藏医疗毒学概述及其研究现状和展望

分析、概括相关文献,从藏医疗毒学的历史渊源、理论基础、分类分型和临床应用等方面综述藏医疗毒学的研究现状,并深入探讨藏医疗毒学的应用前景和研究价值。

藏医疗毒学之合成毒症的分类与诊治探讨

文章以传统藏医学八大核心内容之一的疗毒学为理论依据,通过搜集整理历代藏医典籍中相关合成毒症的文献资料,以及相关的中医学和现代医学的资料,探讨分析了藏医学对“毒”的认识及其理论观点,梳理、阐明了藏医疗毒学中合成毒症的病因、诊断、治疗和预防理论,并以此为依据研究鸦片、海洛因、吗啡和苯丙胺等毒品所引发的疾病;依据藏医疗毒学的理论,对这些疾病的诊断、治疗与预防的临床意义和研究价值进行了深入探讨,为藏药解毒临床思维及研究提供了科学依据。

Hepatitis C virus: Virology, diagnosis and management ofantiviral therapy

Hepatitis C virus (HCV) infects approximately 170 million individuals worldwide. Prevention of HCV infection complications is based on antiviral therapy with the combination of pegylated interferon alfa and ribavirin. The use of serological and virological tests has become essential in the management of HCV infection in order to diagnose infection, guide treatment decisions and assess the virological response to antiviral therapy. Anti- HCV antibody testing and HCV RNA testing are used to diagnose acute and chronic hepatitis C. The HCV genotype should be systematically determined before treatment, as it determines the indication, the duration of treatment, the dose of ribavirin and the virological monitoring procedure. HCV RNA monitoring during therapy is used to tailor treatment duration in HCV genotype 1 infection, and molecular assays are used to assess the end-of-treatment and, most importantly the sustained virological response, i.e. the endpoint of therapy.

Pharmacogenomics in colorectal cancer: The first step for individualized-therapy

Interindividual differences in the toxicity and response to anticancer therapies are currently observed in practically all available treatment regimens. A goal of cancer therapy is to predict patient response and toxicity to drugs in order to facilitate the individualization of patient treatment. Identification of subgroups of patients that differ in their prognosis and response to treatment could help to identify the best available drug therapy according the genetic profile. Several mechanisms have been suggested to contribute to chemo-therapeutic drug resistance: amplification or overexpression of membrane transporters, changes in cellular proteins involved in detoxification or in DNA repair, apoptosis and activation of oncogenes or tumor suppressor genes. Colorectal cancer (CRC) is regarded as intrinsically resistant to chemotherapy. Several molecular markers predictive of CRC therapy have been included during the last decade but their results in different studies complicate their application in practical clinical. The simultaneous testing of multiple markers predictive of response could help to identify more accurately the true role of these polymorphisms in CRC therapy. This review analyzes the role of genetic variants in genes involved in the action mechanisms of the drugs used at present in colorectal cancer.

Pseudocirrhosis in a pancreatic cancer patient with liver metastases: A case report of complete resolution of pseudocirrhosis with an early recognition and management

We report a case of pseudocirrhosis arising in the setting of regression of liver metastases from pancreatic cancer. A 55-year-old asymptomatic woman presented to our clinic with newly diagnosed metastatic pancreatic cancer with extensive liver metastases. She underwent systemic chemotherapy with gemcitabine and oxaliplatin (GEMOX). After 8 cycles of therapy, she had a remarkable response to the therapy evidenced by decline of carcinoembryonic antigen (CEA) and CA19 by > 50% and nearly complete resolution of hepatic metastases in computed tomography (CT) scan. Shortly after, she developed increasing bilateral ankle edema and ascites, associated with dyspnea, progressive weight gain, and declining performance status. Gemcitabine and oxaliplatin were discontinued as other causes of her symptoms such as congestive heart disease or venous thrombosis were ruled out. CT scan 6 mo after the initiation of GEMOX revealed worsening ascites with a stable pancreatic mass. However, it also revealed a lobular hepatic contour, segmental atrophy, and capsular retraction mimicking the appearance of cirrhosis. She was managed with aggressive diuresis and albumin infusions which eventually resulted in a resolution of the above- mentioned symptoms as well as complete resolution of pseudocirrhotic appearance of the liver and ascites in CT scan. This case demonstrates that pancreatic cancer patients can develop pseudocirrhosis. Clinicians and radiologist should be well aware of this entity asearly recognition and management can lead to a near complete recovery of liver function and much improved quality of life as illustrated in this case.

Long-term outcomes of chronic hepatitis C patients with sustained virological response at 6 months after the end of treatment

AIM: To assess the clinical, biochemical, and virological outcome during long-term follow-up of chronic hepatitis C patients with sustained virological response following effective antiviral therapy.METHODS: This study was a retrospective cohort study including 171 sustained responders defi ned as HCV RNA PCR negative at 6 mo after the end of effective antiviral treatment (SVR-6). Clinical signs and symptoms, bio- chemical hepatic parameters, ultrasonography and HCV RNA PCR were followed.RESULTS: Mean follow-up period was 35.38 ± 22.2 mo after the end of treatment. Twenty-seven (15.8%) responders had evidence of cirrhosis before treatment. Forty-eight (28.1%), 107 (62.6%) and 6 (3.5%) patients were genotype 1, 3, and 6 respectively, while 10 patients (5.8%) were unclassifi ed. There were no virological and biochemical relapses during the period of follow-up. None of the patients showed evidence of hepatic decom- pensation. However, there were 3 patients (1.8%) de- veloping hepatocellular carcinoma at 14, 18, 29 mo after treatment discontinuation, two of whom had evidence of cirrhosis prior to therapy.CONCLUSION: The study shows that during a follow- up interval for about 3 years in 171 chronic hepatitis C patients with sustained viral response after effective antiviral treatment there were no evident signs of either biochemical or clinical relapse of liver disease in all but three patients who developed hepatocellular carcinoma.

Antiproliferation and apoptosis induction of paeonol in HepG_2 cells

AIM： To investigate the antiproliferative effect of paeonol （Pae） used alone or in combination with chemotherapeutic agents [cisplatin （CDDP）, doxorubicin （DOX） and 5-fluorouracil （5-FU）] on human hepatoma cell line HepG2 and the possible mechanisms. METHODS： The cytotoxic effect of drugs on HepG2 cells was measured by 3-（4, 5-dimethylthiazol-2- yl）-2, 5-diphenyltetra-zolium bromide （MTT） assay. Morphologic changes were observed by acridine orange （AO） fuorescence staining. Cell cycle and apoptosis rate were detected by flow cytometry （FCM）. Drug-drug interactions were analyzed by the coefficient of drug RESULTS： Pae （7.81-250 mg/L） had an inhibitory effect on the proliferation of HepG2 cells in a dose-dependent manner, with the IC50 value of （104.77±7.28） mg/L. AO fluorescence staining and FCM assays showed that Pae induced apoptosis and arrested cell cycle at S phase in HepG2 cells. Further, different extent synergisms were observed when Pae （15.63, 31.25, 62.5 rag/L） was combined with CDDP （0.31-2.5 mg/L）, DOX （0.16-1.25 mg/L）, or 5-FU （12.5-100 mg/L） at appropriate concentrations. The IC50 value of the three drugs decreased dramatically when combined with Pae （P 〈 0.01）. Of the three different combinations, the sensitivity of cells to drugs was considerably different.CONCLUSION： Pae had a significant growth-inhibitory effect on the human hepatoma cell line HepG2, which may be related to apoptosis induction and cell cycle arrest. It also can enhance the cytotoxicity of chemotherapeutic agents on HepG2 cells, and the S phase arrest induced by Pae may be one of the mechanisms of these interactions.

Myelophil, a mixture of Astragali Radix and Salviae Radix extract, moderates toxic side effects of fluorouracil in mice

AIM: To evaluate the efficacy of Myelophil, an extract containing Astragali Radix and Salviae Radix, for reducing complications induced by 5-fluorouracil (5-FU) in a gastrointestinal cancer model. METHODS: We injected 5-FU into mice and then administered Myelophil to examine the ability of the drug to treat the side effects of 5-FU in mice. Peripheral blood counts, histological examinations, and colony-forming assays of bone marrow were conducted, followed by swimming tests and assessment of survival times. RESULTS: Myelophil restored red and white blood cells and platelets in blood, and recovered cell density in bone marrow to levels comparable to those observed within the control group. In addition, Myelophil significantly increased colony-forming unit granulocyte-macrophage (CFU-GM) and CFU-erythroid (CFU-E) compared to the control group. We confirmed that interleukin-3 gene expression was upregulated by Myelophil in spleen cells. Myelophil administration also doubled the survival rate of mice that were severely myelosuppressed as a result of 5-FU injection at a lethal dose of 70%. Finally, the swimming performance of mice significantly improved as a result of Myelophil treatment. CONCLUSION: These results provide experimentalevidence in support of clinical applications of Myelophil to minimize 5-FU-induced myelosuppression and improve general post-chemotherapy health.

Evolution of systemic therapy of advanced hepatocellular carcinoma

Hepatocellular carcinoma (HCC) commonly occurs in hepatitis B endemic areas, especially in Asian countries. HCC is highly refractory to cytotoxic chemotherapy. This resistance is partly related to its tumor biology, pharmacokinetic properties, and both intrinsic and acquired drug resistance. There is no convincing evidence thus far that systemic chemotherapy improves overall survival in advanced HCC patients. Other systemic approaches, such as hormonal therapy and immunotherapy, have also disappointing results. Recently, encouraging results have been shown in using sorafenib in the treatment of advanced HCC patients. In this review, we concisely summarize the evolution of developments in the systemic therapy of advanced HCC.

Analysis of Cardiotoxicity from rh-Endostatin Therapy Combined with Chemotherapy

OBJECTIVE To evaluate the cardotoxicity from recombinant human endostatin(rh-endostatin)combined with chemotherapy. METHODS A total of 12 cancer patients treated with rh- endostatin combined with chemotherapy were selected,and their clinical data collected.Their symptoms,including cardiopalmus, chest distress,dyspnea and changes in their electrocardiogram (ECG),myocardium enzymogram and left ventricular ejection fraction(LVEF),were observed during the drug treatment.These indicators were used for early diagnosis of cardiotoxicity. RESULTS Compared with a pre-therapeutic value,there was a significant increase in the CK-MB value at one week after starting the treatment as well as at the end of treatment(P<0.05).There was a significant change in the ECG at the end of treatment, compared to a pre-therapeutic condition(P<0.05),but there was no significant difference when comparing the pre-and post- therapeutic LVEF values. CONCLUSION It was recognized that mild cardiac adverse reactions exist in the regimen of recombinant human endostatin combined with chemotherapy.This therapy caused definite injury to the cardiac muscle,but cardiac functions were not obviously changed.CK-MB and ECG may be used as indicators for early monitoring cardiac toxicity.Vigilance against cardiac adverse reactions should be heightened during a course of rh-endostatin combined with chemotherapy.

Comparison of pharmacokinetics,efficacy and toxicity profile of gemcitabine using two different administration regimens in Chinese patients with non-small-cell lung cancer

Objective： To conduct a randomized comparative trial of pharmacokinetics, efficacy and toxicity profile treatment with 1200 mg/m^2 gemcitabine using standard 30-min infusion or fixed dose rate （FDR） infusion [10 mg/（m^2-min）] on days 1 and 8 plus carboplatin AUC （area under curve） 5 on day 1 in Chinese non-small-cell cancer patients. Twelve patients were enrolled in this study. Methods： Plasma gemcitabine concentrations were measured by ion-pair reversed phase high performance liquid chromatography. Antitumoral activity and toxicity of gemcitabine was assessed according to World Health Organization criteria. Results： The obtained mean parameters, such as T1/2 （elimination half time）, AUC, and CL （clearance）, were consistent with those reported in literature. Qualified response rate in our study was 33.3% for standard arm and 50% for FDR ann. Additional 50% and 33.3% patients contracted stable disease （SD） in standard arm and FDR arm, respectively. The predominant toxicity was hematologic, and patients in the standard infusion ann experienced consistently more hematologic toxicity, Conclusion： Pharmacokinetic and clinical data in this trial support the continued evaluation of the FDR infusion strategy with gemcitabine.

SEN virus does not affect treatment response in hepatitis C virus coinfected patients but SEN virus response depends on SEN virus DNA concentration

AIM: To clarify the effect of SEN virus (SENV) infection on a combination therapy including interferon alfa (IFN-α) or pegylated-IFN with ribavirin in patients with chronic hepatitis and the effect of a combination therapy on SENV.METHODS: SENV DNA was determined by polymerase chain reaction in serum samples from 95 patients with chronic hepatitis C. Quantitative analysis was done for SENV H DNA.RESULTS: Twenty-one (22%) of 95 patients were positive for SENV DNA. There was no difference in clinical and biochemical parameters between patients with HCV infection alone and coinfected patients. The sustained response rate for HCV clearance after combination therapy did not differ between patients with SENV (52%) and without SENV(50%, n.s.). SENV DNA was undetectable in 76% of the initially SENV positive patients at the end of follow-up. SENV H response to combination therapy was significantly correlated with SENV DNA level (P=-0.05).CONCLUSION: SENV infection had no influence on the HCV sustained response rate to the combination therapy.Response rate of SENV to the combination therapy depends on SENV DNA level.

Long-term hepatic consequences of chemotherapy-related HBV reactivation in lymphoma patients

AIM: To investigate the long-term consequences of chemotherapy-related HBV reactivation in patients with lymphoma.METHODS: This study was based on the database of published prospective study evaluating HBV reactivation in HBV lymphoma patients during chemotherapy.Deteriorated liver reserve (DLR) was defined as development of either one of the following conditions during follow-up: (1) newly onset parenchyma liver disease, splenomegaly or ascites without evidence of lymphoma involvement; (2) decrease of the ratio (albumin/globulin ratio) to less than 0.8 or increase of the ratio of INR of prothrombin time to larger than 1.2 without evidence of malnutrition or infection. Liver cirrhosis was diagnosed by imaging studies.RESULTS: A total of 49 patients were included. The median follow-up was 6.2 years (range, 3.9-8.1 years).There were 31 patients with and 18 patients without HBV reactivation. Although there was no difference of overall survival (OS) and chemotherapy response rate between the two groups, DLR developed more frequently in patients with HBV reactivation (48.4% vs 16.7%; P= 0.0342). Among the HBV reactivators, HBV genotype C was associated with a higher risk of developing DLR (P = 0.0768) and liver cirrhosis (P = 0.003). Four of five patients with sustained high titer of HBV DNA and two of three patients with multiple HBV reactivation developed DLR. Further, patients with a sustained high titer of HBV DNA had the shortest OS among the HBV reactivators (P= 0.0000). No patients in the non-HBV reactivation group developed hepatic failure or liver cirrhosis.CONCLUSION: Chemotherapy-related HBV reactivation is associated with the long-term effect of deterioration of hepatic function.

Syphilis Serologic Follow-up After Regular Treatment

Objective： To understand the changes in syphilis serology after regular treatment. Methods： Patients with clinical evidence and credible medical history of syphilis were treated regularly. Their serologic tests were followed for two years. Results： At the end of half a year, 22.95% of patients had a negative USR but 26.23% remained positive even after 2 years. More than 3% of patients had a negative FTA-ABS result. These patients tended to be under 40 with a disease course of less than 2 years. Conclusion： The resolution rate was high for patients who were young, had a shorter course of disease and reacted strongly to the infection. In patients older than 40 with a long course of disease, the resolution rate was low.

Intrahepatic HBV DNA as a predictor of antivirus treatment efficacy in HBeAg-positive chronic hepatitis B patients

AIM： To evaluate the effect of antiviral agents on intrahepatic HBV DNA in HBeAg-positive chronic hepatitis B patients. METHODS： Seventy-one patients received treatment with lamivudine, interferon alpha （IFN-α2b） or sequential therapy with lamivudine-IFN-α2b for 48 wk. All subjects were followed up for 24 wk. Serum and intrahepatic HBV DNA were measured quantitatively by PCR. HBV genotypes were analyzed by PCR-RFLP. RESULTS： At the end of treatment, the intrahepatic HBV DNA level in 71 patients decreased from a mean of （6.1 ± 1.0） Iog10 to （4.9± 1.4） Iog10. Further, a larger decrease was seen in the intrahepatic HBV DNA level in patients with HBeAg seroconversion. Intrahepatic HBV DNA level （before and after treatment） was not significantly affected by the patients＇ HBV genotype, or by the probability of virological flare after treatment. CONCLUSION： Intrahepatic HBV DNA can be effectively lowered by antiviral agents and is a significant marker for monitoring antivirus treatment. Low intrahepatic HBV DNA level may achieve better efficacy of antivirus treatment.

HIV/AIDS in Asia:The Shape of Epidemics and Their Molecular Epidemiology

The Asia-Pacific region is a home to 60% of the population in the world and to approximately one quarter of people with HIV/AIDS. Close to a million of people has been infected and a half million people died of AIDS annually in Asia,becoming the second largest epicenter of global AIDS epidemic. Molecular epidemiology has been useful tool to track a course of HIV spread. In-depth knowledge from the studies on molecular epidemiology elucidates the dynamics of HIV spread and the interrelationship of epidemics in the different regions in Asia.

Virological response to adefovir monotherapy and the risk of adefovir resistance

AIM:To evaluate virological response to adefovir(ADV) monotherapy and emergence of ADV-resistant mutations in lamivudine(LAM)-resistant chronic hepatitis B patients.METHODS:Seventy-seven patients with documented LAM resistance who were treated with 10 mg/d ADV for>96 wk were analyzed for ADV resistance.RESULTS:At week 48 and 96,eight(10%)and 14(18%)of 77 LAM-resistant patients developed the ADV-resistant strain(rtA181V/T and/or rtN236T mutations),respectively.Hepatitis B virus(HBV)DNA levels during therapy were significantly higher in patients who developed ADV resistance than in those who did not.Incidence of ADV resistance at week 96 was 11%,8%and 6%among patients with complete virological response(HBV DNA level<60 IU/mL);0%,5%and 19%among patients with partial virological response(HBV DNA level≥60 to 2000 IU/mL);and 32%,34% and 33%among patients with inadequate virological response(HBV DNA levels>2000 IU/mL)at week 12,week 24 and week 48,respectively.HBV DNA levels >2000 IU/mL at week 24 showed best performance characteristics in predicting ADV resistance.CONCLUSION:Development of ADV resistance mutations was associated with HBV DNA levels,which could identify patients with LAM resistance who are likely to respond to ADV monotherapy.

Phase III study of TAC and TP regimens as neoadjuvant chemotherapy in patients withtriple-negative breast cancer

Objective： This study aimed to compare the efficacy and safety of neoadjuvant chemotherapy with TAC and TP regimens of triple negative breast cancer （TNBC）. Methods： A total of 102 patients with TNBC were confirmed by histopathology. They were divided into TAC group （52 cases） and TP group （50 cases）. Group TAC： Docetaxel 75 mg/m2 or paclitaxel （taxol liposome） 135 mg/m2 on all, pirarubicin 40 mg/m2 or epirubicin 75 mg/m2 on d2, cyclophosphamide 600 mg/m2 on dl; Group TP： Docetaxe175 mg/m2 or paclitaxel （taxol liposome） 135 mg/m2 on dl, cisplatin 30 mg/m2 on d2-d4, with 21 days as a cycle. All patients underwent operation after 2-4 cycles of chemotherapy. The short-term effects and toxic and adverse effects were evaluated. Results： In TAC group, 5 cases （9.6%） had pathological complete release （pCR）, 35 cases （67.3%） partial release （PR）, 9 cases （17.3%） stable disease （SD）, and the response rate （RR） was 76.9%. In TP group, 4 cases （8%） had pCR, 32 cases （64%） PR, 5 cases （10%） SD, and RR was 72%. In 102 patients, 12 patients with tumor progression after 2 cycles of chemotherapy, included 3 cases in TAC group, 9 cases in TP group. In TAC group, 2 cases occurred atrial premature contraction; while 3 cases developed grade 2 renal injury in TP group. In TAC group, grade 3-4 hematologic toxicity and alopecia was significantly higher than that in TP group, but grade 3-4 gastrointestinal reaction rate in TP group was significantly higher than TAC group. Conclusion： TAC and TP regimens all had certain efficacy in the neoadjuvant chemotherapy for TNBC, and the toxicity reactions can be tolerated.

N-acetyl cysteine therapy in acute viral hepatitis

AIM: To investigate the effect of N-acetyl cysteine (NAC)on acute viral hepatitis (AVH).METHODS: We administered 200 mg oral NAC three times daily (600 mg/day) to the study group and placebo capsules to the control group. All patients were hospitalized and diagnosed as AVH. Blood total and direct bilirubin, ALT, AST,alkaline phosphatese, albumin and globulin levels of each patient were measured twice weekly until total bilirubin level dropped under 2 mg/dl, ALT level under 100 U/L, follow up was continued and then the patients were discharged.RESULTS: A total of 41(13 female and 28 male) AVH patients were included in our study. The period for normalization of ALT and total bilirubin in the study group was 19.7±6.9 days and 13.7±8.5 days respectively. In the control group it was 20.4±6.5 days and 16.9±7.8 days respectively (P＞0.05).CONCLUSION: NAC administration effected neither the time necessary for normalization of ALT and total bilirubin values nor duration of hospitalization, so we could not suggest NAC for the treatment of icteric AVH cases. However, our results have shown that this drug is not harmful to patients with AVH.

The rationale behind the four major anti-COVID-19 principles of Chinese herbal medicine based on systems medicine

As the novel coronavirus disease 2019(COVID-19)and its variants continue to rage into the second year of a global pandemic,many success stories of applying Chinese herbal medicine(CHM)to treat COVID-19 patients continue to emerge from China and other part of the world.Herewith,from a systems medicine perspective,the authors analyze those experiences and categorize them into four major treatment principles:(1)focusing on eliminating toxins in the early stage of the disease,(2)tonifying deficiency of the body throughout the entire disease course,(3)treating the affected lung and intestine simultaneously based on visceral interactions,(4)cooling blood and removing blood stasis at the later stage,as well as interpret the rationale of these principles.This is helpful not only in reducing the complexity of promoting the CHM applications to enhance anti-COVID-19 efficacy,but also in ramping out the process of integrating traditional Chinese medicine with modern medical practices.