Upregulation of hypothalamic POMC neurons after biliary diversion in GK rats.

Background: Bile acids are important signaling molecules that might activate hypothalamic neurons. This study aimed to investigate possible changes in hypothalamic pro-opiomelanocortin (POMC) neurons after biliary diversion in diabetic rats. Methods: Ten GK rats were randomly divided into the biliary diversion (BD) and sham groups. The glucose metabolism, hypothalamic POMC expression, serum bile acid profiles, and ileal bile acid-specific receptors of the two groups were analyzed. Results: Biliary diversion improved blood glucose (P = 0.001) and glucose tolerance (P = 0.001). RNA-Seq of the hypothalamus showed significantly upregulated expression of the POMC gene (log2-fold change = 4.1, P < 0.001), which also showed increased expression at the protein (P = 0.030) and mRNA (P = 0.004) levels. The POMC-derived neuropeptide α-melanocyte stimulating hormone (α-MSH) was also increased in the hypothalamus (2.21 ± 0.11 ng/g, P = 0.006). In addition, increased taurocholic acid (TCA) (108.05 ± 20.62 ng/mL, P = 0.003) and taurodeoxycholic acid (TDCA) (45.58 ± 2.74 ng/mL, P < 0.001) were found in the BD group and induced the enhanced secretion of fibroblast growth factor-15 (FGF15, 74.28 ± 3.44 pg/ml, P = 0.001) by activating farnesoid X receptor (FXR) that was over-expressed in the ileum. Conclusions: Hypothalamic POMC neurons were upregulated after BD, and the increased TCA, TDCA, and the downstream gut-derived hormone FGF15 might activate POMC neurons.

Predictive Biomarkers for Postmyocardial Infarction Heart Failure Using Machine Learning: A Secondary Analysis of a Cohort Study.

BACKGROUND: There are few biomarkers with an excellent predictive value for postacute myocardial infarction (MI) patients who developed heart failure (HF). This study aimed to screen candidate biomarkers to predict post-MI HF. METHODS: This is a secondary analysis of a single-center cohort study including nine post-MI HF patients and eight post-MI patients who remained HF-free over a 6-month follow-up. Transcriptional profiling was analyzed using the whole blood samples collected at admission, discharge, and 1-month follow-up. We screened differentially expressed genes and identified key modules using weighted gene coexpression network analysis. We confirmed the candidate biomarkers using the developed external datasets on post-MI HF. The receiver operating characteristic curves were created to evaluate the predictive value of these candidate biomarkers. RESULTS: A total of 6,778, 1,136, and 1,974 genes (dataset 1) were differently expressed at admission, discharge, and 1-month follow-up, respectively. The white and royal blue modules were most significantly correlated with post-MI HF (dataset 2). After overlapping dataset 1, dataset 2, and external datasets (dataset 3), we identified five candidate biomarkers, including FCGR2A, GSDMB, MIR330, MED1, and SQSTM1. When GSDMB and SQSTM1 were combined, the area under the curve achieved 1.00, 0.85, and 0.89 in admission, discharge, and 1-month follow-up, respectively. CONCLUSIONS: This study demonstrates that FCGR2A, GSDMB, MIR330, MED1, and SQSTM1 are the candidate predictive biomarker genes for post-MI HF, and the combination of GSDMB and SQSTM1 has a high predictive value.

Cardiovascular disease-specific mortality in 270,618 patients with non-small cell lung cancer.

BACKGROUND: This study aimed to investigate the trend of cardiovascular disease (CVD)-specific mortality in patients with non-small cell lung cancer (NSCLC) and identify prognostic factors for CVD-specific death in stage NSCLC patients. METHODS: In this study, 270,618 NSCLC patients were collected from the Surveillance, Epidemiology, and End Results database. CVD- and NSCLC-specific cumulative mortality and proportion of death were calculated and graphically displayed to describe the probability of specific endpoints. Prognostic factors for CVD-specific mortality were evaluated by cause-specific hazard ratios (HR) with 95% confidence intervals (CI) using the competing risk model with non-cardiovascular death as competing risks. RESULTS: Among all competing causes of death, lung cancer resulted in the highest cumulative mortality, followed by CVDs and other causes. In the proportion of cause-specific death, heart diseases accounted for approximately 5.3% of the total death, only secondary to primary cancer. In all three stages, higher age, squamous cell carcinoma, and no-or-unknown chemotherapy and/or radiotherapy were associated with a higher risk of CVD-specific death, while surgery treatment seemed to be a protective factor. Female gender was statistically related to CVD-specific death in stage I and III patients with HRs of 0.84 (0.78-0.91) and 0.84 (0.77-0.93), respectively. Interestingly, right-sided laterality was correlated with lower CVD-specific mortality with HR of 0.82 (0.74-0.90) in stage III. CONCLUSIONS: This study illustrated the historical trend of CVD-specific death in NSCLC patients and assesses potential prognostic risk factors, highlighting the involvement of cardio-oncology teams in cancer treatment to provide optimal comprehensive care and long-term surveillance for cancer patients.

The Safety and Efficacy of Rivaroxaban Compared with Warfarin in Patients with Atrial Fibrillation and Diabetes: A Systematic Review and Meta-analysis.

AIMS: This meta-analysis was conducted to compare the efficacy and safety of rivaroxaban with warfarin in patients with atrial fibrillation (AF) and diabetes mellitus. METHODS: PubMed, Embase, Cochrane Library, and Web of Science databases were systematically searched from the establishment of databases up to 15 October 2019. Studies on efficacy and safety outcomes of rivaroxaban and warfarin were included. Efficacy and safety outcomes, including stroke, ischemic stroke, stroke or systemic embolism, myocardial infarction, major adverse cardiac events, major bleeding, intracranial hemorrhage, and major gastrointestinal bleeding were collected for meta-analysis. RESULTS: Compared with warfarin, rivaroxaban could significantly reduce stroke (risk ratio [RR] 0.77; 95% confidence interval [CI] 0.63-0.95; P = 0.01), ischemic stroke (RR 0.74; 95% CI 0.63-0.87; P = 0.0004), stroke or systemic embolism (RR 0.73; 95% CI 0.60-0.89; P = 0.002), myocardial infarction (RR 0.68; 95% CI 0.56-0.82; P < 0.0001), and major adverse cardiac events (RR 0.71; 95% CI 0.53-0.94; P = 0.02) in patients with AF and diabetes. Moreover, rivaroxaban was associated with a lower risk of major bleeding (RR 0.79; 95% CI 0.65-0.96; P = 0.02), intracranial hemorrhage (RR 0.52; 95% CI 0.39-0.69; P < 0.00001), and major gastrointestinal bleeding (RR 0.74; 95% CI 0.56-0.98; P = 0.04). Similar results were obtained in stratified meta-analysis of cohort studies. CONCLUSION: Our study suggests a favorable risk-benefit profile of rivaroxaban, with superior efficacy and safety over warfarin in patients with AF and diabetes.

Effect of Kinesio Taping on the Walking Ability of Patients with Foot Drop after Stroke.

OBJECTIVE: The purpose of this study was to investigate the effect of kinesio taping on the walking ability in patients with foot drop after stroke. METHODS: Sixty patients were randomly divided into the experimental group (with kinesio taping) and the control group (without kinesio taping). The 10-Meter Walking Test (10MWT), Timed Up and Go Test (TUGT), stride length, stance phase, swing phase, and foot rotation of the involved side were measured with the German ZEBRIS gait running platform analysis system and were used to evaluate and compare the immediate effects of kinesio taping. All the measurements were made in duplicate for each patient. RESULTS: The demographic variables of patients in both groups were comparable before the treatment (p>0.05). After kinesio taping treatment, significant improvement was found in the 10MWT and the TUGT for patients in the experimental group (p<0.05). There were significant differences in the 10MWT and TUGT between the experimental and control groups after treatment (p<0.05). In terms of gait, we found significant improvement in stride length (p<0.001), stance phase (p<0.001), swing phase (p<0.001), and foot rotation (p<0.001) of the involved side in experimental group after treatment compared with those before treatment. Further, the functional outcomes and gait ability were significantly improved in the experimental group after treatment (p<0.05), compared to the control group. CONCLUSION: Kinesio taping can immediately improve the walking function of patients with foot drop after stroke.

Successful treatment using corticosteroid combined antibiotic for acute acalculous cholecystitis patients with systemic lupus erythematosus.

There is no consensus of treatments for acute acalculous cholecystitis with systemic lupus erythematosus (SLE). The study was aimed to investigate the effect of the corticosteroid for these patients.A series of patients who were diagnosed as acute acalculous cholecystitis with SLE in the period from January 2012 to December 2016 at our hospital were included. They accepted 2 different conservative treatment strategies initially: the treatment using moxifloxacin (the antibiotic group), and the treatment using corticosteroid combined moxifloxacin (the corticosteroid group). Then clinical manifestations, laboratory features, and outcomes were analyzed.The study identified 22 women Han Chinese patients with the SLE history of 2.8 ±â€Š1.4 year. There was no significant difference in SLE history, Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2000), Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SLICC/ACR), hematologic examination results, and corticosteroid dosage between 2 groups. And there was no significant difference in the symptom of acute cholecystitis, duration of the symptoms, white blood level, and the thickness of gallbladder wall between 2 groups either. However, the SLEDAI-2000 of the corticosteroid group was lower than that of the antibiotic group (7.3 ±â€Š1.4 vs 10.7 ±â€Š3.0, P = .03), so was the SLICC/ACR (0.1 ±â€Š0.3 vs 0.3 ±â€Š0.5, P = .01). Moreover, total 11 of 12 patients were successfully treated in the corticosteroid group, only 1 patient got cholecystectomy because no improvement after conservative treatment. While 4 of 10 patients were successfully treated by moxifloxacin alone, 6 patients had to accept cholecystectomy in the antibiotic group. The rate of successful conservative treatment in the corticosteroid group was higher than that of the antibiotic group (P = .02). All patients were followed up at least 6 months, there was no statistical difference in the rate of recurrence of abdominal pain between 2 groups (P = .37).The corticosteroid plays an important role in the management of the acalculous cholecystitis patient with SLE, and it should be considered as a first line of treatment.

Mitigation of Pre-existing Antibodies to a Biotherapeutic in Non-clinical Species When Establishing Anti-drug Antibody Assay Cutpoint.

Biotherapeutics are known for their potential to induce drug specific immune responses, which are commonly evaluated by the detection of anti-drug antibodies (ADAs). For some biotherapeutics, pre-existing ADAs against drug have been observed in drug-naïve matrix. The presence of pre-existing drug specific antibodies may significantly complicate assessment of the screening ADA assay cutpoint value, which is usually established based on the statistical analysis of signal distribution from the drug-naïve individuals. A Gaussian mixture model-based approach is presented herein to address high prevalence of pre-existing ADAs to a modified monoclonal antibody-based biotherapeutic (m-mAb). A high prevalence of pre-existing anti-m-mAb antibodies was observed in drug-naïve individual cynomolgus monkey serum samples with signal ranging from 100 to 7000 relative light units (RLU, as determined in an electrochemiluminescence readout-based assay). Application of the industry standard statistical algorithm resulted in a relatively high floating screening assay cutpoint factor (CPF) of 9.80, which potentially would have reported a high percent of false negative samples. An alternative, Gaussian mixture model-based approach was applied to identify the least reactive individual samples in the tested population, which resulted in a floating screening assay CPF of 2.35. The low CPF value significantly reduced the risk of reporting false negative results. The proposed Gaussian mixture model-based approach described herein provides an alternate method for the calculation of biologically relevant screening assay CPF when high prevalence of pre-existing drug specific antibodies is observed.

Up-Regulation of CYP2C19 Expression by BuChang NaoXinTong via PXR Activation in HepG2 Cells.

BACKGROUND: Cytochrome P450 2C19 (CYP2C19) is an important drug-metabolizing enzyme (DME), which is responsible for the biotransformation of several kinds of drugs such as proton pump inhibitors, platelet aggregation inhibitors and antidepressants. Previous studies showed that Buchang NaoXinTong capsules (NXT) increased the CYP2C19 metabolic activity in vitro and enhanced the antiplatelet effect of clopidogrel in vivo. However, the underlying molecular mechanism remained unclear. In the present study, we examined whether Pregnane X receptor (PXR) plays a role in NXT-mediated regulation of CYP2C19 expression. METHODS: We applied luciferase assays, real-time quantitative PCR (qPCR), Western blotting and cell-based analysis of metabolic activity experiments to investigate the NXT regulatory effects on the CYP2C19 promoter activity, the mRNA/ protein expression and the metabolic activity. RESULTS: Our results demonstrated that NXT significantly increased the CYP2C19 promoter activity when co-transfected with PXR in HepG2 cells. Mutations in PXR responsive element abolished the NXT inductive effects on the CYP2C19 promoter transcription. Additionally, NXT incubation (150 and 250µg/mL) also markedly up-regulated endogenous CYP2C19 mRNA and protein levels in PXR-transfected HepG2 cells. Correspondingly, NXT leaded to a significant enhancement of the CYP2C19 catalytic activity in PXR-transfected HepG2 cells. CONCLUSION: In summary, this is the first study to suggest that NXT could induce CYP2C19 expression via PXR activation.

[Effect of Subcutaneous Injection of Lidocaine in Zusanli (ST 36) and Jiaji (EX-B 2) Regions on Immune Function in Patients Undergoing Laparoscopic Cholecystectomy].

OBJECTIVE: To observe the effect of acupoint injection of Lidocaine on serum IL-1ß, TNF-α and T-lymphocyte subset activities in patients undergoing laparoscopic cholecystectomy (LC), so as to reveal its mechanisms underlying relieving postoperative pain and potentiating rehabilitation. METHODS: Eighty patients scheduled for elective LC surgery (grade I or II, according to American Standards of Association, ASA) were randomly divided into four groups, namely intravenous analgesia (IVA) , right forearm-injection (forearm-), Jiaji (EX-B 2, Thorax 8)-injection (EX-B 2-1), and Zusanli-injection (ST 36-1), with 20 patients in each group. The conventional anesthetic induction and maintenance with Penehyclidine Hydrochloride, Midazolam, Sulfentanil, Propofol, Atracurium Besilate, and Remifentanil were same in all the 4 groups. For patients of the forearm-I, EX-B 2-I and ST 36-1 groups, 5% Lidocaine was injected into the subcutaneous layer of the anterior side of right forearm near the elbow, EX-B 2 and ST 36 regions, respectively. Analgesia pump (filled with Sulfentanil, Ramosetron + normal saline) was connected af- ter the tracheal extubation. The visual analog scale (VAS) was used to assess the patient's pain reaction after tracheal extubation (T 1), and 6 h (T 2), 24 h (T 3) and 48.h (T 4) after surgery. The times of RCA pressing and the total dose of Sufentanil in the process of postoperative analgesia were recorded as well. The contents of serum IL-1ß and TNF-α were analyzed by ELISA, and the counts of CD4+ and CD+ T cells were detected by flow cytometry. RESULTS: Compared with T 1 in the same one group, the VAS scores at time-points of T 2, T 3 and T 4 after surgery of all the IVA, forearm-1, ST 36- and EX-B 2- groups were reduced significaantly (P < 0.05). The times of PCA-pump pressing and the doses of the administrated Sufentanil were considerably lower in the ST 36-1 and EX-B 2-I groups than in the IVA and forearm-I groups (P < 0.05). In comparison with pre-anesthesia in the same one group, serum TNF-α and IL-1ß contents at T 1 were remarkably increased, while the ratios of CD4⁺/CD8⁺ at T 4 in the 4 groups were evidently down-regulated (P < 0.05). The contents of serum TNF-α and IL-1ß at T 3 and T 4 were obviously lower in both ST 36-1 and EX-B 2-1 groups than in the IVA and forearm-I groups (P < 0.05). No significant differences were found among the 4 groups in the VAS scores at the 4 time-points, in the serum TNF-α and IL-1ß contents at T 0 and T 1, in the counts of CD4⁺ and CD8⁺ T cells and ratios of CD4⁺/CD8⁺ at T 0, T 3 and T 4, and between the ST 36-1 and EX-B 2-groups in all the 8 indexes (P > 0.05). CONCLUSION: Acupoint injection of Lidocaine is effective in relieving pain in LC patients, which is demonstrated by reducing VAS score, PCA pump pressing times, and administrated Sufentanil dose, and may be associated with its effects in down-regulating serum TNF-α and IL-1ß contents.

Induction of human CYP3A4 by huperzine A, ligustrazine and oridonin through pregnane X receptor-mediated pathways.

The pregnane X receptor (PXR) is a key regulator of CYP3A4, which is involved in catalyzing the metabolic conversion of a number of endogenous substrates. In this study, we screened 22 compounds isolated from traditional Chinese herbal medicines using luciferase reporter gene assays for inspecting their capabilities in inducing PXR-mediated transactivation of CYP3A4 expression. In addition, the mRNA and protein expressions of CYP3A4 and PXR as well as the enzymatic activites of CYP3A4 were analyzed by real-time PCR, Western blot analysis and UPLC-MS/MS-based metabolite assay in LS174T cells. Huperzine A, ligustrazine and oridonin were identified to be the inducers of CYP3A4. These compounds induced the CYP3A4 reporter luciferase activity, and up-regulated CYP3A4 mRNA and protein levels significantly. Besides, huperzine A, ligustrazine and oridonin significantly up-regulated enzymatic activities of CYP3A4. However, the three compounds showed no effects on PXR mRNA and protein expression. To our knowledge, it is the first identification of these three compounds as PXR activators to induce CYP3A4. These results indicate that huperzine A, ligustrazine and oridonin induced CYP3A4 expression and activation via PXR dependent pathways, and might contribute to drug-drug interactions.

Dose-response of oridonin on hepatic cytochromes P450 mRNA expression and activities in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Oridonin, the major terpene found in Rabdosia rubescens, is widely used as a dietary supplement or therapeutic drug. The effects of oridonin on drug processing genes, such as cytochrome P450 and nuclear receptors, were still unclear. Therefore, the present study investigated the influence of oridonin on the hepatic drug metabolizing system to evaluate the safety through its drug interaction potential. MATERIALS AND METHODS: In this study, eight-week-old male C57BL/6 mice were treated oridonin orally (0, 25, 50, 100, 200 mg/kg, i.g.) for 15 days. The effects of oridonin on major Cyps in mice livers were examined at both the mRNA and enzyme activity levels. RESULTS: In general, there are no significant influence of various dose of oridonin on mice liver function. However, oridonin significantly increased Cyps (1a, 2a, 2d, 2e, 2c and 3a family) mRNA expression. In addition, it could induce Cyps activity in microsome incubation at maximum dosage. To our knowledge, it is the first time to identify oridonin as a Cyps inducer in vivo. It also promotes the expression of CAR, PXR and POR. CONCLUSION: These results indicate that, if studies in mice extrapolate to humans by orthologous genes, oridonin appears to be a risk to herb-drug interactions due to its induction effects on drug processing genes expression and activation.

Inhibitory effects of phytochemicals on metabolic capabilities of CYP2D6(*)1 and CYP2D6(*)10 using cell-based models in vitro.

AIM: Herbal products have been widely used, and the safety of herb-drug interactions has aroused intensive concerns. This study aimed to investigate the effects of phytochemicals on the catalytic activities of human CYP2D6(*)1 and CYP2D6(*)10 in vitro. METHODS: HepG2 cells were stably transfected with CYP2D6(*)1 and CYP2D6(*)10 expression vectors. The metabolic kinetics of the enzymes was studied using HPLC and fluorimetry. RESULTS: HepG2-CYP2D6(*)1 and HepG2-CYP2D6(*)10 cell lines were successfully constructed. Among the 63 phytochemicals screened, 6 compounds, including coptisine sulfate, bilobalide, schizandrin B, luteolin, schizandrin A and puerarin, at 100 µmol/L inhibited CYP2D6(*)1- and CYP2D6(*)10-mediated O-demethylation of a coumarin compound AMMC by more than 50%. Furthermore, the inhibition by these compounds was dose-dependent. Eadie-Hofstee plots demonstrated that these compounds competitively inhibited CYP2D6(*)1 and CYP2D6(*)10. However, their Ki values for CYP2D6(*)1 and CYP2D6(*)10 were very close, suggesting that genotype-dependent herb-drug inhibition was similar between the two variants. CONCLUSION: Six phytochemicals inhibit CYP2D6(*)1 and CYP2D6(*)10-mediated catalytic activities in a dose-dependent manner in vitro. Thus herbal products containing these phytochemicals may inhibit the in vivo metabolism of co-administered drugs whose primary route of elimination is CYP2D6.

Preventive administration of juanbi capsules for knee osteoarthritis: effects on serum MMP-2 and MMP-9 levels and cartilage repair.

OBJECTIVE: To explore the mechanism of action of Juanbi Capsules, a Chinese medicine for invigorating the kidney and replenishing qi, in preventing osteoarthritis of the knee in rabbits. METHODS: Seventy-two 4-month-old, Japanese long-eared white rabbits were randomly divided into 6 groups: control (group A), model (group B), Chinese drug; high-dose (group C), Chinese drug; mid-dose (group D), Chinese drug; low-dose (group E), and drug control (group F). With the exception of the rabbits in group A, each rabbit was subjected to plaster cast fixation for 6 weeks to induce osteoarthritis. In addition, rabbits were administrated with an intragastric injection of the Chinese drug (groups C, D and E) or an aminoglucose hydrochloride capsule (group F) for 4 weeks. Blood was drawn from the central ear artery for serum MMP-2 and MMP-9 concentrations, and the knee joint cartilage was harvested for gross observation and light microscopy. RESULTS: There were significant differences in serum MMP-2 and MMP-9 concentrations between group B and groups C, D and E (P < 0.05), with no significant differences between groups D and F. Histological results showed various changes in tissue staining with treatment, with osteophyte and bone cyst formation, and superficial erosion in the articular surface of the cartilage; in some cases, the defect reached the mid-layer of the cartilage, and these changes were lower than those in the model group. CONCLUSION: Juanbi Capsules assist in preventing osteoarthritis in the rabbit, possibly by decreasing serum MMP-2 and MMP-9 levels.

Effects of preventive administration of juanbi capsules on TNF-alpha, IL-1 and IL-6 contents of joint fluid in the rabbit with knee osteoarthritis.

OBJECTIVE: To probe into the mechanism of the Chinese herbs with functions of reinforcing kidney and supplementing qi for preventing knee osteoarthritis of the rabbit. METHODS: Totally 72 healthy Japan long-ear white rabbits, aged 4 months, were randomly divided into 6 groups, blank group (A), model group (B), high dose Chinese herb group (C), middle dose Chinese herb group (D), small dose Chinese herb group (E), aminoglucose hydrochloride capsule control group (F), 12 rabbits in each group. All the rabbits in the groups, except the group A, were fixed with plaster cast for six weeks to establish rabbit knee osteoarthritis. At the same time of modeling, the different doses of Juanbi Capsules and aminoglucose hydrochloride capsule were administrated intragastrically in the group C, D, E, F, respectively, for 4 weeks, for preventive treatment. In the group B, the rabbit was administrated intragastrically with equal volume of normal saline to the medication groups, twice each day, in the morning and the evening, and in the group A, nothing was administrated. After modeling for 6 weeks, the joint fluid was taken and TNF-alpha, IL-1 and IL-6 contents were detected with ELISA method, and the articular cartilage was taken for macroscopic and microscopic examinations. RESULTS: In all the preventive treatment groups, the articular cartilage color changed to varying degrees with formation of osteophyte and bone cyst, superficial erosion on the chondral articular surface, and the cartilage defect reached to the mid layer in a part of specimens with cartilage exfoliation, but which in the extent were significantly lower than those in the model group. There were significant differences between the group A and B in TNF-alpha, IL-1 and IL-6 contents in the joint fluid (P < 0.05), indicating that the modeling is successful; and there were significant differences as group B compared with the group C,D, E, F, showing that TNF-alpha , IL-1 and IL-6 contents are decreased in all the medication groups; and significant differences between group C, D, E suggests that the increase of Chinese herb doses strengthened the effect of reducing TNF-alpha, IL-1 and IL-6 contents in joint fluid. CONCLUSION: The Juanbi Capsule prevents osteoarthritis possibly through decreasing serum TNF-alpha, IL-1 and IL-6 contents.

[Multi-modal serial therapy for primary liver cancer in senile patients: a report of 153 cases].

OBJECTIVE: To study the feasibility and validity of multi-modal serial therapy for primary liver cancer in senile patients. METHODS: 153 senile primary liver cancer patients (>or= 60 years) were given multi-modal serial therapy from June 1993 to December 2000. Hepatectomy was performed in 37, deep cryosurgery in 32 and non-operative therapy in 84 (intervention as chief therapy in 81, combined local and intervention therapy in 3). The multi-course intervention therapy was given postoperatively in hepatectomy and cryosurgery groups, while bioimmunotherapy and traditional Chinese medicine were used in all groups. RESULTS: The 1-, 3- and 5-year survival rates in the hepatectomy group were 78.4%, 46.4% and 35.7%, without operative mortality. The 1- and 3- and 5-year year survival rates in the cryosurgery group were 64.5%, 40.9% and 25.0% with mortality of 3.1%. Among patients with non-operative therapy, the 1- and 3- and 5-year year survival rates in intervention group were 47.5%, 23.5% and 4.3%. The operative mortality was 1.2%. The 3 patients who received combined local and intervention therapy have survived for 2.5, 3.8 and 7.1 years. CONCLUSION: Multi-modal serial therapy with surgical treatment as the chief means, being precise in the effect and good in safety, is feasible and valid for primary liver cancer in senile patients.