Effect of intravenous thrombolysis in acute ischemic stroke patients with cerebral microbleeds and analysis of risk factors for hemorrhagic transformation.

OBJECTIVE: To investigate the safety and efficacy of intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in patients with acute ischemic stroke (AIS) and cerebral microbleeds (CMBs) and analyze the risk factors for hemorrhagic transformation (HT). PATIENTS AND METHODS: The clinical data of 220 patients with CMB within the first 4.5 h after the onset of acute ischemic stroke treated in our hospital from September 2018 to December 2019 were retrospectively analyzed. Then, these patients were evenly assigned into two groups based on whether the intravenous thrombolysis with rt-PA was adopted or not. Next, the neurological deficit was scored using the National Institute of Health stroke scale (NIHSS) before and after treatment, the modified Rankin scale (mRs) score of patients was recorded at 90 d after treatment, and the incidence rate and death rate of intracranial hemorrhage (ICH) after treatment were recorded and evaluated. Additionally, the univariate and logistic regression analyses were employed for the risk factors for HT in patients after thrombolysis. RESULTS: The NIHSS score declined to (7.08±3.75) points and (7.83±4.22) points at 24 h after treatment and (3.67±3.63) points and (4.92±3.87) points at 7 d after treatment, respectively, in Thrombolysis group and Control group, which were significantly lower than those before treatment (p<0.05). The NIHSS score displayed no statistically significant difference between the two groups at 24 h after treatment (p=0.165), whereas it was markedly lower in Thrombolysis group than that in Control group at 7 d after treatment (p=0.015). At 90 d after treatment, there were 98 (89.1%) and 79 (71.8%) cases of good prognosis in Thrombolysis group and Control group, respectively, and the difference was statistically significant between the two groups (p=0.002). Besides, the number of patients with SICH and aSICH was 3 and 2 (2.7% vs. 1.8%, p=0.651) and 9 and 4 (8.2% vs. 3.6%, p=0.152) in Thrombolysis group and Control group, respectively, and the number of deaths was 7 and 5 (6.4% vs. 4.5%, p=0.553) in the two groups, showing no statistically significant difference. The results of univariate and multivariate analyses revealed that the time from stroke onset to thrombolysis, baseline NIHSS score, and history of atrial fibrillation were independent risk factors affecting the HT of patients undergoing intravenous thrombolysis [odds ratio (OR) =1.330, 95% confidence interval (95% CI) =1.079-1.851, p=0.019; OR=1.592, 95% CI=1.025-2.767, p=0.010; OR=2.428, 95% CI=1.814-3.643, p=0.016]. CONCLUSIONS: Compared with those undergoing no intravenous thrombolysis with rt-PA, patients with acute ischemic stroke and CMB who received intravenous thrombolysis with rt-PA exhibit significantly improved short-term neurological function recovery and long-term prognosis, but the incidence and mortality rates of ICH have no statistically significant differences. Moreover, the time from stroke onset to thrombolysis, baseline NIHSS score, and history of atrial fibrillation are independent risk factors affecting the HT of patients treated with intravenous thrombolysis.

Optical quantum weak measurement coupled with UV spectrophotometry for sensitively and non-separatedly detecting enantiopurity.

Based on the theories of quantum weak measurement, we built a set of linear common-path optical weak measurement systems in frequency domain for detecting chiral molecules. The polarization resolution with this system to detect the optical rotation of chirality molecules is nearly two orders of magnitude higher than that of conventional polarizers. Combined with ultraviolet spectroscopy, the purity of the proline enantiomers mixture was detected. The purity resolution can reach to 0.14%, which is comparable to the liquid chromatography. Weak measurement combined with ultraviolet spectroscopy to non-separatedly detect the purity of chiral enantiomers has great application potential in the pharmaceutical industry.

Does robot-assisted minimally invasive esophagectomy really have the advantage of lymphadenectomy over video-assisted minimally invasive esophagectomy in treating esophageal squamous cell carcinoma? A propensity score-matched analysis based on short-term outcomes.

This study aims to investigate advantages of robot-assisted minimally invasive esophagectomy (RAMIE) over video-assisted minimally invasive esophagectomy (VAMIE) in treating esophageal squamous cell carcinoma by applying propensity score-matched analysis. From April 2016 to January 2018, consecutive patients undergoing a McKeown RAMIE or VAMIE for esophageal squamous cell carcinoma were prospectively included for analysis. Baseline data, pathological findings, and short-term outcomes of the two groups (RAMIE group and VAMIE group) were collected and compared. Propensity score-matched analysis was applied to generate matched pairs for further comparison. Finally, we included a total of 151 patients (RAMIE group: 79 patients, VAMIE group: 72 patients) for analysis. In the analysis of unmatched cohort, RAMIE yielded a significantly larger number of total dissected lymph nodes (mean: 20.6 ± 8.8 vs. 17.9 ± 7.7; P = 0.048) and abdominal lymph nodes (mean: 9.5 ± 6.8 vs. 7.4 ± 5.1; P = 0.039) than VAMIE. However, there was no significantly different risk of major complications between the two groups. In the analysis of matched cohort, RAMIE still yielded a significantly larger number of total dissected lymph nodes (P = 0.006) and abdominal lymph nodes (P = 0.042) than VAMIE. There was still no increased risk of postoperative major complications in the RAMIE group compared to the VAMIE group. Moreover, RAMIE was found to yield significantly more left recurrent laryngeal nerve lymph nodes (mean: 1.0 ± 1.8 vs. 0.4 ± 0.8; P = 0.033) than VAMIE without increasing the risk of recurrent laryngeal nerve paralysis. Therefore, RAMIE may have the advantage of lymphadenectomy over VAMIE without increasing any risk of postoperative major complications. Further well-conducted studies, however, are needed to confirm our conclusions.

To evaluate the correlation between the change of immune system function before and after the treatment of malignant obstructive type jaundice treated with biliary stent.

OBJECTIVE: To evaluate the correlation between the change of immune system function before and after the treatment of malignant obstructive type jaundice (MOJ) treated with a biliary stent. PATIENTS AND METHODS: 148 patients who were admitted to the Department of Digestive System for malignant obstructive jaundice were selected according to the standardized criterion. Amongst the total sample size, 78 were male patients and 70 were female patients, with an average age of (43.6 ± 5.5) years. After admission, the patients completed the blood routine examination and received biliary stent treatment to relieve the sign and symptoms of jaundice. Follow-up observation included total white blood cells, CD4+T cell count, CD8+T cell count, the ratio of CD4+/CD8, neutrophil counts neutrophils percentage, total bilirubin, free bilirubin, alanine aminotransferase (ALT), and inflammatory factors. RESULTS: After three weeks of follow-up visit, CD4+T lymphocyte absolute value of patients markedly increased compared with that of pre-operation, and the difference had statistical significance (p < 0.05). The total bilirubin, free bilirubin, ALT, and inflammatory factors, such as hs-CRP, TNF-α in plasma of patients was significantly lower than that before the operation and the difference was statistically significant (p < 0.05). After six weeks of follow-up visit, the ratio of CD4+/CD8+ increased and the difference had statistical significance (p < 0.05) compared with that before biliary stent implantation. However, the white blood cell and neutrophil granulocyte did not improve significantly. It was found that CD4+/CD8+T lymphocyte had relation with the level of hs-CRP. CONCLUSIONS: The patients with the (MOJ) treated with implanted biliary stent revealed relive in the obstruction of the biliary tract, which will further significantly improve the cholestasis. The ratio of CD4+/CD8+T lymphocyte increased, which will improve the immune system function of the patients, decreases the possibility of infection, and improves the overall survival quality.

Comparison of short-term outcomes between robot-assisted minimally invasive esophagectomy and video-assisted minimally invasive esophagectomy in treating middle thoracic esophageal cancer.

Whether the robot-assisted minimally invasive esophagectomy (RAMIE) has any advantages over the video-assisted minimally invasive esophagectomy (VAMIE) remains controversial. In this study, we tried to compare the short-term outcomes of RAMIE with that of VAMIE in treating middle thoracic esophageal cancer from a single medical center. Consecutive patients undergoing RAMIE or VAMIE for middle thoracic esophageal cancer from April 2016 to April 2017 were prospectively included for analysis. Baseline data and pathological findings as well as short-term outcomes of these two group (RAMIE group and VAMIE group) patients were collected and compared. A total of 84 patients (RAMIE group: 42 patients; VAMIE group: 42 patients) were included for analysis. The baseline characteristics between the two groups were comparable. RAMIE yielded significantly larger numbers of total dissected lymph nodes (21.9 and 17.8, respectively; P = 0.042) and the right recurrent laryngeal nerve (RLN) lymph nodes (2.1 and 1.2, respectively; P = 0.033) as well as abdominal lymph nodes (10.8 and 7.7, respectively; P = 0.041) than VAMIE. Even though RAMIE may consume more overall operation time, it could significantly decrease total blood loss compared to VAMIE (97 and 161 mL, respectively; P = 0.015). Postoperatively, no difference of the risk of major complications or hospital stay was observed between the two groups. In conclusion, RAMIE had significant advantage of lymphadenectomy especially for dissecting RLN lymph nodes over VAMIE with a comparable rate of postoperative complications. Further randomized controlled trials are badly needed to confirm and update our conclusions.

Uncoupling DAPK1 from NMDA receptor GluN2B subunit exerts rapid antidepressant-like effects.

Several preclinical studies have reported the rapid antidepressant effects of N-methyl-D-aspartate receptor (NMDAR) antagonists, although the underlying mechanisms are still unclear. Death-associated protein kinase 1 (DAPK1) couples GluN2B subunits at extrasynaptic sites to regulate NMDAR channel conductance. In the present study, we found that chronic unpredictable stress (CUS) induced extracellular glutamate accumulation, accompanied by an increase in the DAPK1-NMDAR interaction, the high expression of DAPK1 and phosphorylated GluN2B at Ser1303, a decrease in phosphorylated DAPK1 at Ser308 and synaptic protein deficits in the rat medial prefrontal cortex (mPFC). CUS also enhanced GluN2B-mediated NMDA currents and extrasynaptic responses that were induced by bursts of high-frequency stimulation, which may be associated with the loss of astrocytes and low expression of glutamate transporter-1 (GLT-1). The blockade of GLT-1 in the mPFC was sufficient to induce depressive-like behavior and cause similar molecular changes. Selective GluN2B antagonist, DAPK1 knockdown by adeno-associated virus-mediated short-hairpin RNA or a pharmacological inhibitor, and the uncoupling of DAPK1 from the NMDAR GluN2B subunit produced rapid antidepressant-like effects and reversed CUS-induced alterations in the mPFC. The inhibition of DAPK1 and its interaction with GluN2B subunit in the mPFC also rescued CUS-induced depressive-like behavior 7 days after treatment. A selective GluN2B antagonist did not have rewarding effects in the conditioned place preference paradigm. Altogether, our findings suggest that the DAPK1 interaction with the NMDAR GluN2B subunit acts as a critical component in the pathophysiology of depression and is a potential target for new antidepressant treatments.

The safety profile of subcutaneous allergen immunotherapy in children with asthma in Hangzhou, East China

Background: The aim of the current study is to evaluate the prevalence, severity and possible risk factors of systemic reactions (SRs) to subcutaneous allergen immunotherapy (SCIT) in children and adolescents with asthma in Hangzhou, east China's Zhejiang province. Methods: From January 2011 to December 2016, this survey analysed the SCIT-related SRs involving 429 patients (265 children and 134 adolescents) affected by allergic asthma. Recorded data included demographics, diagnosis, patient statuses, pulmonary function testing results before and after each injection, allergen dosage, and details of SRs. Results: All patients finished the initial phase and six patients withdrew during the maintenance phase. There were 2.59% (328/12,655) SRs in all injections (3.28% in children and 1.47% in adolescents); 15.62% (67/429) patients experienced SRs (18.49% children and 10.98% adolescents). There were 54.57% SRs of grade 1; 42.37% SRs of grade 2; 3.05% SRs of grade 3; and no grades 4 or grade 5 SRs occurred in patients. Most reactions were mild, and were readily controlled by immediate emergency treatment. There was no need for hospitalisation. The occurrence of SRs was significantly higher in children than that in adolescents (p < 0.01). A higher ratio of SRs was found among patients with moderate asthma. Conclusion: This retrospective survey showed that properly-conducted SCIT was a safe treatment for children and adolescents with asthma in Hangzhou, East China. Children and patients with moderate asthma may be prone to develop SRs (AU)

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Clinical effects of ascending colon patching ileorectal heart-shaped anastomosis on total colonic aganglionosis.

OBJECTIVE: We studied the clinical effects of ascending colon patching ileorectal heart-shaped anastomosis in treating total colonic aganglionosis. PATIENTS AND METHODS: From June 2006 to June 2013, 15 children with severe abdominal distension, low small intestine obstruction and intestinal perforation in the neonatal period, were enrolled in this study. In phase I, patients received emergency terminal ileum stoma plus multi-site colonic biopsy and 6 to 12 months later, ascending colon patching ileorectal heart-shaped anastomosis was conducted in phase II. The occurrence of postoperative complications was recorded. Patients' defecation and anal manometry during the follow-up period were monitored and recorded. All operations were successful, and the average hospitalization time was 10.5 days, and the average amount of bleeding was 30 mL. RESULTS: There were 2 cases of enterocolitis, but no intestinal anastomotic leakage, no incision infection, no anal stenosis and no mortality. Postoperative follow-up lasted for 1 to 2 years with an average of 1.2 years. Perianal redness and erosion occurred in an early stage after the operation, but disappeared after 6 months. Postoperative defecation frequency was about 6 to 9 times, but after 2 years this frequency reduced to 2 to 3 times. Feces transformed from watery into soft forms. Normal results were obtained in the detection of serum K+, Na+, Cl-, HCO3-, hemoglobin, albumin and globulin levels in postoperative follow-up. Rectal rest pressure and anal canal rest pressure after a radical operation on megacolon were significantly lower than those of before operation (p < 0.05). CONCLUSIONS: Ascending colon patching ileorectal heart-shaped anastomosis preserved right hemicolon with relatively good absorptive capability and complied with the physiology of colon. Meanwhile, the ileorectal heart-shaped anastomosis was conducted. The anastomotic stoma was in an oblique heart shape, and its aperture was wide and in different planes without stenosis, blind bag and gate syndrome. We concluded that ascending colon patching ileorectal heart-shaped anastomosis was an effective and feasible method for the radical operation on total colonic aganglionosis.

Recent perspectives of ependymomas (childhood brain tumors).

Ependymomas are childhood brain tumors that occur throughout the central nervous system, but are most common in the hindbrain, also known as the posterior fossa (PF). Current standard therapy comprises maximal safe surgery, and there is no scope for further increase in survival. Despite the histological similarity, ependymomas from throughout the neuroaxis likely comprise multiple independent entities, each with a distinct molecular pathogenesis. The present review article would discuss both genetics and epigenetics of ependymomas.

The safety profile of subcutaneous allergen immunotherapy in children with asthma in Hangzhou, East China.

BACKGROUND: The aim of the current study is to evaluate the prevalence, severity and possible risk factors of systemic reactions (SRs) to subcutaneous allergen immunotherapy (SCIT) in children and adolescents with asthma in Hangzhou, east China's Zhejiang province. METHODS: From January 2011 to December 2016, this survey analysed the SCIT-related SRs involving 429 patients (265 children and 134 adolescents) affected by allergic asthma. Recorded data included demographics, diagnosis, patient statuses, pulmonary function testing results before and after each injection, allergen dosage, and details of SRs. RESULTS: All patients finished the initial phase and six patients withdrew during the maintenance phase. There were 2.59% (328/12,655) SRs in all injections (3.28% in children and 1.47% in adolescents); 15.62% (67/429) patients experienced SRs (18.49% children and 10.98% adolescents). There were 54.57% SRs of grade 1; 42.37% SRs of grade 2; 3.05% SRs of grade 3; and no grades 4 or grade 5 SRs occurred in patients. Most reactions were mild, and were readily controlled by immediate emergency treatment. There was no need for hospitalisation. The occurrence of SRs was significantly higher in children than that in adolescents (p<0.01). A higher ratio of SRs was found among patients with moderate asthma. CONCLUSION: This retrospective survey showed that properly-conducted SCIT was a safe treatment for children and adolescents with asthma in Hangzhou, East China. Children and patients with moderate asthma may be prone to develop SRs.

Investigation of serum vitamin D levels in Chinese infertile men.

Recently, the question of whether vitamin D exerts an effect on the pathogenic process of infertility has become the centre of attention. There are some controversial conclusions on this issue. Based on previous studies, we sought to explore the difference of serum 25-hydroxyvitamin D3 , 1,25-dihydroxyvitamin D3 levels between infertile patients and fertile men, and to find the influence on semen quality. The analysis of serum 25-hydroxyvitamin D3 level showed no significant difference between infertile patients and fertile men. However, the levels of serum 1,25-dihydroxyvitamin D3 in oligospermia (P < 0.05), asthenospermia (P < 0.01), oligoasthenospermia (P < 0.05) and azoospermia (P < 0.01) patients were significantly lower than those in fertile men. Moreover, serum 1,25-dihydroxyvitamin D3 level was positively correlated with progressive motility and total sperm number in infertile patients. In addition, a positive correlation between serum prolactin and 1,25-dihydroxyvitamin D3 was observed in fertile men. Our results indicated that lower vitamin D could be a risk factor for poor semen quality in infertile men. The 1,25-dihydroxyvitamin D3 , as the biologically active form of vitamin D, may be more significant.

Immunohistochemistry of lymphocytes in benign lymphoadenosis of oral mucosa.

Benign lymphoadenosis of oral mucosa (BLOM) is a common oral mucosa disease and may be regarded as a precancerous lesion. However, the association between its biological behavior and lymphocyte distribution remains unclear. Therefore, to investigate the characteristics of BLOM, we studied the infiltration of lymphocytes associated with it. The expression levels of CD74, CD20, CD3, and CD45RO were evaluated by immunohistochemical staining in 14 sam-ples from BLOM, 9 samples from BLOM with atypia hyperplasia, 11 samples from BLOM with canceration, and 10 samples from normal oral mucosa tissues. The results were analyzed by two-sample t-test using SPSS 10.0 for Windows, and P < 0.05 was considered to be sig-nificant. In normal oral mucosa, positive expression levels of CD3 and CD45RO were presented in the extra-lymphoid follicle, and the expres-sion levels of CD74 and CD20 were negative. In all BLOM groups, the expression level of CD20 was positive except for one case of BLOM with canceration; the expression levels of CD74 were all positive. Posi-tive expression levels of CD3 and CD45RO could be found not only in extra-lymphoid follicles but also in inner-lymphoid follicles in the BLOM groups. The expression levels of CD74 and CD20 in extra-lym-phoid follicles, and CD3 and CD45RO in inner-lymphoid follicles in BLOM were significantly higher than in BLOM with canceration. The infiltrated lymphocytes in BLOM comprise T- and B-cells. This indi-cates that the lymphoid tissue in BLOM is mucosa-associated lymphoid tissue and BLOM is a proliferative lesion.

Prognostic value of metastatic lymph node ratio as an additional tool to the TNM stage system in gastric cancer.

BACKGROUND: Gastric cancer is one of most common malignancies in the world. Currently the prognostic prediction is entirely based on the TNM staging system. In this study, we evaluated whether metastatic lymph node ratio (rN) at the time of surgery would improve the prognostic prediction in conjunction with the TNM staging system. METHODS: This retrospective study includes 745 patients, who had been referred for surgery due to gastric cancer between 1995 and 2007 and had at least 15 lymph nodes examined at the time of surgery without preoperative treatment. Clinicopathologic features and overall survival were analyzed using univariate and multivariate modes to identify the risk factors for overall survival. RESULTS: Median overall survival of all patients analyzed is 57.8 months and 5-year overall survival is 49.5%. Tumor site, macroscopic type, pTNM stage, and rN stage are identified as independent prognostic factors. Increased positive lymph node ratio correlates with shorter survival in all patients and in each T and N stage. In stage III gastric cancer patients, rN stage shows additional prognostic value on overall survival (p < 0.001). CONCLUSIONS: rN stage is a simple and promising prognostic factor of gastric cancer after surgery in addition to the TNM stage system especially in stage III patients. But the independent prognostic value of rN stage in stage I, II and IV gastric cancer is yet to be determined.

Preoperative chemotherapy with a trastuzumab-containing regimen for a patient with gastric cancer and hepatic metastases.

Gastric cancer is the fourth most common cancer worldwide and the leading cause of tumor-related death in China. Gastric cancer is a heterogeneous disease and therefore requires different treatments based on the subtype. We describe a patient who had gastric cancer with liver metastases. Biopsy and tumor analysis using the HercepTest revealed a human epidermal growth factor receptor 2 (HER2)-positive adenocarcinoma as confirmed by fluorescence in situ hybridization. The patient was treated with a regimen of trastuzumab, oxaliplatin, and S-1 (six cycles). When positron emission tomography findings suggested that the metastases had resolved, the patient underwent surgery. Histopathologically, no cancer cells were observed in the resected hepatic tissue. The patient underwent tumor resection surgery, during which the tumor and gastric lymph nodes with lesions were removed. The patient has remained disease-free for 3 months. Therefore, trastuzumab may be an effective agent in the chemotherapeutic treatment of liver metastases in patients with HER2-positive gastric adenocarcinoma.

Expression of nestin in ovarian serous cancer and its clinicopathologic significance.

OBJECTIVE: Nestin has been found to be overexpressed in several human malignancies. The primary goal of this research was to investigate whether nestin expression correlates with the occurrence and development of ovarian cancer. PATIENTS AND METHODS: Expression of nestin was evaluated by immunohistochemistry in 315 cases of various epithelial ovarian lesions as well as 52 cases of normal ovarian epithelia. The association between nestin expression and various clinical pathological parameters was analysed. RESULTS: Immunohistochemical results showed that the positive correlation of nestin expression gradually increased from benign and borderline to malignant ovarian tumours. Nestin overexpression was associated with more advanced International Federation of Gynaecology and Obstetrics stage and higher histological grade in serous adenocarcinoma. Nestin expression was significantly associated with chemoresistance. However, there was no significant correlation between nestin expression and the age and level of CA125 in patients. CONCLUSIONS: We propose that nestin expression might contribute to the initiation, promotion, and progression of serous ovarian carcinoma; nestin expression is associated with poor chemoresponse. It could be a potential therapeutic target in patients with epithelial ovarian carcinoma.

Inhibitory effect of recombinant adenovirus carrying melittin gene on hepatocellular carcinoma.

OBJECTIVES: To search for a new clinical application of melittin (Mel): treating hepatocellular carcinoma with Mel gene. METHODS: Recombinant adenoviruses carrying the Mel gene and alpha-fetoprotein (AFP) promoter (Ad-rAFP-Mel) were constructed through a bacterial homologous recombinant system. The efficiency of adenovirus-mediated gene transfer and the inhibitory effect of Ad-rAFP-Mel on the proliferation of hepatocarcinoma cells were determined by X-gal stain and MTT assay, respectively. The tumorigenicity of hepatocarcinoma cells transfected by Ad-rAFP-Mel and the antitumor effect of Ad-rAFP-Mel on transplanted tumor in nude mice were detected in vivo. RESULTS: The Mel mRNA was transcribed in BEL-7402 hepatocellular carcinoma cells transducted by Ad-rAFP-Mel. The efficiency of adenovirus-mediated gene transferred to BEL-7402 cells was 100% when the multiplicity of infection of Ad-rAFP-Mel was 10 in vitro, and was also high in vivo. The inhibitive rates of Ad-rAFP-Mel and Ad-rAFP for BEL7402 cells were 66.2 +/- 2.7% and 2.9 +/- 2.3% (t=30.83, P=6.6 x 10(-6)) by MTT assay. The inhibitive rates of Ad-CMV-Mel for BEL7402, SMMC7721 and L02 cells were 58.9 +/- 9.6%, 65.9 +/- 3.8% and 31.7 +/- 1.2%, respectively, and of Ad-rAFP-Mel were 66.2 +/- 2.7%, 16.1 +/- 6.6% and 7.5 +/- 3.3%, respectively (t=1.27, P=0.27; t=11.31, P=3.5 x 10(-4); and t=12.12, P=2.7 x 10(-4) versus the Ad-CMV-Mel group in the same cells). The tumorigenicity rates of hepatocarcinoma cells transfected by Ad-rAFP-Mel were decreased. A significant antineoplastic effect was detected on transplanted tumor in nude mice by intratumoral injection of Ad-rAFP-Mel. CONCLUSIONS: Ad-rAFP-Mel can inhibit specifically proliferation of AFP-producing human hepatocarcinoma cells in vitro and in vivo. This suggests that animal toxin gene can be used as an antitumor gene.