Correlation between vaccination doses and duration of positive nucleic acid or antigen tests among COVID-19 patients / 中华全科医师杂志

Objective:To investigate the relationship between vaccination doses and the duration of positive nucleic acid or antigen tests in Corona Virus Disease 2019 (COVID-19) patients during omicron epidemic.Methods:A cross-sectional study was conducted from December 26 to December 31, 2022 among COVID-19 patients from all community health service centers in 16 districts of Beijing municipality selected by multi-stage stratified cluster quota sampling method. A questionnaire was used to collect the basic information, vaccination doses, results of nucleic acid or antigen tests of all subjects. The subjects were divided into 5 groups according to the doses of COVID-19 vaccination: the non-vaccination group, the 1, 2, 3 and 4 doses vaccination group. The relationship between vaccination doses and the duration of positive nucleic acid or antigen tests was analyzed by univariate and multivariate logistic regression models.Results:A total of 10 506 COVID-19 cases were included in the study with the age of (43.3±13.7) years. The duration of positive nucleic acid or antigen tests was longer than 7 days in 59.4%(276/465), 51.5%(67/130), 50.6%(355/701), 46.1% (3 464/7 520) and 39.2%(662/1 690) of non-vaccination, and 1, 2, 3, 4 dose vaccination groups, respectively ( P<0.001). Multivariate logistic regression analysis showed that compared with non-vaccination patients, the vaccination dose was an independent protective factor for duration of positive nucleic acid or antigen tests>7 days, and the OR values were 0.7 (95% CI 0.5-0.9, P=0.015), 0.6 (95% CI 0.5-0.8, P<0.001) and 0.5 (95% CI 0.4-0.6, P<0.001) for 2, 3 and 4 doses of vaccination, respectively. Conclusion:The vaccination doses are independently related to the duration of positive nucleic acid or antigen tests in COVID-19 patients and the risk is gradually decreases with the increasing vaccination doses.

Rapamycin enhances the anti-tumor activity of cabozantinib in cMet inhibitor-resistant hepatocellular carcinoma / 医学前沿

Cabozantinib, mainly targeting cMet and vascular endothelial growth factor receptor 2, is the second-line treatment for patients with advanced hepatocellular carcinoma (HCC). However, the lower response rate and resistance limit its enduring clinical benefit. In this study, we found that cMet-low HCC cells showed primary resistance to cMet inhibitors, and the combination of cabozantinib and mammalian target of rapamycin (mTOR) inhibitor, rapamycin, exhibited a synergistic inhibitory effect on the in vitro cell proliferation and in vivo tumor growth of these cells. Mechanically, the combination of rapamycin with cabozantinib resulted in the remarkable inhibition of AKT, extracellular signal-regulated protein kinases, mTOR, and common downstream signal molecules of receptor tyrosine kinases; decreased cyclin D1 expression; and induced cell cycle arrest. Meanwhile, rapamycin enhanced the inhibitory effects of cabozantinib on the migration and tubule formation of human umbilical vascular endothelial cells and human growth factor-induced invasion of cMet inhibitor-resistant HCC cells under hypoxia condition. These effects were further validated in xenograft models. In conclusion, our findings uncover a potential combination therapy of cabozantinib and rapamycin to combat cabozantinib-resistant HCC.

Imaging anatomical features of donor liver blood vessels in laparoscopic left lateral donor liver acquisition and clinical significance / 中华消化外科杂志

Objective:To investigate the imaging anatomical features of donor liver blood vessels in laparoscopic left lateral donor liver acquisition and their clinical significance.Methods:The retrospective and descriptive study was conducted. The clinical data of 39 living donor liver transplantation (LDLT) donors who were admitted to Huashan Hospital Affiliated to Fudan University between October 2016 and December 2018 were collected. There were 10 males and 29 females, aged (31±7)years. The clinical data of 39 LDLT recipients were collected. There were 26 males and 13 females, aged 8 months (range, 4-68 months). Abdominal enhanced computed tomography and three-dimensional vascular reconstruction were performed on donors to evaluate the anatomical characteristics of hepatic vessels. All the donors underwent laparoscopic left lateral donor liver acquisition. Observation indicators: (1) three-dimensional vascular reconstruction of preoperative imaging; (2) surgical conditions; (3) follow-up. Follow-up was performed using outpatient examination to detect complications of recipients after LDLT up to October 2019. Measurement data with normal distribution were expressed as Mean± SD, and comparison between groups was analyzed by the t test. Measurement data with skewed distribution were represented as M (range). Count data were expressed as absolute numbers or percentages. Results:(1) Three-dimensional vascular reconstruction of preoperative imaging: the anatomical characteristics of hepatic artery and hepatic vein revealed by three-dimensional vascular reconstruction of preoperative imaging of 39 donors included ① middle hepatic artery was present in 11 donors, among which 5 started from the right hepatic artery, 3 from the confluence of the right and left hepatic artery, and 3 from the left hepatic artery. Two donors had anatomical variation in the left hepatic artery which was presentation of left accessory hepatic artery originated from the left gastric artery. The other 26 donors had no middle hepatic artery or anatomical variation in the left hepatic artery. ② The left hepatic vein and the middle hepatic vein of 9 donors were respectively drained into the inferior vena cava. Seven donors had the left upper branch of the left hepatic vein, and 23 donors had a joint trunk of the left hepatic vein and the middle hepatic vein which drained into the inferior vena cava. (2) Surgical conditions: ① all the 39 donors successfully underwent laparoscopic left lateral donor liver acquisition. The operation time and volume of intraoperative blood loss were (160±32)minutes and (142±74)mL. ② Of 11 donors with middle hepatic artery, left hepatic artery was the dominant artery in 8 donors and was used for hepatic artery anastomosis and reconstruction in liver transplantation, middle hepatic artery started from left hepatic artery in 3 donors and the joint trunk of left and middle hepatic artery was used for hepatic artery anastomosis and reconstruction in liver transplantation. Of 2 donors with anatomical variation in the left hepatic artery, one had left accessory hepatic artery as the dominant artery and the other had left hepatic artery as the dominant artery. Left accessory hepatic artery and left hepatic artery were respectively used for hepatic artery anastomosis and reconstruction in liver transplantation. The other 26 donors had left hepatic artery for hepatic artery anastomosis and reconstruction in liver transplantation. ③ Among the 39 donors, 11 received intraoperative left hepatic vein preferred approach and 28 received intraoperative non-left hepatic vein preferred approach. The operation time and volume of intraoperative blood loss of donors with left hepatic vein preferred approach were (147±22)minutes and (110±44)mL, respectively, versus (169±33)minutes and (154±81)mL of donors with non-left hepatic vein preferred approach, showing significant differences in the above indicators between the two groups ( t=4.19, 2.81, P<0.05). (3) Follow-up: 39 donors were followed up for 10 months. During the follow-up, there was no hepatic artery anastomotic bleeding, stenosis, ischemic bile duct injury and biliary stenosis caused by poor hepatic arterial blood supply, or any complications related to hepatic venous outflow tract stenosis. Conclusions:Three-dimensional vascular reconstruction before laparoscopic left lateral donor liver acquisition can reveal the anatomical variation of middle hepatic artery and left hepatic artery, which can guide the selection of surgical approach. The left hepatic vein preferred approach is recommended for the qualified donor in the laparoscopic left lateral donor liver acquisition, which can shorten the operation time and reduce the volume of intraoperative blood loss.

Effect and mechanism of liver X receptor agonist T0901317 on angiogenesis phenotype of liver cancer / 中华消化外科杂志

Objective To explore the effect and mechanism of liver X receptor agonist T0901317 on angiogenesis phenotype of liver cancer.Methods The experimental study was conducted.Hepatocellular carcinoma MHCC97-H and Huh7 cells and human umbilical vein endothelial cells (HUVEC) were cultured in vitro.Each cell line was divided into 3 groups:control group (non-treated),low concentration group (treated using 1 μmot/L T0901317) and high concentration group (treated using 3 μmol/L T0901317).Cell proliferation was counted with a CCK-8 assay.Quantitative real-time polymerase chain reaction (PCR) was applied to confirm the relative mRNA expression of fatty acid synthetase (FAS) of liver X receptor target genes in 3 groups.Subcutaneous xenograft tumor volume and body mass were measured in MHCC97-H nude mice model.Then mice were sacrificed and tumor tissues were analyzed for CD31 relative expression by immunohistochemistry (IHC) staining.Migration and vessel angiogenesis of HUVEC were determined by Transwell method.Observation indicators:(1) effects of T0901317 on MHCC97-H,Huh7 and HUVEC cells proliferation,(2) effects of T0901317 on liver X receptor with MHCC97-H,Huh7 and HUVEC cells,(3) effects of T0901317 on subcutaneous xenograft tumor growth in MHCC97-H nude mice model,(4) effects of T0901317 on CD31 relative expression in subcutaneous xenograft tumor tissues of MHCC97-H nude mice model,(5) effects of T0901317 on migration of HUVEC,(6) effects of T0901317 on vessel angiogenesis of HUVEC.Measurement data with normal distribution were represented as x±s,and comparisons between groups were analyzed by the t test.Results (1)Effects of T0901317 on MHCC97-H,Huh7 and HUVEC cells proliferation:results of CCK-8 assay showed that percentage of living cells was respectively 100.0％± 1.7％,101.0％±0.7％ and 104.6％± 1.9％ in MHCC97-H control,low concentration and high concentration groups,with no statistically significant difference (F =2.632,P＞0.05).Percentage of living cells was respectively 100.0％ ± 2.7％,97.6％ ± 2.4％ and 103.7％ ± 2.8％ in Huh7 control,low concentration and high concentration groups,with no statistically significant difference (F =1.404,P＞0.05).Percentage of living cells was respectively 100.0％ ±0.7％,100.7％± 1.2％ and 101.3％ ±0.8％ in HUVEC control,low concentration and high concentration groups,with no statistically significant difference (F=0.471,P＞0.05).(2) Effects of T0901317 on liver X receptor with MHCC97-H,Huh7 and HUVEC cells:results of quantitative real-time PCR showed that relative mRNA expressions of FAS in MHCC97-H control,low concentration and high concentration groups were respectively 100.0 ％±2.2％,658.5％±7.7％ and 1 241.0％± 106.8％,with a statistically significant difference among groups (F=46.227,P＜0.05),and with a statistically significant difference between MHCC97-H control group and MHCC97-H low concentration and high concentration groups (t =70.025,8.274,P ＜ 0.05) and between MHCC97-H low concentration and high concentration groups (t =4.222,P ＜ 0.05).Relative mRNA expressions of FAS in Huh7 control,low concentration and high concentration groups were respectively 100.0％ ± 15.8％,1 225.0％ ± 26.7 ％ and 2 015.0％ ± 215.1％,with a statistically significant difference among groups (F =49.402,P＜ 0.05),and with a statistically significant difference between Huh7 control group and Huh7 low concentration and high concentration groups (t=39.460,8.879,P＜0.05) and between Huh7 low concentration and high concentration groups (t =2.836,P ＜ 0.05).Relative mRNA expressions of FAS in HUVEC control,low concentration and high concentration groups were respectively 100.0％ ± 19.6％,790.8％ ± 116.5％ and 1 756.0％ ± 55.0％,with a statistically significant difference among groups (F=185.395,P＜0.05),and with a statistically significant difference between HUVEC control group and HUVEC low concentration and high concentration groups (t =7.639,34.375,P＜0.05) and between HUVEC low concentration and high concentration groups (t =7.488,P＜0.05).(3) Effects of T0901317 on subcutaneous xenograft tumor growth in MHCC97-H nude mice model:results of assay showed that subcutaneous xenograft tumor volume in MHCC97-H control group and MHCC97-H T0901317 group were respectively (935±72)mm3 and (552 ± 47)mm3,with a statistically significant difference between groups (t=4.449,P＜0.05).Body masses of nude mice model in MHCC97-H control group and MHCC97-H T0901317 group were respectively (23.8±0.8) g and (21.7± 1.7) g,with no statistically significant difference between groups (t =1.059,P＞0.05).(4) Effects of T0901317 on CD31 relative expression in subcutaneous xenograft tumor tissues of MHCC97-H nude mice model:results of IHC staining showed that CD31 relative expression in subcutaneous xenograft tumor tissues of MHCC97-H nude mice model was 100％±11％ and 35％±7％ in MHCC97-H control group and MHCC97-H T0901317 group,with a statistically significant difference between groups (t =4.919,P＜0.05).(5) Effects of T0901317 on migration of HUVEC:results of Transwell method showed that percentages of membrane cells in HUVEC control,low concentration and high concentration groups were respectively 100.0％±4.0％,57.3％±1.5％ and 32.7％± 1.7％,with a statistically significant difference among groups (F=163.944,P＜0.05),and with statistically significant differences between HUVEC control group and HUVEC low concentration and high concentration groups (t =9.998,15.434,P＜0.05) and between HUVEC low concentration and high concentration groups (t =10.801,P ＜ 0.05).(6) Effects of T0901317 on vessel angiogenesis of HUVEC:results of vessel angiogenesis assay showed that length of vessel angiogenesis in HUVEC control,low concentration and high concentration groups were respectively 100.0％±3.4％,68.4％ ±3.5％ and 44.7％± 0.5％,with a statistically significant difference among groups (F =38.964,P ＜ 0.05),and with statistically significant differences between HUVEC control group and HUVEC low concentration and high concentration groups (t=6.268,9.831,P＜0.05) and between HUVEC low concentration and high concentration groups (t =3.460,P＜0.05).Conclusion Liver X receptor agonist T0901317 can inhibit vessel angiogenesis of liver cancer.

Influence of combination anesthesia of propofol and midazolam to stress in radical resection of colon cancer / 中国基层医药

Objective To explore the influence of combination anaesthesia application of midazolam and propofol on stress reactions in radical resection of colon cancer,and to explore novel clinical compatibility of anaesthesia drugs.Methods 40 patients received radical resection of colon cancer were selected and divided into control group and combination group randomly and evenly.Control group received general anesthesia by propofol,while combination group received additional midazolam when anesthesia induction was taken.Glycemia,CRP,complement C3 and cortisol were observed and compared at T1 (before anesthesia induction),T2 (4h after beginning of surgery) and T3 (24h after surgery).Results Compared with T1,glu increased significantly at T2 and T3 (all P ＜ 0.05) ; Compared with combination group,glycemia increased more significant in control group (P ＜ 0.05) ; CRP and cortisol increased significantly in all patients compared with T1 (P ＜ 0.05),more significant in control group (P ＜ 0.05) ; a significant decrease after increase trend was identified for complement C3 (P ＜ 0.05),more significant decrease was found in control group at T2 (P ＜ 0.05).Conclusion Combination anesthesia of propofol and midazolam could decrease the strength of stress reaction in radical resection of colon cancer.

Effects of Jianpi Bushen Huoxue recipe on hematopoietic cell apoptosis in a mouse model of aplastic anemia / 中西医结合学报

OBJECTIVE: Adopting methods of cell culture to explore the effects and mechanisms of Jianpi Bushen Huoxue Prescription (JPBSHXP), a traditional Chinese compound herbal medicine for strengthening spleen, reinforcing kidney and activating blood circulation, in inhibiting hematopoietic cells apoptosis in a mouse model of aplastic anemia (AA). METHODS: Blood serum of AA mice was made from an AA mouse model. Blood serums containing different traditional Chinese compound herbal medicine were made from rats after intragastric administration of JPBSHXP and its related decoctions, respectively. Bone marrow cells of normal mice were incubated by these blood serums for 24 hours, respectively. The apoptosis of the bone marrow cells were assayed by flow cytometry and transmission electron microscopy (TEM). RESULTS: It was indicated that the bone marrow cells of normal mice incubated with blood serum of AA mice displayed typical apoptosis. The apoptosis rates of bone marrow cells of the AA mice incubated by blood serum containing different traditional Chinese herbal medicine were decreased. The effect of Bushen (reinforcing kidey) Recipe was better than Jianpi (strengthening spleen) Recipe and Huoxue (activating blood circulation) Recipe, while the effect of JPBSHXP was the best. TEM results showed that the effect of Bushen Recipe was better than that of the Jianpi Recipe and the Huoxue Recipe, while the effect of JPBSHXP was the best. CONCLUSION: JPBSHXP and its related decoctions can significantly decrease the apoptosis rate of bone marrow mononuclear cells of the AA mice. It is inferred that JPBSHXP can promote bone marrow hematogenesis.

Antigen-antibody reaction model of solid-phase surface and active biochip system / 生物医学工程学杂志

To overcome the present limitations of passive biochip, based on the basic principle of antigen-antibody reaction, we develop an antigen-antibody reaction model of solid-phase surface and design a novel active biochip system according to this model, which introduces the negative pressure and controlling devices to control the immunoreactions on the nitrocellulose (NC) membrane. From the computer simulation results, this is a rapid, stable, robust and practicable system, which can be used to increase the efficiency of immunoreactions and improve the reproducibility and accuracy of biochip analysis.

Clinical study on idiopathic thrombocytopenic purpura treated with Shengxueling Granule / 中西医结合学报

OBJECTIVE: To observe the clinical effect of Shengxueling Granule (SXLG) in treating idiopathic thrombocytopenic purpura (ITP), and to study its possible mechanism. METHODS: Eighty-six cases of ITP were divided into two groups randomly. Fifty-six cases in the treatment group were treated with SXLG, a traditional Chinese medicine, and 30 cases administered with Western medicine (prednisone) were taken as control. Patients in each group took drugs for three months and were under follow-up observation. RESULTS: In SXLG-treated group, the total effective rate in 3 months was 85.71%, similar to 83.33% in prednisone-treated group (P>0.05), while the total effective rate in 6 months in the SXLG-treated group was 91.07%, higher than 53.33% of the prednisone-treated group (P<0.01), and no obvious side-effects were observed. The patients' bleeding was alleviated or stopped, and their general condition was improved. And the blood platelet count (BPC) was increased, the platelet associated immunoglobulin (PAIg) and interleukin-4 (IL-4) were markedly dropped, the level of natural killer cells activity (NKCA) increased, and the rate of T lymphocyte subsets gradually returned to normal level. Megakaryocytes tended toward maturation on bone marrow smear after SXLG treatment. All differences above were statistically significant. CONCLUSION: SXLG is an effective and safe medicine for ITP. It can regulate the cellular immunity, inhibit the platelet antibody to reduce the destruction of the platelet and to increase the number of platelet, promote the differentiation and maturation of megakaryocyte, facilitate the production and release of platelet, lower the fragility of capillary, and prevent the hemorrhagic tendency.