Learning curve in laparoscopic left lateral hepatic sectionectomy / 中华肝胆外科杂志

Objective:To study the learning curve in laparoscopic left lateral hepatic sectionectomy.Methods:The clinical data of 62 consecutive patients who underwent left lateral hepatic sectionectomy by a single operator from February 2015 to May 2022 in General Hospital of Northern Theater Command were retrospectively analyzed. There were 22 males and 40 females, with mean ±s.d. of (50.7±11.7) years. The learning curve was depicted and evaluated by using the cumulative summation test. The general information, operation and postoperative indicators of the growth level group and the master level group were compared.Results:The average operation time of the 62 consecutive subjects was (172.9±70.1) minutes. Intraoperative blood loss was 100 (50, 200) ml. Two patients were converted to open hepatectomy. Clavien-Dindo grade I postoperative complications occurred in 20 patients (32.3%), with grade Ⅱ in 1 patient (1.6%) and grade Ⅲb in another patient (1.6%). The learning curve reached its highest point on the 20th patient by using the cumulative summation test. The study subjects were then assigned into the growth level group (patient 1-20) and the master level group (patient 21-62). The master level group had a significantly wider spread of patient age [(52.9±11.0) years vs (46.1±11.9) years], decreased operation time [(146.8±55.6) min vs (227.9±66.7) min], shortened drainage tube removal time [4(3, 5) d vs 6(4, 7) d] and decreased postoperative hospital stay [5(5, 7) d vs 6.5(4, 9) d] (all P<0.05) when compared with the growth level group. Conclusion:Left lateral hepatic sectionectomy was safe and feasible, and a single operator went through a learning curve of 20 patients before he/she could master the operation more proficiently.

Icariin Inhibits Proliferation of CLC5 Hepatoma Cells via Akt/GSK3β/CDK Pathway / 中国实验方剂学杂志

ObjectiveTo study the effect of icariin on the proliferative capacity of hepatocellular carcinoma cell line CLC5 and the underlying mechanism. MethodThe targets of icariin were screened out by network pharmacology， and the target network and protein-protein interaction （PPI） network were constructed to predict the possible targets and pathways of icariin. CCK-8 assay was employed to explore the effects of different concentrations （0， 6.25， 12.5， 25， 50 μmol·L-1） of icariin on the viability of CLC5 cells. Further， CLC5 cells were treated with 0， 25， 50 μmol·L-1 icariin， and the effect of icariin on CLC5 cell proliferation was examined by Edu-488 assay and clone formation assay （CFA）. Western blot was employed to measure the expression levels of proteins in the protein kinase B （Akt）/glycogen synthase kinase 3β （GSK3β）/cell cycle-dependent kinase （CDK） pathway in the CLC5 cells exposed to different concentrations of icariin. ResultNetwork pharmacological analysis revealed that icariin may inhibit the hepatocellular carcinoma via cell cycle arrest and inhibition of tumor cell proliferation. Compared with the blank group， icariin decreased the viability of CLC5 cells in a time- and concentration-dependent manner （P<0.01） and reduced the positive rate of Edu-488 and the colonies in CFA （P<0.05， P<0.01）. Moreover， icariin down-regulated the protein levels of p-Akt， p-GSK3β， CDK4， and CyclinD1 （P<0.05， P<0.01）. ConclusionIcariin may block cell cycle to suppress the proliferation of CLC5 cells via inhibiting the Akt/GSK3β/CDK pathway.

Material Basis and Mechanism of Kaixinsan for Treatment of Alzheimer's Disease Based on Integrated Pharmacological Platform of Chinese Medicine / 中国实验方剂学杂志

Objective: To explore the interrelation of "composition-target-disease" of Kaixinsan on treatment of Alzheimer's disease. Method: Through the integrated pharmacological platform of Chinese medicine V1.0,the active ingredients and potential targets of four Chinese herbs in Kaixinsan were collected,disease targets of Alzheimer's disease were searched,and enriched by the gene ontology database and the Kyoto encyclopedia of genes and genomes at hubs. Result: Among the 250 compounds of Kaixinsan,2 877 targets were associated with Alzheimer's disease.The key targets,such as mitochondrial trifunctional enzyme subunit alpha(HADHA),hydroxyacyl coenzyme A dehydrogenase(HADH),sterol-4-alpha-carboxylate 3-dehydrogenase(NSDHL) and others,played their pharmacological effects mainly through regulating purine and nucleotide metabolism,Huntington's disease,Alzheimer's disease,neurodegenerative diseases,oxidative phosphorylation,and endocrine and metabolic diseases in molecular reactions,such as cytoplasm,mitochondria,adenosine triphosphate binding,and mitochondrial matrix. Conclusion: The platform can predict the key targets and related pathways of Kaixinsan for treatment of Alzheimer's disease,which lays the foundation for further revealing material basis and mechanism of this formula,and plays an important role in digging and developing this classic and famous formula.

Mid-term efficacy and prognosis of TPF regimen induction chemotherapy combined with IMRT for locally advanced nasopharyngeal carcinoma / 中华放射医学与防护杂志

Objective To investigate the efficacy,adverse reactions and immune function of time-adjusted chemotherapy combined with intensity-modulated radiation therapy (IMRT) and conventional chemotherapy combined with IMRT for locally advanced nasopharyngeal carcinoma.Methods Random number grouping method was used to divide 66 cases of locally advanced nasopharyngeal carcinoma into 2 groups,of which 36 cases in the time-adjusted chemotherapy group and 30 cases in the conventional group.Both of them received docetaxel + cisplatin + fluorouracil regimen to induce chemotherapy for 2 cycles.The time-adjusted chemotherapy group was treated with intravenous injection of electronic automatic injection pump,the conventional group was treated with conventional intravenous infusion,and both groups were treated with synchronous cisplatin combined with IMRT.Calculated survival rate was generated by Kaplan-Meier method and long-term adverse reactions was evaluated according to CTC 3.0 criteria.Results The 3-year overall survival (OS) rate was 86.1％ and 93.3％ in the time-adjusted chemotherapy group and the regular group,the 3-year progress-free survival (PFS) was 83.3％ and 93.3％,the 3-year RFS was 88.5％ and 93.3％,and the 3-year recurrence-free survival was 94.1％ and 100％ respectively with no statistically significant difference (P ＞ 0.05).The dryness and hearing loss of the time-adjusted chemotherapy group had a decreasing trend compared with the conventional group.However,CD3 +,CD3 + CD4 +,CD3 + CD4 + CD8 +,and CD4 +/CD8 + of the time-adjusted chemotherapy group had an increasing trend compared with the conventional group.Conclusions Both time-adjusted chemotherapy and conventional chemotherapy combined with IMRT had comparable mid-term efficacy,but the former had lower adverse reactions,improved quality of life and immune function.Trial registration Chinese clinical trial registry,ChiCTR1800016809

Phase II clinical trial of two different modes of administration of the induction chemotherapy for locally advanced nasopharyngeal carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To compare the therapeutic effects, toxic side effects and influence on the immune function in patients treated with TPF [docetaxel (DOC) + cisplatin (DDP) + 5-fluorouracil (5-Fu)] induction chronochemotherapy and conventional chemotherapy for locally advanced nasopharyngeal (NPC).</p><p><b>METHODS</b>Seventy patients with locally advanced nasopharyngeal carcinoma were treated in our department at their first visit from April 2013 to December 2013. They were divided randomly into two groups: the chronochemotherapy group (38 patients) and conventional chemotherapy group (32 patients). All of the patients were treated with TPF regimen with 2 cycles of induction chemotherapy in a 21-28-days/cycle. The chronochemotherapy group: DOC: 75 mg/m2, i. v. gtt, d1 (03: 30-04: 30); DDP: 75 mg/m2, 10 am-10 pm, c.i.v, d1-d5; 5-Fu: 750 mg·m(-2)·d(-1), 10 pm-10 am, c. i.v., d1-d5, both chemotherapies were administered by intravenous infusion using an automatic electric pump. The conventional chemotherapy group: Both DOC and DDP were administered intravenously at a dose of 75 mg/m2 on d1. 5-Fu was given at a dose of 750 mg/m2 for 24 hours from d1-d5 with continuous infusion in a total of 120 hours. In this procedure, prescribing the conventional intravenous infusion, intensity modulated radiation therapy was used after the induction chemotherapy. The prescribed nasopharyngeal lesion dose (GTVnx) was 69.96 Gy/33 fractions for the T1-T2 nasopharygeal cancer, while 73.92 Gy/33 fractions nasopharynx lesion dose (GTVnx) for the T3-T4 nasopharyngeal cancer. The planning target volume (PTV) of positive lymph node (PTVnd) dose was 69.96 Gy/33 fractions. Concurrent chemoradiotherapy: cisplatin 100 mg/m2, i. v. gtt. d1-d2, and there were two cycles in total and 21 days each cycle.</p><p><b>RESULTS</b>Sixty-six patients were evaluable for the response assessment. There were 36 patients in the chronochemotherapy group and 30 patients in the conventional chemotherapy group. After the induction chemotherapy, no CR case was found in both of the two groups. The PR was 80.6% in the chronochemotherapy group and 50.0% in the conventional chemotherapy group (P=0.009). After concurrent chemoradiotherapy, the CR rate in the chronocheotherapy group was 45.5%, significantly higher than 20.7% in the conventional chemotherapy group (P=0.040). Secondly, the incidence rates of adverse reactions including bone marrow suppression, nausea, vomiting, diarrhea, constipation, oral mucositis, fatigue, anorexia in the chrono-chemotherapy group were significantly lower than that in the conventional group (P<0.05 for all). Finally, compared the two groups, the CD4+ /CD8+ ratio was significantly lower in the chronochemotherapy group than that in the conventional chemotherapy group (P<0.05). The lymphocytes CD19+ and CD4+/CD8+ were decreased and CD3+, CD4+, CD8+, CD16++CD56+ were increased in the chronochemotherapy group, while only CD3+ and CD8+ were increased in the conventional chemotherapy group.</p><p><b>CONCLUSIONS</b>Compared with the conventional chemotherapy, the chronochemotherapy may be more favorable in the treatment of NPC, with a better therapeutic effects and effectiveness than that of conventional chemotherapy after induction chemotherapy, with less side effects, and can improve the immune function in the patients.</p>

Clinical results of recombinant human endostatin combined with chemoradiotherapy for locally advanced nasopharyngeal carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To compare the short-term efficacy and observe the tolerability and safety of recombinant human endostatin combined with induction chemotherapy followed by chemoradiotherapy for locally advanced nasopharyngeal carcinoma.</p><p><b>METHODS</b>Fifty-three patients with locally advanced nasopharyngeal carcinoma, who received recombinant human endostatin combined with induction chemotherapy followed by chemoradiotherapy, treated in our department from December 2011 to March 2013 were included in the study group of this study. Another 48 patients, who received induction chemotherapy followed by chemoradiotherapy alone in the same period, were chosen as a control group. The short-term outcome, overall survival (OS), progression-free survival (PFS), and acute side effects of the two groups were compared.</p><p><b>RESULTS</b>The complete remission rates of nasopharyngeal tumor in the study and control groups were 77.4% and 72.9%, respectively (P=0.154). The complete remission rates of patients with and without cervical lymph node metastasis were 75.5% and 62.6%, respectively, showing a significant difference (P=0.037). The 2-year OS, PFS, and DMFS rates for the study group were 82.3%, 77.2%, and 82.2%, respectively, versus 87.2%, 84.3% and 84.2% for the control group, showing a non-significant differences between the two groups (P=0.938, P=0.551, and P=0.725).</p><p><b>CONCLUSIONS</b>The short-term results of recombinant human endostatin (Endostar) combined with induction chemotherapy followed by concurrent chemoradiotherapy in the treatment of locally advanced nasopharyngeal carcinoma are slightly better than that of induction chemotherapy followed by concurrent chemoradiotherapy alone, with tolerable treatment-related toxicity and no more side effects.</p>

Clinical study of chrono-chemotherapy in treating nasopharyngeal carcinoma patients with distant metastasis at preliminary diagnosis / 中国肿瘤临床

Objective:To investigate the outcomes of the regimen with docetaxel, cisplatin, and 5-fluorouracil (TPF regimen) in chrono-chemotherapy, and evaluate the feasibility of reducing the toxicity and immunological damage in nasopharyngeal carcinoma (NPC) patients with distant metastasis at preliminary diagnosis, then to compare the advantages and disadvantages between chrono-che-motherapy and traditional chemotherapy. Methods:A total of 46 NPC patients with distant metastasis at preliminary diagnosis (UICC 2010 stage IVc) were enrolled in this study. These NPC patients were randomly divided into chrono-chemotherapy and conventional chemotherapy groups, with 23 cases for each group. TPF neo-adjuvant chemotherapy was conducted in both groups for two cycles, with 21 days to 28 days for each cycle. The following regimen was used for the chrono-chemotherapy group:docetaxel 75 mg/m2, infu-sion, d1;cisplatin 75 mg/m2, 10:00 a.m.-10:00 p.m., continuous infusion, d1-d5;and fluorouracil 750 mg/(m2 · d), 10:00 p.m.-10:00 a. m., continuous intravenous infusion, d1-d5. The following regimen was used for the conventional chemotherapy group:docetaxel 75 mg/m2, infusion, d1;cisplatin 75 mg/m2, infusion, d1;and fluorouracil 750 mg/(m2· d), continuous infusion, d1-d5, 120 h. Patients who obtained therapeutic efficacy via induction chemotherapy were provided with intensity-modulated radiotherapy as a concurrent radio-therapy and chemotherapy (DDP 100 mg/m2, infusion, d1-d2, with 21 days each cycle and a total of two courses). One month after con-current chemoradiation, an adjuvant chemotherapy with the same regimen as the induction chemotherapy was employed for a total of two courses. Acute and late toxicities were graded in accordance with the Common Terminology Criteria for Adverse Events v3.0 scor-ing. Tumor response was evaluated using the 2000 Response Evaluation Criteria in Solid Tumors. The effective rates included complete and partial responses. Relevant data were analyzed by SPSS16.0 statistical software. Results:More emesis was observed at Grade 2 or above in the conventional chemotherapy group than in the chrono-chemotherapy group, with statistical significance between the two groups (P=0.035). After chemotherapy, the value of CD4/CD8 increased in the chrono-chemotherapy group and decreased in the con-ventional chemotherapy group, with statistical significance between the two groups (P=0.033). Conclusion:The proposed chrono-che-motherapy outperforms conventional chemotherapy in reducing the occurrence of severe vomiting. This chrono-chemotherapy may be advantageous in reducing severe bone marrow depression and may play a positive role in the immune function of NPC patients.

PhaseⅡclinical trial of induction chrono-chemotherapy followed by concurrent chemoradiation in loco-regionally advanced nasopharyngeal carcinoma / 中国肿瘤临床

Objective:The present study aimed to investigate the short-term efficacy and adverse effects of induction chrono-che-motherapy including docetaxe1 (TXT), cisplatin (DDP), and 5 fluorouraci1 (5-FU) followed by concomitant chemoradiotherapy in lo-co-regionally advanced nasopharyngeal carcinoma (NPC). Methods:Newly diagnosed locally advanced (Ⅲ~Ⅳb) NPC patients were enrolled in this study. All patients received three cycles of TPF regimen. The TPF chemotherapy regimen was administered as follows:TXT, 75 mg/m2, i.v. infusion, d1; DDP, 75 mg/m2, bolus infusion from 10:00 to 22:00, d1-5; and 5-FU 750 mg/m2/d bolus infusion from 22:00 to 10:00, d1-5, with 21 days each cycle, followed by concomitant IMRT and chemotherapy (paclitaxel 135 mg/m2 i.v. infu-sion, with 21 days each cycle and a total of 2 courses). Acute and late toxicities were graded according to the Common Terminology Cri-teria for Adverse Events v3.0 scoring criteria. Tumor response was evaluated using 2000 Response Evaluation Criteria in Solid Tumors criteria. Results:The CR and PR rates of induction chemotherapy were 23.8%and 68.6%, respectively;whereas the CR and PR rates of the combined modality treatment were 64.8%and 31.4%, respectively. Two-year overall survival rate was 91.4%, two-year progres-sion free survival rate was 87.0%, and two-year distant metastasis-free survival rate was 88.4%. The main side effects from induction chemotherapy include an over grade 3 granulocytopenia of 28.6%. Major toxicity from concurrent chemo-radiotherapy was oral mucosi-tis (81.0%);grade 3 to 4 oral mucositis was 16%. No treatment-related deaths occurred in this study. Conclusion:Induction chrono-che-motherapy using TPF followed by concurrent chemoradiotherapy of paclitaxel is a well-tolerated treatment with short-term efficacy and severity for locally advanced NPC. Further follow-up is required to assess the late effects and long-term efficacy.