Survival outcomes of radium-223 therapy for metastatic castration-resistant prostate cancer following national health insurance reimbursement in Taiwan.

BACKGROUND: Radium-223 dichloride (Ra-223) prolongs overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) with symptomatic bone metastases. However, there is considerable variation in outcomes among individuals. We aimed to evaluate the prognostic determinants associated with patient survival following National Health Insurance (NHI) reimbursement for Ra-223 therapy in Taiwan. METHODS: Patients with mCRPC who underwent Ra-223 treatment at Taipei Veterans General Hospital were retrospectively enrolled. Each intravenous Ra-223 dose was administered at 55 kBq/kg at 4-week intervals. Clinical outcomes were obtained from medical records; potential prognostic factors for survival were assessed. Kaplan-Meier analysis was used to generate cumulative survival curves; between-group differences were evaluated using the Chi-squared test. Statistical significance was set at p < 0.05. RESULTS: Seventy-six patients underwent Ra-223 therapy; 62 patients received NHI reimbursement and the remainder self-paid. Fifty patients (65.8%) completed six cycles of treatment; 26 (34.2%) received 1 to 5 cycles. Mortality occurred in 47 patients. Factors significantly associated with survival included ≤five bone metastases ( p = 0.0018), baseline prostate-specific antigen (PSA) ≤36 ng/mL ( p = 0.0004), baseline alkaline phosphate (ALP) <115 U/L ( p = 0.0007), and baseline hemoglobin (Hb) >12 g/dL ( p = 0.0029). Patients who completed six cycles of treatment achieved significantly higher OS compared to those who did not ( p < 0.0001). There has been a 4.4-fold increase in the number of patients since reimbursement began; there was no significant difference in OS between patients who received NHI reimbursement and those who self-paid. CONCLUSION: Administration of Ra-223 demonstrates considerable potential to extend the survival of patients with mCRPC. Survival outcomes may be influenced by various prognostic factors. However, no significant difference in OS was observed subsequent to reimbursement of Ra-223 therapy for mCRPC through the NHI system in Taiwan.

Measurements of elemental iodine in soy sauces in Taiwan using a modified microplate method.

Background: Soy sauce is widely used in a variety of Asian dishes to enhance flavor. Soybean and most soybean products, including soy sauces, are listed as prohibited foods in a low iodine diet. However, the iodine content in soy sauces is largely unknown. The aim of this study was to determine the iodine content in domestic soy sauces in Taiwan. Methods: Twenty-five different kinds of soy sauces were diluted with distilled water and with a dilution factor of fifty or above. Iodine concentrations of the diluted samples were measured colourimetrically based on the Sandell-Kolthoff reaction by a modified microplate method. All the measurements were repeated twelve times on three different days for determination of mean and standard deviation (SD), and coefficients of variance (CV). Serial dilution and recovery tests were also performed for validation. The results were confirmed by an inductively coupled plasma mass spectrometry (ICP-MS) method. Results: Among the twenty-five surveyed soy sauces, most of them (n=22) were iodine-free (<16 ug/L, and thus un-detectable). The iodine concentrations (mean ± SD) of the three iodine-containing soy sauces were 2.7 ± 0.1, 5.1 ± 0.2, and 10.8 ± 0.6 mg/L, respectively. The inter-assay, intra-assay and total CVs were all <5.3% for the modified microplate method. The results obtained by ICP-MS were consistent with those of the modified microplate method. The recovery rates in the serial dilution test and recovery test ranged from 94.7% to 118.6%. Two of the three iodine-containing soy sauces were supplemented with kelp extract, while the other one without kelp extract had the highest amount of salt among the three iodine-containing soy sauces. Therefore, we postulate that iodized salt instead of kelp extract is the source of higher iodine content in that sauce. Conclusion: The results suggest that most soy sauces are iodine-free and may be allowed during low iodine diets.

Clinicopathological features of gastric carcinomas with NTRK-rearrangement/amplification: report of four cases / 中华病理学杂志

Objective: To investigate the clinicopathological, immunohistochemical and molecular genetic characteristics of gastric carcinoma with NTRK-rearrangement/amplification. Methods: The clinicopathological data of gastric carcinoma cases with NTRK-rearrangement/amplification diagnosed from January 2011 to September 2020 at the Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, China, were collected. The clinicopathological, immunophenotypic and molecular pathological features were analyzed. The relevant literature was reviewed. Results: There were 4 cases of gastric carcinoma with NTRK-rearrangement/amplification. All 4 patients were male, aged 57-67 years (average, 63 years). Tumor sizes ranged from 3.5 to 5.2 cm (average, 4.8 cm). All tumors were in the antrum. All 4 patients underwent radical gastrectomy and were followed up after the surgery. Morphologically, all tumors showed histological features with enteroblastic-differentiated gastric carcinoma. Tumor cells showed predominantly tubular/papillary architecture, with conspicuous vesicular nuclei and pale staining or transparent cytoplasm. Immunohistochemistry showed pan-TRK expression in all cases, with various degrees of positivity in the cytoplasm. All cases were subject to NTRK1/2/3 detection using fluorescence in situ hybridization. There were NTRK translocations in 2 cases and NTRK amplifications in 2 cases. These cases were further verified by RNAseq next generation sequencing which confirmed that NTRK1 gene translocation (TPM3-NTRK1) and NTRK2 gene translocation (NTRK2-SMCHD1) occurred in two cases, respectively. Conclusions: NTRK mutation occurs less frequently in gastric cancer. In this study, the cases mainly occur in the antrum. The morphology has the characteristics of enteroblastic differentiation. The tumors have unique histological, immunophenotypic and molecular characteristics, which require much attention from pathologists to effectively guide clinicians to choose the best treatment.

Expression of GPNMB in renal eosinophilic tumors and its value in differential diagnosis / 中华病理学杂志

Objective: To investigate the expression of glycoprotein non metastatic melanoma protein B (GPNMB) in renal eosinophilic tumors and to compare the value of GPNMB with CK20, CK7 and CD117 in the differential diagnosis of renal eosinophilic tumors. Methods: Traditional renal tumor eosinophil subtypes, including 22 cases of renal clear cell carcinoma eosinophil subtype (e-ccRCC), 19 cases of renal papillary cell carcinoma eosinophil subtype (e-papRCC), 17 cases of renal chromophobe cell carcinoma eosinophil subtype (e-chRCC), 12 cases of renal oncocytoma (RO) and emerging renal tumor types with eosinophil characteristics [3 cases of eosinophilic solid cystic renal cell carcinoma (ESC RCC), 3 cases of renal low-grade eosinophil tumor (LOT), 4 cases of fumarate hydratase-deficient renal cell carcinoma (FH-dRCC) and 5 cases of renal epithelioid angiomyolipoma (E-AML)], were collected at the Affiliated Drum Tower Hospital of Nanjing University Medical School from January 2017 to March 2022. The expression of GPNMB, CK20, CK7 and CD117 was detected by immunohistochemistry and statistically analyzed. Results: GPNMB was expressed in all emerging renal tumor types with eosinophil characteristics (ESC RCC, LOT, FH-dRCC) and E-AML, while the expression rates in traditional renal eosinophil subtypes e-papRCC, e-chRCC, e-ccRCC and RO were very low or zero (1/19, 1/17, 0/22 and 0/12, respectively); the expression rate of CK7 in LOT (3/3), e-chRCC (15/17), e-ccRCC (4/22), e-papRCC (2/19), ESC RCC (0/3), RO (4/12), E-AML(1/5), and FH-dRCC (2/4) variedly; the expression of CK20 was different in ESC RCC (3/3), LOT(3/3), e-chRCC(1/17), RO(9/12), e-papRCC(4/19), FH-dRCC(1/4), e-ccRCC(0/22) and E-AML(0/5), and so did that of CD117 in e-ccRCC(2/22), e-papRCC(1/19), e-chRCC(16/17), RO(10/12), ESC RCC(0/3), LOT(1/3), E-AML(2/5) and FH-dRCC(1/4). GPNMB had 100% sensitivity and 97.1% specificity in distinguishing E-AML and emerging renal tumor types (such as ESC RCC, LOT, FH-dRCC) from traditional renal tumor types (such as e-ccRCC, e-papRCC, e-chRCC, RO),respectively. Compared with CK7, CK20 and CD117 antibodies, GPNMB was more effective in the differential diagnosis (P<0.05). Conclusion: As a new renal tumor marker, GPNMB can effectively distinguish E-AML and emerging renal tumor types with eosinophil characteristics such as ESC RCC, LOT, FH-dRCC from traditional renal tumor eosinophil subtypes such as e-ccRCC, e-papRCC, e-chRCC and RO, which is helpful for the differential diagnosis of renal eosinophilic tumors.

Concordance between three integrated scores based on prostate biopsy and grade-grouping of radical prostatectomy specimen / 中华病理学杂志

Objective: To analyze three different integrated scoring schemes of prostate biopsy and to compare their concordance with the scoring of radical prostatectomy specimens. Methods: A retrospective analysis of 556 patients with radical prostatectomy performed in Nanjing Drum Tower Hospital, Nanjing, China from 2017 to 2020. In these cases, whole organ sections were performed, the pathological data based on biopsy and radical prostatectomy specimens were summarized, and 3 integrated scores of prostate biopsy were calculated, namely the global score, the highest score and score of the largest volume. Results: Among the 556 patients, 104 cases (18.7%) were classified as WHO/ISUP grade group 1, 227 cases (40.8%) as grade group 2 (3+4=7); 143 cases (25.7%) as grade group 3 (4+3=7); 44 cases (7.9%) as grade group 4 (4+4=8) and 38 cases (6.8%) as grade group 5. Among the three comprehensive scoring methods for prostate cancer biopsy, the consistency of global score was the highest (62.4%). In the correlation analysis, the correlation between the scores of radical specimens and the global scores was highest (R=0.730, P<0.01), while the correlations of the scores based on radical specimens with highest scores and scores of the largest volume based on biopsy were insignificant (R=0.719, P<0.01; R=0.631, P<0.01, respectively). Univariate and multivariate analyses showed tPSA group and the three integrated scores of prostate biopsy were statistically correlated with extraglandular invasion, lymph node metastasis, perineural invasion and biochemical recurrence. Elevated global score was an independent prognostic risk factor for extraglandular invasion and biochemical recurrence in patients; increased serum tPSA was an independent prognostic risk factor for extraglandular invasion; increased hjighest score was an independent risk factor for perineural invasion. Conclusions: In this study, among the three different integrated scores, the overall score is most likely corresponded to the radical specimen grade group, but there is difference in various subgroup analyses. Integrated score of prostate biopsy can reflect grade group of radical prostatectomy specimens, thereby providing more clinical information for assisting in optimal patient management and consultation.

Gastric Mobility and Gastrointestinal Hormones in Older Patients with Sarcopenia.

Sarcopenia has serious clinical consequences and poses a major threat to older people. Gastrointestinal environmental factors are believed to be the main cause. The aim of this study was to describe the relationship between sarcopenia and gastric mobility and to investigate the relationship between sarcopenia and the concentration of gastrointestinal hormones in older patients. Patients aged ≥ 75 years were recruited for this prospective study from August 2018 to February 2019 at the emergency department. The enrolled patients were tested for sarcopenia. Gastric emptying scintigraphy was conducted, and laboratory tests for cholecystokinin(CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), nesfatin, and ghrelin were performed during the fasting period. We enrolled 52 patients with mean age of 86.9 years, including 17 (32.7%) patients in the non-sarcopenia group, 17 (32.7%) patients in the pre-sarcopenia group, and 18 (34.6%) in the sarcopenia group. The mean gastric emptying half-time had no significant difference among three groups. The sarcopenia group had significantly higher fasting plasma concentrations of CCK, GLP-1, and PYY. We concluded that the older people with sarcopenia had significantly higher plasma concentrations of CCK, GLP-1, and PYY. In the elderly population, anorexigenic gastrointestinal hormones might have more important relationships with sarcopenia than orexigenic gastrointestinal hormones.

High-Fat-Diet-Induced Oxidative Stress in Giant Freshwater Prawn (Macrobrachium rosenbergii) via NF-κB/NO Signal Pathway and the Amelioration of Vitamin E.

Lipids work as essential energy sources for organisms. However, prawns fed on high-fat diets suffer from oxidative stress, whose potential mechanisms are poorly understood. The present study aimed to explore the regulation mechanism of oxidative stress induced by high fat and the amelioration by vitamin E (VE) of oxidative stress. Macrobrachium rosenbergii were fed with two dietary fat levels (LF 9% and HF 13%) and two VE levels (200 mg/kg and 600 mg/kg) for 8 weeks. The results showed that the HF diet decreased the growth performance, survival rate and antioxidant capacity of M. rosenbergii, as well as inducing hypertrophied lipid droplets, lipophagy and apoptosis. A total of 600 mg/kg of VE in the HF diet alleviated the negative effects induced by HF. In addition, the HF diet suppressed the expression of toll-dorsal and imd-relish signal pathways. After the relish and dorsal pathways were knocked down, the downstream iNOS and NO levels decreased and the MDA level increased. The results indicated that M. rosenbergii fed with a high-fat diet could cause oxidative damage. Its molecular mechanism may be attributed to the fact that high fat suppresses the NF-κB/NO signaling pathway mediating pro-oxidant and antioxidant targets for regulation of oxidative stress. Dietary VE in an HF diet alleviated hepatopancreas oxidative stress and apoptosis.

Application of 20% glucose solution in the treatment of diabetic patients with hypoglycemia / 中华危重病急救医学

Objective:To explore the safety and efficacy of 20% glucose solution in the treatment of adult diabetic patients with hypoglycemia.Methods:A non-randomized controlled paired design trial was conducted. The diabetes patients with hypoglycemia (blood glucose < 3.9 mmol/L) who were admitted to the department of endocrinology and metabolism of Affiliated Hospital of Jiangsu University from December 2020 to May 2021 were enrolled. When the patients developed hypoglycemia for the first time, 75 mL of 20% glucose solution was pumped intravenously at a constant speed within 15 minutes, which was named the 20% glucose solution group. When the patients had hypoglycemia again, 30 mL of 50% glucose solution was pumped intravenously at a constant speed within 3 minutes, which was named the 50% glucose solution group. If the blood glucose was still ≤ 3.9 mmol/L at 15 minutes of hypoglycemia treatment, or the patients were uncomfortable due to too fast drip speed, it should be terminated immediately. The hypoglycemia treatment should be handled according to the Chinese guidelines for the prevention and treatment of type 2 diabetes (2020 edition). The peripheral blood glucose level and the range of increase at 15 minutes of treatment, the success rate of one treatment, the peripheral blood glucose values at 60 minutes after successful hypoglycemia treatment, the incidence of phlebitis and exudation after hypoglycemia treatment, and the pain of local blood vessels in patients with hypoglycemia treatment were analyzed and compared between the two groups. Results:A total of 65 patients completed the treatment of hypoglycemia with 20% glucose solution and the success rate of one treatment was 100%. The peripheral blood glucose value at 15 minutes of hypoglycemia treatment was (8.30±1.37) mmol/L, and the increased range was (4.86±1.30) mmol/L. The peripheral blood glucose value at 60 minutes after successful hypoglycemia treatment was (6.96±1.48) mmol/L, which indicated that 20% glucose solution could effectively increase blood glucose. Among 65 patients, 32 patients had hypoglycemia again, who were treated with 50% glucose solution, and the success rate of one treatment was 100%. When patients who received 50% glucose solution for hypoglycemia formed a paired design with the first 20% glucose solution treatment, the results showed that there was no significant difference in the peripheral blood glucose value and the increased range in blood glucose at 15 minutes of hypoglycemia treatment between the 20% glucose solution and the 50% glucose solution groups [peripheral blood glucose (mmol/L): 8.20 (7.70, 9.70) vs. 8.30 (7.80, 8.80), increase in blood glucose (mmol/L): 4.96±1.39 vs. 4.70±1.32, both P > 0.05], indicating that the glucose changing at 15 minutes of hypoglycemia treatment with 20% glucose solution was similar to that with 50% glucose solution. The peripheral blood glucose value at 60 minutes after successful hypoglycemia treatment of 20% glucose solution group was significantly lower than that of 50% glucose solution group (mmol/L: 6.37±1.04 vs. 7.20±1.36, P < 0.01), which meant that the blood glucose tended to be more stable. There was no phlebitis and exudation after hypoglycemia treatment in both groups. The pain score of 20% glucose solution group was 0, however, 3 patients in 50% glucose solution group complained of local vascular pain, and the pain score was 1. Conclusions:20% glucose solution can effectively treat hypoglycemia in diabetic patients, which has the same curative effect as 50% glucose solution and much safer. It can be used in patients with severe hypoglycemia.

Correlation of NTRK genetic fusions with mismatch repair protein deletion in patients with colorectal cancer / 中华病理学杂志

Objective: To investigate the relationship between the expression of four mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) and NTRK genetic fusions in colorectal cancer. Methods: The paraffin-embedded tissue blocks of 830 cases of colorectal cancer were collected at the Affiliated Drum Tower Hospital, Nanjing University Medical School, China, from 2015 to 2019. Immunohistochemical and fluorescence in situ hybridization(FISH) method were used respectively to detect the expression of mismatch repair proteins and the break-apart of NTRKs; and the relationship between the expression of mismatch repair proteins and the NTRK genetic fusions was analyzed. Results: The overall mismatch repair protein deficiency (dMMR) rate was 9.88% (82/830), the mismatch repair proteins proficiency (pMMR) rate was 90.12%(748/830). The total deficiency rate of MLH1 protein was 9.04% (75/830), hPMS2 protein deficiency rate was 9.04% (75/830), MSH2 protein deficiency rate was 2.53% (21/830), MSH6 protein deficiency rate was 4.10% (34/830), the deficiency rate of synchronous MLH1 and PMS2 were 8.67% (72/830) and the deficiency rate of synchronous MSH2 and MSH6 were 2.17% (18/830). The dMMR group was associated with tumor location, different histological subgroups, tumor differentiation, AJCC stage and N stage (P<0.05). There were six cases (7.32%) carrying NTRK fusion by FISH among the 82 cases of dMMR, but only seven cases (0.94%) carrying NTRK fusion among the 748 cases of PMMR. The NTRKs translocation by FISH in all 13 cases were further confirmed by next generation sequencing. Among the clinicopathological characteristics, only differentiation showed significant difference between NTRK fusion positive and negative groups (P<0.05). More importantly, NTRK fusion was enriched in dMMR group (7.32% vs. 0.94%). Conclusion: In dMMR colorectal cancer group, the prevalence of NTRK fusion is higher than that in pMMR group.

Fractionated deep-inspiration breath-hold ZTE Compared with Free-breathing four-dimensional ZTE for detecting pulmonary nodules in oncological patients underwent PET/MRI.

The zero echo time (ZTE) technique has improved the detection of lung nodules in PET/MRI but respiratory motion remains a challenge in lung scan. We investigated the feasibility and performance of fractionated deep-inspiration breath-hold (FDIBH) three-dimensional (3D) ZTE FDG PET/MRI for assessing lung nodules in patients with proved malignancy. Sixty patients who had undergone ZTE FDG PET/MRI and chest CT within a three-day interval were retrospectively included. Lung nodules less than 2 mm were excluded for analysis. Two physicians checked the adequacy of FDIBH ZTE and compared the lung nodule detection rates of FDIBH 3D ZTE and free-breathing (FB) four-dimensional (4D) ZTE, with chest CT as the reference standard. FDIBH resolved the effect of respiratory motion in 49 patients. The mean number and size of the pulmonary nodules identified in CT were 15 ± 31.3 per patient and 5.9 ± 4.6 mm in diameter. The overall nodule detection rate was 71% for FDIBH 3D ZTE and 70% for FB 4D ZTE (p = 0.73). FDIBH 3D ZTE significantly outperformed FB 4DZTE in detecting lung base nodules (72% and 68%; p = 0.03), especially for detecting those less than 6 mm (61% and 55%; p = 0.03). High inter-rater reliability for FDIBH 3D ZTE and FB 4D ZTE (k = 0.9 and 0.92) was noted. In conclusion, the capability of FDIBH 3D ZTE in respiratory motion resolution was limited with a technical failure rate of 18%. However, it could provide full expansion of the lung in a shorter scan time which enabled better detection of nodules (< 6 mm) in basal lungs, compared to FB 4D ZTE.

Identification of chemical constituents in ethyl acetate soluble extract of Sinopodophylli Fructus based on HPLC-MS~n / 中国中药杂志

A high performance liquid chromatography with a diode array detector combined with electrospray ionization ion trap time-of-flight multistage mass spectrometry(HPLC-DAD-ESI-IT-TOF-MS~n, HPLC-MS~n) method was established for qualitative analysis of the chemical components of ethyl acetate extract from Sinopodophylli Fructus. The analysis was performed on a Kromasil 100-5 C_(18)(4.6 mm×250 mm, 5 μm) column, with a mobile phase consisted of 0.1% formic acid(A) and acetonitrile(B) for gradient at a flow rate of 1.0 mL·min~(-1). Electrospray ionization ion trap time-of-flight multistage mass spectrometry was applied for qualitative analysis under positive and negative ion modes. With use of reference substance, characteristic fragmentation and their HR-MS data, 102 components were identified, including 67 flavonoids and 35 lignans. Among them, 45 compounds were reported in Sinopodophylli Fructus for the first time and 19 compounds were identified as new compounds. PharmMapper was used to predict the bioactivity of compounds that were first reported in Sinopodophylli Fructus, and 20 compounds of them were identified to have potential anticancer activity. The results showed that there were many isomers in the ethyl acetate extract of Folium Nelumbinis, and a total of 19 groups of isomers were found. Among them, C_(21)H_(20)O_8 had the highest number of isomers(18 compounds), all of which were α-peltatin or its isomers; C_(21)H_(20)O_7 ranked second, with 10 compounds, all of which were 8-prenylquercetin-3-methyl ether or its isomers. In conclusion, an HPLC-MS~n method was established for qualitative analysis of the ethyl acetate extract(with anti-breast cancer activity) from Sinopodophylli Fructus in this study, which will provide the evidence for clarifying pharmacological active ingredients of the ethyl acetate extract from Sinopodophylli Fructus against breast cancer.

Study on influence factors of acupoint function based on energetics / 中国针灸

Acupoint is the integration of structure and function. In this paper, the structure and function of acupoint are studied based on energetics. It is viewed that acupoint is the aggregation and release place of energy, acupuncture is the process of applying energy to acupoint, and the variations of speed, direction, time and local temperature are the key factors of acupoint function.

Follicular Thyroid Cancer With Nose-Tip Metastasis and 131I Uptake.

We present a 56-year-old woman with metastatic follicular thyroid cancer at the nose tip with I uptake that is clinically rare, mimicking physiological uptake in the nose, a common finding seen after routine I therapeutic imaging. The lesion revealed a metastatic follicular thyroid cancer with I uptake and response to I therapy. Surgical removal, however, was not performed due to cosmetic and functional considerations. Active surveillance is warranted owing to its relative aggressiveness in nature.

A how-to-guide to building a robust SARS-CoV-2 testing program at a university-based health system

When South Florida became a hotspot for COVID-19 disease in March 2020, we faced an urgent need to develop test capability to detect SARS-CoV-2 infection. We assembled a transdisciplinary team of knowledgeable and dedicated physicians, scientists, technologists and administrators, who rapidly built a multi-platform, PCR- and serology-based detection program, established drive-thru facilities and drafted and implemented guidelines that enabled efficient testing of our patients and employees. This process was extremely complex, due to the limited availability of needed reagents, but outreach to our research scientists and to multiple diagnostic laboratory companies and government officials enabled us to implement both FDA authorized and laboratory developed testing (LDT)-based testing protocols. We analyzed our workforce needs and created teams of appropriately skilled and certified workers, to safely process patient samples and conduct SARS-CoV-2 testing and contact tracing. We initiated smart test ordering, interfaced all testing platforms with our electronic medical record, and went from zero testing capacity, to testing hundreds of healthcare workers and patients daily, within three weeks. We believe our experience can inform the efforts of others, when faced with a crisis situation.

Response of Macrobrachium rosenbergii to Vegetable Oils Replacing Dietary Fish Oil: Insights From Antioxidant Defense.

The study was conducted to evaluate the effects of fish oil replacement by vegetable oils on growth performance, histology, and antioxidant capacity of Macrobrachium rosenbergii. Three isonitrogenous and isoenergetic diets were formulated with different lipid sources included. DFO diet contained 6% fish oil, whereas DSO and DRO diets included 6% soybean oil and rapeseed oil (RO) as alternatives for fish oil, respectively. Prawns were fed thrice daily for 8 weeks. The results showed that prawns in DFO group showed significantly lower final weight, weight gain ratio, and specific growth rate (SGR), but higher feed intake and feed coefficient ratio than those in DSO and DRO groups. In hepatocellular ultrastructure, malformed and atrophic nucleus and higher apoptosis ratio were observed in DFO group. In addition, levels of haemolymph proinflammatory cytokines, activities of anti-superoxide anion, inducible-type NO-synthase (iNOS) and content of nitric oxide, and hepatopancreas NF-κB signal pathway gene expression in DFO group increased markedly compared to those of DSO and DRO groups. The results suggested that vegetable oils, such as soybean oil and RO might be the better lipid sources in diets for Macrobrachium rosenbergii than fish oil, it may be attributed to modified oxidative status induced by NF-κB-NO signal pathway.

Qualitative Analysis on Perilla frutescens Leaves and Stalks by UPLC-Q-Exactive-Orbitrap-MS / 中国实验方剂学杂志

Objective:To establish a method for qualitative analysis of components in Perilla frutescens leaves and stalks by liquid chromatography-mass spectrometry (LC-MS)，so as to explore the substance basis of pharmacodynamics differences between P.frutescens leaves and stalks.Method:P. frutescens leaves and stalks were extracted by 80% methanol-water ultrasound. The samples were analyzed by UPLC-Q-Exactive-Orbitrap-MS comprehensively. Halo-C18 column (2.1 mm×100 mm，2.7 μm) was used for gradient elution with 0.05% formic acid aqueous-0.05% acetonitrile formate as mobile phase in positive and negative ion modes. The flow rate was 0.3 mL·min-1，the column temperature was 40 ℃，and the injection volume was 5 μL.Result:The chemical compound in P. frutescens was deduced and identified based on the retention time of chromatography，and the exact molecular weight，excimer ion peaks，fragment ions and reference materials in Xcalibur software. The chemical composition of P. frutescens was identified by Mass Frontier 7.0 software. Totally 4 amino acids，7 phenylpropanoids，10 flavonoids，12 triterpenoids，7 organic acids，4 fatty acids，10 unknown compounds and 54 compounds were identified. Among them，6 triterpene acids, including glochidone, were identified in P. frutescens for the first time. The structures of five characteristic compounds were analyzed. There were 45 constituents in P.frutescens leaves and 32 constituents in P. frutescens stalks. They had 23 common constituents.Conclusion:LC-MS can identify the components of P. frutescens rapidly and effectively. This study provides an important theoretical basis for the quality control of different parts of P. frutescens and the development and utilization of P. frutescens.

Efficacy-toxicity Evaluation of Mahuang Xixin Fuzi Decoction on Mice with Kidney-yang Deficiency / 中国药学杂志

OBJECTIVE: To study the pharmacodynamic effects of Mahuang Xixin Fuzi Decoction (MXF) on mice with kidney-yang deficiency, its toxic effects on normal mice and effect-toxic mechanism. METHODS: BABL/C male mice were randomly divided into normal groups; normal groups with low, medium and high toxicity; kidney Yang deficiency model group. The low, medium and high dose groups were treated with infected Influenza virus of kidney-yang deficiency. After continuous gavage for 6 days, the body weight anal temperature and other pharmacological indicators were recorded, and the general signs, biochemical indicators and inflammatory factors of the mice were detected. RESULTS: Compared with the normal group, the biochemical parameters of the kidney yang deficiency model group, which means the creatine kinase (CK), creatine kinase-isoenzyme (CK-MB), alpha-hydroxybutyrate dehydrogenase (α-HBDH), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate transferase (AST), alkaline phosphatase (ALP) and urea (urea) were significantly increased (P<0.05), inflammatory factors interleukin-6 (IL-6), monocyte deproteinization protein (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-10 (IL- 10), interferon-γ (INF-γ) and interleukin 12 (IL-12p70) increased significantly (P<0.05). After administration, the levels of biochemical markers such as CK, ALT and urea in each administration groups were slightly reduced compared with the model group. The levels of inflammatory factors such as IL-6, IL-10 and IFN-γ in each administration groups showed different degrees of callback compared with the model group. In the toxicity study, the biochemical indicators of CK, urea, and cysteine (CYS-C) in each drug-administered group were significantly higher than those in the normal group (P<0.05), and the inflammatory factor interleukin-10 (IL-10) increased significantly, and the content of interleukin-12 (IL-12p70) decreased significantly (P<0.05). CONCLUSION: After treatment with MXF, the above biochemical indicators of mice with kidney yang deficiency and external sensation have different degrees of callback. MXF can achieve therapeutic effects by regulating IL-6, IL-10, IFN-γ, MCP-1, TNF-α and other factors on the body′s inflammatory response. While normal mice give different doses of MXF, the heart, liver and kidney function are dysfunctional, the balance of immune response of the body are broken through cell transfer, thus making normal mouse developed an inflammatory response.

Effects of Moringa oleifera leaf extract on growth performance, physiological and immune response, and related immune gene expression of Macrobrachium rosenbergii with Vibrio anguillarum and ammonia stress.

In order to study the effects of Moringa oleifera leaf extract on Macrobrachium rosenbergii under high ammonia exposure, freshwater prawns were randomly divided into five groups: a control group was fed with basal diet, and four treatment groups fed with basal diet supplemented with 0.25%, 0.5% and 1.0% M. oleifera leaf extract and 0.025% Enrofloxacin for 60 days, respectively. Then, freshwater prawns were exposed to high ammonia stress for 72 h and Vibro anguillarum infection. The growth, antioxidant capabilities, related immune genes as well as resistance to infection by V. anguillarum were determined. The results showed that compared with the control group, the weight gain, specific growth rate and protein efficiency rate, haemolymph catalase (CAT), superoxide dismutase (SOD) and inducible nitric oxide synthase (iNOS) increased while feed conversion ratio, haemolymph aspartate aminotransferase, alanine aminotransferase, nitrogen oxide (NO), hepatopancreas heat shock proteins (HSP70), immune deficiency (IMD) expression levels decreased in the group of 0.5% M. oleifera leaf extract before the stress. After ammonia stress, the group of 0.5% M. oleifera leaf extract also could improve the haemolymph SOD, glutathione peroxidase, NO, iNOS, hepatopancreas HSP70 expression levels and reduce haemolymph CAT, hepatopancreas peroxiredoxin 5 and NF kappa B inhibitor alpha expression level compared with the control group. The rate of mortality of the prawns challenged with V. anguillarum was lower in the supplemented groups in comparison with the control group with the lowest being in the group of 0.5% M. oleifera leaf extract. Antioxidant activities as well as biochemical parameters in the enrofloxacin group (0.025%E) were not significantly enhanced both pre and post challenge in comparison with the M. oleifera leaf extract groups, showing the superiority of the natural herb over the synthetic antibiotic. In summary, this study suggested that at an inclusion rate of 0.5%, M. oleifera leaf extract could increase the growth performance, even has positive effects on physiological and immune function and prevents high ammonia stress in the Freshwater prawn, M.rosenbergii.

The effects of crowding stress on the growth, physiological response, and gene expression of the Nrf2-Keap1 signaling pathway in blunt snout bream (Megalobrama amblycephala) reared under in-pond raceway conditions.

We evaluated the effects of high density stress on growth performance, antioxidant parameters, and Nrf2 pathway signaling molecules after different lengths of exposure (30, 60, or 90 days) of Megalobrama amblycephala to in-pond raceway aquaculture systems (IPRS). M. amblycephala (average initial weight 2.33 ±â€¯0.15 g) were reared at two different initial densities (low density group [LD] had 534 fish/m3 and high density group [HD] had 1073 fish/m3) for 90 days. The growth performance was adversely influenced by the high stocking density. The HD group had elevated white blood cell counts, hemoglobin content, and hematocrit on days 60 and 90. The mRNA levels of NOX2 on days 60 and 90, Nrf2 on days 30, 60, and 90, Keap1 on day 30, Bach1 on days 30 and 60, SOD on day 30, and CAT on day 30 were significantly higher in the HD group than in the LD group. Similarly, higher trends were observed in the enzymatic activities of SOD on day 60, CAT on days 60 and 90, and GPx on day 60 in the HD group, compared to the LD group. Furthermore, HD bream showed an increased MDA content on days 60 and 90 compared to that of the LD group. This study demonstrates that high density-induced antioxidant defenses were involved in modifications to the enzymatic and transcriptional regulation of Nrf2-Keap1 signaling molecules and that M. amblycephala growth was reduced in a crowded IPRS.

Toxic effects of combination of Aconiti Lateralis Radix Praeparata with Trichosanthis Fructus on inflammatory response and myocardial fibrosis in pressure overload rats based on β2-AR/PKA signal / 中国中药杂志

To study the effects of combination of Aconiti Lateralis Radix Praeparata( Fuzi) with Trichosanthis Fructus( Gualou) on cardiac function,electrocardiogram,inflammatory response and myocardial fibrosis in pressure overload( PO) rats,and further explore the mechanism based on β2-AR/PKA signaling. PO rat model was established by constricting the abdominal aorta. Twelve weeks after the operation,these rats were randomly divided into model goup( PO),low dose Fuzi group( FL,5. 4 g·kg-1·d-1),Gualou group( GL,5. 4 g·kg-1·d-1),Fuzi and Gualou combination group( FG,5. 4 g·kg-1·d-1+5. 4 g·kg-1·d-1) and high dose Fuzi group( FH,10. 8 g·kg-1·d-1). At the same time,sham operation group was set. After intervention for 6 weeks,carotid blood pressure,cardiac function,electrocardiogram and heart mass index were measured. HE staining was used to observe the inflammatory response in the rat heart and kidney. Masson staining was used to determine the myocardial fibrosis. Western blot was used to detect the protein expression of β2-AR and PKA. As compared with sham operation group,the blood pressure and heart mass index were obviously increased in PO model group,but there was no significant difference in various treatment groups in the above indexes. As compared with PO model group,FH treatment significantly increased the ejection fraction( EF) and GL treatment effectively enhanced the cardiac output( CO),but other treatment groups had no significant effect on these parameters. Moreover,FG treatment can synergistically attenuate QT and QTc internal prolongation,but it also aggravated inflammatory response in the heart and kidney tissues and promoted myocardial fibrosis as compared to FZ or GL alone treatment,with toxic effects equivalent to FH treatment group. Following FG and FH treatment,simultaneously,β2-AR and PKA protein levels were significantly elevated,indicating that the increasing toxicity of FG could be associated with activation of β2-AR/PKA signaling. These results suggested that combination of FZ and GL could synergistically enhance toxicity of FZ in special pathological states such as pressure overload,and caution should be taken in clinical application.