Purpose To detect the expression of osteopontin(OPN) and minkine(MK) protein in paraffin-embedded samples obtained from patients with infiltrating breast carcinoma and to analyze the relationships between their expression and clinical feature and prognosis in order to provide valuable biomarkers for the treatment and prognosis of infiltrating breast carcinoma.Methods The expression of OPN and MK was measured in 90 infiltrating breast cancer tissues and 30 hyperplastic disease of the breast by immunohistochemical PV-9000 two-step method.Results Immunohistochemical results showed that the positive rates of OPN and MK in infiltrating breast carcinoma were 71.11% (64/90) and 78.89 (71/90), respectivelyy, which were significantly higher than that in hyperplastic diseases of breast [30.00% (9/30) and 46.67% (14/30)](P<0.05);the expression of OPN was significantly correlated with tumor size, axillary lymph node metastasis,recurrence of tumor and the expression of p185(P<0.05),but not with the TNM stage,histological type,grade,and ER and PR status(P>0.05).The expression of MK was significantly correlated with tumor size,axillary lymph node metastasis,recurrence of tumor , the expression of p185 and TNM stage(P<0.05), but not with histological type, grade,and ER and PR status(P>0.05).There was a significantly positive relationship between OPN and MK expression (r=0.274,P=0.009). TTP and OS in patients with OPN and MK positive expression were shorter than those with OPN and MK negative expression (P<0.05).Conclusions OPN and MK′s expression may correlate with the progression of breast cancer.OPN and MK′s detection may provide a theoretical basis for the diagnosis and treatment of infiltrating breast carcinoma.

Objective To study the role of expressions of vascular endothelial growth factor C (VEGF-C), vascular endothelial growth factor receptor-3 (VEGFR-3) and lymphatic vessel hyaluronan receptor-1(LYVE-1) on the lymphangio-genesis and prognosis in gastric cancer. Methods The tissue microarray technology was used to detect the expressions of VEGF-C, VEGFR-3 and LYVE-1 in 125 gastric cancer specimens, 96 adjacent normal tissues and 20 benign gastric lesion samples. The lymphatic vessel density (LVD) marked by Podoplanin was detected as well. Results The positive rates of VEGF-C, VEGFR-3 and LYVE-1 in gastric cancer tissues were 62.4%, 56.0%and 58.4%, which were significantly higher than those in adjacent normal tissues (10.4%,12.5%and 9.4%) and benign gastric lesion tissues (20%, 30%and 25%, P<0.05). The LVD score was significantly higher in gastric intra-tumoral and peri-tumoral samples (2.98±0.81 and 4.22±1.09) than that in adjacent normal tissues or benign gastric lesion samples (1.82±0.63 or 0.89±0.45, P<0.01). The LVD score was significantly higher in peri-tumoral samples than that of intra-tumoral samples (P<0.01). There was a positive relationship between expression levels of VEGF-C,VEGFR-3 and LYVE-1 with LVD (P<0.05). The positive expressions of the three indexes were the risk factors of lymph node metastasis and distant metastasis (P<0.05). There was a significantly longer 5-year survival rate in patients with negative expression of the three indexes (P<0.05). Conclusion VEGF-C, VEGFR-3 and LYVE-1 proteins were positively highly expressed in gastric cancer tissues, which were risk factors affecting the progno-sis of gastric cancer. The expression levels of the three indexes can be used to predict the prognosis and lymphangiogenesis of gastric cancer.

Objective To investigate effect of glucose and lipid metabolism on acute cerebral infarction patients by Rhodiola injection. Methods 201 cases of acute cerebral infarction patients were selected,and divided into experiment group and control group.The control group of 101 cases were treated by clinical routine therapy,the experiment group 100 cases were treated with Rhodiola injection.The clinical efficacy, blood rheology and blood lipids, blood glucose index were compared before and after treatment.Results After 2 weeks of treatment, the total effective rate in experimental group was significantly higher than the control group(χ2 =12.596, P<0.05), with statistical difference.Patients in the experimental group,FBG was significantly lower than the control group, the difference was statistically significant (t=8.830, P<0.05).Patients in the experimental group TG, TC, LDL-C were significantly lower than that of control group, HDL-C was significantly higher than control group (P<0.05).Blood rheology indexes decreased significantly better than the control group ( P<0.05 ) .Conclusion Rhodiola injection on patients with acute cerebral infarction has good clinical curative effect, and can effectively improve the blood lipid, blood glucose level, reduce blood viscosity, is of great significance to the clinical treatment of cerebral infarction.

Objective To examine the effects of genetic polymorphisms in GSTM1, GSTT1 and GSTP1 (rs1695) genes on hematologic toxicities of breast cancer patients receiving Anthracycline/Paclitaxel- based chemotherapy. Methods Multiply PCR technique and High Resolution Melting method were used to examine these 3 genes polymorphsim in female breast cancers (n=252). Results The GSTP1(rs1695) AG/GG genotype was a risk factor forⅢ-Ⅳdegree of neu-trophil toxicity when patients received Paclitaxel-based chemotherapy and Anthracycline-Paclitaxel-based chemotherapy (OR=6.111, 95%CI 1.526-24.469, P<0.05 and OR=9.257, 95%CI 2.903-29.522, P<0.01). There were no statistic differ-ence onⅢ-Ⅳdegree hematologic toxicities rates between GSTM1(+) and GSTM1(-), GSTT1(+) and GSTT1(-) patients after they receiced Paclitaxel-based chemotherapy and Anthracycline-Paclitaxel-based chemotherapy( P>0.05);There was no statistic difference onⅢ-Ⅳdegree hematologic toxicities rates between GSTM1(+) and GSTM1(-), GSTT1(+) and GSTT1(-), GSTP1AA and GSTP1AG/GG patients after they receiced Anthracycline-based chemotherapy (P>0.05). Conclusion The genetic polymorphisms in GSTP1(rs1695) can be used as a gene marker for forecasting the chemotherapy, inducing neutrope-nia toxicities in breast cancer patients receiving Paclitaxel-based chemotherapy.

AIM: To investigate the effects of nitric oxide (NO) on hepatic encephalopathy in cirrhotic rats induced by LPS. METHODS: The cirrhotic model of rats was established by complex pathogeny. Since the end of the 8 th week, the rats were intragastrically-infused with 0.9% salt, L-arginine(L-arg) and LNNA respectively for 2 weeks.The hepatic encephalopathy in cirrhotic rats were induced by 3 mg/kg LPS (ip) 4 hours before the rats were sacrificed. RESULTS: The normal behaviors and electroencephalograph were appeared in L-arg group. LNNA group showed hepatic encephalopathy. The content of NO-_2/NO-_3 of brain tissue was markedly higher in L-arg group than LNNA group(P

，and 17.47%.Conclusions Xylitol can lower the blood glucose a littte but without significant difference.It has little effect on blood glucose variability of patients with type 2 diabetes mellitus and can be safely used for rehydration.

OBJECTIVETo study the expression of angiotensin-2 (Ang-2), Tie-2 and vascular endothelial growth factor receptor-2 (VEGFR-2) in colorectal cancer and analyze their relationship with the occurrence, recurrence, metastasis, angiogenesis and prognosis of colorectal cancer.

METHODSImmunohistochemistry with SP method was used to detect the expressions of Ang-2, Tie-2 and VEGFR-2 in 118 colorectal cancer, 40 adjacent normal tissue and 40 benign colorectal lesion specimens.

RESULTSThe positivity rates of Ang-2, Tie-2 and VEGFR-2 in colorectal cancer tissue were 74.58%, 69.49%, and 61.02%, respectively, significantly higher than those in the adjacent normal tissues (25.00%, 17.50%, and 17.50%, P<0.05) and benign colorectal lesion tissues (35.00%, 32.50%, and 32.50%, P<0.05). The rates of two or three coexpression were significantly higher than that of a single expression in the cancer tissues (61.02% vs 15.25%). The microvascular density (MVD) of colorectal cancer tissues was 31.43∓10.50, significantly higher than that of the adjacent normal tissues (10.61∓3.76) and benign colorectal lesions (16.89∓3.83) (P<0.05). The expressions of Ang-2, Tie-2, and VEGFR-2 were positively correlated with carcinoembryonic antigen (CEA) and MVD (P<0.05). The expression of Ang-2, but not Tie-2 and VEGFR-2, was positively correlated with CA199. Ang-2, Tie-2, and VEGFR-2 expressions showed significant differences between cases with tumor recurrence/metastasis and those without 5 years after radical mastectomy, and were all positively correlated with the 5-year survival rates (P<0.05).

CONCLUSIONAng-2, Tie-2 and VEGFR-2 are involved in the development, invasion, metastasis, and prognosis of colorectal cancer, and play important roles in the angiogenesis of the tumors.

Adolescent ; Adult ; Aged ; Angiopoietin-2 ; metabolism ; Colorectal Neoplasms ; blood supply ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Neovascularization, Pathologic ; metabolism ; Prognosis ; Receptor, TIE-2 ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism ; Young Adult

OBJECTIVE：To provide reference for further improving the establishment of drug registration applicant compliance management organizations in China. METHODS ：Through introducing and analyzing the establishment ，responsibility configuration and operation mechanism of drug registration applicant compliance management organizations in the United States ，the suggestions were put forward for improving the establishment of drug registration applicant compliance management institutions in China. RESULTS & CONCLUSIONS ：There were two levels of compliance management organizations for drug registration applicant in the United States ；at Office of the Commissioner of FDA level ，the Compliance Policy Council was responsible for ensuring consistency in the implementation of all compliance policies in the FDA regulated area ；at the level of Center for Drug Evalution and Research （CDER）and Office of Regulatory Affairs （ORA），the compliance management function was mainly undertaken by Office of New Drugs （OND），Office of Generic Drugs （OGD），Office of Compliance （OC） and Office of Communication （OCOMM）under CDER ，as well as Office of Policy and Risk Management （OPRM），OC，Office of Bioresearch Monitoring Operations（OBIMO）and Office of Pharmaceuticl Quality Operations （OPQO）under ORA ，which were responsible for developing compliance documents and procedures ，carrying out compliance education ，compliance guidance ，compliance inspection and punishment for violations. Before submission stage of drug registration application ，the compliance education function of OC and the compliance guidance function of OND/OGD played an important role ；in the application submission stage ，OND/OGD was responsible for the compliance review of application materials ；in the stage of reviewing the application materials ，OND/OGD and OC of CDER ensured drug compliance through collaboration with OC ，OBIMO and OPQO of ORA. The establishment of drug registration compliance management institutions in China was still in the preliminary exploration stage. It is suggested that China can learn from the relevant experience of the United States ，establish a multi-level or ganization structure ，set up an independent compliance education department ， and strengthen thecooperation between evaluation department and compliance inspection department ，and to improve the level of compliance management of drug registration applicants in China.

This article highlighted the invaluable expertise of Academician TONG Xiaolin in managing severe cases of COVID-19， thereby providing ideas for the treatment of severe and critically ill patients with SARS-CoV-2 infection by integrating traditional Chinese and western medicine. It is believed that COVID-19 belongs to the “cold dampness epidemic” in traditional Chinese medicine， which is caused by pathogenic qi of cold and dampness. The course of the disease can be divided into four stages： constraint， block， collapse， and deficiency， and the severe cases are mainly in the block and collapse stages. The pathogenesis at the block stage is described as epidemic toxins blocking the lung， which should be treated by diffusing the lung and unblocking the bowels， resolving phlegm and unblocking collaterals. The primary formula used is Zilong Xuanbai Chengqi Decoction （子龙宣白承气汤） with modifications based on individual condition. The pathogenesis at the collapse stage is described as internal block and external collapse， which should be treated by restoring yang to save from collapse， boosting qi to relieve collapse， diffusing the lung and unblocking the bowels， resolving phlegm and unblocking collaterals， usually with the formula Poge Zilong Xuanbai Chengqi Decoction （破格子龙宣白承气汤） with modifications.

We report a case of a long-term survivor of heart transplant who developed severe COVID-19 and was treated with a traditional Chinese medicine combined with conventional medicine. Throughout the treatment， the patient received active conventional medical treatment， and traditional Chinese medicine interventions included tonifying qi， invigorating the spleen and transforming phlegm， promoting yang and eliminating stagnation， resolving dampness and dissipating phlegm， and promoting blood circulation and eliminating stasis. The main therapeutic principles adopted were to recuperating depleted yang and rescuing the patient from collapse and to resolve phlegm and promote water. Pogezilong Xuanbai Chengqi Decoction （破格子龙宣白承气汤） with modifications was administered. In summary， it is crucial to the timely adjust the immunosuppressive regimen， combine use of various anti-infective agents with a focus on COVID-19， to protect of cardiac and renal function， and to integrate traditional Chinese medicine in the entire treatment process. As this case is rare， the diagnostic and therapeutic methods in traditional Chinese medicine， the use of immunosuppressive agents， and follow-up monitoring strategies can be a valuable reference.