Analysis and comparison of major plant databases in China and ASEAN countries / 国际中医中药杂志

At present, countries around the world are paying greater attention to the protection of medicinal plants and traditional medicinal knowledge resources, and are looking for various ways to protect medicinal plants. Many countries have established their own databases to save the medicinal plant information resources. This paper focuses on the introduction of medicinal plant databases in six countries including Malaysia, Philippines, and Singapore, and compares their basic information. It is difficult to achieve integration and sharing among these databases. It brings certain difficulties to the use of researchers in related fields. It is suggested that the construction of a multinational common medicinal plant database should be included in the "Belt and Road Initiative" to systematically organize massive information, enhance exchanges between countries on traditional medicinal plants, and achieve medicinal plant information sharing, and the establishment of a shared database will reduce optimization and maintenance to a certain extent or renewal work, laying the foundation for the protection, development and sustainable use of traditional medicinal plant resources.

Endothelial METRNL determines circulating METRNL level and maintains endothelial function against atherosclerosis

METRNL is a recently identified secreted protein with emerging functions. This study is to find major cellular source of circulating METRNL and to determine METRNL novel function. Here, we show METRNL is abundant in human and mouse vascular endothelium and released by endothelial cells using endoplasmic reticulum-Golgi apparatus pathway. By creating endothelial cell-specific Metrnl knockout mice, combined with bone marrow transplantation to produce bone marrow-specific deletion of Metrnl, we demonstrate that most of circulating METRNL (approximately 75%) originates from the endothelial cells. Both endothelial and circulating METRNL decrease in atherosclerosis mice and patients. By generating endothelial cell-specific Metrnl knockout in apolipoprotein E-deficient mice, combined with bone marrow-specific deletion of Metrnl in apolipoprotein E-deficient mice, we further demonstrate that endothelial METRNL deficiency accelerates atherosclerosis. Mechanically, endothelial METRNL deficiency causes vascular endothelial dysfunction including vasodilation impairment via reducing eNOS phosphorylation at Ser1177 and inflammation activation via enhancing NFκB pathway, which promotes the susceptibility of atherosclerosis. Exogenous METRNL rescues METRNL deficiency induced endothelial dysfunction. These findings reveal that METRNL is a new endothelial substance not only determining the circulating METRNL level but also regulating endothelial function for vascular health and disease. METRNL is a therapeutic target against endothelial dysfunction and atherosclerosis.

Literature Survey on Edible Medicinal Plants in Lancang-Mekong Countries / 中国实验方剂学杂志

Lancang-Mekong countries refer to the six countries that the Lancang-Mekong River flows through， including China， Laos， Myanmar， Thailand， Cambodia， and Vietnam. These countries are geographically adjacent with similar cultures and have long history of traditional medicine and high plant diversity. Since ancient times， medicinal plants have been introduced into China from the countries along the river， including a variety of medicinal plants with edible and healthcare values， which is an important way for the transnational circulation of medicinal resources. This paper briefly described the history and application of edible medicinal plants in the six Lancang-Mekong countries and summarized more than 150 edible medicinal plants from the other five countries except China. These 150 medicinal plants belong to 66 families such as Labiatae， and 12 species of them are used as edible medicinal plants in all the six countries. Further， we collected the information of these edible medicinal plants， including the origins， efficacy， indications， medicinal edible parts， edible values， and the traditional application of these plants in China. Some valuable edible medicinal plants in the other five countries are considered to have a promising prospect of application in China and may be introduced to China as new medicinal resources. These efforts will be conducive to the cooperation in traditional medicine among Lancang-Mekong countries.

First Report of Rhizoctonia solani AG-4 HG-III Causing Sheath Blight on Foxtail Millet in China.

Foxtail millet (Setaria italica) is an important grain and forage crop. This crop is widely grown in Northern China (Yang et al.2020). In Aug 2021, foxtail millet variety of Jigu42 showing lodging were found in Baoding China with the incidence of 30% and irregular brown lesions were found in sheaths and leaves of infected plants. The center of the lesions was kraurotic and pale, and the edges were gray-brown or dark brown. Twelve samples with typical lesions were collected from the surveyed field to isolate the pathogen. The infected samples were cut into square pieces of about 3 to 5 mm and were immersed into NaOCl (1%) for 1 min followed by washing with sterile water for three times. Then all sterilized tissues were inoculated on potato dextrose agar (PDA) plates and incubated at 25℃. After 3 days, fresh mycelial tips grown from the tissues were transferred to new plates for purification and incubated in the dark at 25°C for 4-5 days until the hyphae covered the whole plates. The colonies of 15 isolates on PDA medium showed similar colonial characteristics, which were fluffy and white initially, gradually turned light brown, and no sclerotia was observed even at 20 days later. Micro-examination revealed that all isolates showed the identical morphological features as Rhizoctonia sp. (Sneh et al. 1991), which contained the septate and right-angled branching hyphae with slight constriction at the base of mycelial branches, and three to seven nuclei per cell (Yang et al. 2013). Total genomic DNA was extracted from 5-day-old cultures, and the internal transcribed spacer (ITS) region of rDNA was amplified with ITS1 and ITS4 as the primers (Garibaldi et al. 2019). The sequencing results showed that the nucleotide sequences of 15 amplicons were identical and shared 100% identity with the corresponding fragments of R. solani AG-4 HG-III from sugar beet (GenBank accession No. MH172666 and MH172663) in Blastn search. The sequencing size of ITS in this study was 3 bp shorter than that of sugar beet, with a length of 722, because the base 'T' in the beginning and 'GA' in the end of the sequences did not detected in our study. Phylogenetic tree of 16 isolates of different AG4 subgroups was created by the software MEGA 7.0 through the NJ method, and the showed that the isolates were clustered to the clade of AG-4 HG-III group. The sequences of three isolates were deposited in GenBank under the accession No. ON810364, ON810365 and ON810366. For pathogenicity test, 5 mm diameters plate of the 5-day-old fungus which cultured on PDA were inoculated to the sheath of 10 foxtail millet plants grown in pots at 5- or 6-leaf stage. Then, the inoculated plants were placed into a growth chamber, and the inoculated sheaths were covered with wet cotton ball for 2 days to keep humidity, while sterile water was inoculated as the control. All plants were cultivated at 26°C with 14 h light and 10 h dark for 14 days. The experiment was repeated for three times. As the result, the same lesions observed in the field appeared on the inoculated plants at 10-14 days post inoculation, whereas the mock was healthy. The pathogen was re-isolated from the infected samples. The morphological characteristics and the nucleotide sequences of ITSs were same as that of the original isolates. All in above, the pathogen cusing sheath blight on foxtail millet was identified as R. solani AG-4 HG-III. To our knowledge, this is the first report of R. solani AG-4 HG-III causing sheath blight on S. italica in China. This finding expands the host range known for R. solani AG-4 HG-III and will be helpful for developing effective control strategies of foxtail millet sheath blight.

Investigation of medication adherence for superficial mycoses among students in a college based on Morisky Medication Adherence Scale / 药学实践杂志

Objective To investigate the medication adherence of military academy students with superficial mycoses. Methods A 8-item Morisky medication adherence scale (MMAS) was modified into 7-item scale to evaluate the compliance of antifungal drugs in the sick students. The reliability and validity of the scale were analyzed. Results A total of 243 questionnaires were collected, of which 242 were valid questionnaires. 90.08% of the students took topical medication and 8.68% were treated both with topical and systematic combination. High, medium and low medication adherence rates as assessed by the modified MMAS were 9.09%, 23.97% and 66.94%, respectively. The reliability analysis showed that the internal consistency coefficient (Cronbach’s α ) was 0.781，and the adjusted Cronbach’s α was 0.790, indicating the high reliability of the scale. The KMO value was 0.798, and the Bartlett’s spherical test value was 440.866, P=0.000. One factor was extracted by exploratory factor analysis. The factor loadings of the items were all above 0.5. Therefore, the high convergent validity was good. Conclusion The modified MMAS has good reliability and validity and is applicable for the evaluation of medication compliance for superficial mycoses. In this study, the military students have a low level of medication adherence for superficial mycoses. Effective measures should be taken to help students strengthen their daily medication management and improve compliance.

Study on optimization and stability of Artemisia annua pollen-induced allergic rhinitis model in mice / 中华微生物学和免疫学杂志

Objective:To optimize the challenge scheme for establishing a stable mouse model of Artemisia annua pollen-induced allergic rhinitis. Methods:BALB/c mice were subcutaneously injected with 0.1 ml allergen extract containing 20 μg/ml Art a1 from Artemisia pollen on 1 d, 4 d and 7 d. One week after the sensitization, these mice were divided into three groups and intranasally challenged with Artemisia annua pollen allergen extract containing 500 μg/ml Art a1 for 7 (7 d group), 10 (10 d group) and 14 (14 d group) consecutive days, respectively. The first challenge was followed by another 7 days of challenge every four weeks. Blank control group was set up through sensitizing and challenging BALB/c mice with normal saline. Behavioral changes and nasal pathological changes were observed. The changes in humoral and cellular responses were also detected. After the first challenge cycle was decided, the challenge frequency was further optimized. Results:After the first challenge, the allergic symptoms of mice in 10 d group were significantly severe than those in 7 d and 14 d groups, and the levels of serum specific IgE antibody in 10 d and 14 d groups were significantly higher than that in 7 d group. After the second challenge, the mice in the three model groups still had obvious allergic symptoms as compared with the blank control group. There were obvious pathological changes in the nose, including epithelial cell proliferation, turbinate enlargement and inflammatory cell increase. Moreover, the level of serum specific IgE antibody increased significantly and the proliferation of antigen-specific IL-4 and IL-6 lymphocytes was significantly up-regulated, especially in 10 d and 14 d groups. The frequency of challenge had a great impact on the stability of the allergic model. The allergic symptoms of sensitized mice challenged every two weeks were significantly severe than those of mice challenged every four weeks and the level of serum antigen-specific antibody was also higher.Conclusions:This study optimized the first challenge cycle and challenge frequency for establishing a mouse model of Artemisia annua pollen-induced allergic rhinitis, which provided reference for the establishment of drug efficacy evaluation system for desensitization therapy.

Application of rapamycin eluting stent in popliteal artery acute plaque events: a report of four cases / 中国综合临床

Short segment lesions in the middle and upper segment of popliteal artery caused by acute plaque events can lead to moderate and severe limb ischemia, but there is little professional attention and research reports. The effect of rapamycin eluting stent in the treatment of short segment popliteal artery lesions was reviewed. The characteristics, operation methods and follow-up results of 4 cases were analyzed to summarize the operation experience and evaluate the treatment effect. In 4 cases, the operation time was short, the operation was smooth, and the technical success rate was 100%. The blood flow of the stent was good, no complications such as displacement, rupture and vascular injury were found, and the blood supply of the lower limbs was improved satisfactorily. Rapamycin eluting stent implantation can achieve good medium and long-term results in the treatment of specific middle and upper popliteal artery lesions.

Progress of programmed death ligand 2 in immunotherapy of solid tumors / 肿瘤研究与临床

With the breakthrough of immune checkpoint blocking therapy in the clinical treatment of a variety of malignant solid tumors, tumor immunotherapy has opened a new era. However, clinical practice has proved that the response rate of this therapy is low. Seeking for the key factors limiting its response rate has become a research hotspot in this field. Programmed death ligand 2 (PD-L2) is the second important ligand binding to programmed death 1 (PD-1) after programmed death ligand 1 (PD-L1). The encoded protein can bind to PD-1 and then inhibit immune cells. This paper reviews the biological characteristics of PD-L2, its mechanism in immune regulation and its research progress in solid tumor immunotherapy to provide more theoretical support for solid tumor immunotherapy.

Shear wave elastography to evaluate the protective effect of testicular torsion fascial compartment decompression treatment on spermatogenesis / 中华超声影像学杂志

Objective:To investigate the feasibility of shear wave elastography (SWE) to evaluate the protective effect of testicular compartment decompression on spermatogenesis after testicular torsion reduction.Methods:Thirty-two rabbits were randomly divided into 4 groups: control group (S group), testicular torsion simple reduction group (I group), and testicular torsion reduction+ compartment decompression group (T group: T1 group, T2 group), 8 rabbits per group. After the complete testicular torsion model was established in the I and T groups, the I group was simply reperfused, and the T group was reperfused before decompression of the compartment. Rabbits in each group were kept for 30 days after successful modeling. Each group of rabbits underwent testicular fascia intracompartment pressure measurement and SWE examination before operation, after successful complete torsion modeling, after reperfusion and 30 days later. After the experiment, the surgical side testicles were taken for pathological examination.Results:After testicular torsion, the pressure of testicular fascia and the average Young′s modulus (Emean) of testicular tissue in each experimental group increased (all P<0.05), and further increased with the extension of torsion time (all P<0.05). After reperfusion, the testicular fascial compartment pressure and testicular tissue Emean value in group I further increased (all P<0.05), while the testicular fascial compartment pressure and testicular tissue Emean value in group T decreased (all P<0.05). Thirty days later, testicular fascial compartment pressure and testicular tissue Emean value in group I were higher than those in group T (all P<0.05), while Johnsen′s score of testicular tissue was lower than that in group T ( P<0.05), and testicular tissue apoptosis index and malondialdehyde content were higher than those in group T Group T (all P<0.05). Conclusions:Decompression of the testicular compartment has a protective effect on spermatogenesis after testicular torsion reduction. SWE can indirectly evaluate the severity of testicular compartment syndrome after testicular torsion and reduction, and the protective effect of compartment decompression on spermatogenesis.

Analyses of low-dose chemotherapy effect and prognostic factors in advanced gastrointestinal cancer patients with weak physical condition / 肿瘤研究与临床

Objective:To investigate the clinical therapeutic effect of low-dose chemotherapy in advanced gastrointestinal cancer patients with weak physical condition, and to evaluate the related factors affecting the prognosis.Methods:The clinical data of 118 advanced gastrointestinal cancer patients with weak physical condition who were admitted to Xiamen Branch, Zhongshan Hospital, Fudan University from March 2018 to May 2019 were retrospectively analyzed. Kaplan-Meier method was used to make survival analysis in patients stratified by different factors, and log-rank was used to test. Multiple factor analysis of prognosis was performed by using Cox regression model. The association of clinicopathological factors with the prognosis was evaluated.Results:Among 118 patients, 16 (13.6%) cases were esophageal cancer, 41 (34.7%) cases were gastric cancer, 48 (40.7%) cases were colorectal cancer, 13 (11.0%) cases were pancreatic cancer. The overall survival (OS) rates of 6 months and 1-year were 44.1% and 10.2%, respectively. Survival analysis showed that patients with hemoglobin ≥100 g/L, serum albumin > 40 g/L and normal gastrointestinal function had better OS (all P < 0.05), while patients with physical status score of 3 scores and pain had worse OS (all P < 0.05). Cox multivariate analysis showed that after adjusting age and gender, hemoglobin level ( HR = 0.314, 95% CI 0.241-0.977, P = 0.001), pain ( HR = 2.016, 95% CI 1.697-7.038, P = 0.008) and gastrointestinal function ( HR = 1.751, 95% CI 1.607-6.080, P = 0.036) were independent influencing factors of OS in advanced gastrointestinal cancer patients with weak physical condition after receiving low-dose chemotherapy. Conclusions:Low-dose chemotherapy can still benefit advanced gastrointestinal cancer patients with weak physical condition. Hemoglobin level, pain and gastrointestinal function are independent prognostic factors for these patients.

Virus-free and live-cell visualizing SARS-CoV-2 cell entry for studies of neutralizing antibodies and compound inhibitors

The ongoing COVID-19 pandemic, caused by SARS-CoV-2 infection, has resulted in hundreds of thousands of deaths. Cellular entry of SARS-CoV-2, which is mediated by the viral spike protein and host ACE2 receptor, is an essential target for the development of vaccines, therapeutic antibodies, and drugs. Using a mammalian cell expression system, we generated a recombinant fluorescent protein (Gamillus)-fused SARS-CoV-2 spike trimer (STG) to probe the viral entry process. In ACE2-expressing cells, we found that the STG probe has excellent performance in the live-cell visualization of receptor binding, cellular uptake, and intracellular trafficking of SARS-CoV-2 under virus-free conditions. The new system allows quantitative analyses of the inhibition potentials and detailed influence of COVID-19-convalescent human plasmas, neutralizing antibodies and compounds, providing a versatile tool for high-throughput screening and phenotypic characterization of SARS-CoV-2 entry inhibitors. This approach may also be adapted to develop a viral entry visualization system for other viruses.

Development and Multicenter Performance Evaluation of The First Fully Automated SARS-CoV-2 IgM and IgG Immunoassays

BACKGROUNDThe outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread globally. The laboratory diagnosis of SARS-CoV-2 infection has relied on nucleic acid tests. However, there are many limitations of nucleic acid tests, including low throughput and high rates of false negatives. More sensitive and accurate tests to effectively identify infected patients are needed. METHODSThis study has developed fully automated chemiluminescent immunoassays (CLIA) to determine IgM and IgG antibodies to SARS-CoV-2 in human serum. The assay performance has been evaluated at 10 hospitals. Clinical specificity was evaluated by measuring 972 hospitalized patients with diseases other than COVID-19, and 586 donors of a normal population. Clinical sensitivity was assessed on 503 confirmed cases of SARS-CoV-2 by RT-PCR and 52 suspected cases. RESULTSThe assays demonstrated satisfied assay precision with coefficient of variation (CV) of less than 4.45%. Inactivation of specimen does not affect assay measurement. SARS-CoV-2 IgM shows clinical specificity of 97.33% and 99.49% for hospitalized patients and normal population respectively. SARS-CoV-2 IgG shows clinical specificity of 97.43% and 99.15% for the hospitalized patients and the normal population respectively. SARS-CoV-2 IgM and IgG show clinical sensitivity of 85.88% and 96.62% respectively for confirmed SARS-Cov-2 infection with RT-PCR, of 73.08% and 86.54% respectively for suspected cases. CONCLUSIONSwe have developed fully automated immunoassays for detecting SARS-CoV-2 IgM and IgG antibodies in human serum. The assays demonstrated high clinical specificity and sensitivity, and add great value to nucleic acid testing in fighting against the global pandemic of the SARS-CoV-2 infection.

Robust neutralization assay based on SARS-CoV-2 S-bearing vesicular stomatitis virus (VSV) pseudovirus and ACE2-overexpressed BHK21 cells

The global pandemic of Coronavirus disease 2019 (COVID-19) is a disaster for human society. A convenient and reliable in vitro neutralization assay is very important for the development of neutralizing antibodies, vaccines and other inhibitors. In this study, G protein-deficient vesicular stomatitis virus (VSVdG) bearing full-length and truncated spike (S) protein of SARS-CoV-2 were evaluated. The virus packaging efficiency of VSV-SARS-CoV-2-Sdel18 (S with C-terminal 18 amino acid truncation) is much higher than VSV-SARS-CoV-2-S. A neutralization assay for antibody screening and serum neutralizing titer quantification was established based on VSV-SARS-CoV-2-Sdel18 pseudovirus and human angiotensin-converting enzyme 2 (ACE2) overexpressed BHK21 cell (BHK21-hACE2). The experimental results can be obtained by automatically counting EGFP positive cell number at 12 hours after infection, making the assay convenient and high-throughput. The serum neutralizing titer of COVID-19 convalescent patients measured by VSV-SARS-CoV-2-Sdel18 pseudovirus assay has a good correlation with live SARS-CoV-2 assay. Seven neutralizing monoclonal antibodies targeting receptor binding domain (RBD) of SARS-CoV-2-S were obtained. This efficient and reliable pseudovirus assay model could facilitate the development of new drugs and vaccines.

Serology characteristics of SARS-CoV-2 infection since the exposure and post symptoms onset

BackgroundTimely diagnosis of SARS-CoV-2 infection is the prerequisite for treatment and preventive quarantine. The serology characteristics and complement diagnosis value of antibody test to RNA test needs to be demonstrated. MethodA patient cohort study was conducted at the first affiliated hospital of Zhejiang University, China. Serial plasma of COVID-19 patients and were collected and total antibody (Ab), IgM and IgG antibody against SARS-CoV-2 were detected. The antibody dynamics during the infection were described. ResultsThe seroconversion rate for Ab, IgM and IgG in COVID-19 patients was 98.8% (79/80), 93.8% (75/80) and 93.8% (75/80), respectively. The first detectible serology marker is total antibody and followed by IgM and IgG, with a median seroconversion time of 15, 18 and 20 day post exposure (d.p.e) or 9, 10 and 12 days post onset, separately. The antibody levels increased rapidly since 6 d.p.o and accompanied with the decline of viral load. For patients in the early stage of illness (0-7d.p.o),Ab showed the highest sensitivity (64.1%) compared to the IgM and IgG (33.3% for both, p<0.001). The sensitivities of Ab, IgM and IgG detection increased to 100%, 96.7% and 93.3% two weeks later, respectively. ConclusionsTypical acute antibody response is induced during the SARS-CoV-2 infection. The serology testing provides important complementation to RNA test for pathogenic specific diagnosis and helpful information to evaluate the adapted immunity status of patient. It should be strongly recommended to apply well-validated antibody tests in the clinical management and public health practice to improve the control of COVID-19 infection. Take-Home MessageAntibody responses are induced after SARS-CoV-2 infection and complement diagnosis value of antibody test to RNA test was observed. Antibody tests are critical tools in clinical management and control of SARS-CoV-2 infection and COVID-19.

Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019

BackgroundThe novel coronavirus SARS-CoV-2 is a newly emerging virus. The antibody response in infected patient remains largely unknown, and the clinical values of antibody testing have not been fully demonstrated. MethodsA total of 173 patients with confirmed SARS-CoV-2 infection were enrolled. Their serial plasma samples (n = 535) collected during the hospitalization period were tested for total antibodies (Ab), IgM and IgG against SARS-CoV-2 using immunoassays. The dynamics of antibodies with the progress and severity of disease was analyzed. ResultsAmong 173 patients, the seroconversion rate for Ab, IgM and IgG was 93.1% (161/173), 82.7% (143/173) and 64.7% (112/173), respectively. Twelve patients who had not seroconverted were those only blood samples at the early stage of illness were collected. The seroconversion sequentially appeared for Ab, IgM and then IgG, with a median time of 11, 12 and 14 days, respectively. The presence of antibodies was < 40% among patients in the first 7 days of illness, and then rapidly increased to 100.0%, 94.3% and 79.8% for Ab, IgM and IgG respectively since day 15 after onset. In contrast, the positive rate of RNA decreased from 66.7% (58/87) in samples collected before day 7 to 45.5% (25/55) during days 15 to 39. Combining RNA and antibody detections significantly improved the sensitivity of pathogenic diagnosis for COVID-19 patients (p < 0.001), even in early phase of 1-week since onset (p = 0.007). Moreover, a higher titer of Ab was independently associated with a worse clinical classification (p = 0.006). ConclusionsThe antibody detection offers vital clinical information during the course of SARS-CoV-2 infection. The findings provide strong empirical support for the routine application of serological testing in the diagnosis and management of COVID-19 patients.

Biomechanical models and numerical studies of atherosclerotic plaque / 生物医学工程学杂志

Atherosclerosis is a complex and multi-factorial pathophysiological process. Researches over the past decades have shown that the development of atherosclerotic vulnerable plaque is closely related to its components, morphology, and stress status. Biomechanical models have been developed by combining with medical imaging, biological experiments, and mechanical analysis, to study and analyze the biomechanical factors related to plaque vulnerability. Numerical simulation could quantify the dynamic changes of the microenvironment within the plaque, providing a method to represent the distribution of cellular and acellular components within the plaque microenvironment and to explore the interaction of lipid deposition, inflammation, angiogenesis, and other processes. Studying the pathological mechanism of plaque development would improve our understanding of cardiovascular disease and assist non-invasive inspection and early diagnosis of vulnerable plaques. The biomechanical models and numerical methods may serve as a theoretical support for designing and optimizing treatment strategies for vulnerable atherosclerosis.

Multi-disciplinary management for metastatic renal cell carcinoma in the ear of targeted therapy: a single center experience / 中华泌尿外科杂志

Objective@#To report the experience on the multi-disciplinary management of metastatic renal cell (mRCC) patients in a single center.@*Methods@#Data of 168 mRCC patients treated by multi-disciplinary team (MDT) at Sun Yat-sen University Cancer Center from December 2007 to February 2019 was retrospectively analyzed.Three treatment groups were identified, including 76 patients with 55 males and 21 females, received anti-angiogenic agents alone (Group A), 66 patients with 55 males and 11 males, received anti-angiogenic agents plus local therapy (Group B)and 26 patients, with 19 males and 7 females, received anti-angiogenic agents plus immunotherapy and local therapy (Group C). The Sunitinib, Sorafenib, Axitinib were chosen for the TKI. The Pembrolizumab was used for immunotherapy. The stereotactic body radiation therapy and surgical excision were considered as the local therapy. The study aims to compare the age, gender, IMDC score, pathology, nbephrectomy, adverse events, progression-free survival and overall survival (OS).@*Results@#Of all patients, the median follow-up duration was 23 months (ranging 6-117 cmonths). The PFS was 18.3 months and median OS was 33.5 months. The 2 years and 5 years survival rate was 66% and 35%, respectively. The median OS of Group A, B and C were 29.8 months, 44.6 months and not reached. 2y-OS was 58%, 67% and 89%, while 5y-OS 12%, 46% and 57%.There was no difference in age, gender, IMDC score, pathology, synchronous metastases or nephterectomy between the three groups. The prognostic result in TKI based combination therapy was superior to TKI therapy alone, which the 5y-OS was 51% and 11%, respectively. The prognostic result in group C's moderate-high risk mRCC patients was superior to group A and B. The median OS in TKI+ DC and CIK+ Pembrolizumab was 49.1 months and 53.1 months. On univariate analyses, IMDC score, nephrectomy and treatment group was associated with OS (P<0.05). On multivariate analyses, treatment group, nephrectomy was associated with OS (P<0.05). The risk of death of Group C decreased about 60% [HR 0.39 (0.17, 0.89), P=0.026]. 78 (46.4%) patients on TKI alone and 16 (61.5%) patients treated with TKI plus immunotherapy had Grade 3 or 4 adverse events. 16 (20.3%) patients had Clavien Ⅲ-Ⅳ toxicity after surgical procedures. 6 (5.7%) patients had Grade 3 toxiciy after SBRT.@*Conclusions@#Patients treated with combined therapy had better survival than those treated with anti-angiogenic agents alone. MDT approach could bring survival benefit to mRCC patients.

Experimental study on the chronic alcohol-induced testicular microvascular injury and spermatogenic cell morphological changes by contrast-enhanced ultrasound / 中华超声影像学杂志

Objective:To explore the value of contrast-enhanced ultrasound and its quantitative analysis technology in the evaluation of testicular microvascular injury caused by chronic alcoholism, as well as its relationship with the morphological changes of testicular spermatogenic cells.Methods:Seventy-two New Zealand white rabbits were randomly divided into control group (S group), low-dose alcohol group (L group), medium-dose alcohol group (M group), and high-dose alcohol group (H group). Then, the rabbits were subdivided into the groups of S1, S2, S3, L1, L2, L3, M1, M2, M3, H1, H2, H3 according to different time points (30 d, 60 d, 90 d). The rabbits in each group were examined by routine ultrasound before the experiment, followed by contrast-enhanced ultrasound examination. Testicular tissues were taken for pathological examination under light and electron microscope.Results:①The peak intensity and area under the curve of ultrasound contrast parameters gradually decreased with the increase of dosage and duration of alcohol feeding (all P<0.05), and the curvature also gradually decreased (all P<0.05). The differences of peak time, mean transit time, and peak half-time were not statistically significant (all P>0.05). ②With the increase of alcohol dosage and duration under the light microscope, the seminiferous tubule epithelium gradually became thinner, and the sperm in the cavity gradually decreased or no sperm was produced. The Johnsen′s score of testicular tissue decreased with the increase of alcohol dosage and duration (all P<0.05). The cytoplasmic mitochondria of the microvascular endothelial cells were vacuolated under the electron microscope. With the dosage and duration of alcohol feeding, the endothelial cells were vacuolated and even shed, and the basement membrane was interrupted. Conclusions:Alcohol could damage the testicular microvessels and spermatogenic cells in a dose-effect and time-effect relationship. Contrast-enhanced ultrasound can be used to evaluate the microvessel damage of testis caused by chronic alcoholism and indirectly reflect the morphological changes of spermatogenic cells.

Clinical study of Naoxintong capsule combined with levamlodipine tablets in the treatment of essential hypertension / 中国基层医药

Objective:To investigate the clinical effect of Naoxintong capsule combined with levamlodipine tablets in the treatment of essential hypertension.Methods:From February 2018 to February 2019, 182 cases of essential hypertension were selected in Jiangshan Hospital of Traditional Chinese Medicine and divided into treatment group (91 cases) and control group (91 cases) according to the random digital table.The treatment group was treated with Naoxintong capsule combined with levamlodipine tablets, while the control group was treated with levamlodipine tablets.Both two groups were treated for 12 weeks.The therapeutic effects, blood pressure, urinary microalbumin (MAU), vascular endothelial function and inflammatory mediators before and after treatment were compared between the two groups.Results:The total effective rate of the treatment group[91.21%(83/91)]was higher than that of the control group[79.12%(72/91)](χ 2=5.262, P<0.05). After treatment, SBP[(132.36±8.27)mmHg], DBP[(84.35±5.32)mmHg]and MAU[(26.47±5.47)mg/L] in the treatment group were lower than those in the control group[(139.62±6.58)mmHg, (89.74±4.12)mmHg and (33.82±3.76)mg/L]( t=6.553, 7.641, 10.563, all P<0.05). The NO[(52.17±5.36)μmol/L]and FMD[(7.98±0.42)%] in the treatment group were higher than those in the control group[(41.09±7.28)μmol/L and (6.79±0.37)%], while ADMA[(0.23±0.06)μmol/L]in the treatment group was lower than that in the control group[(0.34±0.07)μmol/L], the differences were statistically significant( t=11.692, 20.281, 11.382, all P<0.05). The serum levels of IL-1[(128.32±13.25)ng/L] and IL-4[(24.35±5.71)ng/L] in the treatment group were lower than those in the control group[(173.79±23.19)ng/L and (32.19±6.57)ng/L], while the serum IL-10 level[(23.54±3.25)ng/L] in the treatment group was higher than that in the control group[(18.09±4.86)ng/L], the differences were statistically significant( t=16.240, 8.592, 8.892, all P<0.05). Conclusion:Naoxintong capsule combined with levamlodipine tablets is effective in the treatment of essential hypertension, which can reduce MAU, improve vascular endothelial dysfunction and alleviate inflammation.

Analysis of risk factors for recurrent laryngeal nerve injury in secondary thyroidectomy / 国际外科学杂志

Objective:Exploring the risk factors of recurrent laryngeal nerve injury in thyroid surgery.Methods:The hundred and sixteen patients undergoing secondary thyroid surgery from January 2016 to January 2019 were selected in the general surgery department of the First Affiliated Hospital of Harbin Medical University. The patients were divided into an injury group ( n=20) and a control group ( n=296) according to whether the recurrent laryngeal nerve injury occurred after the secondary operation. SPSS 23.0 was used to perform univariate analysis and multivariate regression analysis. Results:The total injury rate of recurrent laryngeal nerve in secondary thyroid surgery was 6.33% (20/316). In the univariate analysis, the size of the thyroid, the first operation, the interval between two operations, the tumor aggressiveness, the secondary operation, and whether nerve monitoringa were statistically significant in the injury group and the control group( χ2=1.495, 1.503, 1.628, 1.299, 1.938, 1.262, P<0.05). Logistic regression analysis showed that the size of the thyroid gland ( OR=4.962, P=0.001), the first operation ( OR=12.296, P=0.002), the interval between two operations ( OR=3.590, P=0.025) and the secondary operation ( OR=2.319, P=0.002) were an independent risk factors for recurrent laryngeal nerve injury in secondary thyroid surgery. Conclusions:Secondary thyroid surgery is more likely to cause recurrent laryngeal nerve damage. For the thyroid disease with a high risk of recurrence, total thyroidectomy should be selected for the first surgery to to avoid the risk of complications caused by secondary surgery; For some complicated secondary surgery patients, the use of recurrent laryngeal nerve monitoring technology during operation can minimize the recurrent laryngeal nerve injury and improve the patient′s postoperative quality of life.