[The efficacy and safety of computed tomography-guided percutaneous cryoablation for malignant liver tumors at high-risk sites].

Objective: To assess the efficacy and safety of computed tomography (CT)-guided percutaneous cryoablation in treating malignant liver tumors located explicitly at high-risk sites. Methods: Data were collected retrospectively from patients with malignant liver tumors undergoing percutaneous cryoablation at Tianjin Medical University Cancer Hospital between January 2018 and December 2021. In all, 46 patients with malignant liver tumors at non-high-risk sites were matched 1∶1 according to the maximum tumor diameter. Technical success rate, complete ablation rate, and complications at 12 and 24 months post-surgery were evaluated. A statistical analysis of the ablation effect difference between the high-risk site and non-high-risk site groups was conducted. Univariate and multivariate logistic regression analyses were performed to identify risk factors. Results: Both groups demonstrated a 100% intraoperative technical success rate, and no major complications related to cryoablation were observed. The complete ablation rate was 82.6% (38/46) and 71.7% (33/46) in the high-risk group and 84.8% (39/46) and 73.9% (34/46) in the non-high-risk group at 12 and 24 months, respectively. There was no significant difference in complete ablation rates between the two groups (P>0.05). Multivariate analysis identified the distance between the tumor edge and high-risk site ≤5 mm and preoperative trans-arterial chemoembolization (TACE) treatment as independent risk factors for cryoablation effect. Conclusion: CT-guided percutaneous cryoablation is a safe and effective approach for patients with malignant liver tumor at high-risk sites. Our results emphasize the importance of proper preoperative planning and intraoperative manipulation.

[Analysis of factors associated with severe bleeding after percutaneous nephrolithotomy and evaluation of interventional embolization efficacy in male patients].

Objective: To explore the factors associated with severe bleeding after percutaneous nephrolithotomy (PCNL) in male patients and evaluate the efficacy of interventional embolization. Methods: A retrospective case series study was conducted at Nankai Hospital of Tianjin, China, from January 2018 to October 2021. The clinical data of 230 male patients with upper urinary tract stones were analyzed. The observation indicators included age, hypertension, diabetes, renal function abnormalities, history of preoperative anticoagulant use, stone size, stone type, number of puncture channels, operation time and degree of hydronephrosis. To describe the clinical characteristics of bleeding after percutaneous nephrolithotomy in men, and analyze the factors associated with severe bleeding after PCNL. Single factor analysis was performed using the Chi-square (χ2) test, and multivariate analysis was performed using logistic regression analysis. Results: Univariate analysis showed that diabetes mellitus (χ2=4.90, P=0.027), abnormal renal function (χ2=18.32, P<0.001), history of preoperative oral anticoagulants (χ2=5.10, P=0.024), abnormal bleeding and coagulation function (χ2=8.22, P=0.004) and the number of puncture channels (χ2=22.08, P<0.001) were the related factors affecting bleeding after PCNL. Multivariate logistic regression analysis showed that diabetes mellitus (P=0.032), abnormal renal function (P<0.001), and the number of puncture channels (P<0.001) were the independent risk factors of bleeding after PCNL. Of the 28 patients with bleeding after PCNL, 25 were treated with interventional embolization, with a technical success rate of 100.0% and a clinical success rate of 89.3%. Conclusions: For patients with renal calculi and comorbid diabetes, renal function abnormalities, and multiple punctures, relevant preventive measures should be actively administered before PCNL to reduce the risk of postoperative bleeding. For patients with severe bleeding of the kidney after PCNL, TAE is a safe and effective minimally invasive treatment method.

[Chinese expert consensus on perioperative management of renal tumor cryoablation (2022 edition)].

In recent years, the incidence of renal cancer has been increasing continuously. Surgical resection is the "gold standard" for the treatment of small renal cancer. However, local ablation therapy of renal cancer is undoubtedly the best choice for patients with short life expectancy, other complications, and impaired renal function who are not suitable for surgery. In recent years, with the development of ablation techniques and long-term follow-up, local ablation has shown good therapeutic effects. As many domestic hospitals are performing or planning to perform renal tumor cryoablation to improve the clinical cure rate and surgical safety of renal tumor cryoablation, it is necessary to standardize the surgical indications, contraindications, perioperative management, efficacy evaluation, and other common problems. Currently, there is no expert consensus regarding perioperative renal tumor cryoablation in China. To standardize the perioperative management of renal tumor cryoablation and related technical operations in clinical practice, and improve the effectiveness and safety of cryoablation, the expert committee of Tumor Interventional and Minimally Invasive Diagnosis and Treatment Continuing Education Base of the Chinese Anti-Cancer Association convened experts in related fields to discuss and formulate this consensus, which is hereby published, for clinical reference and application.

[Prognostic factors of autologous hematopoietic stem cell transplantation in intermediate-risk acute myeloid leukemia patients with minimal residual disease negativity].

To explore prognostic factors in intermediate-risk acute myeloid leukemia (AML) patients with minimal residual disease (MRD) negativity (MRD<0.1%,MRD-)receiving autologous hematopoietic stem cell transplantation (auto-HSCT).A total of 59 intermediate-risk AML patients with MRD-were treated with auto-HSCT from January 2015 to September 2021 at Affiliated People's Hospital of Ningbo University. The clinical data and laboratory results were collected retrospectively. Efficacy, clinical outcome and prognostic factors were analyzed. Univariate analysis was conducted by using log-rank test, the multivariate analysis by Cox proportional risk model.Among 59 patients, there were 27 males and 32 females with median age of 55 (31-69) years old.The median follow-up was 761(317-1 861)days. The 2-year overall survival (OS) rate and event-free survival (EFS) rate were 76.1%±11.4% and 73.4%±11.6% respectively.The univariate analysis showed that age older than 50 years, TET2 gene mutation (TET2+), achieving MRD negativity over 30 days (MRD30+) were unfavorable factors of OS (χ2=6.20, 33.20, 7.18;P=0.013,<0.001, 0.007). TET2+, WT1 gene mutation (WT1+), CD34+cells<2×106/kg, MRD30+were negative factors of EFS (χ2=17.29, 4.47, 3.94, 9.393;P<0.001, 0.035, 0.047, 0.002).Multivariate analysis showed that MRD30+, TET2+ were independent prognostic factors of OS and EFS (OS:HR=9.251, 25.839, P=0.036, 0.001;EFS:HR=5.851, 9.199, P=0.043, 0.002). Intermediate-risk AML patients with MRD30+or TET2+ have very poor prognosis after auto-HSCT. Alternative regimens should be investigated.

Endostar blocks the metastasis, invasion and angiogenesis of ovarian cancer cells.

Endostar (ES) inhibits metastasis in some tumors, but its role in ovarian cancer invasion has not been elucidated. In this study, the effects of ES on ovarian cancer cells were further analyzed, to excavate an effective strategy for treating ovarian cancer. Ovarian cancer cell lines (SKOV3 and HO-8910PM) were treated with different concentrations of ES. Cell activity and half-maximal inhibitory concentration (IC50) detected by MTT were used for subsequent experiments. The migration and invasion abilities of treated cells were detected by wound healing and Transwell assays. The expressions of epithelial-mesenchymal transition (EMT)-related proteins in treated cells were determined by western blot analysis. Moreover, in vitro angiogenesis, the expressions of related proteins in treated cells and STAT3, and PD-L1 expressions were determined. We found that with the increase of ES concentrations, the cell activity showed a decreasing trend, and that the compositive IC50 of SKOV3 and HO-8910PM was 50 µg/ml. Moreover, ES observably inhibited migration, invasion, and EMT of ovarian cancer cell lines. In angiogenesis experiments, the angiogenesis ability and the expressions of related proteins in ovarian cancer cell lines were downregulated after ES treatment. Furthermore, ES reduced the expression of PD-L1 and suppressed the phosphorylation of STAT3 in ovarian cancer cell lines. ES blocked the metastasis, invasion, and angiogenesis of ovarian cancer cells by suppressing the activation of PD-L1 and STAT3, which might be considered as the potential mechanism of ES in the treatment of ovarian cancer.

[Clinical characteristics of 13 neuroendocrine prostate cancer patients].

Objective: To explore the radiological, pathological features and clinical characteristics of neuroendocrine prostate cancer patients(NEPC). Methods: The clinical characteristics and pathology data of 13 neuroendocrine prostate cancer patients treated in the Affiliated Hospital of Tianjin Medical University from January 2004 to January 2015 were analyzed retrospectively. Results: Of all 13 patients, three cases were primally diagnosed small cell cancer, and 10 cases were translated to neuroendocrine type from adenocarcinoma after endocrine therapy. Frequent urination, urgency, nocturia, and dysuria were main symptoms. Serum prostate-specific antigen (PSA) was (14.5±3.2)µg/L; the volume of prostate was enlarged, mean volume, range 28-176(45±4)ml. The lesion was moderately low signal intensity in T(2)WI, while slightly higher signal in DWI. Signal characteristic of dynamic enhanced MRI was "fast in fast out" . The expression of Synaptophysin, Chromogranin A , CD56 and Ki-67 in NEPC were highly expressed by immunohistochemistry analysis. Among them, five patients accepted intravenous chemotherapy, two cases received external radiation therapy, three cases received cryoablation and three cases received palliative therapy. Median survival time in all 13 patients was 10 months, while median survival time in patients treated by chemotherapy was 16 months . Conclusion: NEPC is a highly aggressive subtype of prostate cancer characterized by rapid disease progression, lack of treatment and worse prognosis. Therefore, patients with NEPC may benefit from early diagnosis and comprehensive treatment with chemotherapy.

A Subgroup Analysis of Chinese Patients Switched to Paliperidone Palmitate One-Month Injectable by Prior Oral Antipsychotic Treatment.

INTRODUCTION: Safely tapering current antipsychotic medication, while balancing efficacy and tolerability, is an important consideration when switching patients from their antipsychotic therapy to a new treatment. The efficacy and tolerability of paliperidone palmitate one-month (PP1M) in Chinese patients switched from previous antipsychotic treatments were examined in order to develop effective switching and dosing strategies. METHODS: A 13-week open-label, single arm, prospective, interventional study was conducted in Chinese patients (n = 610) with acute schizophrenia to examine their response, by previous treatment group, when switched to PP1M (75-150 mg eq). RESULTS: Among 610 patients with ≥ 30% reduction in PANSS total score were 191/263 (72.6%) risperidone/paliperidone extended-release patients, 36/52 (69.2%) olanzapine patients, and 214/293 (73.0%) other antipsychotic patients. Patient functioning and adherence were significantly (p ≤ 0.05) improved for all subgroups. DISCUSSION: Patients on higher doses of prior antipsychotics generally took longer to withdraw from their current medication. Most patients were administered the 100 mg eq dose, and all subgroups received a similar mean dose (114-119 mg eq) of PP1M. Recommendations for transitioning patients to PP1M from each subgroup are discussed.

Comparative study of phosphorylated histone H2AX expressions in the cervical cancer patients of pre- and post-neoadjuvant chemotherapy. .

OBJECTIVE: This study aimed to determine whether phosphorylation of histone H2AX (γH2AX) is a predictive marker for neoadjuvant chemotherapy patients of cervical cancer. MATERIALS AND METHODS: The sections were divided into three sets. Set 1 consisted of 40 pre-treatment biopsies. Post-treatment tissues includes 38 patients in set 2 and 34 patients in set 3 who received cisplatin concurrent docetaxel treatment for one or two cycles, respectively. Formalin-fixed paraffin-embedded sections were analyzed after antigen retrieval and fluorescence antibody labeling for γH2AX staining. RESULTS: The expressions of γH2AX in cervical cancer tissues of post-neoadjuvant chemotherapy decreased to 22.94 ± 14.02% and 23.68 ± 13.55% (one and two cycles treatment, respectively) compared to preneoadjuvant chemotherapy (28.29 ± 15.67%), however there was no significant difference for γH2AX expression between pre- and post-neoadjuvant chemotherapy patients (F = 1.425, p = 0.245). There was no significant correlation between γH2AX expression and clinicopathologic parameters in patients of pre- and post-neoadjuvant chemotherapy. CONCLUSIONS: As a predictive marker for neoadjuvant chemotherapy of cervical cancer, more extensive research regarding γH2AX expression should be explored.

Short-term effects of escitalopram on regional brain function in first-episode drug-naive patients with major depressive disorder assessed by resting-state functional magnetic resonance imaging.

BACKGROUND: Most knowledge regarding the effects of antidepressant drugs is at the receptor level, distal from the nervous system effects that mediate their clinical efficacy. Using functional magnetic resonance imaging (fMRI), this study investigated the effects of escitalopram, a selective serotonin reuptake inhibitor (SSRI), on resting-state brain function in patients with major depressive disorder (MDD). METHOD: Fourteen first-episode drug-naive MDD patients completed two fMRI scans before and after 8 weeks of escitalopram therapy. Scans were also acquired in 14 matched healthy subjects. Data were analyzed using the regional homogeneity (ReHo) approach. RESULTS: Compared to controls, MDD patients before treatment demonstrated decreased ReHo in the frontal (right superior frontal gyrus), temporal (left middle and right inferior temporal gyri), parietal (right precuneus) and occipital (left superior occipital gyrus and right cuneus) cortices, and increased ReHo in the left dorsal medial prefrontal gyrus and left anterior lobe of the cerebellum. Compared to the unmedicated state, ReHo in the patients after treatment was decreased in the left dorsal medial prefrontal gyrus, the right insula and the bilateral thalamus, and increased in the right superior frontal gyrus. Compared to controls, patients after treatment displayed a ReHo decrease in the right precuneus and a ReHo increase in the left anterior lobe of the cerebellum. CONCLUSIONS: Successful treatment with escitalopram may be associated with modulation of resting-state brain activity in regions within the fronto-limbic circuit. This study provides new insight into the effects of antidepressants on functional brain systems in MDD.

Percutaneous cryoablation of liver metastases from breast cancer: initial experience in 17 patients.

AIM: To assess the feasibility, safety, and effectiveness of percutaneous cryoablation for the treatment of liver metastases from breast cancer. MATERIALS AND METHODS: This study included 39 liver metastases in 17 female breast cancer patients who underwent computed tomography (CT)-guided percutaneous cryoablation. The mean age of the cohort was 55 years (range 30-66 years). The tumour response was evaluated by CT performed before treatment, 1 month after treatment, and every 3 months thereafter. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) was used to assess the patients' quality of life before, 1 week, 1 month, and 3 months after cryoablation. The primary endpoints were technique effectiveness, quality of life, and complications. RESULTS: The technical success rate was 92% with no major complication reported. At the 1-month follow-up, the primary technique effectiveness was 87.1% (34 of 39 tumours). At the 3-months follow-up, local tumour progression was observed in six of 39 lesions (15.4%). The 1-year survival from the time of cryoablation was 70.6%. The quality of life symptoms and functioning scales were preserved in patients alive at 3 months after cryoablation. The global quality of life, mean value of "pain" and "fatigue" between 3 months after cryoablation and prior to treatment showed statistically significant differences, but no clinical significance. CONCLUSIONS: Cryoablation is a safe and effective ablative therapy, providing a high rate of local tumour control in breast cancer liver metastases.

Anti-tumor immunological response induced by cryoablation and anti-CTLA-4 antibody in an in vivo RM-1 cell prostate cancer murine model.

Cryoablation combination therapy with blockade of the T-cell inhibitory receptor CTL-associated antigen-4 (CTLA-4) may augment the anti-tumor immune response (ATIR). It is crucial to determine the duration of ATIR after cryoablation and anti-CTLA-4 antibody therapy to determine the most appropriate treatment interval of therapy. To investigate the characteristics of ATIR induced by cryoablation and anti-CTLA-4 antibody therapy, we developed a prostate cancer model system to test the capacity of cryoablation and anti -CTLA-4 antibody to generate ATIR. Mice were randomly assigned to receive no treatment (group A), cryoablation only (group B), cryoablation plus anti-CTLA-4 antibody (group C), or anti-CTLA-4 antibody only (group D). We collected specimens on days 0, 7, 14 and 21 to study the ATIR through different techniques. Our results indicated that cryoablation induced ATIR and further enhanced this effect and reduced the number of distant metastases through combination with anti-CTLA-4 antibody. ATIR induced by cryoablation was achieved through decreasing regulatory T cell (Treg) number. The number of Tregs induced by cryoablation was lowest on day 14 but then returned to preoperative levels on day 21, indicating that ATIR induced by cryoablation was time-dependent. However, ATIR induced by anti-CTLA-4 antibody might be mainly achieved through influencing Treg function, which was exactly not by decreasing Treg number and still maintain its ATIR effect on day 21 after therapy. In conclusion, ATIR induced by cryoablation was achieved through decreasing Treg number and is time-dependent, whereas ATIR caused by anti-CTLA-4 antibody was achieved exactly not by decreasing Treg number and not time-dependent in the first 21 days after therapy.

Adjunctive mood stabilizer and benzodiazepine use in older Asian patients with schizophrenia, 2001-2009.

OBJECTIVE: This study surveyed the use of adjunctive mood stabilizers (MS) and benzodiazepines (BZD) in older Asian schizophrenia patients and examined their demographic and clinical correlates. METHOD: Information on hospitalized schizophrenia patients aged 55 years or more were extracted from the database of the Research on Asian Psychotropic Prescription Patterns (REAP) study. A total of 1,452 patients from 9 Asian countries and territories was included in the study. The patients' sociodemographic and clinical characteristics and the prescriptions of antipsychotics, MS and BZD were recorded using a standardized protocol and data collection procedure. RESULTS: The frequency of MS prescription was 26.7% in the pooled sample, with 25.5% in 2001, 26.9% in 2004 and 27.7% in 2009. The corresponding figures for BZD were 20.7%, 20.2%, 18.4% and 23.1%, respectively. Multiple logistic regression analysis of the whole sample revealed that patients on MS were younger and more likely to be men and to have extrapyramidal side effects (EPS) and a longer duration of illness. Compared to patients in China, those in Japan were more likely to receive MS, while Korean patents were prescribed less MS. In contrast, there were no significant sociodemographic or clinical correlates of BZD use. Compared to patients in China, their Korean and Singaporean counterparts were more likely to be on BZD. CONCLUSIONS: The use of MS and BZD is not uncommon in older Asian patients with schizophrenia. Given the paucity of empirical data on the efficacy of these agents in individuals with schizophrenia of any age and concerns about added side effects in older patients in particular, the rationale for the prescription of these agents in this population warrants further examination.

Antipsychotic polypharmacy in inpatients with schizophrenia in Asia (2001-2009).

OBJECTIVE: This study aimed to identify trends in the use of antipsychotic polypharmacy (APP) and their demographic and clinical correlates in the treatment of schizophrenia in Asia between 2001 and 2009. METHOD: A total of 6,761 schizophrenia inpatients in 9 Asian countries and territories were examined; 2,399 in 2001, 2,136 in 2004, and 2,226 in 2009. Patients' socio-demographic and clinical characteristics and prescriptions of psychotropic drugs were recorded using a standardized protocol and data collection procedure. RESULTS: The proportion of APP prescription decreased from 46.8 % in 2001, to 38.3 % in 2004, and increased to 43.4 % in 2009, with wide intercountry variations at each survey. Multiple logistic regression analysis of the whole sample revealed that patients on APP were younger, had a higher dose of antipsychotics in chlorpromazine equivalents, and more severe positive and negative symptoms. They were also more likely to receive depot and fi rst-generation antipsychotic drugs. CONCLUSIONS: The frequency of APP prescription varied between countries and territories, suggesting that a host of clinical and socio-cultural factors played a role in determining APP use in Asia. To resolve the discrepancy between treatment recommendation and clinical practice, regular reviews of prescription patterns are needed.

Effect of transcatheter renal arterial embolization combined with cryoablation on regulatory CD4+CD25+ T lymphocytes in the peripheral blood of patients with advanced renal carcinoma.

OBJECTIVE: To analyze the effect of Argon-Helium cryosurgery (AHCS) combined with transcatheter renal arterial embolization (TRAE) on the differentiation of regulatory CD4+ CD25+ T cell (Treg) and its implication in patients with renal carcinoma. METHODS: Seventy seven patients are included in the study, and divided into two groups: TRAE group (n=45, receiving TRAE only) and TRAE+cryoablation group (n=32, receiving cryoablation 2-3 weeks after TRAE). The percentage of Treg cells and T lymphocyte subsets (CD4+T, CD8+T, and CD4+T/CD8+T) in the peripheral blood is measured by flow cytometry previous to the therapy and 3 months after therapy. Meanwhile, the extent of tumor necrosis is measured by MRI or CT 1 month after therapy. RESULTS: The percentages of Treg cells of patients in TRAE + cryoablation group decrease from (6.65±1.22)% to (3.93±1.16)%, (t=42.768, P<0.01), and the percentages of CD4+T and CD4+T/CD8+T increase significantly (P<0.01). However, the results of patients in TRAE group show that the percentages of Treg, CD4+T, CD8+T and CD4+T/CD8+T increase slightly although the differences had no statistical significance (P>0.05). The tumor necrosis rate of TRAE+cryoablation group is 57.5%, significantly higher than those of TRAE group, which shows 31.6% (t=6.784, P<0.01). The median survival duration of the TRAE+cryoablation group is 20 months, significantly longer than that of the TRAE group (χ² = 7.368, P<0.01). The decreasing extent of Treg cells is correlated with tumor necrosis rates (r=0.90, P<0.01) and life time (r=0.67, P<0.01). CONCLUSION: The therapy of TRAE combined with cryoablation contributes to reduce the percentage of Treg cells and improve the immune situation of patients with renal cell carcinoma, which consequently increase tumor necrosis rate and prolong the patients' survival duration.

Use of anticholinergic drugs in patients with schizophrenia in Asia from 2001 to 2009.

OBJECTIVE: The aim of this study was to survey the use of anticholinergic medication (ACM) in Asia between 2001 and 2009 and examine its demographic and clinical correlates. METHOD: A total of 6 761 hospitalized schizophrenia patients in 9 Asian countries and territories were examined between 2001 and 2009. The patients' socio-demographic and clinical characteristics and the prescriptions of psychotropic drugs were recorded using a standardized protocol and data collection procedure. RESULTS: The frequency of ACM prescription decreased from 66.3% in 2001, to 52.8% in 2004 and 54.6% in 2009, with wide inter-country variations at each time period. Multiple logistic regression analysis of the whole sample showed that patients taking ACM presented with more severe positive, negative, and extrapyramidal symptoms. They were also more likely to receive first-generation and depot antipsychotics and antipsychotic polypharmacy, and less likely to receive second-generation ones. CONCLUSIONS: The wide variation in ACM prescription across Asia suggests that a combination of clinical, social, economic and cultural factors play a role in determining the use of these drugs. Regular reviews of ACM use are desirable to reveal the discrepancy between treatment guidelines and clinical practice.

Tardive dyskinesia in the treatment of schizophrenia: the findings of the Research on Asian Psychotropic Prescription Pattern (REAP) survey (2001 - 2009).

OBJECTIVE: The aim of the study was to survey the frequency of tardive dyskinesia (TD) in patients with schizophrenia and its demographic and clinical correlates in selected Asian countries. METHOD: A total of 6,761 hospitalized schizophrenia patients in nine Asian countries and territories were examined from 2001 to 2009. TD was evaluated as "present" or "absent" according to the clinical judgment of experienced psychiatrists. The patients' socio-demographic and clinical characteristics and the prescriptions of psychotropic drugs were recorded using a standardized protocol and data collection procedure. RESULTS: The frequency of TD in the whole sample was 5.0% with wide variations between countries (0 - 14.9%). Multiple logistic regression analysis showed that the following variables were independently associated with TD: study time, study site, older age, male gender, more severe negative and extrapyramidal symptoms and less anticholinergic drugs. CONCLUSIONS: A generally low frequency of TD in Asian schizophrenia patients with inter-ethnic variations was recorded. It is unclear whether the low prevalence of TD compared with Western data is real or the result of it being insufficiently recognized.

[Effects of N-trimethyl chitosan-recombinant tissue factor pathway inhibitor complex on avulsion flap with roll compaction in rat].

Objective: To investigate the effect of N-trimethyl chitosan-recombinant tissue factor pathway inhibitor (rTFPI) complex on avulsion flap with roll compaction in rat. Methods: The experimental methods were adopted. The N-trimethyl chitosan-rTFPI complex solution was prepared by ion cross-linking method. The morphology of the complex was observed by scanning electron microscope, and its diameter was measured. The encapsulation rate of rTFPI in the complex and drug loading rate of the complex was determined and calculated by enzyme-linked immunosorbent assay (ELISA) method (n=3). The concentration of rTFPI in the solution at 0, 10, 30, 45, 60, 90, 120, 240 minutes of storage was measured by ELISA method to observe the release of rTFPI, and its half-life was calculated (n=3). Twenty-four 6-week-old male Sprague-Dawley rats were divided into phosphate buffered saline (PBS) group, N-trimethyl chitosan alone group, rTFPI alone group, and N-trimethyl chitosan-rTFPI group according to the random number table, with 6 rats in each group. The avulsion flaps with roll compaction were prepared on the backs of rats with pedicles located on the line of the bilateral iliac spine and lifted from the surface of the muscle membrane. One injection of corresponding reagents was carried out immediately after in-situ suture and on post operation day (POD) 1, 2, and 3. General changes of the flap were observed on POD 1, 3, and 7. On POD 7, the survival area of the flap was measured and the survival rate of the flap was calculated; the flaps were divided into pedicle, proximal, middle, and distal segments, and the blood perfusion in the proximal, middle, and distal segment tissue of the flap was detected by the laser speckle blood flow imager; tissue samples in the middle of the flap were cut and stained with hematoxylin and eosin to observe the changes in tissue structure and the infiltration of inflammatory cells, and the numbers of embolized blood vessels and new blood vessels per 100 times visual field were counted. Data were statistically analyzed with one-way analysis of variance and least significant difference test. Results: The N-trimethyl chitosan-rTFPI complex had an irregular spherical structure with a diameter of 150-200 nm. The encapsulation rate of rTFPI in the complex and drug loading rate of the complex were (88.7±2.1)% and (2.83±0.09)%, respectively. The concentration of rTFPI in the solution of the N-trimethyl chitosan-rTFPI complex gradually increased with prolonged storage time, and the release was basically stable at 90 min, with half-life of (651±36) min. On POD 1, the distal parts of flaps of rats in N-trimethyl chitosan alone group darkened significantly. On POD 3, scabs and necrosis were relatively mild on the distal segment of the flaps of rats in rTFPI alone group and N-trimethyl chitosan-rTFPI group as compared with those of the other two groups. On POD 7, the necrosis boundaries of the flaps of rats in each group were clear. On POD 7, the flap survival rates of rats in rTFPI alone group and N-trimethyl chitosan-rTFPI group were (63±7)% and (73±5)%, respectively, which were significantly higher than (41±3)% in PBS group and (52±7)% in N-trimethyl chitosan alone group. Moreover, the flap survival rate of rats in N-trimethyl chitosan-rTFPI group was significantly higher than that in rTFPI alone group (P<0.05). On POD 7, the flaps of rats in each group had blood perfusion; the blood perfusion values in the proximal segment tissue of the rat flaps in N-trimethyl chitosan alone group and the blood perfusion values in the proximal, middle, and distal segment tissue of the rat flaps in rTFPI alone group and N-trimethyl chitosan-rTFPI group were significantly higher than those in PBS group (P<0.05 or P<0.01); the blood perfusion values in the distal segment tissue of the rat flaps in rTFPI alone group and the blood perfusion values in the middle and distal segment tissue of the rat flaps in N-trimethyl chitosan-rTFPI group were significantly higher than those in N-trimethyl chitosan alone group (P<0.05 or P<0.01); the blood perfusion value in the middle segment tissue of the rat flaps in N-trimethyl chitosan-rTFPI group was significantly higher than that in rTFPI alone group (P<0.01). On POD 7, inflammatory cells infiltrated more and cell edema was obvious in the middle segment tissue of the rat flaps in PBS group and N-trimethyl chitosan alone group. Compared with those of the previous two groups, the inflammation degrees in the middle segment tissue of the rat flaps in rTFPI alone group and N-trimethyl chitosan-rTFPI group were significantly milder, the number of embolized blood vessels was significantly decreased (P<0.05 or P<0.01), and the number of new blood vessels was significantly increased (P<0.05 or P<0.01). Compared with that of rTFPI alone group, the number of new blood vessels in the middle segment tissue of the rat flaps in N-trimethyl chitosan-rTFPI group increased significantly (P<0.05). Conclusions: The effect of sustained release of rTFPI can be achieved by loading rTFPI with N-trimethyl chitosan. Compared with rTFPI alone, the N-trimethyl chitosan-rTFPI complex can further improve the blood perfusion of the avulsion flaps with roll compaction in rat and improve the survival rate of the flap.

Double benefits of mechanical wounding in enhancing chilling tolerance and lodging resistance in wheat plants.

Chilling and lodging are major threats to wheat production. However, strategies that can be used to effectively mitigate the adverse effects of these threats are still far from clear. Mechanical wounding is a traditional agronomic measure, whereas information about the role it plays in wheat chilling and lodging is scant. The aim of the present study was to investigate mechanisms underlying the protective roles of mechanical wounding in alleviating damage from chilling at jointing stage and enhancing lodging resistance after anthesis of winter wheat (Triticum aestivum L.). Our data show that net photosynthesis rate, maximum photochemical efficiency of photosystem II, activity of the antioxidant enzymes and osmolytes were significantly increased in the latest fully expanded leaves of wounded plants under chilling. Wounding also reduced hydrogen peroxide accumulation, electrolyte leakage and water loss in wounded plants. Moreover, mechanical wounding significantly reduced the length but increased the diameter and wall thickness of the basal second internode of the main stem. Quantitative and histochemical analysis further indicated that wounding increased lignin accumulation and activity of enzymes involved in lignin synthesis, which resulted in increased mechanical strength and the lodging resistance index in the main stem. We conclude from our data that mechanical wounding confers both cold tolerance by alleviating the damage caused by chilling at jointing stage and lodging resistance after anthesis of wheat plants.

Strategy and Efficacy of Generic and Pan-genotypic Sofosbuvir/Velpatasvir in Chronic Hepatitis C Virus: A Myanmar Experience.

BACKGROUND: In resource-constrained areas, generic direct-acting antivirals (DAAs) have considerably reduced the cost of hepatitis C virus (HCV) therapy while there remain significant costs related to the baseline and follow-up virologic assays. AIM: The aim was to assess the efficacy and safety of HCV therapy in Myanmar with pan-genotypic generic DAA sofosbuvir/velpatasvir (SOF/VEL) and with and without the baseline genotype testing, while the duration of treatment and use of ribavirin (RBV) was dictated by cirrhosis and prior treatment failure. METHODS: Between September 2016 and June 2017, data from the 359 participants who completed treatment with SOF/VEL (± RBV) for 12-24 weeks were analyzed. Two hundred one patients did not have the baseline HCV genotype tested. RESULTS: Regimens included SOF/VEL for 12 weeks (n = 43), SOF/VEL/RBV for 12 weeks (n = 275), or SOF/VEL/RBV for 24 weeks (n = 41). The mean age was 52 years, 44% were men (n = 159), 41 (11.4%) had a history of previous DAA therapy, 7 (1.9%) had a history of hepatocellular carcinoma, and 55 (15.3%) had cirrhosis. Overall, the sustained viral response (SVR)12 rate was 98.6% (354/359) and with a good adverse event profile. SVR rates were similar to those with and without baseline genotype testing and also across all genotypes in those who had genotype tested. CONCLUSIONS: In Myanmar, generic and pan-genotypic SOF/VEL ± RBV is a highly effective and safe treatment for HCV, regardless of the HCV genotype, and therefore, the requirement for the baseline genotype can be eliminated. Future strategies should include elimination of treatment and end of treatment HCV RNA testing to enhance treatment uptake and further reduce cost.

Can catheter-directed thrombolysis be applied to acute lower extremity artery embolism after recent cerebral embolism from atrial fibrillation?

PURPOSE: To assess the feasibility and efficacy of catheter-directed thrombolysis with recombinant tissue plasminogen activator (rt-PA) for acute limb embolism in patients with recent cerebral embolism due to atrial fibrillation. MATERIALS AND METHODS: Eight patients (six men, two women; mean age 63.5 years) with acute embolic occlusion of two left common iliac arteries, four femoral arteries (three left; one right), and two right popliteal arteries were treated. All patients had a history of recent cerebral embolism (mean 6 days, range 5-15 days) and all had a history of atrial fibrillation (duration 5-10 years). Catheter-directed thrombolysis started a few hours (mean 6.2h; range 3-10h) after the onset of arterial embolism. Two 5mg boluses of rt-PA were injected into the proximal clot through a 5 F end-hole catheter and, subsequently, two additional boluses of 5mg rt-PA were injected into the emboli. In patients with residual emboli, infusion with rt-PA (1mg/h) was continued. Percutaneous transluminal angioplasty was performed in three patients, and a stent was deployed in one patient. RESULTS: Technical success was achieved in all patients. Clinical success rate was 87.5% (7/8). The one clinical failure was secondary to chronic occlusion of outflow runoff vessels. The mean duration of continuous rt-PA infusion was 3.6h, the mean total dose of rt-PA administered was 23.6 mg (range 20-28 mg). There was no significant change in stroke scale scores during thrombolysis and no intracerebral haemorrhage was found at computed tomography (CT) after thrombolysis. Minor complications included haematomata at puncture sites (6/8), bleeding around the vascular sheath (2/8), and haematuria (1/8). During the follow-up period of 3-6 months, one patient suffered from recurrent cerebral embolism and died. CONCLUSIONS: Catheter-directed thrombolysis with rt-PA is an option for acute lower extremity arterial embolism in patients with recent cerebral embolism and a history of atrial fibrillation. Further studies should be undertaken to determine the risk of intracerebral haemorrhage caused by catheter-directed thrombolysis in individual stroke patients.