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.

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.

Semi-quantitative risk assessment of the contamination of Vibrio parahaemolyticus in oysters from Jinshan District, Shanghai / 上海预防医学

Objective To investigate the prevalence of Vibrio parahaemolyticus(VP)in oysters in Jinshan District, Shanghai and make assessment on the risks that may cause, providing the basis for prevention and control of foodborne disease. Methods Raw oyster samples with shells were randomly collected from markets, supermarkets and restaurants in Jinshan District from July to October in 2017. The content of VP in oysters was tested in accordance with the national standard methods. The semi-quantitative risk assessment for VP in oysters was made by Risk Ranger combining with the monitoring results of diet and health status of residents in Jinshan District of Shanghai in 2012-2013. Results The overall positive rate of VP in the 40 oyster samples was 80.0%(32/40). The positive rate of VP in oyster samples from farmer's markets was the highest, 85.7%(12/14), followed by those from restaurants and supermarkets. The relative risk for VP in raw oysters was 63. The probability of illness caused by VP in oysters per day per consumer of interest was 6.85×10-4, and the total predicted patients annual incidence rate in this population was 1 247.8/105. Conclusion The contamination of VP in seafood oysters in Jinshan District is serious. Eating raw oysters is at high risk; consumers are advised to reduce or avoid eating raw oysters, and processing food before eating is an effective method to decrease VP infection. Strengthening surveillance and management is imperative in this regard.

Wutoutang Modulation Hippocampal BDNF/TrkB Pathway to Relieve Pain-emotion Co-curation / 中国实验方剂学杂志

<b>Objective::To explore the mediating effect of Wutoutang (WTT) on brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) pathway in hippocampus and to clarify the mechanism of therapeutic action of WTD on pain-emotion comorbidity by inhibiting neuropathic pain (NP) preliminarily. <b>Method::The mice were divided into sham group, spinal cord ligation (SNL) group, Wutoutang (WTT) group, Wutoutang-ANA12 antagonist (WTT-ANA12) group, pregabalin (PGB) group, Fluoxetine Hydrochloride (FLU) group randomly. Mice were fixed with the drug delivery cannula for hippocampal CA3.The L5 spinal cord of mice were tightly ligated but sham group (only exposed). During the 10-16^th day after surgery, WTT, WTT-ANA12 groups were gavaged with 126 mg·kg^-1 WTT, PGB and FLU groups were respectively given 25 mg·kg^-1 PGB and 3 mg·kg^-1 FLU, sham and SNL groups were given the physiological saline once a day. Then, 50 nmol·L^-1 ANA12 were given to the hippoicampal CA3 of the WTT-ANA12 mice by drug delivery cannula, and physiological saline were given to the others on the 10-16^th day after surgery. Mechanical pain were detected by Von Frey tests, anxiety and depression behaviors were separately detected by the open field and the tail tailing experiments, while the morphology of CA3 pyramidal neurons were qualified by the Golgi-staining. <b>Result::Compared with sham group, significant decreases of the mechanical pain thresholds, decreases of the duration time in the open field, as well as the increases of the no-struggling time during the tail-suspension were detected in the SNL mice(<italic>P</italic><0.01). In addition, as illustrated by the Golgi-staining, the atrophy of hippocampal pyramidal neurons were found in SNL mice as compared with sham(<italic>P</italic><0.05, <italic>P</italic><0.01). On the contrary, as compared to the SNL, significant increases of the mechanical pain thresholds, increases of the duration time in the open field, the decreases of the no-struggling time during the tail-suspension(<italic>P</italic><0.01), as well as the morphological improvements of the hippocampal CA3 pyramidal neurons were detected in the WTT mice. Furthermore, after 7 d hippocampal injections, There is no significant distinction of the mechanical pain thresholds, the duration time in the open field, the no-struggling time during the tail-suspension, as well as the atrophy of hippocampal neurons were detected in the WTT-ANA12 groups as compared with SNL. <b>Conclusion::The data suggested that the effective inhibition of WTT on SNL-induced vertebral neuron injury in hippocampus CA3 and pain-emotion disorder, which might attribute to it' s regulation of BDNF/TrkB pathway in hippocampus.

Neuroprotective Effect by Wutoutang in Spinal Nerve Ligation Mice via BDNF/TrkB Signaling Pathway / 中国实验方剂学杂志

Objective::To investigate the neuroprotective effect and mechanism by Wutoutang (WTT) in the spinal nerve ligation (SNL) mice by neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) signaling BDNF/tyrosine kinase receptor B (TrkB). Method::The 40 mice were randomly divided into Sham group, SNL group, WTT group(126 mg·kg-1), ANA-12+ WTT group.The L5 spinal nerve ligation model mice were established in mice, After that, WTT was administrated from the first day to the 10th day, then the consecutive 7-day hippocampal injection of ANA-12(0.05 nmol·L-1)were lasted for 7 days.The levels of brain-derived BDNF, cAMP-response element binding protein(CREB), and protein kinase B(Akt)and the change of hippocampal glutamatergic and GABAergic neurons in mice were detected by tissue immunofluorescence.E14 pregnant ICR mice were sacrificed and the hippocampus were dissected which were divided into control group, glycine group, tumo necrosis factor(TNF)-α(5 mg·L-1)+ glycine group, TNF-α+ WTT(5 mg·L-1)+ glycine group, TNF-α+ WTT+ glycine+ BDNF-siRNA group, TNF-α+ WTT+ glycine+ Akt-siRNA group, TNF-α+ WTT+ glycine+ CREB-siRNA group, the primary and secondary dendrrictes, in which the arrowheads indicate the expression od postsynapti desity protein 95(PSD95) in the shafts and arrows were tested by cellular immunofluorescence.The neurons were divided into control group, glycine group, ANA-12 group(0.5 mmol·L-1), ANA-12+ glycine group, ANA-12+ WTT group, ANA-12+ WTT+ glycine group, the morphology of hippocampal neurons were tested by cellular immunofluorescence. Result::Compared with Sham group, BDNF, Akt and CREB positive cell of SNL group decreased significantly(P<0.01), the hippocampal glutamatergic and GABAergic neurons out of balance(P<0.01). Compared with SNL group, the BDNF, Akt and CREB positive cell of WTT group increased significantly(P<0.01), Glutamine-aminobutyric acid neurons regein balance(P<0.01). Compared with WTT group, BDNF and CREB positive cell of ANA-12+ WTT group decreased significantly(P<0.05), Glutamine-aminobutyric acid neurons was disorderedd(P<0.05). Comparaed with control group, the level of PSD95 of glycine group were increase significantly(P<0.01). The number of dendritic spine density apically and basally of glycine group were increase significantly(P<0.01), but the primary and secondary dendrites of ANA-12 group, ANA-12+ glycine group, ANA-12+ WTT group, ANA-12+ WTT+ glycine group were not change.Comparaed with glycine group, the level of PSD95 of TNF-α+ glycine group were decreased significantly(P<0.01). Comparaed with TNF-α+ glycine group, the level of PSD95 of TNF-α+ WTT+ glycine group were increase significantly(P<0.01). Comparaed with TNF-α+ WTT+ glycine group, the level of PSD95 of TNF-α+ WTT+ glycine+ BDNF-siRNA group, TNF-α+ WTT+ glycine+ Akt-siRNA group, TNF-α+ WTT+ glycine+ CREB-siRNA group were decreased significantly(P<0.01). Conclusion::In vivo and in vitro studies have shown that the WTT mediated remission of the primary hippocampal glutamatergic neurons were dependent on the BDNF/TrkB pathway.

Effect of Celastrol on Neuropathic Pain Model Mice / 中国实验方剂学杂志

Objective:To investigate the effect of celastrol on painful and the emotional of anxiety and depression comorbidity on neuropathic pain model animal and to explore its possible mechanism．Method:Mice were randomly divided into sham group， model group， pregabalin group(25 mg·kg-1)， low， medium and high-dose celastrol groups (5，10，20 mg·kg-1). The mice model of neuropathic pain were established by the L5 spinal nerve ligation (SNL). After successful modeling， the treatment groups were given intragastric administration， the sham group and the model group were given the same volume of warm water.Mechanical pain were detected by Von Frey tests， anxiety and depression behaviors were separately detected by the open field and the tail tailing experiments， the pathological changes of microglial cells in hippocampus of mice in each group were observed by immunohistochemical staining (IHC). The inflammation of BV2 microglial cell made by 1 mg·L-1 lipopolysaccharide (LPS). Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of tumor necrosis factor-α (TNF-α). The expression levels of TNF-α protein were detected by immunofluorescence（IF） staining.Result:Compared with sham group， significant change of mechanical pain thresholds， anxiety and depression were detected in the SNL mice (P<0.05，P<0.01)， the significant decreases of the body size of hippocampal microglia (P<0.05). Compared with SNL model group， 20 mg·kg-1 celastrol significantly increased the 50% paw withdraw threshold and the time of the open feld tests (P<0.05，P<0.01)，and decreased the time of the tail tailing experiments in the SNL mice (P<0.05)， and the cell body area of hippocampal microglia in SNL mice was reduced (P<0.05). Experiment in vitro show， compared with control group， the expression of TNF-α mRNA and protein expression in LPS-induced BV2 microglia increased significantly from 2-4 h (P<0.05，P<0.01). Compared with the LPS group， after 100 nmol·L-1 celastrol administration， LPS-induced microglia inflammatory factor TNF-α mRNA and TNF-α protein expression were significantly decreased (P<0.01).Conclusion:Celastrol can relieve pain-emotion comorbidity on neuropathic pain model mice， and its mechanism may be related to the anti-inflammation in the central nerves system.

Effect of Hei Xiaoyaosan on Expression of CaMKⅡα Protein and Its Phosphorylation in Hippocampus and Cerebral Cortex of APP/PS1 Double Transgenic Mice / 中国实验方剂学杂志

Objective::To study the effect of Hei Xiaoyaosan on the expression of calcium calmodulin-dependent protein kinase Ⅱ alpha(CaMKⅡα) and its phosphorylation in hippocampus and cortex of mice with Alzheimer's disease. Method::After weighing, 30 APP/PSI transgenic male mice were divided into model group, donepezil hydrochloride group and Hei Xiaoyaosan group according to random principle and 10 in each group.At the same age, wild-type C57BL/6 10 mice of the same species were treated as blank group. Donepezil hydrochloride group (6 g·kg-1) and Hei Xiaoyaosan group (3.25 mg·kg-1) were administered for 90 days, then the behavior of all the mice were detected by Morris water maze, the expression of CaMKⅡα, p-CaMKⅡα proteins in hippocampus and cortex by immunohistochemical technique and Western blot. Result::After intervention 3 months, compared with blank group, the average escaping latency periods prolonged significantly and the number of cross-platform and effective areas were decreased distinctly in model group mice(P<0.01), CaMKⅡα protein relative expression decreased significantly(P<0.01), p-CaMKⅡα protein relative expression increased significantly(P<0.01). Compared with the model group, the escape latency of donepezil hydrochloride and Hei Xiaoyaosan group were significantly shortened, and the number of crossing platforms and effective areas was significantly increased (P<0.05, P<0.01), the expression of CaMKⅡα protein in the hippocampus and cortex of drug groups was significantly increased (P<0.01), p-CaMKⅡα protein in the hippocampus and cortex of drug groups was significantly decreased (P<0.05, P<0.01). Conclusion::Hei Xiaoyaosan can improve the learning and memory ability of AD mice by regulating the expression of CaMKⅡα and its phosphorylation, which are key proteins involved in the mechanism of cell memory formation in different brain regions of AD mice.

Feasibility of Hei Xiaoyaosan in Preventing and Treating Alzheimer's Disease Based on Theory of 'Correlation of Liver and Kidney' Based on Ca2+-CaM/CaMKⅡ-CREB Signal Pathway / 中国实验方剂学杂志

Alzheimer's disease（AD） is an incipient aging neurodegenerative disease， which increases rapidly along with the development trend of social aging and seriously threatens the health of the people. In the absence of effective preventive measures， it will have an enormous impact on the socio-economic and healthcare system. The study found that abnormal cell signal transduction is a key link in many diseases. Cell signal transduction theory has been widely used to clarify the essence of traditional Chinese medicine visceral image and the mechanism of traditional Chinese medicine. 'Correlation of Liver and Kidney' is one of the core plates of the theory of 'Correlation of Five Organs'， which is suitable for explaining the pathogenesis of complex diseases and the correlation of multiple syndromes， and guiding the prescription of clinical syndrome. Hei Xiaoyaosan， as the first choice compound for the prevention and treatment of AD based on the theory of "Correlation of Liver and Kidney' in our team， can play the effects of prevention and treatment by soothing liver and nourishing blood， strengthening spleen and tonifying kidney， and promoting brain collaterals and dredging viscerab spirit. Based on the theory of 'Correlation of Liver and Kidney'， this paper expounds the pathogenesis of AD from the perspective of traditional Chinese medicine， and puts forward the methods and ideas of the preventing and treating of AD from Ca2+-calcium/calmodulin dependent protein （CaM）/calcium/calmodulin dependent protein kinaseⅡ（CaMKⅡ）-cyclic adenosine phosphate reactive element binding protein （CREB） cell signal transduction pathway by consulting literatures and previous studies.

Effect of Hei Xiaoyaosan on Expressions of Aβ1-42, GSK-3β, NEP, IDE in Hippocampus Area of Alzheimer's Dementia Mice / 中国实验方剂学杂志

Objective: To observe the effect of Hei Xiaoyaosan on expressions of β-amyloid 1-42 peptide(Aβ1-42),glycogen synthase kinase-3β(GSK-3β),neprilysin(NEP),insulin-degrading enzyme(IDE) in the hippocampus area of Alzheimer's dementia mice. Method: After weighing, 42 APP/PSI bivalent transgenic mice were randomly divided into 4 groups:10 mice in the model group, 10 mice in the positive drug control group, 11 mice in the high-dose Hei Xiaoyaosan group, and 11 mice in the low-dose Hei Xiaoyaosan group; 10 wild C57BL/6J mice of the same age and strain were used for negative control group. Drugs were administered to mice by gavage once a day for 12 weeks. Then the behavior of all the mice were detected by Morris water maze, the morphological changes in hippocampal neurons were observed by hematoxylineosin(HE) staining, the expressions of Aβ1-42, GSK-3β, NEP and IDE proteins in hippocampus were detected by immunohistochemistry. Result: After 3 months of treatment, compared with negative control groups, the average escaping latency periods prolonged significantly, and the number of cross-platform was decreased significantly in model group (Pβ1-42 and GSK-3β proteins in model mice hippocampus were significantly increased (PPPβ1-42 and GSK-3β proteins in the hippocampus of drug groups were significantly decreased (PPPConclusion: Hei Xiaoyaosan can significantly improve the learning and memory abilities of AD mice, which may be related to the reduction of cognitive impairment in AD mice by regulating abnormal deposition and degradating Aβ in the hippocampus.

Effect of Hei Xiaoyaosan on Expressions of APP，PERK in Hippocampus Area of Alzheimer's Dementia Mice / 中国实验方剂学杂志

Objective: To study the effect of Hei Xiaoyaosan on endoplasmic reticulum stress in hippocampal neurons of Alzheimer's disease (AD) model mice, including behavioral, histopathology and amyloid precursor protein (APP), protein kinase endoplasmic reticulum kinase (PERK) expressions. Method: The 42 4-month-old SPF-grade double transgenic (APP/PS1) mice were randomly divided into the high-dose group and the low-dose group, the donepezil hydrochloride group and the model group, and 10 C57BL mice of the same age were used as the blank group. Firstly, they were adapted to the environment for one week. After 2 months of treatment with different drug interventions, Morris water maze behavior was used to test the learning and memory abilities of each group of mice. After 1 month of treatment, histopathological changes in the hippocampus of each group of mice were observed by light microscopy. The expressions of APP, PERK protein and mRNA in the endoplasmic reticulum of hippocampus were detected by immunohistochemistry (IHC) and real-time fluorescent quantitative polymerase chain reaction (Real-time PCR). Result: After drug intervention, compared with the blank group, the escape latency of the AD model group was significantly prolonged (PPPPPConclusion: Hei Xiaoyaosan can significantly improve the learning and memory abilities of AD mice, which may be related to the reduction of the excessive stress response of endoplasmic reticulum to alleviate cognitive impairment in AD mice.

Clinical symptoms effect of Tripterygium Glycosides Tablets alone or combined with methotrexate in treatment of rheumatoid arthritis: a Meta-analysis / 中国中药杂志

To systematically review the improvement effects of Tripterygium Glycosides Tables( TGT) alone or in combination with methotrexate( MTX) on the clinical signs and symptoms of rheumatoid arthritis( RA),and provide a basis for the rational use of TGT in clinic,in the current study,six literature databases including CNKI,Wan Fang,VIP,PubMed,EMbase,and Cochrane Library,were systematically searched,according to the inclusion and exclusion criteria. Review Manager 5.3 software was used to input the literatures,and we assessed the risk bias on the level of outcome indicators for each included literature. A total of 18 literatures were included,and the classification results showed that: compared with MTX,TGT alone can reduce the number of joint swelling( MD =0. 18,95%CI[-1.06,1.42],P = 0.78) and joint tenderness( MD =-0.06,95% CI[-1.69,1.56],P = 0.94) in RA patients with the same effect as MTX. In terms of drug combination,TGT combined with MTX had an advantage over MTX alone in lessening the morning stiffness time( MD = 18. 24,95% CI[12. 64,23. 84],P < 0. 000 01) of RA,joint tenderness( MD = 2. 65,95% CI[1. 85,3. 44],P<0.000 01) and joint swelling( MD = 3.01,95% CI[2.09,3.39],P< 0.000 01). In conclusion,this Meta-analysis suggest that TGT alone was superior to MTX in improving joint swelling and tenderness in RA patients,TGT combined with MTX may improve the clinical manifestation of RA patients better than MTX alone.

Meta-analysis of laboratory index of Tripterygium Glycosides Tablets in treatment of rheumatoid arthritis / 中国中药杂志

The aim of this study was to systematically evaluate the clinical efficacy of Tripterysium Glycosides Tablets( TGT) alone or in combination with methotrexate( MTX) in the treatment of rheumatoid arthritis( RA) based on the laboratory index criteria and to provide a basis for the clinical application of TGT against RA. Six databases including CNKI,Wan Fang,VIP,PubMed,EMbase and Cochrane were retrieved for randomized controlled trials( RCT) about TGT alone or combination with MTX in the treatment of RA.Then risk assessment tools were used for quality evaluation of the studies,and data extraction and analysis were conducted by using Rev Man 5.3 software for Meta-analysis. A total of 1 709 articles were retrieved,and finally 25 studies were included,with a total sample size of 2 507 cases. Meta-analysis results showed that between TGT alone and TGT alone,MDESR=-2. 66,95%CI[-8.17,2.86],P = 0.35; MDCRP=-2.38,95%CI[-9.01,4.24],P = 0.48; between TGT combined with MTX and MTX alone,MDESR= 8.74,95%CI[6.72,10.76],P<0.000 01; MDCRP= 5.37,95%CI[3.71,7.03],P<0.000 01; SMDRF= 1.05,95%CI[0.51,1.60],P = 0.000 1.The effect of TGT on decreasing CRP and ESR in RA patients was similar to the MTX. In addition,TGT combined with MTX were more effective in decreasing CRP,ESR,RF than MTX alone. However,due to the potential bias in the included studies,more and high-quality randomized controlled trials would be needed to improve the level of evidence.

Expression of c-MET, EGFR and HER-2 of human gastric adenocarcinoma / 临床与实验病理学杂志

Purpose To investigate the expression status and their clinical significances of c-MET, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor-2 (HER-2) in gastric adenocarcinoma (GC). Methods Tissue samples from 442 cases of GC in patients who accepted D2/D3 radical gastrectomy with R0 resection were stained by immunohistochemistry against c-MET, EGFR and HER-2.Results Over expression of c-MET, EGFR and HER-2 was identified in 195/442 (44.1％), 47/442 (10.6％) and 152/442 (34.4％) GC patients, respectively. Over expression of cMET was more often identified in GC patients with deeper T (P= 0.016), nerve involvement (P = 0.006) and the Lauren diffuse type (P = 0.029). EGFR in cases with vessel permeation (P = 0.012), and HER-2 in cases of distant metastasis (P =0.031), non-nerve involvement (P = 0.024), the Lauren intestinal type (P < 0.001) and G1/G2 grade (P < 0.001). Conclusion The receptors tyrosine kinase (RTKs) markers of cMET, EGFR and HER-2 might involve in the advance of GC, such as invasion and metastasis. The expression status of them could be used as the risk prediction and even the basis for future personalized therapy, especially for tyrosine kinase inhibitor (TKI) therapy, for GC patients.

Effects of Angelica Polysaccharide on Learning and Memory Abilities and Aβ Metabolism in Model Rats with Alzheimer Disease / 中国中医药信息杂志

Objective To investigate effects of angelica polysaccharide on learning and memory abilities, Ach, ChAT, AChE, SOD, MDA in serum, APP and Aβ1-42 in hippocampus in model rats with Alzheimer disease (AD); To explore the mechanism of angelica polysaccharide for the treatment of AD. Methods Seventy SPF Wistar rats were selected for learning and memory ability by water maze. 10 rats were randomly selected (half female and half male) as sham-operation group, and the others were injected with Aβ25-35 by stereotatic techniques, copying AD model rats. 50 rats for learning and memory ability by water maze were successfully divided into model group, positive group, angelica polysaccharide low-, medium-, and high-dose groups, with 10 rats in each group. Rats in model group and sham-operation group were given normal saline for gavage, while rats in medication groups were given relevant medicine for gavage, 2 mL/(100 g?d), for 28 d. The learning and memory ability of rats in each group was tested by Morris water maze during 25-28 days, and the contents of Ach, ChAT, AChE, SOD, MDA in serum and APP and Aβ1-42 in hippocampus were determined. Results Compared with the sham-operation group, the escape latent period of model group was significantly prolonged in place navigation experiment; the target quadrant time was shortened; the latent time for the first time to reach the original escape platform was longer in spatial probe test; the residence time of crossing the original platform position and the target quadrant was shorter; the levels of Ach, the activity of ChAT and SOD in serum decreased; the levels of MDA, the activity of AChE in serum increased; the levels of APP and Aβ1-42 in hippocampus increased, with statistical significance (P<0.05, P<0.01). Compared with model group, the escape latent period of each medication group was shortened in different degrees after the intervention treatment; the residence time of target quadrant was prolonged; the latent time for the first time to reach the original escape platform was shortened; the number of cross platform increased; the levels of Ach, the activity of ChAT and SOD in serum increased; the levels of MDA and the activity of AChE in serum decreased; the levels of APP and Aβ1-42 in hippocampus significantly decreased, with statistical significance (P<0.05, P<0.01). Conclusion Angelica polysaccharide may effectively improve the learning and memory of ability of AD model rats to improve anti-free radical oxidation and promote Aβ metabolism and promote learning and memory ability of AD model rats, which have some preventive and therapeutic effects on AD.

siRNA-mediated antizyme inhibitor down-regulates the expression of ornithine decarboxylase of prostate cancer cell PC3 / 基础医学与临床

Objective To evaluate whether down-regulating antizyme inhibitor(AZIN) can regulate the expression of ornithine decarboxylase(ODC) and the proliferation of prostate cancer cell PC3 or not.Methods siRNA-AZIN transfected prostate cancer cell PC3,the level of antizyme(AZ),AZIN and ODC were measured by RT-PCR and westernblot. MTT was used to measure the proliferation of cells. Results The mRNA level of AZIN declined(P<0.01);the protein level of AZIN and ODC declined(P<0.05). Knockdown of AZIN significantly inhibited the proliferation of PC3(P<0.05). Conclusions Transfecting siRNA-AZIN can decrease the level of AZIN, then the decline level of ODC inhibits the proliferation of PC3.

Effects of Jinqi Zhizhu Decoction on Gastric Motility of GK Rats with Diabetic Gastroparesis / 中国中医药信息杂志

Objective To investigate the effects of Jinqi Zhizhu Decoction (JQZZD) on gastric motility of GK rats with diabetic gastroparesis (DGP); To discuss its mechanism of action. Methods 12 out of 80 male GK rats were randomly selected as normal group, and others were induced to be DGP model by irregular feeding with high sugar and high fat diet for 8 weeks. The model rats were randomly divided into model group, positive medicine group, JQZZD low-, medium-, and high-dose groups. All rats were given continuous intragastric administration for 12 weeks. The residual rate of pigment in stomach was detected and calculated. The concentration of DA, ACh and 5-HT in plasma were detected by ELISA. The morphological changes of gastric antrum were observed by HE staining. The ultrastructure of mucous layer of gastric antrum was observed by transmission electron microscope. The protein expressions of Rho A, ROCK1 and ROCK2 were detected by Western blot. Results Compared with normal group, the residual rate of pigment in model group increased, while DA, ACh and 5-HT, relative amount of protein expressions of Rho A, ROCK1 and ROCK2 decreased (P＜0.01). Compared with model group, the residual rate of pigment in positive medicine group and JQZZD high-dose group decreased, while DA, ACh and 5-HT, relative amount of protein expressions of Rho A, ROCK1 and ROCK2 increased (P＜0.05, P＜0.01), and morphological changes and ultrastructure of mucous layer obviously improved. There was no significant differences in the residual rate of pigment, DA content and protein expressions of Rho A, ROCK1 and ROCK2 between positive medicine group and JQZZD high-dose group (P＞0.05). Compared with JQZZD low-dose group, the residual rate of pigment in JQZZD high-dose group decreased, while DA, ACh and 5-HT, relative amount of protein expressions of Rho A, ROCK1 and ROCK2 increased (P＜0.05, P＜0.01). Conclusion JQZZD may improve gastric motility, promote gastric emptying, and improve and repair damage of mucous membrane in the gastric antrum. All of these may be related to regulating protein expressions of Rho A/ROCK signal pathway.

Effect of Xiaoyao Powder on the ethology, morphology, and activities of neurotransmitters of Alzheimer's disease model mice / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the effect of Xiaoyao Powder (XP) and its compatible prescriptions on the ethology, morphology, and activities of neurotransmitters, thus exploring their effects and mechanism in preventing and treating D-galactose induced Alzheimer's disease (AD) model mice, and clarifying the compatibility mechanism for soothing Gan, nourishing blood, and invigorating Pi.</p><p><b>METHODS</b>Sixty SPF mice were randomly divided into the blank control group, the model group, and the XP group, Shugan Jianpi group (SJ), Shugan Yangxue group (SY), and Jianpi Yangxue group (JY), 10 in each group.The AD mouse model was prepared by peritoneal injecting D-galactose. Meanwhile, mice in the blank control group and the model group were administered with physiological saline (at the daily dose of 24 mL/kg) by gastrogavage. Mice in the XP group (2.485 g/kg), the SY group (1.136 g/kg), the SJ group (1.775 g/kg), and the JY group (2.059 g/kg) were administered with corresponding medicated decoction by gastrogavage, with the gastric volume of 24 mL/kg. On the 41st day the training of capability for learning and memory was started. On the 42nd day capability for learning and memory was tested. The brain tissue was cut. One half was used to determine the contents of homogenate acetyl cholinesterase (AchE), choline acetyltransferase (ChAT), and monoamine oxidase (MAO).Another half was used to carry out morphological observations.</p><p><b>RESULTS</b>The capability for learning and memory could be improved and the latency time could be lowered in all the treatment groups. Besides, the homogenate AchE and MAO could also be elevated, ChAT could be lowered; the morphology, number, and distribution of neurons could be improved. But the improvement of ethology, morphology, and activities of neurotransmitters were most obviously seen in the XP group.</p><p><b>CONCLUSIONS</b>XP could improve the ethology, morphology, and activities of neurotransmitters, and showed better effects on prevention and treatment of AD. The rationality of compatibility methods and combination thinking ways of soothing Gan, nourishing blood, and invigorating Pi were clarified.</p>

Percutaneous sonography-guided radiofrequency ablation in the management of parathyroid adenoma

Parathyroid adenoma is a major cause of primary hyperparathyroidism. Treatment usually involves the surgical removal of one or more parathyroid glands. However, specific localising techniques have boosted the development of nonsurgical, minimally invasive procedures, such as percutaneous radiofrequency ablation (RFA) under ultrasonographic guidance, which are gaining popularity as a method of treatment. This paper reports two male patients who presented with hypercalcaemia (highest serum calcium level 4.56 mmol/L and 4.57 mmol/L, respectively) and hyperparathyroidism (highest serum parathyroid hormone [PTH] level 772 ng/L and > 1,900 ng/L, respectively) due to solitary parathyroid adenoma. Four days after percutaneous RFA, the serum calcium levels in both patients decreased and PTH levels showed a significant decreasing trend. Both patients recovered well with normal levels of calcium and improvement of symptoms. Thus, we conclude that RFA may be a safe and effective therapeutic option in the treatment of parathyroid adenoma.

Prognostic value of Her-2/neu and clinicopathologic factors for evaluating progression and disease-specific death in Chinese men with prostate cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Her-2/neu gene overexpression has been found in several malignancies, and is associated with poor prognosis; while its role in the tumorigenesis and progression of prostate cancer (PCa) is still controversial. This study aimed to evaluate the prognostic value of Her-2/neu protein expression and clinicopathologic factors in antiandrogen-treated Chinese men with PCa for disease progression and PCa-specific death.</p><p><b>METHODS</b>Her-2/neu protein expression was determined using immunohistochemistry (IHC) in specimens collected from 124 prostate biopsies and transurethral resection of prostate (TURP) from seven prostate cancer patients.</p><p><b>RESULTS</b>Her-2/neu protein expression was 0, 1+, 2+, and 3+ in 40 (30.5%), 8 (6.1%), 67 (51.1%), and 16 (12.2%) cases, respectively. Her-2/neu protein expression showed significant correlation as judged by Gleason score (P = 0.049), clinical tumor-node-metastases (cTNM) stage (P = 0.018) and disease progression (P = 0.001), but did not correlate with prostate-specific antigen (PSA) (P = 0.126) or PCa-specific death (P = 0.585). PSA (P = 0.001), Gleason score (P = 0.017), cTNM (P = 0.000) and Her-2/neu protein expression (P = 0.001) had prognostic value for evaluating the progression of PCa in univariate analysis. In Kaplan-Meier plots, both Gleason score (P = 0.035) and cTNM (P = 0.013) correlated with PCa-specific death. In multivariate analysis, only cTNM was significant for both disease progression (P = 0.001) and PCa-specific death (P = 0.031).</p><p><b>CONCLUSIONS</b>Her-2/neu protein expression is significantly correlated with Gleason score, cTNM and disease progression, although it is not an independent predictor of disease progression and PCa-specific death. cTNM staging serves as an independent prognostic factor for disease progression and PCa-specific death.</p>