Concurrent chemoradiotherapy followed by adjuvant cisplatin-gemcitabine versus cisplatin-fluorouracil chemotherapy for N2-3 nasopharyngeal carcinoma: a multicentre, open-label, randomised, controlled, phase 3 trial.

BACKGROUND: Patients with N2-3 nasopharyngeal carcinoma have a high risk of treatment being unsuccessful despite the current practice of using a concurrent adjuvant cisplatin-fluorouracil regimen. We aimed to compare the efficacy and safety of concurrent adjuvant cisplatin-gemcitabine with cisplatin-fluorouracil in N2-3 nasopharyngeal carcinoma. METHODS: We conducted an open-label, randomised, controlled, phase 3 trial at four cancer centres in China. Eligible patients were aged 18-65 years with untreated, non-keratinising, stage T1-4 N2-3 M0 nasopharyngeal carcinoma, an Eastern Cooperative Oncology Group performance status score of 0-1, and adequate bone marrow, liver, and renal function. Eligible patients were randomly assigned (1:1) to receive concurrent cisplatin (100 mg/m2 intravenously) on days 1, 22, and 43 of intensity-modulated radiotherapy followed by either gemcitabine (1 g/m2 intravenously on days 1 and 8) and cisplatin (80 mg/m2 intravenously for 4 h on day 1) once every 3 weeks or fluorouracil (4 g/m2 in continuous intravenous infusion for 96 h) and cisplatin (80 mg/m2 intravenously for 4 h on day 1) once every 4 weeks, for three cycles. Randomisation was done using a computer-generated random number code with a block size of six, stratified by treatment centre and nodal category. The primary endpoint was 3-year progression-free survival in the intention-to-treat population (ie, all patients randomly assigned to treatment). Safety was assessed in all participants who received at least one dose of chemoradiotherapy. This study was registered at ClinicalTrials.gov, NCT03321539, and patients are currently under follow-up. FINDINGS: From Oct 30, 2017, to July 9, 2020, 240 patients (median age 44 years [IQR 36-52]; 175 [73%] male and 65 [27%] female) were randomly assigned to the cisplatin-fluorouracil group (n=120) or cisplatin-gemcitabine group (n=120). As of data cutoff (Dec 25, 2022), median follow-up was 40 months (IQR 32-48). 3-year progression-free survival was 83·9% (95% CI 75·9-89·4; 19 disease progressions and 11 deaths) in the cisplatin-gemcitabine group and 71·5% (62·5-78·7; 34 disease progressions and seven deaths) in the cisplatin-fluorouracil group (stratified hazard ratio 0·54 [95% CI 0·32-0·93]; log rank p=0·023). The most common grade 3 or worse adverse events that occurred during treatment were leukopenia (61 [52%] of 117 in the cisplatin-gemcitabine group vs 34 [29%] of 116 in the cisplatin-fluorouracil group; p=0·00039), neutropenia (37 [32%] vs 19 [16%]; p=0·010), and mucositis (27 [23%] vs 32 [28%]; p=0·43). The most common grade 3 or worse late adverse event (occurring from 3 months after completion of radiotherapy) was auditory or hearing loss (six [5%] vs ten [9%]). One (1%) patient in the cisplatin-gemcitabine group died due to treatment-related complications (septic shock caused by neutropenic infection). No patients in the cisplatin-fluorouracil group had treatment-related deaths. INTERPRETATION: Our findings suggest that concurrent adjuvant cisplatin-gemcitabine could be used as an adjuvant therapy in the treatment of patients with N2-3 nasopharyngeal carcinoma, although long-term follow-up is required to confirm the optimal therapeutic ratio. FUNDING: National Key Research and Development Program of China, National Natural Science Foundation of China, Guangdong Major Project of Basic and Applied Basic Research, Sci-Tech Project Foundation of Guangzhou City, Sun Yat-sen University Clinical Research 5010 Program, Innovative Research Team of High-level Local Universities in Shanghai, Natural Science Foundation of Guangdong Province for Distinguished Young Scholar, Natural Science Foundation of Guangdong Province, Postdoctoral Innovative Talent Support Program, Pearl River S&T Nova Program of Guangzhou, Planned Science and Technology Project of Guangdong Province, Key Youth Teacher Cultivating Program of Sun Yat-sen University, the Rural Science and Technology Commissioner Program of Guangdong Province, and Fundamental Research Funds for the Central Universities.

Jinfukang regulates integrin/Src pathway and anoikis mediating circulating lung cancer cells migration.

ETHNOPHARMACOLOGICAL RELEVANCE: Metastasis is the main cause of death in lung cancer patients. Circulating tumor cells (CTCs) may be an important target of metastasis intervention. Previous studies have shown that Jinfukang could prevent the recurrence and metastasis of lung cancer, and we have established a circulating lung tumor cell line CTC-TJH-01. However, whether Jinfukang inhibition of lung cancer metastasis is related to CTCs is still unknown. AIM OF THE STUDY: To further explore the mechanism of Jinfukang in anti-metastasis of lung cancer from the perspective of intervention of CTCs. MATERIALS AND METHODS: CTC-TJH-01 and H1975 cells were treated with Jinfukang. Cell viability was detected by CCK8, and the cell apoptosis was detected by flow cytometry. Transwell was used to detected cell migration and invasion. Cell anoikis was detected by anoikis detection kit. Protein expression was analysis by Western blot. RESULTS: Jinfukang could inhibit the proliferation, migration and invasion of CTC-TJH-01 and H1975 cells. Besides, Jinfukang could also induce anoikis in CTC-TJH-01 and H1975 cells. Analysis of the mRNA expression profile showed ECM-receptor interaction and focal adhesion were regulated by Jinfukang. Moreover, it was also find that Jinfukang significantly inhibited integrin/Src pathway in CTC-TJH-01 and H1975 cells. When suppress the expression of integrin with ATN-161, it could promote Jinfukang to inhibit migration and induce anoikis in CTC-TJH-01 and H1975 cells. CONCLUSIONS: Our results indicate that the migration and invasion of CTCs are inhibited by Jinfukang, and the mechanism may involve the suppression of integrin/Src axis to induce anoikis. These data suggest that Jinfukang exerts anti-metastatic effects in lung cancer may through anoikis.

Efficacy of Acupuncture and Moxibustion as a Subsequent Treatment after Second-Line Chemotherapy in Advanced Gastric Cancer.

OBJECTIVE: To explore whether acupuncture and moxibustion can prevent disease progression of advanced gastric cancer patients completing second-line chemotherapy and, if so, the related mechanism. METHOD: Progression-free survival (PFS) and overall survival (OS) were main outcome measures. The real-time quantitative PCR was used to detect the expression of genes including T-bet, IFN-γ, GATA3, and IL-4 in peripheral blood mononuclear cells (PBMCs). IL-4, IL-6, Ca199, CRP, and IFN-γ in plasma levels were checked. RESULTS: 170 patients were randomly assigned in a 3 : 2 ratio to receive either acupuncture and moxibustion or sham acupuncture until progression. 135 patients were included in the primary analysis. Both PFS and OS in treatment group were proven to be better than control group. Acupuncture and moxibustion promoted typical Th1 cells drifting, as confirmed by increased T-bet/IFN-γ and decreased GATA3/IL-4 in mRNA levels from PBMCs, as well as upregulating IFN-γ and downregulating IL-4 in plasma levels. IL-6, Ca199, and CRP in plasma levels were also reduced by acupuncture and moxibustion. CONCLUSIONS: Acupuncture and moxibustion can prolong PFS and OS of advanced gastric cancer patients completing second-line chemotherapy by reversing Th1/Th2 shift and attenuating inflammatory responses.

Cognitive modelling of Chinese herbal medicine's effect on breast cancer.

PURPOSE: Traditional Chinese medicine (TCM) has recently attracted increasing interests in cancer treatment. It was found that TCM-based treatment, combined with other therapies, can help improve patients' life quality. However, the existing research in TCM lacks a systematic modelling for the causal relationship of the factors related to the diagnosis and decision making. METHODS: In this paper, we proposed the use of fuzzy cognitive map (FCM) to represent the cognition of TCMs usage in cancer treatment. RESULTS: Through a case analysis, we analyse and summarise the effects of Chinese herbal medicine in breast cancer management. CONCLUSION: FCMs can visually represent the cognitive knowledge, particularly the causal relationship among key factors of TCM effects and the related breast cancer status.

[Effect of moxibustion combined with autohemotherapy of acupoint injection for life quality of allergic rhinitis with qi deficiency of lung and spleen:a randomized controlled trial].

OBJECTIVE: To observe the effects of moxibustion combined with autohemotherapy of acupoint injection and simple moxibustion for allergic rhinitis(AR) with qi deficiency of lung and spleen and to explore its mechanism. METHODS: By random number table,75 patients who matched the criteria were assigned into a moxibustion combined with autohemotherapy of acupoint injection group(a combination group,37 cases) and a moxibustion group(38 cases). In the combination group,moxibustion was used at bilateral Yingxiang(LI 20) and injection bila-teral Feishu(BL 13),Pishu(BL 20) and Zusanli(ST 36). In the moxibustion group,moxibustion was applied bilaterally at all the above acupoints. Acupoint injection was given twice a week,and moxibustion once a day,seven days as a course. The patients were observed for four courses and followed up half a year after treatment. Rhinoconjunctivitis quality of life questionnaire(RQLQ) was compared before and after treatment and at follow-up. The short-term and long-term effects as well as the changes of interferon-γ(IFN-γ),interleukin-4(IL-4) and immunoglobulin E(IgE) were observed in the two group. RESULTS: After treatment,the obviously effective rate of the combination group was 75.68%(28/37),which was higher than 52.63%(20/38) of the moxibustion group(P<0.05). But at follow-up, the obviously effective rate of the moxibustion group was 47.37%(18/38),which was better than 24.32%(9/37) of the combination group(P<0.05). Life quality of the two group in all aspects after treatment and at follow-up were apparently improved compared with the baseline(P<0.01,P<0.05). After treatment,the life quality,sleep condition,non nasal-eye symptoms,behavior issue of the combination group were superior to those of the moxibustion group(all P<0.05),and at follow-up,the above outcomes,the eye and nasal symptoms as well as emotional response of the mo-xibustion group were better(all P<0.05). There was statistical significance in the two group about serum IFN-γ,IgE,IL-4 before and after treatment(P<0.01,P<0.05),and significance existed between the two groups(P<0.05). CONCLUSIONS: Moxibustion combined with autohemotherapy of acupoint injection can effectively improve the short-term quality of life of AR with qi deficiency of lung and spleen. The mechanism may be related to balancing the immune response of Th1 and Th2.

Protective mechanism of Panax notoginseng saponins on rat hemorrhagic shock model in recovery stage.

To explore protective mechanism of Panax notoginseng saponins (PNS) on rat hemorrhagic shock model in recovery stage. 72 Wistar rats were selected and divided into control group, model group and PNS group with 24 rats in each group. 200 mg/kg PNS was injected intravenously at 60 min of hemorrhagic shock stage in PNS groups. Changes of endotoxin, MPO, IL-6, SOD, MDA and TNF α were observed at 30 and 120 min of recovery stage by ELISA; water content of lung and intestine was detected; HE staining was applied to observe morphological change of intestinal mucosa, kidney, liver and lung; western blot was used to detect intercellular adhesion molecule-1 (ICAM-1) level in lung tissue and intestine tissue. At 30 min and 120 min of recovery stage, MDA, MPO, endotoxin, TNF α and IL-6 levels significantly increased in model group compared with control group, however SOD level significantly decreased, the difference was statistically significant (P < 0.05); PNS dose-dependently decreased MDA, MPO, endotoxin, TNF α and IL-6 levels, and increased SOD level, which was statistically significant (P < 0.05); In results of water content detection, water content in lung tissue and intestine tissue was significantly higher than in control group, however, after being treated with PNS, the water content was significantly decreased; HE staining showed the morphologic change of lung tissue cells; Western blot showed that in lung tissue and intestine tissue, ICAM-1 level in model group was significantly higher than in control group, and it was lower in PNS group than in model group. PNS can increase SOD activity, decrease levels of MDA, endotoxin and MPO, decrease expression of TNF α and IL-6, and decrease water content in lung tissue and intestine tissue. Thus, PNS is protective to rat hemorrhagic shock model by anti oxidative stress and anti-inflammatory pathways, and ICAM-1 may play an important role in the mechanism.

Effect of temperature on the occurrence and distribution of colorado potato beetle (Coleoptera: Chrysomelidae) in China.

Colorado potato beetle, Leptinotarsa decemlineata (Say), is the most destructive pest of potato in many countries of the world. It first invaded China from Kazakhstan in 1990s and now is a major pest of potato in many areas of Xinjiang Uygur Autonomous Region (Xinjiang). The objective of this study was to determine the effect of temperature on the spread of Colorado potato beetle in China after its invasion. Cold temperature in winter (December) and high temperature in summer (July) were analyzed in accordance with the absence and presence of Colorado potato beetle in Xinjiang. The boundary between the absence and presence of Colorado potato beetle in Xinjiang nearly coincided with the -8°C isotherm of monthly mean minimum temperature in winter. The stress of the low temperature in winter for Colorado potato beetle basically disappeared in the southeastern Hexi Corridor in Gansu Province of China, suggesting that the Hexi Corridor is the best channel to prevent any long-distance invasions of Colorado potato beetle into the Central Plains region. However, in Turpan City in northeastern Xinjiang, the extremely hot weather in the summer prevents the local colonization of Colorado potato beetle. Furthermore, according to our monitoring, high temperature in summer also limited Colorado potato beetle to diffuse eastward through Turpan. Results of this study suggest that it is essential to strengthen inspection and quarantine measures to prevent any artificial transmissions of Colorado potato beetle spreading eastward and thus to ensure the sustainable production of potato and other Solanaceae crops in northwest regions of China.

[Multi-central clinical evaluation of ginger-partitioned moxibustion for treatment of leukopenia induced by chemotherapy].

OBJECTIVE: To prove the therapeutic effect of ginger-partitioned moxibustion on leukopenia induced by chemotherapy and effect on life quality of the patient with tumor after chemotherapy. METHODS: Randomized, controlled, multi-central cooperative method was used and the patients confirmed to the enrolled criteria were divided in-to two groups. The test group were treated with ginger-partitioned moxibustion at Dazhui (GV 14), Geshu (BL 17), Pishu (BL 20), etc.; and the control group with oral administration of Chinese patent medicine. RESULTS: Out of the 221 cases confirmed to program analysis, 113 cases were in the test group and 108 cases in the control group. After 10 days, the cured rate and the effective rate were 84.1% and 66.4% in the test group and 35.2% and 33.3% in the control group, respectively, with very significant differences between the two groups (both P < 0.01); fifteen days later, the therapeutic effects in the two groups were maintained. The two methods could improve clinical symptoms, with the test group being better than the control group. Any adverse response was not found in the two groups, and the injuries of functions of the heart, lung and kidney induced by chemotherapy had some improvement. CONCLUSION: The therapeutic effect of ginger-partitioned moxibustion on luekopenia induced by chemotherapy is reliable and is better than oral administration of Chinese patent medicine, with a better duplication.

[Application of electro-acupuncture-anesthesia device in brachiplex nerve blocking].

OBJECTIVE: To investigate the effect of electro-acupuncture-anesthesia device (EAAD) as an auxiliary localizing method for brachiplex nerve blocking. METHODS: One hundred and twenty patients scheduled for operation in upper limbs were randomly divided into group A and group B, 60 in each group. Bupivacaine 25 ml (0.375% in concentration) was used to block intermuscular plexus brachialis in the operation for anesthesia and EAAD was used for adjunctive localizing in group A, while in group B paresthesia elicitation was used. RESULTS: In group A, the blocking was complete in 56 cases and incomplete in 4, the anesthesia effect was superior to that in group B, complete in 46, incomplete in 9, and of inefficient in 5 (P < 0.01). CONCLUSION: EAAD provides a localizing method for plexus brachialis blocking more precise than paresthesia elicitation.

[Analysis on therapeutic effect of Western and Chinese drug in treating intrahepatic cholestasis pregnancy].

OBJECTIVE: To evaluate the therapeutic effect of Yinchenghao decoction (YCHD) and S-adenosy-L-methionine (SAM) in treating intrahepatic cholestasis of pregnancy (ICP) and improving prognosis of perinatal newborn babies. METHODS: Sixty in-patients of ICP were randomly divided into two groups, the group A treated with YCHD and the group B treated with SAM. The symptom of itching and serum biochemical indexes, including glycocholic acid, bilirubin and transaminase, were observed after 3 weeks treatment, and the prognosis of perinatal newborn babies between the two groups was compared after delivery. RESULTS: After treatment, the symptom of itching, serum levels of glycocholic acid, bilirubin and transaminase improved significantly (P < 0.05) in both groups, and the prognosis of newborn in the two groups was similar (P > 0.05). CONCLUSION: Both YCHD and SAM could effectively treat ICP. The former is rather cheaper, so it is more feasible for spreading.

[The effects of continuous stimulation with different doses of parathyroid hormone 1-34 fragment on human SaoS-2 cells].

OBJECTIVE: To observe the effects of different doses of human parathyroid hormone fragment (hPTH)1-34 on SaoS cells and to explore the signal pathway and mechanism. METHODS: 5 x 10(4) cells/ml SaoS cells were seeded. Doses of 5, 50, 500 and 5 000 micro g/L hPTH1-34 were supplemented respectively. Total RNA was extracted by Trizol kit. Alkaline phosphatase (ALP), osteocalcin (BGP) and cAMP concentrations were measured by chemical, radioimmunoassay and competitive protein binding methods. c-fos gene expression level was semi-quantified by reverse transcriptase (RT)-PCR. RESULTS: ALP activity was higher in 500 micro g/L dose (P < 0.05 vs. control). BGP level was inhibited in 5 000 micro g/L dose (P < 0.05 vs. control and pretreatment). 50 and 500 micro g/L hPTH1-34 enhanced cAMP level significantly (P < 0.05 vs. control). No obvious increase of cAMP level was found in 5 000 micro g/L and 5 micro g/L dose groups (P > 0.05 vs. control and pretreatment). c-fos expression was higher in 50 and 500 micro g/L group. CONCLUSION: Different doses of hPTH1-34 exert distinct effects on osteoblasts. hPTH1-34 affects ALP and c-fos depending on protein kinase A signal pathway. hPTH1-34 exerts its action via regulation of osteoblasts by c-fos.