Exogenous hydrogen sulfide and methylglyoxal alleviate cadmium-induced oxidative stress in Salix matsudana Koidz by regulating glutathione metabolism.

BACKGROUND: Cadmium (Cd) is a highly toxic element for plant growth. In plants, hydrogen sulfide (H2S) and methylglyoxal (MG) have emerged as vital signaling molecules that regulate plant growth processes under Cd stress. However, the effects of sodium hydrosulfide (NaHS, a donor of H2S) and MG on Cd uptake, physiological responses, and gene expression patterns of Salix to Cd toxicity have been poorly understood. Here, Salix matsudana Koidz. seedlings were planted in plastic pot with applications of MG (108 mg kg- 1) and NaHS (50 mg kg- 1) under Cd (150 mg kg- 1) stress. RESULTS: Cd treatment significantly increased the reactive oxygen species (ROS) levels and malondialdehyde (MDA) content, but decreased the growth parameters in S. matsudana. However, NaHS and MG supplementation significantly decreased Cd concentration, ROS levels, and MDA content, and finally enhanced the growth parameters. Cd stress accelerated the activities of antioxidative enzymes and the relative expression levels of stress-related genes, which were further improved by NaHS and MG supplementation. However, the activities of monodehydroascorbate reductase (MDHAR), and dehydroascorbate reductase (DHAR) were sharply decreased under Cd stress. Conversely, NaHS and MG applications restored the MDHAR and DHAR activities compared with Cd-treated seedlings. Furthermore, Cd stress decreased the ratios of GSH/GSSG and AsA/DHA but considerably increased the H2S and MG levels and glyoxalase I-II system in S. matsudana, while the applications of MG and NaHS restored the redox status of AsA and GSH and further improved glyoxalase II activity. In addition, compared with AsA, GSH showed a more sensitive response to exogenous applications of MG and NaHS and plays more important role in the detoxification of Cd. CONCLUSIONS: The present study illustrated the crucial roles of H2S and MG in reducing ROS-mediated oxidative damage to S. matsudana and revealed the vital role of GSH metabolism in regulating Cd-induced stress.

Medical Therapy of Hearing Impairment and Tinnitus with Chinese Medicine: An Overview.

The current review gives a comprehensive overview of the recent development in Chinese medicine (CM) for treating several kinds of acquired nerve deafness and tinnitus, as well as links the traditional principle to well-established pharmacological mechanisms for future research. To date, about 24 herbal species and 40 related ingredients used in CM to treat hearing loss and tinnitus are reported for the treatment of endocochlear potential, endolymph growth, lowering toxic and provocative substance aggregation, inhibiting sensory cell death, and retaining sensory transfer. However, there are a few herbal species that can be used for medicinal purposes. Nevertheless, clinical studies have been hampered by a limited population sample, a deficiency of a suitable control research group, or contradictory results. Enhanced cochlear blood flow, antiinflammatory antioxidant, neuroprotective effects, and anti-apoptotic, as well as multi-target approach on different auditory sections of the inner ear, are all possible benefits of CM medications. There are numerous unknown natural products for aural ailment and tinnitus identified in CM that are expected to be examined in the future utilizing various aural ailment models and processes.

Dryness-alleviating effect of processed Aurantii Fructus from Lingnan based on correlation of fecal metabolomics and dryness / 中国中药杂志

With the approach of untargeted metabolomics and correlation analysis, this study aimed to explore the mechanism of Aurantii Fructus from Lingnan region in alleviating dryness by analyzing the different effects of raw Aurantii Fructus(RAF) and processed Aurantii Fructus(PAF) on fecal endogenous metabolism in normal rats. Eighteen Sprague-Dawley(SD) rats were randomly divided into a control group(C), an RAF group(10 g·kg~(-1)), and a PAF group(10 g·kg~(-1)). After seven days of administration, the effects of RAF and PAF on dryness-related indexes were compared, including water intake, fecal water content, salivary secretion, the expression of AQP5, VIP, and 5-HT in the submandibular gland, as well as the expression of AQP3, VIP, and 5-HT in the colon. The fecal samples in each group were determined by LC-MS. Multivariate statistical analysis and Pearson correlation coefficient were used for screening the differential metabolites and metabolic pathways in alleviating dryness of RAF. The results indicated that both RAF and PAF showed certain dryness, and the dryness of RAF was more significant. Moreover, PAF could alleviate dryness of RAF to a certain extent by reducing the water intake, fecal water content, and the expression of AQP3, VIP, and 5-HT in the colon and increasing the salivary secretion and the levels of AQP5, VIP, and 5-HT in the submandibular gland. According to the analysis of fecal metabolomics, 99 and 58 metabolites related to dryness were found in RAF and PAF respectively, where 16 of them played an important role in alleviating dryness of RAF. Pathway analysis revealed that the mechanism of PAF in alleviating dryness of RAF was presumably related to the regulation of riboflavin metabolism, purine metabolism, arginine biosynthesis, pyrimidine metabolism, alanine metabolism, aspartate metabolism, glutamate metabolism, and retinol metabolism pathways. This study suggested that PAF might alleviate dryness of RAF by affecting the metabolic levels of the body, which provides a new basis for further clarifying the processing mechanism of PAF.

Analysis of vitamin D status among children under 7 years of age in some regions of China / 中华儿科杂志

Objective: To explore current vitamin D status and influential factors of vitamin D deficiency and insufficiency among children under 7 years of age in 11 provinces, autonomous regions or municipalities of China. Methods: According to the "province-city-hospital" sampling technical route, a total of 1 531 healthy children under 7 years of age were sampled from 11 provinces, autonomous regions or municipalities in China by the cluster random sampling method from November 2020 to November 2021. The demographic information, family conditions, behavior and living habits and feeding behaviors were collected using unified questionnaire. Serum 25-hydroxyvitamin D(25(OH)D) levels were measured by liquid chromatography-tandem mass spectrometry. Serum 25(OH)D<30 nmol/L was considered deficient and 30-50 nmol/L was considered insufficient. With 25(OH)D≤50 nmol/L as the dependent variable, multivariate Logistic regression was applied to analyze the association between vitamin D deficiency and insufficiency and potential influential factors. Results: The prevalence of vitamin D deficiency and insufficiency among children under 7 years of age in 11 provinces, autonomous regions or municipalities of China was 14.0% (215/1 531), 3.8% (25/664) and 21.9% (190/867) in 0-<3 and 3-<7 of age years, respectively. Compared to children aged 0-<3 years, children aged 3-<7 years had a 2.6-fold increased risk of vitamin D deficiency and insufficiency (OR=3.60, 95%CI 1.93-6.72, P<0.001). Frequent sunlight exposure (OR=0.46, 95%CI 0.29-0.73, P=0.001), vitamin D supplementation (sometimes, OR=0.33, 95%CI 0.21-0.51, P<0.001; daily, OR=0.20, 95%CI 0.11-0.36, P<0.001) and infant formula intake(4-7 times per weeks, OR=0.43, 95%CI 0.28-0.68, P<0.001) were protective factors for vitamin D deficiency and insufficiency. Conclusion: Vitamin D deficiency and insufficiency are common among children under 7 years of age in 11 provinces, autonomous regions or municipalities of China, which is affected by age, sunlight exposure, vitamin D supplementation and infant formula intake.

Biopathway construction of plant natural products / 药学学报

Plant natural products (PNPs) are important sources of innovative drugs. They are mainly obtained by isolation or extraction from plants. Low content and with structural analogues in plants result in high production cost, which restricts the research and application of PNPs. While biopathway construction by synthetic biology provides an alternative for production of PNPs. By biosynthetic pathway analysis of PNPs and reconstructing the biopathway in microorganisms, we can produce PNPs in cell factories efficiently. Recently, several predominantly international reports about biosynthesis of PNPs and its synthetic biology production, triggered the researches of PNPs. Abundant traditional Chinese medicine resources and profound cultural heritage of Chinese medicine make biosynthesis pathway analysis of PNPs to be a research hotspot. And some of the studies have achieved significant progress. Here, recent progress in the biosynthesis of plant natural products and its synthetic biology was reviewed. In particular, the application of new methods and technologies in recent years were summarized and discussed. This will provide reference for the biopathway construction of plant natural products.

Evaluation of the National Comprehensive Cancer Network and European Society for Medical Oncology Nasopharyngeal Carcinoma Surveillance Guidelines.

Purpose: The National Comprehensive Cancer Network (NCCN) and European Society for Medical Oncology (ESMO) provide surveillance guidelines for nasopharyngeal carcinoma (NPC). We evaluated the ability of these guidelines to capture disease recurrence. Materials and methods: All 749 NPC patients were stratified for analysis by T and N stage. We evaluated the guidelines by calculating the percentage of relapses detected when following the 2018 NCCN, 2015 NCCN, and 2012 ESMO surveillance guidelines, and related surveillance costs were compared. Results: At a median follow-up of 100.8 months, 168 patients (22.4%) had experienced recurrence. Nineteen recurrences (11.3%) were detected using the 2018 NCCN, 53 (31.5%) using the 2015 NCCN and 46 (27.4%) using the ESMO guidelines. To capture 95% recurrences, surveillance would be required for 85.57 months for T1/2, 67.45 months for T3/4, 83.57 months for N0/1, and 55.80 months for N2/3 disease. In T1/2 disease, Medicare surveillance costs per patient were US$1642.66 using 2018 NCCN or ESMO and US$2179.81 using 2015 NCCN. Costs per recurrence detected were US$42,578.64, 62,088.70, and 73,329.76 using 2018 NCCN, 2015 NCCN, and ESMO, respectively. Conclusions: If strictly followed, the NCCN and ESMO guidelines will miss more than two-thirds recurrences. Improved surveillance algorithms to balance patient benefit against costs are needed.

Russian Characteristic Medicinal Plant Resources Based on DNA Barcode Technology / 中国实验方剂学杂志

Objective::To investigate the distribution status of medicinal plants in the wild areas of Russian Caucasus and Altai, and clarify the types and efficacy information of medicinal plants in the area, so as to dig deep into new resources and new functions of medicinal plants in the countries along the Belt and Road. Method::Medicinal plants in the wild were searched and collected to make waxy specimens, and sent back to the country to extract the total DNA of the leaves of the leaves. Internal Transcribed Spacer(ITS)sequence universal primers were used for Polymerase Chain Reaction (PCR)amplification. The PCR products were sent for the two-way sequencing, and the sequencing results are spliced by software according to National Center for Biotechnology Information(NCBI). The same ITS sequence of the highest similarity species obtained by database BLAST was analyzed by DNAman software to identify the ITS sequence of the species and the ITS sequence of the same species. The MEGA 7 software was used as the phylogenetic tree, and the Kimura-2 parameter genetic distance was used to construct the neighbor joining(NJ) phylogenetic tree by the neighbor-joining method. The confidence of each branch of the development tree was tested by the bootstrap test method. A total of 2 000 cycles were performed, and the results were identified based on the clustering results. On this basis, the key medicinal plants in the Russian Caucasus and Altay wild areas were summarized and analyzed. Result::After BLAST alignment in NCBI database, the ITS sequences of each specimen were clustered with the login sequences on the NCBI database, which were separated from the outer group. The species classification of the specimens to be identified was determined by combining the characteristics of the specimens. A total of 51 plants were identified from the specimens collected in the field, covering 44 genera of 17 families, and 29 plants had clear efficacy records. The National Drug List of the Russian Federation and the Chinese Pharmacopoeia were retrieved to summarize commonly used medicinal plants in China and conclude that 20 kinds of Chinese and Russian common medicinal materials have different medicinal effects in local areas. This study has a reference significance for expanding the scope and clinical experience of traditional Chinese medicines, and provides a basis for strengthened local species conservation, development and utilization of wild medicinal plant resources.

Effects of Electroacupuncture on Learning-memory and P35/P25-Cyclin-dependent Kinase 5-Tau Phosphorylation Signal Pathway in Prefrontal Cortex of Rats with Alzheimer's Disease / 中国康复理论与实践

Objective:To observe the effect of electroacupuncture at Baihui (DU20) and Shenshu (BL23) acupoints on learning-memory ability and expression of the relative protein of P35/P25-cyclin-dependent kinase 5 (CDK5)-Tau phosphorylation signaling pathway in the prefrontal cortex (PFC) in rats with Alzheimer's disease (AD), so as to reveal its potential mechanisms in treating AD. Methods:Male adult Sprague-Dawley rats were randomly divided into normal control group, sham group, model group and treatment group with six rats in each group. The AD model was constructed by bilateral hippocampal injection of Aβ25-35 in latter two groups. Equal amount of normal saline was injected into the sham group. The treatment group was acupunctured at Baihui and Shenshu once a day for ten days. All the rats were tested with Morris Water Maze. Immunohistochemistry staining and Western blotting were used to detect the related protein of P35/P25-CDK5-Tau protein phosphorylation in the PFC. Results:Compared with the normal control group and the sham group, the escape latency and escape length increased (P < 0.05) and the times crossing the platform reduced (P < 0.05) in the model group; compared with the model group, the escape latency and escape length reduced (P < 0.05), and the times crossing the platform increased (P < 0.05) in the treatment group. The optical density of P35/P25 and CDK5 were significantly higher in the model group than in the normal control group and the sham group (P < 0.01), and they were lower in the treatment group than in the model group (P < 0.001). The relative expression of P35/P25, CDK5, Tau[pS199] and Tau[pS202] were higher in the model group than in the normal control group and the sham group (P < 0.05), and the expression of the above proteins was lower in the treatment group than in the model group (P < 0.05). Conclusion:Electroacupuncture could improve the learning-memory and spatial exploration ability, which associate with inhabiting the P35/P25-CDK5-Tau protein phosphorylation signaling pathway in the PFC to delay the development of AD.

[Effects of acupuncture, tuina combined with phacoemulsification for cataract with glaucoma].

OBJECTIVE: To observe the effects of acupuncture combined with phacoemulsification for cataract with glaucoma. METHODS: Sixty-eight patients with cataract and angle-closure glaucoma were randomly divided into an observation group and a control group, 34 cases in each one. The patients in the control group were treated with phacoemulsification. Based on the treatment in the control group, the patients in the observation group were treated with tuina and acupuncture at acupoints around eyes; the treatment was given once every other day, and 15-day treatment constituted a course, and 2 courses (60 days) were given. The intraocular pressure (IOP), visual acuity, pain severity, aqueous outflow (F value) and clinical symptoms were observed in the two groups before treatment and after 1 d, 7 d, 30 d and 60 d of treatment. RESULTS: The IOP after 1 d, 7 d, 30 d and 60 d of treatment in the observation group was lower than that in the control group (all P<0.05), while the visual acuity after 7 d, 30 d and 60 d of treatment in the observation group was higher than that in the control group (all P<0.05). Compared before treatment, the IOP was significantly decreased after 1 d, 7 d, 30 d and 60 d of treatment in the two groups, and the visual acuity was significantly increased after 7 d, 30 d and 60 d of treatment in the two groups (all P<0.05). The pain scores and F value after 7 d, 30 d and 60 d of treatment in the observation group were lower than those in the control group (all P<0.05). Compared before treatment, the pain scores and F value after 7 d, 30 d and 60 d of treatment were significantly reduced in the two groups (all P<0.05). After 60 d of treatment, the number of patients who presented general clinical symptoms in the observation group was significantly lower than that in the control group (P<0.05). CONCLUSION: Based on phacoemulsification, acupuncture and tuina could significantly reduce the IOP and F value, relieve pain and improve visual acuity in patients with cataract and glaucoma.

Evidence Underlying Recommendations and Payments from Industry to Authors of the National Comprehensive Cancer Network Guidelines.

BACKGROUND: The National Comprehensive Cancer Network (NCCN) guidelines are among the most widely used guidance in oncology. It is critical to understand the extent to which the recommendations in these guidelines are supported by evidence and to investigate whether these recommendations have been influenced by payments from industry to authors. MATERIALS AND METHODS: We examined the quality and consistency of evidence, as scored by guidelines authors, for systemic treatment incorporated in the NCCN guidelines. Payments data in 2015 were manually abstracted using the Open Payments database, which discloses all payments between the industry and American physicians. Correlations between the percentage of authors who received payments and the proportion of recommendations developed from low-level evidence per guideline were calculated using Spearman rank correlation. RESULTS: In total, 1,782 recommendations were identified in 29 guidelines, of which 1,282 (71.9%) were based on low-quality or low-consistency evidence (low-level evidence), including "case reports or clinical experience only" (18.9%). A substantial proportion (31/143, 21.7%) of category 1 (the highest level) recommendations were based on low-level evidence. The majority of authors (87.1%) received payments from industry. However, no association was found between the prevalence of payments among authors and the percentage of recommendations developed from low-level evidence per guideline. CONCLUSION: The majority of systemic treatment recommendations in the NCCN guidelines are based on low-level evidence, including more than one in five category 1 recommendations. Payments from industry were prevalent among authors. However, industrial payments among authors were not associated with inclusion of regimen/agent for which there is no conclusive evidence in the guidelines. IMPLICATIONS FOR PRACTICE: The authors found that the majority (71.9%) of systemic treatment recommendations issued in the current National Comprehensive Cancer Network guidelines were based on low-level evidence. Physicians should remain cautious when using current guidelines as the sole source guiding patient care decisions.

Effects of acupuncture, combined with phacoemulsification for cataract with glaucoma / 中国针灸

OBJECTIVE@#To observe the effects of acupuncture combined with phacoemulsification for cataract with glaucoma.@*METHODS@#Sixty-eight patients with cataract and angle-closure glaucoma were randomly divided into an observation group and a control group, 34 cases in each one. The patients in the control group were treated with phacoemulsification. Based on the treatment in the control group, the patients in the observation group were treated with and acupuncture at acupoints around eyes; the treatment was given once every other day, and 15-day treatment constituted a course, and 2 courses (60 days) were given. The intraocular pressure (IOP), visual acuity, pain severity, aqueous outflow (F value) and clinical symptoms were observed in the two groups before treatment and after 1 d, 7 d, 30 d and 60 d of treatment.@*RESULTS@#The IOP after 1 d, 7 d, 30 d and 60 d of treatment in the observation group was lower than that in the control group (all <0.05), while the visual acuity after 7 d, 30 d and 60 d of treatment in the observation group was higher than that in the control group (all <0.05). Compared before treatment, the IOP was significantly decreased after 1 d, 7 d, 30 d and 60 d of treatment in the two groups, and the visual acuity was significantly increased after 7 d, 30 d and 60 d of treatment in the two groups (all <0.05). The pain scores and F value after 7 d, 30 d and 60 d of treatment in the observation group were lower than those in the control group (all <0.05). Compared before treatment, the pain scores and F value after 7 d, 30 d and 60 d of treatment were significantly reduced in the two groups (all <0.05). After 60 d of treatment, the number of patients who presented general clinical symptoms in the observation group was significantly lower than that in the control group (<0.05).@*CONCLUSION@#Based on phacoemulsification, acupuncture and could significantly reduce the IOP and F value, relieve pain and improve visual acuity in patients with cataract and glaucoma.

Observations on the Therapeutic Effect of Kinetic Rectification Acupuncture on Acute Facial Neuritis / 上海针灸杂志

Objective To investigate the clinical efficacy of kinetic rectification acupuncture in treating acute facial neuritis. Method Sixty patients with acute facial neuritis were randomized to observation and control groups. The observation group received kinetic rectification acupuncture and the control group, conventional acupuncture alone. Acupuncture was given five times a week, five times as one course. The therapeutic effects were evaluated after three courses of treatment. Result The total efficacy rate was 93.3% in the observation group and 73.3% in the control group; there was a statistically significant difference between the two groups (P<0.05). The latencies and amplitudes of the frontal muscle, orbicularis oculi muscle and quadrate muscle of upper lip improved in the two groups after treatment and had statistically significant pre-/post-treatment differences (P < 0.01). There were statistically significant differences in the pre-/post-treatment difference values of the latencies and amplitudes of the frontal muscle and orbicularis oculi muscle (P<0.01) and no statistically significant difference in the pre-/post-treatment difference values of the latency and amplitude of the quadrate muscle of upper lip (P>0.05) between the two groups. Conclusion Kinetic rectification acupuncture has a marked therapeutic effect on acute facial neuritis. This study provides a particular therapeutic method for clinical practice.

A network meta-analysis in comparing prophylactic treatments of radiotherapy-induced oral mucositis for patients with head and neck cancers receiving radiotherapy.

OBJECTIVES: The objective of this network meta-analysis is to optimize the prophylactic treatment for radiotherapy-induced oral mucositis in patients with head and neck cancer (HNSCC) receiving postoperative or definitive radiotherapy with or without chemotherapy. MATERIALS AND METHODS: We searched electronic databases to identify all eligible randomized clinical trials on oral mucositis. The endpoint was grade 0-2 oral mucositis. Odds ratios (OR) and the corresponding 95% confidence intervals (CI) were extracted. Network meta-analysis was performed using the frequentist approach to conduct multiple treatment comparisons. RESULTS: In total, 57 trials with 5261 patients were eligible for this study. Both direct and network meta-analysis revealed that low-level laser additional to standard oral care (SOC) was better than most of the other treatments and achieved the highest effect on grade 0-2 oral mucositis, with a surface under the cumulative ranking curve (SUCRA) of 95.8%; however, SOC with or without placebo had worse effect than most of the other treatments and was ranked worst (SUCRA = 0.4%). Moreover, sensitivity analysis performed after we had combined the SOC and placebo groups (non-medication treatment, NMT) yielded similar results, with SUCRA of 91.3% and 3.5% for low-level laser and NMT, respectively. CONCLUSIONS: Low-level laser additional to SOC may be a more effective prophylactic treatment for reducing severe radiotherapy-induced oral mucositis; SOC alone is insufficient for patients with HNSCC receiving postoperative or definitive radiotherapy with or without chemotherapy.

Refining the Role of Lymph Node Biopsy in Survival for Patients with Nasopharyngeal Carcinoma: Population-Based Study from the Surveillance Epidemiology and End-Results Registry.

BACKGROUND: The updated version of the National Comprehensive Cancer Network (NCCN) guidelines revised pretreatment workup for nasopharyngeal carcinoma (NPC) into "biopsy of the primary site or neck." Despite provision of important diagnostic information, concerns regarding tumor cell dissemination limit the application of lymph node biopsy. This study aimed to investigate whether biopsy of the neck is associated with impaired survival in NPC. METHODS: A propensity score-matched, population-based cohort identified from the Surveillance, Epidemiology, and End Results database was used to compare overall survival (OS) and disease-specific survival (DSS) of patients who underwent pretreatment cervical lymph node biopsy without subsequent neck dissection or removal of node compared with patients who did not undergo node biopsy. RESULTS: Of 2910 eligible patients, 416 (14.3%) underwent pretreatment lymph node biopsy. After use of control for patient, tumor, and demographic characteristics, biopsy was not associated with impaired OS (hazard ratio [HR], 1.15; 95% confidence interval [CI] 0.89-1.47; P = 0.29) or DSS (HR, 1.07; 95% CI 0.81-1.40; P = 0.63). Interestingly, in the subgroup analysis, the unfavorable effect of biopsy was observed for patients with differentiated non-keratinizing squamous cell carcinoma (but not other histologic types). Race did not positively alter the survival outcomes. CONCLUSIONS: The findings provide reference for clinical practice, showing that pretreatment cervical lymph node biopsy is not associated with impaired survival in NPC, except for patients with differentiated non-keratinizing squamous cell carcinoma. The recommended NCCN guidelines would be more specific by adding details to the general recommendation that neck biopsy is safe for all patients. Future prospective studies are needed to verify the study findings.

Functionalized Selenium Nanosystem as Radiation Sensitizer of 125I Seeds for Precise Cancer Therapy.

Although radiotherapy has been extensively applied in cancer treatment, external beam radiation therapy is still unable to avoid damage to adjacent normal tissues in the process of delivering a sufficient radiation dose to the tumor sites of patients. To overcome this limitation, chemoradiotherapy, as a combination of chemotherapy and radiotherapy of a radioactive seed, has been proposed to decrease the damage to tumor-surrounding tissues and enhance the radiosensitivity of solid tumors. In this study, we designed and synthesized folic acid-conjugated selenium nanoparticles (FA@SeNPs) as a cancer-targeting agent that could be synergistically enhanced by radioactive 125I seeds to realize anticancer efficacy and inhibited colony formation ability. Interestingly, when compared with X-ray irradiation, 125I seeds demonstrate a larger synergistic effect with the FA@SeNPs, drastically increasing reactive oxygen species overproduction to trigger apoptosis and influencing the cell cycle distribution in human breast cancer cells, inducing DNA damage and activating the mitogen-activated protein kinase and p53 signaling pathways. Moreover, this combination treatment demonstrates better in vivo antitumor activity and lower systemic toxicity. Therefore, this study demonstrates a new strategy for using functionalized SeNPs as a radiation sensitizer for 125I seeds for cancer therapy.

Adjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: Long-term results of a phase 3 multicentre randomised controlled trial.

AIM OF THE STUDY: Previous results from our trial showed that adjuvant cisplatin and fluorouracil chemotherapy did not significantly improve survival after concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) at 2 years. Here, we present the data of long-term survival and late toxicities to further assess the ultimate therapeutic index of adjuvant chemotherapy (AC). METHODS: Patients with stage III-IVB (except T3-4N0) NPC were randomly assigned to receive CCRT plus AC or CCRT only at seven institutions in China. Patients in both groups received cisplatin 40 mg/m2 weekly up to 7 weeks concurrently with radiotherapy. The CCRT plus AC group subsequently received adjuvant cisplatin 80 mg/m2 and fluorouracil 800 mg/m2/d for 120 h every 4 weeks for three cycles. The primary end-point was failure-free survival. RESULTS: Two hundred and fifty-one patients were randomised to the CCRT plus AC group and 257 to the CCRT only group. After a median follow-up of 68.4 months, estimated 5-year failure-free survival rate was 75% in the CCRT plus AC group and 71% in the CCRT only group (hazard ratio 0.88, 95% confidence interval 0.64-1.22; p = 0.45). 66 (27%) of 249 patients in the CCRT plus AC group and 53 (21%) of 254 patients in the CCRT only group developed one or more late grade 3-4 toxicities (p = 0.14). CONCLUSION: Adjuvant cisplatin and fluorouracil chemotherapy still failed to demonstrate significant survival benefit after CCRT in locoregionally advanced NPC based on the long-term follow-up data, and addition of adjuvant cisplatin and fluorouracil did not significantly increase late toxicities. REGISTRATION NUMBER: NCT00677118.

Progress report of a randomized trial comparing long-term survival and late toxicity of concurrent chemoradiotherapy with adjuvant chemotherapy versus radiotherapy alone in patients with stage III to IVB nasopharyngeal carcinoma from endemic regions of China.

BACKGROUND: The objective of this study was to evaluate the long-term survival and late toxicities of concurrent-adjuvant chemotherapy in patients with stage III through IVB nasopharyngeal carcinoma (NPC) from endemic regions of China. METHODS: Patients with stage III to IVB NPC were assigned randomly to receive radiotherapy (RT) alone (the RT group) or RT plus concurrent adjuvant chemotherapy (the CRT group). CRT patients received concurrent cisplatin (40 mg/m2) weekly during RT followed by cisplatin (80 mg/m2) and fluorouracil (800 mg/m(2) daily for 5 days) every 4 weeks for 3 cycles. The primary endpoint was overall survival. RESULTS: In total, 316 patients underwent randomization, with 158 to each group. At a median follow-up of 70 months, the 5-year overall survival rate was 72% for the CRT group and 62% for the RT group (hazard ratio, 0.69; 95% confidence interval, 0.48-0.99; P = .043). Failure-free survival was significantly higher in the CRT group (P = .020). Most late toxicities were similar (33% vs. 26%; P = .089), except for cranial neuropathy (P = .042), peripheral neuropathy (P = .041), and ear damage (P = .048), which were significantly increased in the CRT group. CONCLUSIONS: The addition of concurrent adjuvant chemotherapy to RT provides survival benefits to patients with stage III through IVB NPC in endemic regions of China, and it does not increase most late toxicities apart from cranial neuropathy, peripheral neuropathy, and ear damage.

Effect of jingui shenqi pill and its disassembled recipes on ovarian functions in shen yang deficiency female rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of Jingui Shenqi Pill (JSP) and its disassembled recipes (supplementing Shen yang, supplementing Shen yin, and supplementing Shen yang and Shen yin) on ovarian functions of female rats of Shen yang deficiency syndrome (SYDS).</p><p><b>METHODS</b>Totally 55 SD female rats were randomly divided into 5 groups, i.e., the normal control group, the model group, the Shen yang supplementing group, the Shen yin supplementing group, the Shen yang and Shen yin supplementing group, 11 in each group. Except the normal control group, rats in the rest group were injected with hydrocortisone at the daily dose of 25 mg/kg at the muscle of femoribus internus for 12 successive days. From the 13th day after successful modeling, rats were administered by gastrogavage with different recipes at the dose of 1 mL/100 g (2.75 g/kg Shen yang supplementing recipe; 6.25 g/kg Shen yin supplementing recipe; 6.75 g/kg JSP), once daily for 20 successive days. Equal volume of normal saline was given to those in the normal control group and the model group, once daily for 20 successive days. Blood was withdrawn from the orbit on the 2nd day after intervention. The serum estradiol (E2) and progesterone (P) were detected using ELISA. The weight of uterus and ovarian index (VI) were calculated. The pathological changes were observed by HE staining.</p><p><b>RESULTS</b>The general condition of rats in the Shen yang and Shen yin supplementing group were improved. The body weight (g) was added by 35.0 +/- 12.5 in the normal control group, 16.7 +/- 7.4 in the model group, 20.2 +/- 6.9 in the Shen yang supplementing group, 18.3 +/- 3.6 in the Shen yin supplementing group, and 29.4 +/- 12.2 in the Shen yang and Shen yin supplementing group. The uterus VI (mg/100 g) was 183.4 +/- 11.6 in the normal control group,144.0 +/- 6.5 in the model group,158.7 +/- 6.3 in the Shen yang supplementing group,152.1 +/- 6.9 in the Shen yin supplementing group, and 172.8 +/- 8.1 in the Shen yang and Shen yin supplementing group. The ovarian VI (mg/100 g) were 32.9 +/- 2.4 in the normal control group, 22.6 +/- 1.1 in the model group, 25.0 +/- 1.4 in the Shen yang supplementing group, 23.0 +/- 0.4 in the Shen yin supplementing group, and 31.4 +/- 3.3 in the Shen yang and Shen yin supplementing group. Compared with the model group, the body weight and ovarian VI increased in the Shen yang supplementing group and the Shen yang and Shen yin supplementing group (P < 0.05, P < 0.01). The uterus VI increased in each medicated group (P < 0.05, P < 0.01). Compared with the Shen yang supplementing group and the Shen yin supplementing group, all indices increased in the Shen yang and Shen yin supplementing group (P < 0.05, P < 0.01). The E2 and P levels increased in the Shen yang supplementing group and the Shen yang and Shen yin supplementing group (P < 0.05, P < 0.01). The content of E2 (pg/mL) was 22.1 +/- 9.4 in the normal control group, 9.8 +/- 3.0 in the model group, 11.3 +/- 2.2 in the Shen yang supplementing group, 10.5 +/- 0.8 in the Shen yin supplementing group, and 16.0 +/- 5.5 in the Shen yang and Shen yin supplementing group. The content of P (ng/mL) was 14.6 +/- 7.5 in the normal control group, 4.3 +/- 1.8 in the model group, 8.3 +/- 2.8 in the Shen yang supplementing group, 5.9 +/- 2.9 in the Shen yin supplementing group, and 9.5 +/- 3.4 in the Shen yang and Shen yin supplementing group. Compared with the Shen yang supplementing group and the Shen yin supplementing group, the E2 level increased in the Shen yang and Shen yin supplementing group (P < 0.05, P < 0.01). Compared with the Shen yin supplementing group, the P level increased in the Shen yang and Shen yin supplementing group (P < 0.05). Compared with the model group, the ovarian follicle at each stage increased and pathological follicular ovarian follicles decreased in the Shen yang and Shen yin supplementing group (P < 0.01). Less primary follicles, secondary follicles, and mature follicles could be seen in the Shen yang supplementing group and the Shen yin supplementing group. The total numbers of all-level follicles were obviously higher in the Shen yang and Shen yin supplementing group than in the Shen yang supplementing group and the Shen yin supplementing group (P < 0.05). The number of pathological follicles was obviously less in the Shen yang and Shen yin supplementing group than in the Shen yin supplementing group (P < 0.05).</p><p><b>CONCLUSIONS</b>As for SYDS, JSP and its dissembled recipes could improve damaged ovarian functions to some degree. But better effect could not be obtained by Shen yang supplementing method or Shen yin supplementing method alone. Shen yang and Shen yin supplementing method could elevate the efficacy.</p>

Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial.

BACKGROUND: The effect of the addition of adjuvant chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is unclear. We aimed to assess the contribution of adjuvant chemotherapy to concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone. METHODS: We did an open-label phase 3 multicentre randomised controlled trial at seven institutions in China. Randomisation was by a computer-generated random number code. Patients were stratified by treatment centre and randomly assigned in blocks of four. Treatment allocation was not masked. We randomly assigned patients with non-metastatic stage III or IV (except T3-4N0) nasopharyngeal carcinoma to receive concurrent chemoradiotherapy plus adjuvant chemotherapy or concurrent chemoradiotherapy alone. Patients in both groups received 40 mg/m(2) cisplatin weekly up to 7 weeks, concurrently with radiotherapy. Radiotherapy was given as 2·0-2·27 Gy per fraction with five daily fractions per week for 6-7 weeks to a total dose of 66 Gy or greater to the primary tumour and 60-66 Gy to the involved neck area. The concurrent chemoradiotherapy plus adjuvant chemotherapy group subsequently received 80 mg/m(2) adjuvant cisplatin and 800 mg/m(2) per day fluorouracil for 120 h every 4 weeks for three cycles. Our primary endpoint was failure-free survival. We did efficacy analyses in our intention-to-treat population. Our trial is ongoing; in this report we present the 2 year survival results and acute toxic effects. This trial is registered with ClinicalTrials.gov, number NCT00677118. FINDINGS: 251 patients were assigned to the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 257 to the concurrent chemoradiotherapy alone group. After a median follow-up of 37·8 months (range 1·3-61·0), the estimated 2 year failure-free survival rate was 86% (95% CI 81-90) in the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 84% (78-88) in concurrent chemoradiotherapy only group (hazard ratio 0·74, 95% CI 0·49-1·10; p=0·13). Stomatitis was the most commonly reported grade 3 or 4 adverse event during both radiotherapy (76 of 249 patients in the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 82 of 254 in the concurrent chemoradiotherapy alone group) and adjuvant chemotherapy (43 [21%] of 205 patients treated with adjuvant chemotherapy). INTERPRETATION: Adjuvant cisplatin and fluorouracil chemotherapy did not significantly improve failure-free survival after concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma. Longer follow-up is needed to fully assess survival and late toxic effects, but such regimens should not, at present, be used outside well-designed clinical trials. FUNDING: Sun Yat-sen University Clinical Research 5010 Programme (No 2007037), Science Foundation of Key Hospital Clinical Programme of Ministry of Health PR China (No 2010-178), and Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2010).

Fine mapping of a gene causing hybrid pollen sterility between Yunnan weedy rice and cultivated rice (Oryza sativa L.) and phylogenetic analysis of Yunnan weedy rice.

Weedy rice represents an important resource for rice improvement. The F(1) hybrid between the japonica wide compatibility rice cultivar 02428 and a weedy rice accession from Yunnan province (SW China) suffered from pollen sterility. Pollen abortion in the hybrid occurred at the early bicellular pollen stage, as a result of mitotic failure in the microspore, although the tapetum developed normally. Genetic mapping in a BC(1)F(1) population (02428//Yunnan weedy rice (YWR)/02428) showed that a major QTL for hybrid pollen sterility (qPS-1) was present on chromosome 1. qPS-1 was fine-mapped to a 110 kb region known to contain the hybrid pollen sterility gene Sa, making it likely that qPS-1 is either identical to, or allelic with Sa. Interestingly, F(1) hybrid indicated that Dular and IR36 were assumed to carry the sterility-neutral allele, Sa ( n ). Re-sequencing SaM and SaF, the two component genes present at Sa, suggested that variation for IR36 and Dular may be responsible for the loss of male sterility, and the qPS-1 sequence might be derived from wild rice or indica cultivars. A phylogenetic analysis based on microsatellite genotyping suggested that the YWR accession is more closely related to wild rice and indica type cultivars than to japonica types. Thus it is probable that the YWR accession evolved from a spontaneous hybrid between wild rice and an ancient cultivated strain of domesticated rice.