Objective:To investigate the efficacy and safety of programmed death-1 (PD1) inhibitor combined with transcatheter arterial chemoembolization (TACE) in the treatment of huge primary liver cancer.Methods:From June 2016 to December 2019, the clinical data of 31 patients with huge primary liver cancer enrolled in the Central Hospital of Lishui were retrospectively collected and analyzed. The tumor size ranged from 10.1 to 18.8 cm, with an average of (14.2±2.3) cm. The patients were divided into TACE group (TACE treatment, 18 cases) and combined group (one week after TACE, patients receiving a dose of 200 mg PD1 inhibitor administration every 21 days, 13 cases), according to whether patients receiving PD1 inhibitors. The patients were followed up. The disease control rate (DCR) were compared between the two groups using Mann-Whitney U test. The median overall survival (OS) and progression free survival (PFS) were calculated by Kaplan-Meier method. Results:The DCR in combined group (53.8%, 7/13) was higher than that in TACE group (22.2%, 4/18), and the difference was statistically significant ( Z=-2.13, P=0.04). The median PFS (5.0 months) in combined group was longer than that in TACE group (3.0 months), the difference was statistically significant (χ2=4.39, P=0.04). The median OS (15 months) in combined group was longer than that in control group (9 months), and the difference was statistically significant (χ2=5.51, P=0.02). Conclusion:The combine PD1 inhibitors with TACE is an effective and safe therapy for huge primary liver cancer.

Objective:To discuss the effective of artesunate in the treatment of coronavirus disease 2019 (COVID-19).Methods:Using prospective method, the 43 cases of confirmed COVID-19 patients in Nanning Fourth People's Hospital from January 22nd to February 15th in 2020 were enrolled and divided into routine treatment group ( n = 25) and artesunate treatment group ( n = 18) by odd-even rule after admission. According to the guidelines, the routine treatment group was recommended to receive lopinavir/ritonavir 500 mg + α-aerosolized interferon 500×10 4 U, twice daily; the artesunate treatment group was given artesunate 60 mg, twice daily besides the routine treatment, for 10 days in both groups. During the treatment period, the pharynx swab test of 2019 novel coronavirus (2019-nCoV) nucleic acid was carried out every 2 days, and the routine blood test, liver and kidney functions, blood coagulation function and myocardial enzymes were re-examined. Chest CT was checked every 3 days after the treatment, and re-examined every 5 days after the condition was improved. The routine blood test and biochemical results of two groups were observed, and the efficacy evaluation was performed by monitoring the time for significant improvement of symptoms, negative conversion time of throat swab virus nucleic acid, lung lesion absorption time, adverse drug reactions and the length of hospital stay of the two groups. Results:There were no significant differences between the two groups in terms of gender, age, body weight, routine blood test and biochemical results before treatment. In artesunate treatment group, the time for significant improvement of symptoms (days: 3.33±1.91 vs. 4.84±2.19), negative conversion time of 2019-nCoV nucleic acid (days: 4.72±2.16 vs. 6.68±3.76), lung lesion absorption starting time (days: 5.39±2.36 vs. 7.48±3.78), lung lesion absorption greater than 70% time (days: 14.11±4.16 vs. 17.04±4.42) and the length of hospital stay (days: 16.56±3.71 vs. 18.04±3.97) were significantly shorter than those in routine treatment group, with significant differences (all P < 0.05). The incidence of adverse drug reactions in two groups had no significant difference (72.2% vs. 80.0%, P > 0.05). Conclusion:Artesunate can shorten the treatment time of COVID-19, improve prognosis and eliminate pathogens, with fewer adverse reactions and a good application prospect.

Objective:To investigate the efficacy and safety of short-term transcatheter arterial chemoembolization （TACE）-radiofrequency ablation （RFA） sequential therapy for advanced hepatocellular carcinoma (HCC).Methods:The clinical data of 117 patients with advanced HCC enrolled in the Central Hospital of Lishui from March 2010 to January 2019 were retrospectively analyzed. All patients received TACE and RFA sequential therapy. The patients were divided into 2 groups including short interval group (interval≤7 d, 61 cases) and long interval group (interval>7 d, 56 cases) according to interval between TACE and RFA. The difference of response rate was analyzed by Wilcoxon test. Kaplan-Meier survival curve was used to calculate the overall survival (OS) time and progression free survival (PFS) time.The risk factors of TACE-RFA sequential therapy were tested using Cox multivariate analysis. The complications in the two groups were compared using χ 2 test. Results:The response rate in the short interval group (72.1%, 43/61) was significantly higher than that in the long interval group (41.1%，23/56) with significant difference ( Z=-2.50, P=0.01). The median PFS in the short interval group (14.9 months) was longer than that in the long interval group (9.1 months). The difference of PFS survival curve between the 2 groups was statistically significant (χ2 =5.90, P=0.01).The median OS in the short interval group (34.7 months) was longer than that in the long interval group (20.3 months). The difference of OS survival curve between the 2 groups was statistically significant (χ2 =6.60, P=0.01). Cox multivariate analysis showed that tumor size [hazard ratio (HR)=2.42, P<0.01], cirrhosis (HR=2.04, P<0.01), interval (HR=0.44, P<0.01), aspartate aminotransferase (HR=1.71, P=0.03) were the independent risk factors for advanced HCC.There were no significant differences in the complication incidence between the 2 groups ( P>0.05). Conclusion:Short-term interval TACE-RFA sequential therapy as a protective factor is efficient and safe for advanced HCC treatment.

Objective To observe the feasibility in neurosurgical brain tumor resection using ultrasound fusion navigation technology . Methods Thirty patients undergoing brain tumor rescetion accepted fusion ultrasound ( US ) navigation with magnetic renounce/computed tomography ( MR/CT ) technique and cognitive fusion" by neurosurgeon based on the tumor′s localization of magnetic renounce imaging (MRI) separately to definite the position and size of the craniotomy window flaps . After removal cranial bone ,conventional B-mode ultrasound scanning was used to detect lesion firstly . Then ,fusion US/MR navigation was applied again after automatically registration;the images of tumors from B-mode ultrasound and contrast-enhanced ultrasound separately were compared to those from coplanar reconstructive MR/CT in a real time . Results Fusion US/MR navigation was useful to define the position and size of the craniotomy window flaps ,and tumors in all patients were fully exposed to the microscope field of view . In all of 30 cases ,26 cases of fusion imaging of volume navigation technology were successfully registrated . The tumors in 3 cases of glioma ( WHO Ⅰ - Ⅱ grade) and 1 patient with pathologically verified inflammatory couldn′t be localized by conventional B-mode ultrasound but could be accurately localized after fusion ( US/MR) imaging navigation . Compared to contrast-enhanced MR ,high-grade glioma with contrast-enhanced ultrasound (CEUS) showed enhancement in arterial phase and clear tumor boundary rapidly . The enhanced modality with CEUS and MR was functioned equal . Low-grade glioma with CEUS showed scattered point or linear enhancement in arterial phase and the tumor′s margin was blurred . The preoperative T1-weighted enhanced MRI demonstrated no enhancement in the low-grade glioma . Conclusions Fusion ultrasound navigation can be used to definite size of bone flap before craniotomy . It is more suitable for fusion with preoperative T 2 Flair phase to localize low grade glioma . High-grade glioma is suitable to preoperative T 1 weighted enhanced phase for discerning margin of tumor .

Objective To explore the advantages and disadvantages of ultrasound guided puncture microwave ablation and traditional surgical treatment of nodular goiter.Methods From January 2014 to June 2015,102 cases of nodular goiter who were treated in the Traditional Chinese Medicine Hospital of Gaozhou Affiliated to Guangzhou University of Traditional Chinese Medicine were randomly divided into two groups,51 cases in each group.Respectively by ultrasound guided puncture nodules of thyroid swollen microwave ablation (microwave ablation group) and traditional operation type removed most of the thyroid nodules (traditional surgery group) in the treatment of containing.The amount of bleeding,operation time,hospital stay,medical cost,clinical efficacy,postoperative complications and the degree of pain,and thyroid function were compared between the two groups.Results The amount of bleeding,operation time and length of hospital stay in the microwave ablation group were better than those in the traditional operation group((2.02±0.79) ml vs.(28.24±18.49) ml,(34.20 ±9.60) min vs.(75.59±25.41) min,(3.55± 1.05) d vs.(10.27±2.68) d),the medical cost of the microwave ablation group was higher than that of the traditional operation group((14 341±593) yuan vs.(5 812±970) yuan),the differences were statistically significant (t =-10.12,-10.88,-16.68,53.54;P ＜0.01).There were significant difference in terms of the postoperative pain and complications between the groups (x2=50.86,13.22;P＜0.01).The total absorption rate was 100％ in 18 months after the ablation of the nodule.There was no significant difference about postoperative residual small nodules between the two groups(P ＞0.05).Conclusion Compared with the traditional treatment,the microwave ablation treatment of nodular goiter with less complications,is a new technique of minimally invasive,beauty,safe and feasible,the exact clinical effect,and worthy of popularization and application.

OBJECTIVETo investigate the dynamic features of angiogenesis in residual tumors after high intensity focused ultrasound (HIFU),and to determine the temporal effect and mechanism of hypoxia inducible factor-2 alpha (HIF-2a) in the angiogenic process of residual tumors.

METHODSXenograft tumors of HepG2 cells were generated by subcutaneously inoculating athymic BALB/c nu/nu mice with the hepatoma cells.About 30 days after inoculation,all mice (except in the control group) were treated by HIFU and assigned randomly to the following 7 groups according to various time intervals post-treatment:1st,3rd,5th day and 1st,2nd,3rd,4th week when the residual tumor tissues were obtained from the experimental groups.Protein levels of HIF-2a and vascular growth factor A (VEGF-A) were quantified by immunohistochemistry and western blotting,and mRNA levels were measured by (real-time quantitative) qPCR. Microvascular density (MVD) was calculated by counting the CD31-positive vascular endothelial cells identified by means of an immunohistochemical staining method.

RESULTSCompared with results from the control group,the protein and mRNA levels of HIF-2a expression reached the highest level in the experimental mice at the 2nd week (P=0.000 and P < 0.01 respectively),and were decreased thereafter(3rd week and 4th week, P=0.000 and P < 0.05).VEGF-A expression in the residual tumor tissues group that received HIFU was significantly decreased,compared with the control group,at all time points uPto 1 week (all P=0.000 and P < 0.01),but the levels increased compared to controls in the 2nd through 4th week (all P=0.000, P < 0.05). Similar results were obtained for MVD.

CONCLUSIONHIFU treatment can inhibit angiogenesis in residual hepatoma tissues in the short-term (1 to 2 weeks post-treatment) in mice with hepatocellular carcinoma,but can promote angiogenesis overtime (2 to 4 weeks post-treatment); the angiogenic process may involve the HIF-2α/VEGFA pathway.

Animals ; Blotting, Western ; Carcinoma, Hepatocellular ; pathology ; Hep G2 Cells ; High-Intensity Focused Ultrasound Ablation ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Immunohistochemistry ; Liver Neoplasms ; pathology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Neovascularization, Pathologic ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVETo study the changes in hypoxia-inducible factor (HIF1α, HIF2α) in the residual tumor cells in nude mice bearing hepatocellular carcinoma (HCC) following treatment with high-intensity focused ultrasound (HIFU).

METHODSThirty nude mice bearing human HCC received treatment with HIFU. At 1, 3, and 5 days and 1 and 2 weeks after the treatment, the mice were examined for pathological changes of the residual tumor with HE staining; SP immunohistochemistry, Western blotting and real-time quantitative PCR were used to detect the protein and mRNA expressions of HIF1α and HIF2α in the tumor.

RESULTSHE staining revealed the presence of residual tumor cells and large necrotic areas after the treatment. Immunohistochemistry showed a gradual increment of HIF1α protein and mRNA expressions after the treatment, reaching the peak level at 3 days (P<0.05) followed by progressive reduction at 5 days and 1 and 2 weeks. HIF2α expressions at either the protein or mRNA levels exhibited no significant changes within 3 days after the treatment (P>0.05) but increased significantly at 5 days and 1 and 2 weeks (P<0.05).

CONCLUSIONThe changes of HIF1α and HIF2α in the residual tumor after HIFU treatment in nude mice bearing HCC can be associated with tumor cell apoptosis and angiogenesis after the treatment.

Animals ; Carcinoma, Hepatocellular ; metabolism ; pathology ; therapy ; Hep G2 Cells ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Liver Neoplasms ; metabolism ; pathology ; therapy ; Mice ; Neoplasm, Residual ; metabolism ; pathology ; Ultrasonic Therapy ; methods

Objective To study the changes in hypoxia-inducible factor (HIF1α, HIF2α) in the residual tumor cells in nude mice bearing hepatocellular carcinoma (HCC) following treatment with high-intensity focused ultrasound (HIFU). Methods Thirty nude mice bearing human HCC received treatment with HIFU. At 1, 3, and 5 days and 1 and 2 weeks after the treatment, the mice were examined for pathological changes of the residual tumor with HE staining; SP immunohistochemistry, Western blotting and real-time quantitative PCR were used to detect the protein and mRNA expressions of HIF1α and HIF2α in the tumor. Results HE staining revealed the presence of residual tumor cells and large necrotic areas after the treatment. Immunohistochemistry showed a gradual increment of HIF1αprotein and mRNA expressions after the treatment, reaching the peak level at 3 days (P<0.05) followed by progressive reduction at 5 days and 1 and 2 weeks. HIF2αexpressions at either the protein or mRNA levels exhibited no significant changes within 3 days after the treatment (P>0.05) but increased significantly at 5 days and 1 and 2 weeks (P<0.05). Conclusion The changes of HIF1αand HIF2αin the residual tumor after HIFU treatment in nude mice bearing HCC can be associated with tumor cell apoptosis and angiogenesis after the treatment.

Objective To study the changes in hypoxia-inducible factor (HIF1α, HIF2α) in the residual tumor cells in nude mice bearing hepatocellular carcinoma (HCC) following treatment with high-intensity focused ultrasound (HIFU). Methods Thirty nude mice bearing human HCC received treatment with HIFU. At 1, 3, and 5 days and 1 and 2 weeks after the treatment, the mice were examined for pathological changes of the residual tumor with HE staining; SP immunohistochemistry, Western blotting and real-time quantitative PCR were used to detect the protein and mRNA expressions of HIF1α and HIF2α in the tumor. Results HE staining revealed the presence of residual tumor cells and large necrotic areas after the treatment. Immunohistochemistry showed a gradual increment of HIF1αprotein and mRNA expressions after the treatment, reaching the peak level at 3 days (P<0.05) followed by progressive reduction at 5 days and 1 and 2 weeks. HIF2αexpressions at either the protein or mRNA levels exhibited no significant changes within 3 days after the treatment (P>0.05) but increased significantly at 5 days and 1 and 2 weeks (P<0.05). Conclusion The changes of HIF1αand HIF2αin the residual tumor after HIFU treatment in nude mice bearing HCC can be associated with tumor cell apoptosis and angiogenesis after the treatment.

Objective To compare postoperative outcomes and complications between subtotal colectomy combined with modified Duhamel procedure and simple subtotal colectomy for severe functional constipation (SFC). Methods Between January 2006 and June 2010,40 SFC patients after strict but inefficient nonoperative treatments were randomized by number table method to control group (20 cases, receiving simple subtotal colectomy) and combined group (20 cases,receiving subtotal colectomy and modified Duhamel procedure). The selection criteria were normal colonoscopy,and abnormal dynamic proctography (DPG). The functional outcomes after surgery were assessed from 6 months to 2 years period. Results The preoperative clinical manifestations of the two groups were similar. No statistically significant difference was observed between the two groups for time for recovery of the bowel function,length of postoperative hospitalization.and the early postoperative complications (P > 0.05). Functional outcomes of combined group with CIQOL score [(110.5 ±5.0) scores],relieving of costive gastrointestinal symptoms [(79.0 ±6.5)%], recurrent constipation rate [10.0% (2/20)], satisfaction rate of defecation frequency [85.0%(17/20)], satisfaction rate of quality of life[90.0%(18/20)] were significantly better than those of control group[(90.5 ± 3.5) scores, (60.5 ± 2.8)% ,35.0%(7/20), 15.0%(3/20),20.0%(4/20)](P< 0.05). Conclusion Combined application of subtotal colectomy and modified Duhamel procedure for SFC has better outcomes.