Objective:To discuss the differences in eosinophil(EOS)infiltration in cervical tissue and its relationship with cervical-related diseases,and to clarify the effect of EOS on the occurrence and development of cervical intraepithelial neoplasia(CIN)and cervical cancer.Methods:The clinical data of 256 patients with cervical diseases were collected and divided into cervical cancer group(n=46,including 26 cases of squamous cell carcinoma,15 cases of adenocarcinoma,and 5 cases of adenosquamous carcinoma),chronic cervicitis group(n=50),CIN stage Ⅰ group(n=50),CIN stage Ⅱ group(n=50),CIN stage Ⅲ group(n=30),and normal group(adjacent normal cervical tissue,n=30)based on their conditions.Colposcopy was used to observe the morphology of cervical tissue of the patients in various groups;thin-layer liquid-based cytology test(TCT)was used to observe the morphology of the cervical exfoliated cells in various groups;hybrid capture-chemiluminescence method was used to detect the human papillomavirus(HPV)infection in cervical tissue of the patients in various groups;HE staining was used to observe the pathomorphology of cervical tissue of the patients in various groups;Congo red staining was used to detect the numbers of EOS infiltration in cervical tissue of the patients in various groups;Pearson correlation analysis was used to analyze the correlation between the number of EOS infiltration and the malignancy degree of cervical cancer.Results:The cervical surface of the patients in normal group was smooth and pink,with uniformly distributed capillaries;the cervical surface of the patients in chronic cervicitis group showed red inflammatory changes,with some accompanied by Nabothian cysts and varying degrees of erosion and ulcers;the patients in CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups showed epithelial ulcers,thickening,and irregular morphology,with mosaic and punctate vessels;the cervical surface of the patients in cervical cancer group showed raised areas with neoplasms and necrotic ulcers,and they were fragile and prone to bleeding.After acetic acid staining,no obvious changes of the patients in normal group were observed.The cervix of the patients in chronic cervicitis group showed slight white changes that lasted for a short time;in CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups,irregular thin acetowhite epithelium with map-like borders was observed,with increasingly acetowhite reactions and larger areas as the stages advanced.The cervix of the patients in cervical cancer group showed thick acetowhite epithelium that lasted longer,with rigid and clear contours.After iodine staining,the cervix of the patients in normal group was brown,with uniform coloration;the cervix of the patients in chronic cervicitis group showed poor coloration in inflammatory lesion areas;the cervix of the patients in CIN stage Ⅰ group showed iodine coloration in metaplastic areas,while the cervix of the patients in CIN stage Ⅲ group showed poor coloration in larger lesion areas;the cervix of the patients in cervical cancer group showed irregular surfaces with cauliflower-like growth and no coloration after iodine staining,appearing orange-yellow or mustard yellow.The TCT observation results showed there were no heteromorphic cells and few inflammatory cells in cervical exfoliated cells of the patients in infiltration in normal group;there were numerous neutrophils and EOS in exfoliated cervical cells without heteromorphic cells in chronic cervicitis group.The heteromorphic binucleated cells with high nuclear-cytoplasmic ratios and deeply stained nuclei were observed in cervical exfoliated cells of the patients in CIN stage Ⅰ and CIN stage Ⅱ groups.More heteromorphic cells with high nuclear-cytoplasmic ratios and irregular nuclear membranes were showed in cervical exfoliated cells of the patients in CIN stage Ⅲ group.The cervical exfoliated cells of the patients in cervical cancer group showed large and prominent nucleoli,clustering into syncytial changes.Compared with normal group,the atypial of cervical exfoliated cells in CIN stage Ⅰ,CIN stage Ⅱ,CIN stage Ⅲ,and cervical cancer groups was increased.The hybrid capture-chemiluminescence results showed that compared with normal and chronic cervicitis groups,the numbers of HPV infection and TCT heteromorphic cells of the patients in CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups were increased(P<0.05);compared with CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups,the numbers of HPV infection and TCT heteromorphic cells of the patients in cervical cancer group were increased(P<0.05).The HE staining results showed normal cell morphology and structure in normal group,with infiltration of inflammation cells such as neutrophils,monocytes,macrophages,EOS,and lymphocytes;in chronic cervicitis group,the infiltration of inflammatory cells was increased;in CIN group,the cervical cells showed slightly larger nucleoli and heteromorphic cells,with inflammatory cells mainly distributing around the hetermomorphic cells;in cervical cancer group,the cervical cells showed large and deeply stained nucleoli with significant atypia,and the infiltration of inflammatory cells around the cancer cells was increased.Compared with normal group,the numbers of inflammatory cells and EOS infiltration in cervical tissue of the patients in chronic cervicitis group were increased(P<0.05),and the numbers of inflammatory cells and EOS infiltration of the patients in CIN group were increased(P<0.05);compared with chronic cervicitis group,the number of inflammatory cells and EOS infiltration of the patients in CIN group were decreased(P<0.05);compared with chronic cervicitis group and CIN group,the numbers of inflammatory cells and EOS infiltration of the patients in cervical cancer group were increased(P<0.05).The EOS in cervical cancer tissue was mainly distributed around the cancer nests;compared with CIN stage Ⅰ group,the numbers of EOS infiltration in CIN stage Ⅱ and CIN stage Ⅲ groups were increased(P<0.05);compared with CIN stage Ⅱ group,the number of EOS infiltration in CIN stage Ⅲ group was increased(P<0.05).The higher the malignancy degree of the tumor,the more EOS infiltration was observed,and the number of EOS infiltration was positively correlated with the invasion depth of cervical cancer(r=0.533 0,P<0.01).Conclusion:HPV infection and EOS infiltration play a role in promoting the and occurrence development of cervical precancerous lesions and cervical cancer.

In order to evaluate the efficacy of peroral endoscopic myotomy (POEM) for achalasia, data of 63 patients with achalasia who were treated with POEM in China-Japan Union Hospital of Jilin University from 2017 to 2021 were collected. Postoperative Eckardt score, high-resolution manometry and upper gastrointestinal radiography were compared with preoperative data. The mean age of the 63 patients was 49.0 years, and there were 31 famales. The preoperative Eckardt score was 9 (3), and the postoperative Eckardt score was 2 (2), with significant difference ( V=1 953, P<0.001). The lower esophageal sphincter pressure decreased significantly after operation compared with that before operation [9.90 (3.35) mmHg VS 26.80（13.85）mmHg， V=2 016, P<0.001]. Fifty-three patients (84.1%) had satisfactory curative effects. The incidence of adverse events was 3.2% (2/63). POEM is safe, effective and minimally invasive for the treatment of achalasia.

Antiviral Agents/pharmacology* ; COVID-19 ; Coronavirus 3C Proteases ; Humans ; Lactams ; Leucine ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Nitriles ; Proline ; Protease Inhibitors/pharmacology* ; SARS-CoV-2

Objective:To compare the curative effects of different venous cannulas and drainage to improve patient's whole body oxygenation during the auxiliary process of venous-arterial extracorporeal membrane oxygenation (VA-ECMO) in lung transplantation.Methods:From December 2016 to December 2019, 12 patients who were assisted by VA-ECMO in one lung transplantation in People's Hospital of Henan Province were selected as the research objects. According to the number of side holes of venous cannulas, they were divided into two groups: one group with few side holes and other group with multiple side holes. The differences in blood gas indexes among the right radial artery, left radial artery, and right internal jugular vein before and after assistance were compared, and the assistance effect was evaluated.Results:The arterial partial pressure of oxygen (PaO 2) of blood gas indexes of the right and left radial arteries in both groups were significantly higher than that before assistance [mmHg (1 mmHg = 0.133 kPa): right and left radial artery in few side holes group: 79.5±4.2 vs. 48.3±3.8 and 88.1±3.5 vs. 48.3±3.8; right and left radial artery in multiple side holes group: 67.7±5.9 vs. 48.7±3.2 and 84.0±3.8 vs. 48.7±3.2, all P < 0.05]. The arterial partial pressure of carbon dioxide (PaCO 2) of blood gas index was significantly lower than that before assistance (mmHg: 44.2±2.6 vs. 71.7±4.4 for the right radial artery and 44.7±1.4 vs. 71.7±4.4 for the left radial artery in the group with few side holes; 46.2±2.1 vs. 71.2±3.5 for the right radial artery and 44.1±1.9 vs. 71.2±3.5 for the left radial artery in the group with multiple side holes, all P < 0.05). The partial pressure of oxygen in venous blood (PvO 2) of blood gas index of ECMO system in the group with few side holes was significantly lower than that of the multiport side holes group (mmHg: 56.4±3.2 vs. 88.7±1.5, P < 0.01), and the partial pressure of carbon dioxide in venous blood (PvCO 2) was significantly higher than that of multiport side holes group (mmHg: 63.6±3.7 vs. 44.2±1.7, P < 0.01). Conclusions:When VA-ECMO is used in lung transplantation, the superior vena cava blood flow can be fully drained by using intravenous cannula with few side holes. It can effectively improve the oxygenation of the upper body of lung transplant patients, avoid the dilemma of hypoxemia in the upper body and hyperxemia in the lower body, provide more effective assistance to patients undergoing single lung transplantation, and is more meaningful for improving the oxygenation status of the whole body in patients undergoing single lung transplantation.

Objective:To investigate the independent predictors of the long-term clinical outcomes in patients with branch atheromatous disease (BAD) in lenticulostriate artery (LSA) territory.Methods:Patients with LSA-BAD admitted to the Department of Neurology, Zhongnan Hospital of Wuhan University from January 1, 2016 to June 1, 2019 were enrolled retrospectively. Their demography, vascular risk factor, and baseline clinical data were collected. The National Institutes of Health Stroke Scale (NIHSS) was used to evaluate the severity of stroke. The clinical outcomes were evaluated by the modified Rankin Scale at 6 months. 0-2 was defined as good outcome, and >2 was defined as poor outcome. Multivariate logistic regression analysis was used to determine the independent influencing factors of clinical outcomes in patients with LSA-BAD. Results:A total of 81 patients with LSA-BAD were enrolled. Their age 59.20±11.75 years (range, 39-81 years), 53 were male (65.4%), and median baseline NIHSS score was 1.0 (interquartile range, 0-4.0). Forty-one patients (50.6%) received intravenous thrombolysis. At 6-month follow-up after the onset, 63 patients (77.8%) had a good outcome, and 18 (22.2%) had a poor outcome. The baseline NIHSS score of the poor outcome group was significantly higher than that of the good outcome group (6.5 [0-9.0] vs. 1.0 [0-3.0]; Z=2.395, P=0.017), while the proportion of mild stroke (61.6% vs. 98.4%; χ2=17.595, P<0.001) and patients receiving intravenous thrombolysis (38.9% vs. 54.0%; χ2=4.450, P=0.035) were significantly lower than those of the good outcome group. Multivariate logistic regression analysis showed that after adjusting for other confounding factors, venous thrombolysis was independently correlated with the good outcome (odds ratio 0.099, 95% confidence interval 0.011-0.924; P=0.042), while the high baseline NIHSS score was independently associated with the poor outcome (odds ratio 1.736, 95% confidence interval 1.262-2.388; P=0.001). Conclusion:Intravenous thrombolysis is helpful to improve the outcomes of patients with LSA-BAD, and a higher baseline NIHSS score is an independent predictor of the poor outcome.

Objective:To investigate the 2 years’ efficacy of intravesical instillation of domestic BCG versus epirubicin in the prevention of recurrence of intermediate-risk or high-risk non-muscular invasive bladder cancer and predictive factors of BCG instillation.Methods:From July 2015 to June 2020, 18-75 years old patients with moderate to high-risk non muscle invasive bladder cancer (NMIBC) confirmed by pathological examination were involved. The ECOG score was 0-2. Exclusion criteria included ①immune deficiency or impairment (such as AIDS), using immunosuppressive drugs or radiotherapy, suspected allergic to BCG or epirubicin or excipients of the two drugs, fever or acute infectious diseases including active tuberculosis or receiving anti tuberculosis treatment, with severe chronic cardiovascular and cerebrovascular diseases or chronic kidney disease; ②combined with other urogenital system tumors or other organ tumors; ③combined with muscle invasive bladder urothelial carcinoma (≥T 2); ④undergoing chemotherapy, radiotherapy or immunotherapy within 4 weeks (immediate instillation after surgery not included); ⑤ pregnant or lactating women; ⑥ comfirmed or suspected bladder perforation; ⑦gross hematuria; ⑧cystitis with severe bladder irritation that may affect the evaluation; ⑨participat in other clinical trials within 3 months; ⑩alcohol or drug addiction; ?any risk factors that may increasing the risk of patients. Epirubicin 50 mg was irrigated immediately after the operation(TURBT or laser resection). The patients were randomly divided into BCG15 group, BCG19 group and epirubicin group by the ratio of 2∶2∶1, and the patients were maintained intravescical instillation for 1 year. The recurrence and adverse events of the three groups were compared. Univariate and multivariate analysis was performed to predict the risk factors of BCG irrigated therapy failure. Result:By June 15, 2020, the median follow-up duration was 22.1 months(12.1, 32.3), and there was no statistical difference between the groups ( P=0.9024). There were 274 patients enrolled in BCG19 group, 277 patients enrolled in BCG15 group and 130 patients enrolled in the epirubicin group. The drop-off rate was 16.6%(113 cases)and made no difference between groups( P=0.6222). There were no significant difference in age, gender, BMI, or ECOG score( P>0.05). During the follow-up, 116 cases was detected recurrence or progression. The recurrence rate of the three groups was 14.2% and 14.8% in BCG19 group and BCG15 group, and 27.7% in the epirubicin group. There was no difference in recurrence rate between BCG19 and BCG15 group( P=0.9464). The recurrence rate of BCG19 group was lower than that of the epirubicin group ( P=0.0017). The recurrence rate of BCG15 group was lower than that of the epirubicin group ( P=0.0020). There was no difference in the cumulative recurrence free survival rate between BCG19 and BCG15 group (95% CI0.57-1.46, P=0.7173). The cumulative recurrence free survival rate of BCG 19 group was better than that of the epirubicin group( HR=0.439, 95% CI0.26-0.74, P=0.0006), and the cumulative recurrence free survival rate of BCG15 group was better than that of the epirubicin group ( HR=0.448, 95% CI0.29-0.80, P=0.0021). The total incidence of adverse events in 19 BCG19, BCG15 and epirubicin group were 74.5%, 72.6% and 69.8% respectively. There was no difference in the incidence of adverse events between BCG19 and BCG15 group( P=0.6153). The incidence of adverse events in epirubicin group was lower than that of BCG19( P=0.0051) and BCG15( P=0.0167) groups.There was no significant difference in the incidence of serious adverse events (SAE) among the three groups ( P=0.5064). Log rank test univariate analysis and Cox risk regression model multivariate analysis showed that the history of bladder cancer recurrence( HR=6.397, 95% CI1.95-20.94, P=0.0001)was independent risk factor for BCG irrigation failure. Conclusions:The 2 years’ efficacy of intravesical instillation of domestic BCG is better than than of epirubicin with good tolerance and safety. There is no difference between BCG19 and BCG15 group. BCG doesn’t increase SAE compared with epirubicin. Recurrence status was an independent prognostic factor regarding recurrence-free survival.

Lung cancer is one of the most common malignancies with the highest incidence rate and mortality rate worldwide, and non-small cell lung cancer (NSCLC) accounts for about 85%. Only 5% NSCLC patients are anaplastic lymphoma kinase (ALK) rearrangement positive NSCLC, but the prognosis of these patients is poor, and treatment is urgent. Ensartinib (X-396), a next-generation ALK tyrosine kinase inhibitor (ALK-TKI), has shown greater potency on inhibiting ALK activity and controlling brain metastases than crizotinib, which is indicated for the treatment of crizotinib-resistant, ALK-positive NSCLC patients. Several phase I to III clinical trials included both healthy volunteers and NSCLC patients have been conducted both in China and abroad. In this review, we briefly summarized the results of these trials, and preliminary efficacy, safety, pharmacology and pharmacokinetics/pharmacodynamics of ensartinib were discussed.

Objective:To evaluate the feasibility and efficacy of partial superficial parotidectomy with V-shaped incision by comparing with the Blair incision and hairline N-shaped incision.Methods:From January 2015 to January 2016, 60 patients (47 males and 13 females, with an age range of 25- 63 years) required for superficial partial parotid gland resection were randomly divided into three groups: V-shaped incision (VI) group, Blair incision (BI) group and hairline N-shaped incision (NI) group, with 20 cases in each group.Intraoperative, postoperative and follow-up indexes were compared between three groups. Operative time and drainage volume in the surgery of tumors at different sites in VI group were compared. SPSS18.0 software was used for statistic analysis.Results:There were no statistically significant differences among the three groups in operative time, drainage volume, postoperative hospital stay, periauricular numbness, fistulas, pain score, facial palsy, and scar score at the 3rd month after surgery ( P>0.05). For appearance satisfaction score at the 6th month after surgery, VI group was better than BI group or NI group, with significant differences(VI group vs. BI group: 9.00[8.00, 9.00] vs. 5.00[4.00, 5.25], χ 2=6.629, P<0.001; VI group vs. NI group: 9.00[8.00, 9.00] vs. 7.00[6.00, 8.00], χ 2=2.942, P=0.010; BI group vs. NI group: 5.00[4.00, 5.25] vs. 7.00[6.00, 8.00], χ 2=-3.687, P=0.001). For tumors located in the front, upper and middle of parotid gland, there were no statistically significant differences in operative time and drainage volume between the three groups ( P>0.05). For tumors located at the lower part of parotid gland, the difference in operative time between the three groups was statistically significant ( F=7.278, P=0.01). With pairwise comparison, operative time in VI group was longer than that in BI group or NI group, but there was no significant difference between BI group and NI group (VI group vs. BI group: (181.00±22.89) min vs. (132.50±9.01) min, t=3.694, P=0.004; VI group vs. NI group:(181.00±22.89) min vs. (149.00±15.94) min, t=2.585, P=0.025; BIgroup vs. NI group, (132.50±9.01) min vs. (149.00±15.94) min, t=1.257, P=0.235). For tumors located at the lower part of parotid gland, the differences in intraoperative drainage volume were not statistically significant between three groups ( P>0.05). There were no statistically significant differences in operative time and drainage volume in the surgery of tumors at different sites in VI group ( P>0.05). Conclusions:By use of V-shaped incision for the surgery of benign parotid gland tumors, the operation time of tumors located only in the lower part of the parotid gland will be prolonged. For tumors in different sites without increasing surgical complications, this modality can get good cosmetic effect.

Objective To investigate the efficacy and safety of intravesical instillation of BCG vaccine in the prevention of early recurrence of middle and high risk non-muscle invasive bladder cancer.Methods From July 2015,patients with non-muscle invasive bladder cancer aged 18-75 years with informed consent were screened and underwent transurethral resection of bladder tumor (TURBT).Immediately intravesical instillation of epirubicin 50 mg was given postoperatively.After pathology was comfirmed,patients was enrolled in group 1 (BCG15) or group 2 (BCG 19) or the control group (epirubicin 18) randomly with SAS 9.3 software.Data of follow-up and Adverse event was collected and analyzed.Results By May 31,2019,531 patients were enrolled in the study.The drop-off rate was 20.1％.167 patients (143 males and 24 females)in group 1,172 patients (141 males and 31 females)in group2 and 84(75 males and 9 females) in the control group with follow-up data were analyzed.There were no significant differences in age,gender,BMI,ECOG score,risk stratification between the three groups (P =0.8641,P =0.2906,P =0.9384,P =0.6126).The median follow-up time makes no statistical difference between the groups (P =0.9251),12.0 (6.0,22.5) months,13.0 (6.0,22.3) months,and 13.0 (7.0,22.3) months.The median recurrence time of the three groups was 4.0 (3.0,6.0) months,4.5 (3.0,9.8) months,4.5 (3.0,8.8) months.There was no statistical difference between the three groups (P =0.2852).Risk stratification in the patients got no significant difference between the three groups (P ＞ 0.05).The 1-year recurrence-free survival rates were 80.0％ in the group 1 and 88.3％ in the group 2 and 73.7％ in the control group.The group 2 was superior to the group 1 and the control group (P =0.0281,P =0.0031).There was no significant difference between group 1 and control group (P =0.2951).There was no significant difference in the cumulative recurrence-free survival between the experimental group 1 and the experimental group 2,(95％ CI 0.80-2.43,P =0.2433).The cumulative recurrence-free survival in the group 1 and the group 2 was better than the control group (95 ％ CI 0.31-0.92,P =0.0266;95 ％ CI 0.20-0.65,P =0.0008).All the cases underwent instillation were analyzed for adverse events.The incidence of overall AE(adverse events) in group 1 was 68.5％ (152/222),the incidence of grade Ⅰ-Ⅱ AE was 53.2％ (118/222),the incidence of grade Ⅲ-Ⅳ AE was 15.3％ (32/222).The incidence of overall AE in the group 2 was 71.8％ (160/223),the incidence of grade Ⅰ-Ⅱ AE was 60.1％ (134/223),and the incidence of grade Ⅲ-Ⅳ AE was 11.7％ (26/223).The overall AE rate in the control group was 53.2％ (59/111),of which the incidence of grade Ⅰ-Ⅱ AE was 42.4％ (47/111),and the incidence of grade Ⅲ-Ⅳ AE was 10.8％ (12/111).There was no difference in the incidence of overall AE between the group 1 and the group 2 (P =0.4497).The incidence of AE in the two experimental groups was higher than that in the control group (P =0.0062,P =0.0008).There was no difference in the incidence of grade Ⅲ-Ⅳ AE between the three groups (P =0.3902).Conclusions BCG(19 instillation schedule) has a better effect on preventing recurrence after 1 year of bladder surgery,which is superior to epirubicin group.The long-term efficacy of BCG in preventing recurrence and the efficacy of different schedules need to be further followed up.The lower urinary tract symptoms,which are mainly urinary frequency,are one of the causes of case fallout and should be fouced in future.Compared with epirubicin,BCG perfusion does not increase the incidence of grade Ⅲ-Ⅳ adverse reactions,and is safe to use.

Objective To assess the efficacy and side effects of intravesical instillation of BCG after transurethral resection of the bladder tumor (TURBT) in non-muscle invasive bladder cancer (NMIBC) patients.Methods The clinical data of patients treated with BCG 120 mg per course induced perfusion or more after TURBT from December 2013 to October 2016 in 18 hospitals of northeast China region,were analyzed retrospectively.The first part,data of 106 patients with moderate,high-risk NMIBC were collected.A total of 83 patients were male,while the other 23 patients were female.The average age was 66.7 years old.The clinical staging were T1 in 86(81.1％) cases,Ta in 20(18.9％) cases and carcinoma in situ in 6 (5.7％) patients.Intravesical instillation of BCG was executed after transurethral resection of the bladder tumor.The incidence rate of recurrence and progression during more than 6 months' follow-up time were observed.Multivariate analyses were done by using logistic analysis and Cox proportional hazards regression model with Kaplan-Meier method.The second part,treatment compliance of 276 patients with bladder cancer,including moderate/high-risk NMIBC in 263 cases,moderate/high-risk NMIBC followed with renal pelvis/ureteral carcinoma in 8 cases were and moderate/high-risk NMIBC with renal pelvis/ureteral carcinoma in 5 cases who treated with BCG after the surgeries,were observed.Patients consisted of 211 males and 65 females with average age of 68.3 years.Results With a median follow-up of 12 months,9 (8.5％) patients experienced tumor recurrence and 2 (1.9％) patients were found progression in the first part.The one-year cancer free recurrence rate of the patients was 91.5％.Statistically significant prognostic factors for recurrence identified by multivariable analyses were prior recurrence of the tumors (OR =3.214,95％CI0.804-12.845,P =0.099).In the second port,an incidence rate of adverse effects was 64.1％ (177/276).The Ⅲ/Ⅳ degree complications were occurred in 11 patients and satisfactory outcomes achieved with active treatment.A total of 36 patients withdrawal with the major causes were recurrence and progression of bladder tumor in 12 cases (4.4 ％),9 cases (3.3 ％) with economic reasons and 11 cases (4.0％) with serious complications.Conclusions NMIBC patients treated with intravesical BCG therapy have approving cancer free recurrence rates and acceptable adverse effects.Prior recurrence may be prognostic factor of recurrence after intravesical BCG therapy.