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2021 Vol. 51, No. 9 Published: 2021-09-25   689 Theoretical study on the structure and properties of Remdesivir and its synthetic intermediates CHEN Mengyi, SUN Xiang, HUANG Luoyi, WANG Chaojie DOI: 10.3969/j.issn.2095-9400.2021.09.001 Guide::null null 2021 Vol. 51 (9): 689-698 [Abstract] ( 943 ) HTML (1 KB)  PDF (2091 KB)  ( 895 ) 699 The therapeutic effect of Kangfuxin liquid on ulcerative colitis mice JIN Xumin, SUN Jie, XUE Pengpeng, DONG Weijie, TAO Xinjie, XU Helin DOI: 10.3969/j.issn.2095-9400.2021.09.002 Objective: To prepare Kangfuxin liquid (KFX) and Dexamethasone (DXM) enema and to evaluate its therapeutic effect on DSS induced ulcerative colitis mice. Methods: The dextran sulfate induced ulcerative colitis mice model was established and the model mice were divided into three groups: Saline group,DXM group and KFX group. The therapeutic effect of these treatment on UC mice was evaluated from aspects of symptom relief, spleen swelling, colon length, and MPO level of colon tissue. Besides, the morphology and mucosal barrier of colon were evaluated by HE staining, IHC staining and immunofluorescence staining  respectively. Results: After DXM or KFX treatment, DSS induced UC mice had significantly reduced  diarrhea,hematochezia, spleen swelling, colon swelling, colon length growth and MPO level in comparison with Saline group (P<0.05). Moreover, HE staining showed more complete mucosa epithelium layer, crypt, muscle layer mucosa and better-repaired submucosa after KFX treatment in comparison with DXM. No swelling or inflammatory cell infiltration in each layer of colon was observed in KFX group, indicating the effective morphological repair of the damaged colon. IHC staining showed that the secretion of inflammatory factors in KFX group was significantly reduced, compared with DXM group (P<0.05), indicating that colon tissue was effectively repaired. IF staining showed that the secretion of tight junction protein in KFX group was significantly increased (P<0.05), indicating that the damaged colonic mucosal barrier was effectively repaired. Conclusion:KFX oral liquid can effectively relieve UC symptoms and repair the damaged colon. 2021 Vol. 51 (9): 699-704,712 [Abstract] ( 777 ) HTML (1 KB)  PDF (2182 KB)  ( 804 ) 705 The regulating effect of Eg5 on the malignant proliferation of castration resistant prostate cancer cells through c-Myc/SP1/CDK1 signaling pathway HU Junbiao, ZHANG Chunting, XIA Jianhong, YAO Yong,LU Junyi DOI: 10.3969/j.issn.2095-9400.2021.09.003 Objective: To investigate the effect of kinesin-5 (Eg5) on the proliferation, apoptosis, cell cycle,invasion and metastasis of castration resistant prostate cancer DU145 cells and its corresponding mechanism.Methods: Eg5 expression was silenced through transfecting DU145 cells with Eg5 shRNA and its function in DU145 cells was inhibited with SB-743921. The experiment were divided as the control group, NC shRNA group,Eg5 shRNA group and SB-743921 treated group. MTT assay and Colony formation assay were used to analyze cell proliferation. Annexin V-FITC and PI double dyeing assay was used to determine cell apoptosis and PI dyeing assay to detect cell cycle. Wound healing assay was used to analyze cell metastasis. Q-PCR and Western blot was used to analyze the expression of c-Myc, SP1, CDK1, Cyclin A1, Cyclin B1, CDC25B, N-cadherin, E-cadherin and Vimentin. Results: There was no significant difference between NC shRNA group and the control group.Compared with the control group, the proliferation and metastasis of DU145 cells were decreased in Eg5 shRNA group and SB-743921 treated group, while the apoptosis of DU145 cells was increased and the cell cycle was blocked at G2/M phase, with statistical difference among groups (P<0.05). The expression of c-Myc (P<0.05) and SP1 (P<0.05) were decreased in Eg5 shRNA group and SB-743921 treated group and the expression of G2/M phase related genes CDK1, Cyclin A1, Cyclin B1 and CDC25B were also inhibited (P<0.05). Meanwhile, the expression of metastasis related genes Vimentin and N-cadherin were blocked (P<0.05), and E-cadherin expression was increased (P<0.05). Conclusion: As a potential therapeutic target, Eg5 may regulate the c-Myc/SP1/CDK1 signaling pathway to inhibit the proliferation and metastasis of Castration resistant prostate cancer. 2021 Vol. 51 (9): 705-712 [Abstract] ( 607 ) HTML (1 KB)  PDF (3726 KB)  ( 770 ) 713 Advantages of vNOTES hysterectomy combined with salpingectomy/adnexectomy in ERAS ZHU Jiawei,ZHU Li, LIANG Zongwen, CHEN Sailing, ZHAO Manman, FANG Nan, WANG Fang, DUAN Ping DOI: 10.3969/j.issn.2095-9400.2021.09.004 Objective: To compare the advantages of vNOTES, U-LESS and traditional laparoscopy in ERAS after hysterectomy combined with salpingectomy/adnexectomy. Methods: A total of 115 patients who underwent hysterectomy combined with salpingectomy/adnexectomy by vNOTES, U-LESS, and traditional laparoscopy were selected. The primary indicators included the first time off-bed after surgery, postoperative exhaust time, length of hospital stay after operation, the 24-hour pain score and the 48-hour pain score after operation, incidence of nausea, vomiting and abdominal distension. The secondary indicators included intraoperative blood loss, length of operation, the rate of postoperative fever, the cost of hospitalization,intraoperative and postoperative complication rate and incision cosmetic score. Additional indicators included the first urination time after surgery, rate of urinary retention, rate of urinary tract infection rate and the rate of dysuria.Results: In the vNOTES group, the first time to get out of bed was shorter, the time of first anal exhaust was the shortest, the length of hospital stay was the shortest, and the pain score was the lowest at 24 hours and 48 hours after operation (P<0.05). There was no significant difference in postoperative nausea, vomiting and abdominal rate among the three groups (P>0.05); the incision aesthetic score was also the highest (P<0.05); the postoperative micturition was not worse than the other two groups. Conclusion: vNOTES hysterectomy combined with salpingectomy/adnexectomy is worthy of clinical application with the benefits of get out of bed earlier, less pain,earlier exhaust, earlier discharge, sooner recovery and higher incision cosmetic score. 2021 Vol. 51 (9): 713-718 [Abstract] ( 813 ) HTML (1 KB)  PDF (1422 KB)  ( 717 ) 719 Correlation between quality parameter based on thin-section CT and clinical symptoms of COVID-19 pneumonia FU Gangze, TAO Jiejie, SUN Houchang, YANG Yunjun, WANG Meihao DOI: 10.3969/j.issn.2095-9400.2021.09.005 Objective: To calculate the lung quality of CT lesions in patients with COVID-19 pneumonia,and explore its correlation with early clinical features and laboratory indicators. Methods: The DICOM format of thin-section CT of 48 patients with COVID-19 during January 19, 2020 to February 31, 2020 were collected and transmitted to the post-processing software for segmentation of lesions by artificial intelligence. The volume and average density of the lesion were obtained, and the mass of the diseased lung calculated. The correlation between the quality of diseased lungs and gender, age, body temperature, onset time and laboratory tests was explored, and the quality difference among groups with different clinical characteristics was compared. Results: Forty-eight patients, aged (45.2±16.5)years, 26 males and 22 females, had a median onset of 3 days. The lung quality was significantly correlated with the patient’s body temperature, fever days, and C-reactive protein values (P<0.05),with r values of 0.373, 0.360, and 0.713, respectively. The lung quality in the moderate or high fever group was 65.7 (41.8, 101.7)g, which was significantly larger than that in the low fever group [10.0 (3.1, 49.3)g] or the nonfever group [5.5 (1.0, 16.0)g]. The quality in patients with initial CT scan≥5 days from illness onset was 45.7(16.4, 86.3)g, which was significantly higher than patients≤4 days from illness onset [10.0 (2.6, 39.3)g]; the quality in patients with high C-reactive protein was 45.4 (11.3, 88.4)g, significantly higher than patients with normal Creactive protein [4.0 (1.2, 14.2)g]. All differences were statistically significant (P<0.05). Conclusion: The quality of the diseased lung is significantly correlated with the clinical symptoms and laboratory indicators of COVID-19 patients, which can be used as one of the effective CT quantitative parameters reflecting the severity of viral pneumonia. 2021 Vol. 51 (9): 719-723 [Abstract] ( 617 ) HTML (1 KB)  PDF (1550 KB)  ( 714 ) 724 CsgRNA reduces mutation caused by APOBECs during Cas9-D10A-mediated gene editing REN Rongrong,CHEN Hongquan DOI: 10.3969/j.issn.2095-9400.2021.09.006 Objective: To investigate whether csgRNA strategy could reduce the indels induced by APOBECs when performing gene editing of Cas9-D10A/sgRNA. Methods: In this study, csgRNA was designed on sgRNA4 and FANCF targeting sites. In order to block on-target indels induced by D10A, csgRNA was optimized finely for its length and space location, with the indels detected in 293FT-APOBEC3B overexpression cell line.Results: CsgRNA dramatically reduced the unwanted mutations caused by APOBECs, which was further improved through optimizing its conditions, and it was playing a better role when 16 bp length and 2 bases extended to the PAM or 20 bp length and 4 bases extended to the PAM. Conclusion: The unexpected mutations caused by APOBECs was significantly lowered using the csgRNA strategy. 2021 Vol. 51 (9): 724-728 [Abstract] ( 501 ) HTML (1 KB)  PDF (2472 KB)  ( 676 ) 729 Influencing factors and predictors of weaning from high-flow nasal cannula oxygen therapy in patients with pneumonia-related respiratory failure ZHENG Jian, HUANG Shu’e, WANG Xuetao, WANG Liangxing DOI: 10.3969/j.issn.2095-9400.2021.09.007 Objective: To study the influencing factors of weaning from high-flow nasal cannula oxygen therapy (HFNC) in patients with pneumonia-related respiratory failure during the recovery phase and to find the ideal predictors. Methods: Retrospective analysis was performed on 159 patients with pneumonia-associated respiratory failure treated with HFNC in the intensive care unit of Wenzhou Integrated Traditional Chinese and Western Medicine Hospital from January 2018 to December 2020. According to whether reapplication of the HFNC or mechanical ventilation was required within 48 h of conversion to conventional oxygen therapy after weaning from HFNC, they were divided into the successful group and the failure group. Then the two groups were compared in the baseline characteristics, comorbidities, pneumonia typing, machine setup parameters,physiological parameters, laboratory indexes, drugs used, treatment duration, ROX index (SpO2/FiO2 divided by respiratory rate) at the time of the patient’s first attempt to disengage from HFNC treatment, and treatment modality after weaning from HFNC. Logistic regression analyses were used to determine independent influencing factors and the value of the indicators was analyzed. Results: The number of patients successfully weaned from HFNC at the first attempt was 128, while 31 patients failed to wean. The logistic regression analysis showed that FiO2,ROX index, and combined chronic heart failure were independent influencing factors of successful weaning from HFNC (P<0.05). The ROX index was used to build a model for predicting successful HFNC disengagement with an AUROC of 0.836, with an optimal threshold point of 9.9, sensitivity of 93.0%, and specificity of 64.5%. The ROX index outperformed the FiO2 in comparison of the model’s predictive efficacy, sensitivity, and specificity.Conclusion: FiO2, ROX index, and combined chronic heart failure were independent influencing factors of successful weaning from HFNC in patients with pneumonia-related respiratory failure. And the ROX index was more valuable than FiO2 in predicting successful weaning from HFNC in patients with pneumonia-related respiratory failure. 2021 Vol. 51 (9): 729-734 [Abstract] ( 566 ) HTML (1 KB)  PDF (1398 KB)  ( 1179 ) 735 Psychological status of children with spinal cord injury and their primary caregivers with an analysis of its impact on family management of the diseacse ZENG Xiaolei, ZHAO Sufan, LIN Baoli, HUANG Xiaoxia DOI: 10.3969/j.issn.2095-9400.2021.09.008 Objective: To investigate the psychological status of spinal cord injury (SCI) children and their primary caregivers to find out the influencing factors on family management of SCI. Methods: A total of 94 SCI children in the Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University from February 2015 to June 2020 were enrolled, and their anxiety and depression levels were respectively evaluated via SCARED (the screen for child anxiety related emotional disorders) and DSRSC (depression self-rating scale for children). Besides, questionnaires were also carried out on the primary caregivers of SCI children by using General Information Scale, Connor-Davidson resilience scale (CD-RISC), self-rating anxiety scale (SAS), self-rating depression scale (SDS) and family management measure (FaMM). Pearson correlation analysis and multiple linear regression analysis were made to explore the influencing factors of household management. Results: Both SCI children and their primary caregivers had significantly higher level of depression and anxiety than those in the domestic normative model (both P<0.05). In addition, the psychological resilience of primary caregivers was lower than the domestic normative model (P<0.001). The “daily living standards of children” in FaMM was influenced by anxiety level (β=-0.810, P<0.001) and depression level (β=-3.144, P=0.002) of children. “Parents’ management ability on disease” was affected by “tenacity” (β=0.061, P=0.004) and “strength” (β=0.944, P<0.001);“parental concern” was affected by children’s anxiety (β=0.078, P=0.041), and caregiver’s anxiety (β=0.990,P=0.041) and “strength” (β=0.019, P=0.044); “parental difficulty in disease management” was associated with “psychological resilience” (β=-0.098, P=0.004) and “tenacity” (β=-0.892, P<0.001); “parents’ energy expenditure on disease” was affected by “optimism” (β=0.874, P<0.001); the “parents’ mutual support” was affected by“depression” (β=-0.145, P<0.001), “strength” (β=0.088, P<0.001) and “optimism” (β=1.155, P<0.001).Conclusion: The psychological status of SCI children and their primary caregivers was a vital factor affecting family management of the illness. 2021 Vol. 51 (9): 735-740 [Abstract] ( 541 ) HTML (1 KB)  PDF (1351 KB)  ( 988 ) 741 Construction of the nomogram model for predicting platelet transfusion refractoriness SU Gaofan,CHEN Jingsi, ZHENG Tingting, JIN Fangsi, JIANG Minghua DOI: 10.3969/j.issn.2095-9400.2021.09.009 Objective: To construct and validate a nomogram that can be used to predict platelet transfusion refractoriness in patients who received platelet transfusions. Methods: A total of 174 patients who received platelet transfusions were selected from the Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University from January 2019 to December 2019. Among 174 patients, 46 (26.4%) were platelet transfusion refractoriness. Pertinent clinical data were collected including patient age, gender, multiple pregnancies,active bleeding, skin and mucous membrane bleeding, splenomegaly, fever, ABO blood group, number of platelet transfusions, platelet antibody and platelet count. Multivariate logistic regression was used to screen independent factors and to construct the nomogram. Results: Multivariate logistic regression indicated that female (OR=2.43,95%CI=1.08-5.44, P=0.0310), platelet antibody (OR=4.46, 95%CI=1.11-17.85, P=0.035), infection (OR=2.42,95%CI=1.03-5.71, P=0.042), splenomegaly (OR=2.14, 95%CI=1.01-5.92, P=0.045), infusion times (OR=4.90,95%CI=2.10-11.42, P=0.002) were associated with higher odds of platelet transfusion refractoriness. Afterwards,the above variables were incorporated into the nomogram. Bootstrap test (Bootstrap resampling times=500),used for internal validation, revealed that the AUC was 0.858. Conclusion: The constructed nomogram could potentially predict platelet transfusion refractoriness in patients who received platelet transfusion. 2021 Vol. 51 (9): 741-745 [Abstract] ( 693 ) HTML (1 KB)  PDF (1381 KB)  ( 659 ) 746 The protective effect of pterostilbene on rat diaphragm during sepsis via PI3K-Akt pathway ZENG Haiping, WU Dongfang, HU Yunshuang DOI: 10.3969/j.issn.2095-9400.2021.09.010 Objective: To explore the protective effect of pterostilbene (PTS) on sepsis-induced diaphragm injury and its possible mechanism in a rat model. Methods: Sepsis model was induced by cecal ligation and puncture (CLP) in rats. The rats, randomly divided into three groups: sham group, CLP group and PTS groups(25 mg/kg), were killed after CLP for 24 h. Diaphragm tissues were collected for pathological analysis and diaphragm Damage Score (DDS) detection. The apoptosis of diaphragm tissues was evaluated using TUNEL assay. The content of IL-1β, TNF-α, IL-6, AST, LDH, CK and MPO in diaphragm specimen was measured by ELISA assay. Western blot was used to explore the level of p-Akt and p-PI3K in diaphragm tissues. Results:Compared with sham group, the DDS score, apoptotic rate and the content of IL-1β, TNF-α, IL-6, AST, LDH, CK and MPO in CLP group were all promoted markedly. The level of p-Akt and p-PI3K was reduced during sepsis.However, the DDS score, apoptotic rate and the content of IL-1β, TNF-α, IL-6, AST, LDH, CK and MPO in CLP group were all markedly decreased by the administration of PTS, while the expression of p-Akt and p-PI3K was both increased after PTS treatment. Conclusion: PTS plays a protective role in diaphragm via PI3K/Akt pathway in a CLP-induced sepsis rat model, which provides a candidate for drug therapy of sepsis-induced diaphragm injury. 2021 Vol. 51 (9): 746-750,754 [Abstract] ( 502 ) HTML (1 KB)  PDF (1690 KB)  ( 869 ) 751 A clinical analysis of cervical cancer associated with pregnancy YANG Simeng, ZHOU Kai DOI: 10.3969/j.issn.2095-9400.2021.09.011 Objective: To analyze the clinical manifestations, diagnosis, treatment strategies and prognosis of cervical cancer associated with pregnancy. Methods: The clinicopathological data of patients with cervical cancer associated with pregnancy, who were admitted to the First Affiliated Hospital of Wenzhou Medical University from April 2018 to June 2020, were collected and retrospectively analyzed. Results: The patients ranged in age from 30 to 35 averaged 31 years old. Among them, 4 cases were diagnosed during pregnancy, 1 case in the early pregnancy, 2 cases in the second trimester, 1 case in the third trimester and 1 case in postpartum.The most common clinical manifestation was irregular vaginal bleeding. According to FIGO 2018 staging,there was 1 case of stage IA2, 1 case of stage IB2, and 3 cases of stage IB3. Pathological type: 4 squamous cell carcinoma cases and one adenocarcinoma case. One patient received radical hysterectomy in early pregnancy,and the other 3 patients received radical hysterectomy in cesarean section at the same time. Among them, 2 patients received neoadjuvant chemotherapy (NACT) to extend the gestational age, and the gestational age at delivery was (33.0±1.5) weeks. One patient was postpartum and underwent radical trachelectomy. Three cases received chemoradiotherapy and 2 cases did postoperative chemotherapy. All 4 newborns were healthy and alive.Conclusion: The vaginal irregular bleeding during pregnancy needs timely gynecological examination to exclude cervical cancer. Cervical cancer associated with pregnancy should be combined with FIGO stage, gestational age and the patient’s fertility desire, combined with radiotherapy and chemotherapy department as well as neonatal department for multidisciplinary discussions in order to develop individualized treatment plan. Appropriate application of neoadjuvant chemotherapy is recommended to prolong gestational age, control tumor progression and improve fetal survival rate. 2021 Vol. 51 (9): 751-754 [Abstract] ( 539 ) HTML (1 KB)  PDF (1331 KB)  ( 664 ) 755 Autophagy of placental cells in the pathogenesis of preeclampsia rats and the interventional effect of baicalin XU Qiulian, WANG Jianfang, XU Heng, NIU Yanxin, DAI Xiwang DOI: 10.3969/j.issn.2095-9400.2021.09.012 Objective: To discover the role of autophagy of placental cells in the occurrence and development of rat preeclampsia and the interventional effect of baicalin on it. Methods: Totally 48 pregnant Wistar rats were randomly divided into four groups, with 12 in each. Rats in normal pregnancy group were administered with a subcutaneous injection of 1.5 mL normal sodium from Day 13 of pregnancy until Day 21. Rats in preeclampsia group were given a subcutaneous injection of Nitro L Arginine Methyl Ester at 100 mg/kg per day from Day 13 of pregnancy until Day 21. Rats in baicalin group and autophagy inhibition group were treated the same as in preeclampsia group but simultaneously given intraperitoneally injection with baicalin at 50 mg/kg and 3-methyladenine respectively at 15 mg/kg per day from Day 16 of pregnancy until Day 21. At pregnant day 21, the rat tail artery blood pressure and 24 h urine protein level were measured and Western blot was used to determine the expression level of Beclin1, LC3-II and P62 proteins in placental cells. Results: Compared with normal pregnancy group, the expression level of Beclin 1 and LC3-II proteins in placental cells of rats was significantly elevated in preeclampsia group (P<0.05), and tail arterial systolic and diastolic blood pressures and 24 h urine protein level were substantially raised (P<0.05), while expression level of P62 protein was markedly decreased (P<0.05);when compared with preeclampsia group, the expression level of Beclin 1 and LC3-II proteins in placental cells of rats were significantly declined in baicalin group and autophagy inhibition group (P<0.05), and tail arterial systolic and diastolic blood pressures and 24 h urine protein level were substantially decreased (P<0.05), while the expression level of P62 protein was markedly increased (P<0.05). Conclusion: Autophagy of placental cells may be implicated in the occurrence and development of rat preeclampsia, and intraperitoneal injection of baicalin can obviously depress autophagy of placental cells of preeclampsia rats, subsequently exerting its therapeutic effect on preeclampsia. 2021 Vol. 51 (9): 755-758 [Abstract] ( 546 ) HTML (1 KB)  PDF (1656 KB)  ( 660 ) 759 A comparison of predictive effect of two scales for the neonatal pressure injury on the neonatal intensive care unit LYU Junying, WU Yujie, XIA Fangqin, Ruan Shuqin, LU Ping DOI: 10.3969/j.issn.2095-9400.2021.09.013 Objective: To compare the neonatal skin risk assessment scale (NSRAS) and neonatal/infant Braden Q scale (N/I Braden-Q scale) in predicting the formation of pressure injury (PI) in the NICU. Methods:A continuous convenient sample of 106 infants were included from a hospital of Zhejiang Province. Scale score and skin examination were performed on the newborns every day. A self-made questionnaire was used for data collection and the occurrence of PI was taken as the end point of the outcome. Results: PI developed in 13 neonates(12.3%), which distributed at nose (8 cases), posterior occipital (3 cases), underlip (1 case) and sacrococcygeal (1 case). The scores of Cronbach’s coefficient of NSRAS on the day of admission, 24 h before PI occurred/interim hospitalization and the highest day ranged from 0.539, 0.557, 0.579, while the Cronbach’s coefficient scores of N/I Braden-Q scale ranged from 0.559, 0.568, 0.679. The area under the ROC curve of NSRAS ranged from 0.539 to 0.737, and that of N/I Braden-Q scale ranged from 0.725 to 0.875. Conclusion: N/I Braden-Q scale has higher predictive validity than NSRAS, and is more suitable for predicting PI formation in NICU neonates. 2021 Vol. 51 (9): 759-762 [Abstract] ( 525 ) HTML (1 KB)  PDF (1379 KB)  ( 743 )

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