proliferation, migration and tube formation of vein endothelial cells, and has a strong inhibitory effect on angiogenesis, which can be further studied in the treatment of ocular fundus neovascularization.

Interpretation of guidance on non-clinical safety evaluation for nanomedicines / 药学学报

With the rapid development of nanotechnology, the research and development of nanomedicines have become one of the development directions of drug innovation. Nanomedicines have special physical and chemical properties, such as nanoscale effects and nanostructure effects, so they have special biological properties, which may change the pharmacokinetic profiles such as absorption and tissue distribution of drug molecules, and thus affect their safety and effectiveness. There are many special concerns on the non-clinical safety evaluation of nanomedicines at the basis of ordinary drug because of the particularity of nanomedicines. On August 25, 2021, China issued Guidance on Non-clinical Safety Evaluation for Nanomedicines(interim). This article interprets comprehensively the guidance, focuses on the key points of non-clinical safety evaluation for nanomedicines, and expounds combined with some cases, aiming to provide reference for drug researchers.

Non clinical pharmacodynamic evaluation system of high-altitude hypoxic brain injury / 药学学报

The air at high altitude is thin and belongs to the environment of low temperature, low oxygen and low pressure. The human brain is the most sensitive to hypoxia. Hypoxia will cause dysfunction of the central nervous system, resulting in high-altitude hypoxic brain injury, including mild high altitude headache and more destructive high altitude cerebral edema (HACE). Recently, with more and more people work and live in high altitude areas, the development of high-altitude hypoxic brain injury drugs would produce great economic value and social significance. Non clinical pharmacodynamic evaluation is the basic of drug development, which plays a key role in improving the success rate of clinical transformation and reducing the risk of clinical research. This review summarizes the cell models and animal models, and the evaluation indicators usually used to explore the candidates of high-altitude hypoxic brain injury. We aim at establishing a standardized non clinical efficacy evaluation system for high altitude hypoxic encephalopathy, and provide a standardized reference for drug development in hypoxic encephalopathy at high altitude at nonclinical stage.

Chemotherapy initiation with single-course methotrexate alone or combined with dactinomycin versus multi-course methotrexate for low-risk gestational trophoblastic neoplasia: a multi-centric randomized clinical trial / 医学前沿

We aimed to evaluate the effectiveness and safety of single-course initial regimens in patients with low-risk gestational trophoblastic neoplasia (GTN). In this trial (NCT01823315), 276 patients were analyzed. Patients were allocated to three initiated regimens: single-course methotrexate (MTX), single-course MTX + dactinomycin (ACTD), and multi-course MTX (control arm). The primary endpoint was the complete remission (CR) rate by initial drug(s). The primary CR rate was 64.4% with multi-course MTX in the control arm. For the single-course MTX arm, the CR rate was 35.8% by one course; it increased to 59.3% after subsequent multi-course MTX, with non-inferiority to the control (difference -5.1%,95% confidence interval (CI) -19.4% to 9.2%, P = 0.014). After further treatment with multi-course ACTD, the CR rate (93.3%) was similar to that of the control (95.2%, P = 0.577). For the single-course MTX + ACTD arm, the CR rate was 46.7% by one course, which increased to 89.1% after subsequent multi-course, with non-inferiority (difference 24.7%, 95% CI 12.8%-36.6%, P < 0.001) to the control. It was similar to the CR rate by MTX and further ACTD in the control arm (89.1% vs. 95.2%, P =0.135). Four patients experienced recurrence, with no death, during the 2-year follow-up. We demonstrated that chemotherapy initiation with single-course MTX may be an alternative regimen for patients with low-risk GTN.

New discovery and short-term effect analysis of tensor tympani muscle tenotomy for Meniere's disease under otoscope / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the feasibility and short-term effect of tensor tympani muscle Tenotomy in the treatment of Meniere's disease under otoscope. The possible pathogenesis was discussed and our views were put forward. Methods: The clinical data of 9 cases of Meniere's disease treated by otoscopic Tenotomy were analyzed retrospectively, including 2 males, 7 females, 5 right ones, 2 left ones and 2 bilateral ones. The average age was (56.33± 10.56) years, ranging from 38 to 75 years. We evaluated intraoperative findings and short-term postoperative efficacy, respectively evaluated postoperative aural fullness, tinnitus and hearing recovery, and evaluated postoperative vertigo attack in a short time. Results: Nine patients were completed the operation under general anaesthesia and otoscopy, and no serious complications occurred. We found new pathological changes in tympanic cavity in some cases during operation. There were rupture of round window membrane in 1 case, severe fibrous hyperplasia near the round window membrane and vestibular window and adhesion with ossicular chain in 1 case, fibrous cord and membranous hyperplasia near vestibular window and round window membrane in 1 case, fibrous hyperplasia and adhesion near the round window membrane in 2 cases, membranous hyperplasia and adhesion around vestibular window in 1 case. No fibrous hyperplasia was found in 3 cases in the tympanic cavity. The round window membrane can be exposed in 4 cases and failed in 5 cases. After 3 months of follow-up, we found that we found that 5/5 cases of aural fullness disappeared, 2/2 cases of earache disappeared, 3/8 cases of tinnitus improved, 5/8 cases presented with improvement and no aggravation, 3/3 cases of hearing allergy improved, 4/9 cases of hearing improved, and 5/9 cases showed no improvement or decrease. 9 patients were followed up for 3 months, of whom 8 patients had no vertigo, one patient suffered from vertigo twice within 3 months after operation, and the patient suffered from rupture of round window membrane. Conclusions: Endoscopic Tenotomy for Meniere's disease has obvious curative effect and quick recovery after operation. During the operation, we find that most of Meniere's patients have fibrous cord hyperplasia near the inner ear window membrane, which may be the pathological manifestation after repeated rupture and repair of the inner ear window membrane. The vertigo of Meniere's disease may be related to the destruction and repair of inner ear membrane structure caused by improper contraction or spasm of tympanic tensor muscle.

Relationship between Small-world Network and Cognitive Impairment for Patients with White Matter Lesions Based On Diffusion Tensor Imaging / 中国康复理论与实践

Objective:To explore the relationship between small-worldness of brain network and cognitive impairment in patients with white matter lesions (WMLs) based on diffusion tensor imaging (DTI). Methods:From January, 2016 to December, 2017, 46 WMLs patients and 36 controls matched genders, ages and education levels from Beijing Tiantan Hospital were screened with DTI. The patients were divided into vascular cognitive impairment non-dementia (VCIND) and vascular dementia (VaD) groups according to the results of cognitive assessments. The brain structure network was created based on DTI data, and the topological properties of the whole-brain small-world network were calculated, and the correlation between the small-worldness and the severity of cognitive impairment was analyzed. Results:The global efficiency, local efficiency, shortest path length and clustering coefficient were different between the patients and the controls (F > 3.252, P < 0.05), as well as the properties of the small-world network, λ, γ and σ (F > 7.378, P < 0.01). The λ, γ and σ were correlated with the total score of Montreal Cognitive Assessment (|r| > 0.402, P < 0.05). Conclusion:The brain structure network is small-world network for patients with WMLs, and the decrease of small-world properties may relate to the cognitive impairment.

Effect of Shexiang Baoxin Pill () in Alleviating Early Hypertensive Renal Injury in Rats / 中国结合医学杂志

OBJECTIVE@#To investigate the effect of Shexiang Baoxin Pill (, SBP) on early hypertensive renal injury in rats and to explore the possible mechanism.@*METHODS@#Twelve-week-old spontaneous hypertensive rats (SHRs) with high-salt diet (dietary containing 8% NaCl) were randomized into the SBP group [40 mg/(kg·d)], losartan potassium group [20 mg/(kg·d)] and saline group by stratified random sampling method, 12 in each group. Blood pressure and urea albumin creatinine ratio were measured. After 10 weeks, the expression levels of serum creatinine (Scr), hypersensitive C-reactive protein (hs-CRP), interleukin (IL)-1 β, IL-6, tumor necrosis factor α (TNF-α), and transforming growth factor β (TGF-β) in serum were assessed. Kidney pathology periodate-schiff staining was performed. Semi-quantitative count of macrophage infiltration was determined by immunochemistry of CD68 staining. Real-time quantitative polymerase chain reaction and Western blot were performed to examine the mRNA and protein expressions of Toll-like receptor 4 (TLR4), nuclear factor κB (NF-κB), monocyte chemokine peptide (MCP-1), inducible nitric oxide synthase (iNOS), and arginase-1 (Arg-1).@*RESULTS@#SBP did not affect the mortality of SHR (P<0.05). SBP significantly reduced the level of elevated blood pressure of SHRs, but the effect was less significantly than that of losartan potassium. SBP decreased urine protein (P<0.01) and the expression levels of IL-1 β, IL-6, TNF-α, and TGF-β in serum. The 22-week-old SHRs showed mild proliferation of glomerular endothelial cells, glomerular ischemic lesions, inflammatory cell infiltration in renal tubular interstitium and arteriosclerosis. Both SBP and losartan potassium had alleviated renal pathological change, and significantly reduced the infiltration of macrophage (P<0.05, P<0.01). SBP and losartan potassium decreased the expressions of TLR4, NF-κB, MCP-1, iNOS, and Arg-1.@*CONCLUSION@#SBP significantly modified the early hypertensive renal injury by reducing inflammation, and the effect was similar to losartan potassium.

Influencing factors of diabetic retinopathy in patients with type 2 diabetes mellitus with standard glycemic control / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To explore the serum retinol binding protein 4(RBP4), inflammatory index neutrophil to lymphocyte ratio(NLR), platelet to lymphocyte ratio(PLR)in patients with type 2 diabetes mellitus(T2DM)after diabetic retinopathy(DR)levels and factors affecting the occurrence of DR in patients. <p>METHODS: The clinical data of 142 patients with T2DM who reached the standard of blood glucose control in our hospital from February 2017 to February 2020 were analyzed retrospectively. According to the results of fundus angiography, the patients were divided into Normal group(<i>n</i>=74), NPDR group(<i>n</i>=36)and PDR group(<i>n</i>=32). Compared the general data and blood test indexes of the three groups, and analyzed the factors affecting the occurrence of DR by multivariate Logistic regression analysis. Constructed a line chart prediction model to predict the occurrence of DR and evaluated its predictive efficiency. <p>RESULTS: The course of DM, serum GH, IGF-I, LDL-C, UA, RBP4, NLR and PLR in PDR group were significantly higher than those in Normal group and NPDR group, while C-P and 2h C-P were significantly lower than those in Normal group and NPDR group. The course of disease >12a, IGF-I >145μg/L, C-P <0.75ng/mL, UA >245ng/mL, RBP4 >54mg/L, NLR >1.8 and PLR >110 were independent risk factors for DR. The line chart model has high degree of differentiation and calibration, and has good prediction efficiency. <p>CONCLUSION: In addition to the common risk factors such as the course of DM, IGF-I, C-P and UA, the increase of RBP4, NLR and PLR is also related to DR, which may be involved in the occurrence and development of DR.

Evaluation of non-clinical anxiety disorder models / 药学学报

Anxiety disorders are one of the most common mental disorders in adults, the cause of which derives from a combination of genetics and environmental factors. A series of animal models have been established according to their pathogenesis to measure the level of anxiety or induce anxiety only, and these models have been widely applied in the non-clinical evaluation of anxiolytics. In this review, we present the current trends in the study of anxiety disorders and summarize typical non-clinical anxiety animal models, including models that both measure anxiety levels and induce anxiety, and models that induce anxiety only. This review summarizes the important issues in standardized non-clinical research of anxiety disorders and proposes criteria for the selection of an appropriate R&D model.

Exploration of nonclinical pharmacodynamics evaluation system of Alzheimer's disease / 药学学报

Alzheimer's disease (AD) is the most common neurodegenerative disease that causes dementia among elderly people. The pathogenesis of AD is still unclear, and currently approved drugs only provide symptomatic benefits and do not prevent or delay progressive neurodegeneration. Meanwhile, potential drugs in development are facing great challenges in clinical translation. Therefore, finding effective treatment for the unmet clinical needs of AD is of great economic value and social significance. In this review, we will summarize the current models and pharmacodynamics evaluation methods of anti-AD drug based on the recent studies at home and abroad, and provide reference for drug development in AD at nonclinical stage.

Single center standardized procedure of laparoscopic anterior approach for right hepatectomy / 中华肝胆外科杂志

With the development of technology and instruments, more and more giant liver tumors have been resected under laparoscopy. Compared with traditional approach hepatectomy, anterior hepatectomy is more suitable for laparoscopic resection of huge liver tumors, and it is also more in line with the " tumor-free principle" when it is used in the resection of liver malignant tumors. Our team summarized the experiences and lessons of laparoscopic hepatectomy and communicated with domestic and foreign experts to form a set of single center standardized process of laparoscopic anterior right hepatectomy, which is summarized as follows.

Relationship between the intake of salt and salted food and the infection of Helicobacter pylori in 40-69 years old local residents in a county with high gastric cancer risk in Anhui Province / 中华疾病控制杂志

Objective The aim of the present study was to investigate the relationship between the intake of salt and salted food and the infection of Helicobacter pylori (Hp) among 40-69 years old local residents in a county with high gastric cancer risk in Anhui province. Methods From July 2015 to August 2018, we conducted a questionnaire and a serological test for Hp among 40-69 years old local residents in Lujiang county, Anhui province. The questionnaire focused on the consumptions of salt and salted food. The relationship between Hp infection and risk factors was analyzed by gender. Univariate and multivariate logistic regression analysis were used to analyze the relevant influencing factors. Results The Hp infection rate of total local residents was 50.07%. Among male subjects, age, body mass index(BMI), marital status, educational level, job, labor intensity and income had no link to Hp infection (all P>0.05). But among female subjects, BMI was associated with Hp infection ( 2=13.454,P=0.001). Besides, alcohol consumption was a risk factor for Hp infection in male subjects(OR=1.789，95% CI:1.188-2.694，P=0.003). But, high intake of salt and salted food had no effect on Hp infection after adjustment for alcohol consumption variable in men using multivariate analysis (all P>0.05). After adjusted for BMI variable among female individuals, high salt intake (≥9 g/day) (OR=1.462，95% CI:1.060-2.015，P=0.021) and the high salted food intake (≥1 times /day) were risk factors for Hp infection in women(OR=1.560，95% CI:1.021-2.383，P=0.040). Conclusions In one county with high gastric cancer risk in Anhui province, high salt intake (≥9 g/day) and high salted food intake (≥1 times/day) are risk factors for Hp infection among 40-69 years old female local residents.

In vivo longitudinal and multimodal imaging of hypoxia-inducible factor 1α and angiogenesis in breast cancer / 中华医学杂志(英文版)

BACKGROUND@#Angiogenesis and hypoxia-inducible factor 1α (HIF-1α) play major roles in solid tumors. This study aimed to establish a longitudinal and multimodal imaging model for in vivo evaluation of HIF1α and angiogenesis in breast cancer.@*METHODS@#By transfection of a 5 hypoxia-responsive element (HRE)/green fluorescent protein (GFP) plasmid, the cell line Ca761-hre-gfp was established, which emitted green fluorescence triggered by HIF-1α under hypoxia. The cells were subjected to CoCl2-simulated hypoxia to confirm the imaging strategy. We grew Ca761-hre-gfp cells in the left rear flanks of twelve 615 mice. Experiments were conducted on days 4, 9, 15, and 19. For in vivo analysis, Ca761-hre-gfp subcutaneous allografted tumors were imaged in vivo using contrast-enhanced ultrasound (CEUS) and fluorescence imaging (FLI) during tumor development. The tumor size, CEUS peak intensity, and FLI photons were measured to evaluate tumor growth, angiogenesis, and HIF-1α activity, respectively. After each experiment, three mice were randomly sacrificed and tumor specimens were collected to examine HIF-1α activity and the microvessel density (MVD).@*RESULTS@#In vitro, both green fluorescence and HIF-1α expression were detected in Ca761-hre-gfp cells treated with CoCl2, indicating the suitability of the cells to detect HIF-1α activity. In vivo, HIF-1α activity first increased and then decreased, which was significantly correlated with angiogenic changes (r = 0.803, P = 0.005). These changes were confirmed by immunohistochemical staining of HIF-1α and MVD.@*CONCLUSIONS@#The findings validated the Ca761-hre-gfp murine allograft model for reliable evaluation of HIF-1α activity and angiogenesis longitudinally using both molecular and pre-clinical non-invasive imaging modalities. The cell line may be useful for studies of anti-HIF pathway therapies.

High-frequency ultrasound features of basal cell carcinoma and its association with histological recurrence risk / 中华医学杂志(英文版)

Background@#Due to advances in high-frequency ultrasound technology, it is easier to detect fine structures of skin lesions. The aim of this study was to examine the ultrasonographic features and use recurrence risk stratification to assess the diagnostic performance of pre-operative ultrasound examination of basal cell carcinoma (BCC).@*Methods@#This was a retrospective study. Forty-six BCC lesions underwent pre-operative ultrasound examination using 50- and 20- MHz probes. Ultrasonographic shape, margin, internal echoes, hyper-echoic spots, posterior echoes, and depth of the lesion were evaluated and correlated with the risk of recurrence based on histological features.@*Results@#Forty-two patients had 46 skin lesions in total. The high-risk (n = 6) and low-risk (n = 40) groups exhibited considerable overlap in the ultrasonographic manifestations and no significant difference in margin (χ2 = 3.231, P = 0.072), internal echo (χ2 = 1.592, P = 0.207), or posterior echo (P = 0.169). However, high-risk BCCs tended to be irregular in shape than low-risk lesions (χ2 = 4.313, P = 0.038). Both types presented hyper-echoic spots (χ2 = 1.850, P = 0.174). Additionally, 78% of low-risk lesions were confined to the dermis (31/40), and 100% of high-risk lesions infiltrated into the sub-cutaneous tissue, resulting in a significant difference between the two groups (χ2 = 10.951, P = 0.001). Ultrasound detected sub-clinical lesions in five patients.@*Conclusions@#High-frequency ultrasound can provide important information for pre-operative evaluation of risk in BCC foci and reveal hidden lesions. The technique may play a crucial role in guiding therapeutic options for BCC.

Resting-state Neural Networks and Granger Causal Connectivity for Patients with Cognitive Impairment Associated with Leukoaraiosis / 中国康复理论与实践

Objective:To compare the difference in resting state networks among leukoaraiosis (LA) patients with or without mild cognitive impairment, and healthy controls, as well as the functional connectivity under Granger causality analysis (GCA). Methods:Subjects aged 40 to 80 years, including 34 LA-MCI patients, 15 LA patients with normal cognition and 33 healthy controls, accepted resting-state functional magnetic resonance imaging. Independent component analysis was used to separate functional brain networks, and difference of activation was determined with two sample t-test. GCA was used to analyze effective connectivity of these functional networks. Results:Eight resting state networks were obtained, including default mode network, motor network, medial visual network, lateral visual network, right-memory network, left-memory network, auditory network and executive network. Activation was different among three groups. Effective connectivity of RSNs was also different among three groups. Conclusion:Components of the resting state networks keep changing as LA progressing. Activation decreases as patients' cognition impaired. The direction and strength of connections remodel.

Effect of Jieyu Tongluo Method in Regulating Levels of Neurotransmitter from Patients with Post-stroke Depression / 中国实验方剂学杂志

Objective: To observe the clinical efficacy of Jieyu Tongluo decoction on post-stroke depression (PSD) and its regulatory effect on neurotransmitter. Method: One hundred and twenty-five patients with PSD were randomly divided into control group (62 cases) and observation group (63 cases) by random number table. Both groups got psychological support, health education, and sertraline hydrochloride tablets, 25-50 mg/time, 2 times/days. Patients in control group got Shugan Jieyu capsules, 2 grains/time, 2 times/days. Patients in observation group got Jieyu Tongluo decoction, 1 dose/day. And a course of treatment was 6 weeks. Before and after treatment, hamilton depression scale (HAMD-17), patient health questionnaire-9 (PHQ-9), national institutes of health stroke scale (NHISS),traditional Chinese medicine(TCM) syndrome and activity of daily living scale (ADL) were scored. And levels of 5-serotonin (5-HT), norepinephrine (NE), dopamine (DA), brain-derived neurotrophic factor (BDNF), serum S100-β and neuron enolase (NES) were detected. Result: By rank sum test, after treatment, the clinical efficacy of observation group was superior to that in control group (Z=2.384, PPZ=2.266, PZ=2.817, Pβ and neuron enolase (NES) were lower than those in control group (PPConclusion: In addition to psychotherapy and SSRI, Jieyu Tongluo decoction can relieve degree of depression, depressive symptoms and degree of neurologic impairment, increase activities of daily living, regulate neurotransmitter expression, and improve the reparation of cranial nerve tissue, with obvious clinical effects, and is worthy to be used in clinic.

Clinical Effect of Shugan Granule on Depression of Liver Qi Stagnation Type in Perimenopausal Period / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of Shugan granule on perimenopausal depressive disorder (stagnation of liver Qi and Qi stagnation) and its effect on sex hormone and inflammatory factors. Method:One hundred and twenty patients were randomly divided into control group (60 cases) and observation group (60 cases) by random number table. Both groups got Tibolone tablets, 2.5 mg/time, 1 time/day. Patients in control group got flupentixol and melitracen tablets once every morning and noon, 1 tablet/time. In addition to the therapy of control group, patients in observation group got Shugan granule, 1 pack/time, 2 times/days. And a course of treatment was 8 weeks. Main indexes were graded by Hamilton depression scale (HAMD-17), self-rating depression scale (SDS) and Eysenck Personality Questionnaire (EPQ). And secondary indexes were scored by self-rating anxiety scale (SAS), stagnation of liver Qi and Qi stagnation, improved kupperman (KI), levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), 5-serotonin (5-HT), brain derived neurotrophic factor (BDNF), interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) before and after treatment. Result:By rank sum test, the clinical efficacy on depressed and perimenopausal syndrome in observation groups was better than that in control group (Z=2.038, PZ=2.316, PPPβ, IL-6 and TNF-α were lower than those in control groups (P2, BDNF and 5-HT were higher than those in control groups (PConclusion:Shugan granule can relieve depression, inquietude and symptoms caused by perimenopausal syndrome, regulate sex hormone, 5-HT, BDNF and inflammatory reaction, with a better clinical effect than pure western medicine treatment.

Clinical efficacy of radical resection for stage T3 gallbladder cancer and prognostic analysis / 中华消化外科杂志

Objective@#To investigate the clinical efficacy of radical resection for stage T3 gallbladder cancer and prognostic factors.@*Methods@#The retrospective case-control study was conducted. The clinico-pathological data of 87 patients with T3 gallbladder cancer who were admitted to Tianjin Medical University Cancer Institute and Hospital from January 2005 to June 2016 were collected. There were 44 males and 43 females, aged 29-79 years, with a median age of 61 years. According to the different preoperative pathological classification and intraoperative exploration of gallbladder cancer, corresponding surgeries were performed. Observation indicators: (1) surgical and postoperative conditions; (2) clinical efficacy of stage T3 gallbladder cancer and prognostic factors analysis; (3) clinical efficacy of stage T3 gallbladder adenocarcinoma and prognostic factors analysis; (4) clinical efficacy of stage T3 gallbladder adenosquamous carcinoma and prognostic factors analysis. Follow-up by outpatient examination or telephone interview was performed to detect the postoperative survival of patients up to June 2018. Measurement data with skewed distribution were represented as M (range), and count data were described as absolute numbers. Survival curve, survival time and survival rate were drawn and calculated by the Kaplan-Meier method. Survival analysis was performed by the Log-rank test. Univariate analysis was performed using the Log-rank test and multivariate analysis using the COX proportional hazard model.@*Results@#(1) Surgical and postoperative conditions: all the 87 patients underwent radical resection of gallbladder cancer, including 29 cases of hepatic wedge resection and 58 cases of extended hepatectomy. Of the 87 patients, 42 underwent standard lymph node dissection and 45 underwent enlarged lymph node dissection. There were 27 cases receiving extrahepatic bile duct reconstruction. The postoperative pathological results of 87 patients showed that 64 were diagnosed with gallbladder adenocarcinoma and 23 were diagnosed with gallbladder adenosquamous carcinoma. There were 59 cases comorbid with liver invasion and 3 cases comorbid with vascular invasion. The marginal histopathological examination showed negative margin in 63 cases and positive margin in 24 cases. The degree of tumor differentiation: there were 23 patients with highly differentiated tumor and 64 with poorly differentiated tumor. Of the 87 patients, 43 received postoperative adjuvant therapy and 44 didn′t receive adjuvant therapy. (2) Clinical efficacy of stage T3 gallbladder cancer and prognostic factors analysis. ① All the 87 patients were followed up for 1.8-128.0 months, with a median follow-up time of 26.3 months. All the 87 patients had survived for 1.1-82.7 months, with a median time of 20.1 months. The 2-year overall survival rate of patients was 59.8%, and the 2-year disease-free survival rate was 49.4%. ② Univariate analysis showed that preoperative alkaline phosphatase (ALP) level, tumor diameter, pathological type of tumor, lymph node metastasis, and range of hepatectomy were associated factors for the postoperative 2-year overall survival rate of patients (χ2=5.451, 4.900, 8.256, 4.419, 5.858, P<0.05), and pathological type of tumor, lymph node metastasis, and range of hepatectomy were associated factors for the postoperative 2-year disease-free survival rate of patients (χ2=5.828, 6.968, 4.077, P<0.05). Multivariate analysis showed that preoperative ALP level, tumor diameter, and lymph node metastasis were independent factors influencing the postoperative 2-year overall survival rate of patients [hazard ratio (HR)=2.539, 2.619, 2.201, 95% confidence interval (CI) : 1.174-5.491, 1.209-5.673, 1.104-4.391, P<0.05)]; pathological type of tumor and lymph node metastasis were independent factors influencing the postoperative 2-year disease-free survival rate of patients (HR=2.254, 2.296, 95%CI: 1.170-4.344, 1.206-4.374, P<0.05). ③ Survival analysis: pathological type of tumor was an associated factor for the postoperative 2-year overall survival rate and 2-year disease-free survival rate of patients. Of the 87 patients with T3 gallbladder cancer, there was no significant difference in the postoperative 2-year overall survival rate between the 64 patients with gallbladder adenocarcinoma and 23 with gallbladder adenosquamous carcinoma (68.8% vs. 34.8%, χ2=8.256, P>0.05), but a significant difference in the postoperative 2-year disease-free survival rate between them (56.3% vs. 30.4%, χ2=5.828, P<0.05). (3) Clinical efficacy of stage T3 gallbladder adenocarcinoma and prognostic factors analysis. ① Sixty-four patients with gallbladder adenocarcinoma had the median survival time of 23.1 months, with a range from 3.2 to 82.7 months. The postoperative 2-year overall survival rate was 68.8%, and the postoperative 2-year disease-free survival rate was 56.3%. ② For the 64 patients with T3 stage gallbladder adenocarcinoma, univariate analysis showed that preoperative CA19-9 level and range of lymph node dissection were associated factors for the postoperative 2-year overall survival rate (χ2=4.012, 8.837, P<0.05). The range of lymph node dissection was an associated factor for the postoperative 2-year disease-free survival rate (χ2=6.361, P<0.05). Multivariate analysis showed that range of lymph node dissection was an independant factor for both the postoperative 2-year overall survival rate and postoperative 2-year disease-free survival rate (HR=0.244, 0.382, 95%CI: 0.088-0.674, 0.176-0.831, P<0.05). ③ Survival analysis: range of lymph node dissection was an associated factor for both the postoperative 2-year overall survival rate and postoperative 2-year disease-free survival rate of patients. Of the 64 patients with T3 stage gallbladder adenocarcinoma, the postoperative 2-year overall survival rate and disease-free survival rate of patients undergoing enlarged lymph node dissection were 84.8% and 69.7%, versus 51.6% and 41.9% of the patients undergoing standard lymph node dissection (χ2=8.837, 6.361, P<0.05). (4)Clinical efficacy of stage T3 gallbladder adenosquamous carcinoma and prognostic factors analysis. ① Twenty-three patients with gallbladder adenosquamous carcinoma had the median survival time of 13.2 months, with a range from 1.1 to 70.3 months. The postoperative 2-year overall survival rate was 34.8%, and the postoperative 2-year disease-free survival rate was 30.4%. ② For the 23 patients with T3 stage gallbladder adenosquamous carcinoma, univariate analysis showed that preoperative ALP level, lymph node metastasis, range of hepatectomy, and extrahepatic bile duct reconstruction were associated factors for the postoperative 2-year overall survival rate of patients (χ2=5.288, 4.574, 12.960, 4.106, P<0.05). The lymph node metastasis and range of hepatectomy were associated factors for the postoperative 2-year disease-free survival rate of patients (χ2=7.364, 10.582, P<0.05). Multivariate analysis showed that range of hepatectomy was an independant factor for both the postoperative 2-year overall survival rate and postoperative 2-year disease-free survival rate (HR=0.102, 0.153, 95%CI: 0.012-0.880, 0.033-0.718, P<0.05). ③ Survival analysis: range of hepatectomy was an independant factor for both the postoperative 2-year overall survival rate and postoperative 2-year disease-free survival rate of patients. Of the 23 patients with T3 stage gallbladder adenosquamous carcinoma, the postoperative 2-year overall survival rate and postoperative 2-year disease-free survival rate of patients undergoing extended hepatectomy were 87.5% and 75.0%, versus 6.7% and 6.7% of the patients undergoing hepatic wedge resection (χ2=12.960, 10.528, P<0.05).@*Conclusions@#Lymph node metastasis is an independent factor influencing the postoperative 2-year overall survival rate and postoperative 2-year disease-free survival rate of patients with T3 stage gallbladder cancer. The range of lymph node dissection is an independent factor for the postoperative 2-year overall survival rate and postoperative 2-year disease-free survival rate of patients with stage T3 gallbladder adenocarcinoma. Range of hepatectomy is an independent factor for the postoperative 2-year overall survival rate and postoperative 2-year disease-free survival rate of patients with stage T3 gallbladder adenosquamous carcinoma. Patients with gallbladder adenocarcinoma should undergo enlarged lymph node dissection, and patients with gallbladder adenosquamous carcinoma need to undergo extended hepatectomy.

Clinical efficacy of radical resection for stage T3 gallbladder cancer and prognostic analysis / 中华消化外科杂志

Objective To investigate the clinical efficacy of radical resection for stage T3 gallbladder cancer and prognostic factors.Methods The retrospective case-control study was conducted.The clinicopathological data of 87 patients with T3 gallbladder cancer who were admitted to Tianjin Medical University Cancer Institute and Hospital from January 2005 to June 2016 were collected.There were 44 males and 43 females,aged 29-79 years,with a median age of 61 years.According to the different preoperative pathological classification and intraoperative exploration of gallbladder cancer,corresponding surgeries were performed.Observation indicators:(1) surgical and postoperative conditions;(2) clinical efficacy of stage T3 gallbladder cancer and prognostic factors analysis;(3) clinical efficacy of stage T3 gallbladder adenocarcinoma and prognostic factors analysis;(4) clinical efficacy of stage T3 gallbladder adenosquamous carcinoma and prognostic factors analysis.Follow-up by outpatient examination or telephone interview was performed to detect the postoperative survival of patients up to June 2018.Measurement data with skewed distribution were represented as M (range),and count data were described as absolute numbers.Survival curve,survival time and survival rate were drawn and calculated by the Kaplan-Meier method.Survival analysis was performed by the Log-rank test.Univariate analysis was performed using the Log-rank test and multivariate analysis using the COX proportional hazard model.Results (1) Surgical and postoperative conditions:all the 87 patients underwent radical resection of gallbladder cancer,including 29 cases of hepatic wedge resection and 58 cases of extended hepatectomy.Of the 87 patients,42 underwent standard lymph node dissection and 45 underwent enlarged lymph node dissection.There were 27 cases receiving extrahepatic bile duct reconstruction.The postoperative pathological results of 87 patients showed that 64 were diagnosed with gallbladder adenocarcinoma and 23 were diagnosed with gallbladder adenosquamous carcinoma.There were 59 cases comorbid with liver invasion and 3 cases comorbid with vascular invasion.The marginal histopathological examination showed negative margin in 63 cases and positive margin in 24 cases.The degree of tumor differentiation:there were 23 patients with highly differentiated tumor and 64 with poorly differentiated tumor.Of the 87 patients,43 received postoperative adjuvant therapy and 44 didn't receive adjuvant therapy.(2) Clinical efficacy of stage T3 gallbladder cancer and prognostic factors analysis.① All the 87 patients were followed up for 1.8-128.0 months,with a median follow-up time of 26.3 months.All the 87 patients had survived for 1.1 -82.7 months,with a median time of 20.1 months.The 2-year overall survival rate of patients was 59.8％,and the 2-year disease-free survival rate was 49.4％.② Univariate analysis showed that preoperative alkaline phosphatase (ALP) level,tumor diameter,pathological type of tumor,lymph node metastasis,and range of hepatectomy were associated factors for the postoperative 2-year overall survival rate of patients (x2 =5.451,4.900,8.256,4.419,5.858,P ＜ 0.05),and pathological type of tumor,lymph node metastasis,and range of hepatectomy were associated factors for the postoperative 2-year disease-free survival rate of patients (x2 =5.828,6.968,4.077,P＜ 0.05).Multivariate analysis showed that preoperative ALP level,tumor diameter,and lymph node metastasis were independent factors influencing the postoperative 2-year overall survival rate of patients [hazard ratio (HR) =2.539,2.619,2.201,95％ confidence interval (CI):1.174-5.491,1.209-5.673,1.104-4.391,P＜ 0.05)];pathological type of tumor and lymph node metastasis were independent factors influencing the postoperative 2-year disease-free survival rate of patients (HR =2.254,2.296,95％CI:1.170-4.344,1.206-4.374,P＜0.05).③ Survival analysis:pathological type of tumor was an associated factor for the postoperative 2-year overall survival rate and 2-year disease-free survival rate of patients.Of the 87 patients with T3 gallbladder cancer,there was no significant difference in the postoperative 2-year overall survival rate between the 64 patients with gallbladder adenocarcinoma and 23 with gallbladder adenosquamous carcinoma (68.8％ vs.34.8％,x2 =8.256,P＞0.05),but a significant difference in the postoperative 2-year disease-free survival rate between them (56.3％ vs.30.4％,x2=5.828,P＜0.05).(3) Clinical efficacy of stage T3 gallbladder adenocarcinoma and prognostic factors analysis.① Sixty-four patients with gallbladder adenocarcinoma had the median survival time of 23.1 months,with a range from 3.2 to 82.7 months.The postoperative 2-year overall survival rate was 68.8％,and the postoperative 2-year disease-free survival rate was 56.3％.② For the 64 patients with T3 stage gallbladder adenocarcinoma,univariate analysis showed that preoperative CA19-9 level and range of lymph node dissection were associated factors for the postoperative 2-year overall survival rate (x2=4.012,8.837,P＜0.05).The range of lymph node dissection was an associated factor for the postoperative 2-year disease-free survival rate (x2 =6.361,P＜0.05).Multivariate analysis showed that range of lymph node dissection was an independant factor for both the postoperative 2-year overall survival rate and postoperative 2-year disease-free survival rate (HR =0.244,0.382,95％CI:0.088-0.674,0.176-0.831,P＜0.05).③ Survival analysis:range of lymph node dissection was an associated factor for both the postoperative 2-year overall survival rate and postoperative 2-year disease-free survival rate of patients.Of the 64 patients with T3 stage gallbladder adenocarcinoma,the postoperative 2-year overall survival rate and disease-free survival rate of patients undergoing enlarged lymph node dissection were 84.8％ and 69.7％,versus 51.6％ and 41.9％ of the patients undergoing standard lymph node dissection (x2 =8.837,6.361,P＜0.05).(4)Clinical efficacy of stage T3 gallbladder adenosquamous carcinoma and prognostic factors analysis.① Twenty-three patients with gallbladder adenosquamous carcinoma had the median survival time of 13.2 months,with a range from 1.1 to 70.3 months.The postoperative 2-year overall survival rate was 34.8％,and the postoperative 2-year disease-free survival rate was 30.4％.② For the 23 patients with T3 stage gallbladder adenosquamous carcinoma,univariate analysis showed that preoperative ALP level,lymph node metastasis,range of bepatectomy,and extrahepatic bile duct reconstruction were associated factors for the postoperative 2-year overall survival rate of patients (x2 =5.288,4.574,12.960,4.106,P＜0.05).The lymph node metastasis and range of hepatectomy were associated factors for the postoperative 2-year disease-free survival rate of patients (x2 =7.364,10.582,P＜0.05).Multivariate analysis showed that range of hepatectomy was an independant factor for both the postoperative 2-year overall survival rate and postoperative 2-year disease-free survival rate (HR=0.102,0.153,95％CI:0.012-0.880,0.033-0.718,P＜0.05).③ Survival analysis:range of hepatectomy was an independant factor for both the postoperative 2-year overall survival rate and postoperative 2-year disease-free survival rate of patients.Of the 23 patients with T3 stage gallbladder adenosquamous carcinoma,the postoperative 2-year overall survival rate and postoperative 2-year disease-free survival rate of patients undergoing extended hepatectomy were 87.5％ and 75.0％,versus 6.7％ and 6.7％ of the patients undergoing hepatic wedge resection (x2 =12.960,10.528,P＜0.05).Conclusions Lymph node metastasis is an independent factor influencing the postoperative 2-year overall survival rate and postoperative 2-year disease-free survival rate of patients with T3 stage gallbladder cancer.The range of lymph node dissection is an independent factor for the postoperative 2-year overall survival rate and postoperative 2-year disease-free survival rate of patients with stage T3 gallbladder adenocarcinoma.Range of hepatectomy is an independent factor for the postoperative 2-year overall survival rate and postoperative 2-year disease-free survival rate of patients with stage T3 gallbladder adenosquamous carcinoma.Patients with gallbladder adenocarcinoma should undergo enlarged lymph node dissection,and patients with gallbladder adenosquamous carcinoma need to undergo extended hepatectomy.

Exploration of non-clinical pharmacodynamics evaluation system of amyotrophic lateral sclerosis / 药学学报

Amyotrophic lateral sclerosis (ALS) is among the most common type of motor neuron diseases, and its pathogenesis remains unclear. In recent years, our understanding of the genetic basis of ALS has led to the development of various ALS disease models, which allow for screening of ALS-related drugs and treatment methods. This review focuses on the research progress of ALS, summarizes the systems of commonly used experimental animal models, including transgenic animals, gene knockout approaches and autonomous animal models, points to the problems needing attention in standardized ALS non-clinical research, and proposes the criteria for selection of standardized R&D model.