Medical Therapy of Hearing Impairment and Tinnitus with Chinese Medicine: An Overview / 中国结合医学杂志

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.

Observation of PD-1+CXCR5+CD4+T lymphocyte and sPD-1 levels in HBeAg positive chronic hepatitis B virus carriers treated with entecavir / 中华肝脏病杂志

Objective: To dynamically observe the clinical efficacy of entecavir and the changes of PD-1+CXCR5+CD4+T lymphocytes and sPD-1 levels in peripheral blood of HBeAg-positive chronic hepatitis B virus carriers treated with entecavir, and further explore its clinical significance. Methods: There were 31 cases of chronic hepatitis B virus carriers in the treatment group (A), 32 cases of chronic hepatitis B virus carriers in the treatment group (B), and 15 cases of chronic hepatitis B virus carriers in the non-treatment group (C).Three groups peripheral blood samples and clinical data at 0, 24 and 48 weeks were collected and compared. PD-1+CXCR5+CD4+T lymphocytes were detected by flow cytometry, and the level of sPD-1 was detected by enzyme-linked immunosorbent assay. ANOVA and Spearman correlation analysis were performed on the measurement data among the three groups. Results: At week 0, the serum levels of HBsAg, HBeAg and HBV DNA were significantly higher in groups A and C than group B. PD-1+CXCR5+CD4+T lymphocytes in peripheral blood were significantly higher in group B (4.70%±1.58%) than group A (3.25%±1.01%) and group C (2.77%±0.67%) (F=16.65, P<0.05). There was no significant difference between group A and group C (P>0.05). Peripheral blood sPD-1 in group B [(1 866.62±1 472.70) pg/ml] was significantly higher than group A [(824.86±538.66) pg/ml] and group C [(618.19±602.62) pg/ml] (F=10.95, P<0.05). There was no significant difference between group A and group C (P>0.05). At 48 weeks, the serum HBsAg did not decrease significantly in groups A and C than baseline (P>0.05), but were significantly higher than group B (P<0.05). Serum HBeAg levels were decreased significantly in groups A and B than baseline (P<0.05). <0.05), but group A was significantly higher than group B (P<0.05), and there was no significant difference between group A and group C (P>0.05). Serum HBV DNA level was significantly lower in groups A and B than group C (P<0.05), and there was no significant difference between group A and group B (P>0.05). Peripheral blood PD-1+CXCR5+CD4+T lymphocytes were significantly lower in Group A (1.56%±0.73%) and group B (1.32%±0.43%) than group C (2.64%±0.85%) (P<0.05). Peripheral blood sPD-1 were significantly lower in group A [(289.05±215.86) pg/ml] and group B [(236.01±173.92) pg/ml] than group C [(650.34±598.46) pg/ml] (P<0.05). There was no significant difference between group A and group B. Correlation analysis results: In group A at 48 weeks, the decreased level of PD-1+CXCR5+CD4+T lymphocyte ratio had no correlation with the decreased level of HBsAg and HBV DNA, but was positively correlated with the decreased level of HBeAg (r=0.376, P<0.05). The decreased level of sPD-1 had no correlation with the changes of HBsAg, but was positively correlated with the decreased levels of HBeAg and HBV DNA (r=0.598 and 0.384, P<0.05). In group B at 48 weeks, the decreased levels of PD-1+CXCR5+CD4+T lymphocytes and sPD-1 were positively correlated with the decreased levels of HBsAg, HBeAg, and HBV DNA (P<0.05). Conclusion: Hepatitis B virus replication and expressions in HBeAg-positive chronic hepatitis B virus carriers were significantly inhibited after 48 weeks of antiviral treatment, which is related not only to entecavir treatment, but also to the immunological mechanism involved in sPD-1. Moreover, the inhibition of HBeAg expression is associated with a decrease in the number and/or activity of PD-1+CXCR5+CD4+T lymphocytes.

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.

Factors influencing difference in location of cricothyroid membrane between surface palpation and ultrasonic biplane / 中华麻醉学杂志

Objective:To analyze the factors influencing the difference in location of cricothyroid membrane between traditional surface palpation and ultrasonic biplane.Methods:One hundred and seven subjects of both sexes, aged 18 yr, underwent neck ultrasound examination in our hospital from August 2021 to December 2021, were selected.The structure of cervical airway was observed by ultrasound.The subjects in whom the structure of cricothyroid membrane was clearly shown were selected.The middle point of cricothyroid membrane was located by otorhinolaryngologist using surface palpation method and by ultrasonic doctor using ultrasonic biplane method.The distance between two positioning points was measured by a ruler.The subjects were divided into accurate group (distance between two points≤3 mm) and difference group (distance between two points>3 mm). The distance between cricoid cartilage and thyroid cartilage (spacing of cricoid cartilage and thyroid cartilage) and distance between the midpoint of cricothyroid membrane and skin (spacing of cricothyroid membrane and skin) were measured by ultrasound.The neck length and the maximum submaxillary distance in head up were measured by a ruler.The factors influencing the difference in location between the two methods were analyzed by multivariate logistic regression.Results:One hundred and four subjects with clear cricoid cartilage and cricothyroid membrane under ultrasound were selected.There were significant differences in the ratio of gender, body mass index (BMI), cricothyroid membrane-skin distance, neck length, and maximum submandibular distance between the two groups ( P<0.05). Multivariate logistic analysis showed that female ( OR=9.091, P<0.001), BMI ( OR=11.214, P=0.001) and increased cricothyroid membrane-skin distance ( OR=5.649, P=0.015) were the factors influencing the difference in location between the two cricothyroid membrane localization methods. Conclusions:Female, obesity (BMI>28.0 kg/m 2) and increased distance between cricothyroid membrane and skin are the factors affecting the difference in location of cricothyroid membrane between ultrasonic biplane method and surface palpation method, and bedside ultrasound is recommended for location in those with the factors mentioned above.

Clinical characteristics in patients with persistent positive pharyngeal swab of omicron variant and analysis on nucleic acid testing of anal swabs / 中华危重病急救医学

Objective:To analyze the clinical characteristics in patients with persistent positive pharyngeal swab of 2019 novel coronavirus Omicron variant and results of nucleic acid testing of anal swabs to provide basis for prevention and control measures.Methods:This study included 93 patients whose pharyngeal swab nucleic acid test were persistent positive and admitted to the ward of Daping Hospital in the National Exhibition and Convention Center (Shanghai) Makeshift Hospital from May 1 to May 24, 2022. The gender, age, underlying diseases, vaccination status, clinical symptoms, interval between infection onset and anal sampling, length of hospital stay, the nucleic acid test result of pharyngeal swabs and anal swabs and the time turning negative were collected and analyzed.Results:The age of 93 patients ranged from 8 to 72 years old with a median of (46.0±16.0) years old. Among them, 30 cases (32.3%) were male and 63 cases (67.7%) were female. Sixty-five patients (69.9%) received 2-3 shots of vaccine, 2 patients (2.1%) received 1 shot, and 26 patients (28.0%) did not receive any vaccination. Twenty patients (21.5%) had underlying diseases, of which hypertension (13 cases, 14.0%) and type 2 diabetes mellitus (6 cases, 6.5%) were the most common. Twenty-four patients (25.8%) had asymptomatic infection and the rest (69 cases, 74.2%) had mild symptoms. Cough (50 cases, 53.8%) and sore throat (28 cases, 30.1%) were the most common clinical manifestations of the upper respiratory tract in these patients. Only 6 patients (6.5%) had gastrointestinal symptoms (including diarrhea in 5 patients and diarrhea with vomiting in 1 patient). Pharyngeal and anal swabs were collected simultaneously from all 93 patients at 8-16th days [(11.55±2.27) days] after 2019 novel coronavirus Omicron variant infection. The pharyngeal swabs were positive in 79 patients (85.0%) and the anal swabs were positive in 5 patients (5.4%). The time of pharyngeal swabs turning negative was (14.7±2.9) days, and that of anal swab turning positive was (14.2±1.9) days. The median length of hospital stay was (16.7±2.9) days.Conclusions:In patients with persistent positive nucleic acid of the 2019 novel coronavirus Omicron variant, there were more mild infection than asymptomatic. The upper respiratory tract symptoms such as cough and sore throat were the most. The likelihood of transmission of 2019 novel coronavirus Omicron variant through the digestive tract may be low. The correlation between gastrointestinal symptoms and 2019 novel coronavirus Omicron variant RNA in the digestive tract is uncertain.

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.

Molecular Mechanism of Salvia miltiorrhiza Quality Formation Based on Single Nucleotide Polymorphism of Functional Genes / 中国实验方剂学杂志

Objective:To investigate the relationship between the single nucleotide polymorphism（SNP）of function genes and effective components of <italic>Salvia miltiorrhiza</italic> and the molecular mechanism of specific quality formation of <italic>S. miltiorrhiza</italic>. Method:The fingerprints of components in <italic>S. miltiorrhiza</italic> from eight different habitats and varieties were obtained by high-performance liquid chromatography （HPLC）. The full-length cDNA of three functional genes<italic> </italic>acetyl-CoA C-acetyltransferase（<italic>SmAACT</italic>），4-diphosphocytidyl-2-C-methyl-<italic>D</italic>-erythritol kinase（<italic>SmCMK</italic>） and isopentenyl diphosphate isomerase（<italic>SmIPPI</italic>） in tanshinone metabolic pathway were amplified by polymerase chain reaction（PCR），cloned， and sequenced，followed by bioinformatics analysis. Result:The full-length cDNA sequences of three functional genes <italic>SmAACT</italic>，<italic>SmCMK</italic>， and <italic>SmIPPI</italic> in tanshinone metabolic pathway were obtained from 23 strains of <italic>S. miltiorrhiza</italic> from eight different habitats and varieties. As revealed by the analysis of SNP and amino acid polymorphisms of three functional genes，18，16， and 14 SNP sites were found respectively. HPLC results showed the samples from Beijing，Hubei，Shandong （No. SDB），Shanxi，Henan， and Shandong （No. SDZ） were clustered into one branch，and those from Hebei and Inner Mongolia were clustered into another branch， which suggested that the variation trend of <italic>S. miltiorrhiza</italic> components had little correlation with geographical distance，but the variety was a critical factor for the quality. Conclusion:There was an obvious genetic differentiation trend in <italic>S. miltiorrhiza</italic> from different habitats，and different origin-specific genotypes were formed. The molecular mechanism of the formation of the specific quality of <italic>S. miltiorrhiza</italic> from different habitats was discussed，which laid a foundation for the stability and effectiveness of clinical medication，and guided the breeding of excellent varieties of <italic>S. miltiorrhiza</italic>.

The Pattern of Time to Onset and Resolution of Immune-Related Adverse Events Caused by Immune Checkpoint Inhibitors in Cancer: A Pooled Analysis of 23 Clinical Trials and 8,436 Patients / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The occurrence pattern of immune-related adverse events (irAEs) induced by immune checkpoint inhibitor (ICI) in cancer treatment remains unclear. @*Materials and Methods@#Phase II-III clinical trials that evaluated ICI-based treatments in cancer and were published between January 2007 and December 2019 were retrieved from public electronic databases. The pooled median time to onset (PMT-O), resolution (PMT-R), and immune-modulation resolution (PMT-IMR) of irAEs were generated using the metamedian package of R software. @*Results@#Twenty-two eligible studies involving 23 clinical trials and 8,436 patients were included. The PMT-O of all-grade irAEs ranged from 2.2 to 14.8 weeks, with the longest in renal events. The PMT-O of grade ≥ 3 irAEs was significantly longer than that of all-grade irAEs induced by programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) inhibitors (27.5 weeks vs. 8.4 weeks, p < 0.001) and treatment of nivolumab (NIV) plus ipilimumab (IPI) (7.9 weeks vs. 6.0 weeks, p < 0.001). The PMT-R of all-grade irAEs ranged from 0.1 to 54.3 weeks, with the shortest and longest in hypersensitivity/infusion reaction and endocrine events, respectively. The PMT-IMR of grade ≥ 3 irAEs was significantly shorter than that of all-grade irAEs caused by PD-1/PD-L1 blockade (6.9 weeks vs. 40.6 weeks, p=0.002) and NIV+IPI treatment (3.1 weeks vs. 5.9 weeks, p=0.031). @*Conclusion@#This study revealed the general and specific occurrence pattern of ICI-induced irAEs in pan-cancers, which was deemed to aid the comprehensive understanding, timely detection, and effective management of ICI-induced irAEs.

Electroacupuncture Inhibits Neuronal Apoptosis Induced by Bilirubin Encephalopathy in SD Suckling Rats by Regulating NGB and PI3K/Akt Signaling Pathways / 中国生物化学与分子生物学报

Objective In this study, electroacupuncture (EA) was used to analyze the expression changes of related proteins in neuroglobin (NGB), PI3K/AKT and apoptotic pathways in the temporal cortex of bilirubin encephalopathy (BE) rats, so as to investigate the therapeutic effect of EA on BE and the relevant mechanism of NGB in this process. Totally 39 seven-day-old SD rats were divided into Sham, BE model and BE+EA groups. The neonatal BE model was established by injecting bilirubin solution (10 μg UCB/g Weight) into the cerebellomedullary cistern, Sham group was injected with the same amount of normal saline. BE rats were treated with EA at Baihui (GV20) and Quchi (LI11) acupoints with the frequency of 2/15 Hz for 15 min. Treatment was performed 12 h before modeling, followed by treatment every 12 h, in a total of three times. HE, Nissl staining and electron microscopy (TEM) were used to observe the pathological and ultrastructural changes of nerve cells in each group. Results showed that EA treatment reduced the damage of cortical neurons of BE rats and increase the number of Nissl bodies. TEM confirmed that EA treatment could alleviate the degree of mitochondria edema. Immunofluorescence staining was used to detect the expression sites and cell types of NGB. Results showed that NGB was mainly expressed in cortical neurons. Western blotting showed that EA treatment increased the expression of NGB, PI3K (p110 alpha), pAKT (Ser473) (P< 0. 05, P< 0. 05 and P< 0. 01, respectively) and the ratio of apoptosis-related protein Bcl-2/Bax (P < 0. 001), decreased the expression of Cleaved Caspase-3 (P< 0. 05) in the temporal cortex of rats. TUNEL staining showed that EA reduced the number of apoptotic cells (BE group 186. 00±13. 86 vs BE+EA group 78. 67±11. 85, P< 0. 01) . This study confirms that EA can promote the expression of NGB in the temporal cortex of BE rats, then activate the PI3K/AKT pathway to exert its neuroprotective function and inhibit the occurrence of apoptosis. EA may become a potential treatment method for BE.

Comparative study on anti-cancer effect of digoxin on human lung cancer in nude mice bearing subcutaneously or orthotopicly implanted xenografts / 中国药理学通报

Aim To establish subcutaneous and orthotopic transplantation models of human lung cancer in nude mice, and compare the anti-cancer effects of digoxin between the two models. Methods After subcutaneous inoculation of H460 tissues in nude mice, the tumor volume was measured; HE staining and immunohistochemistry were performed; H460-Luc cell suspension was injected into the lung of nude mice toestablish orthotopic tumor model, the in vivo imaging and fluorescence values were recorded, and the tumor lesions in other organs were observed after dissection. Results Compared with control group, the gemcitabine group had a significant anti-tumor effect (P 0.05). HE staining showed that the cell density in each treatment group decreased, and necrosis and/or fibrous hyperplasia were obvious. Immunohistochemistry indicated that the protein expression of p-p38, p-ERK and Nur77 in each treatment group significantly increased in the subcutaneous transplantation model; in the orthotopic transplantation model, the gemcitabine, the middle (P < 0.05) and low dose of digoxin group could inhibit the tumor growth, while the high dose of digoxin group accelerated the development of tumor (P < 0.05). Conclusion Digoxin is more sensitive to orthotopic transplanted tumor than subcutaneous transplanted tumor, anddigoxin may inhibit the tumor growth by up-regulating the expression of p-p38, pERK and Nur77.

The Pattern of Time to Onset and Resolution of Immune-Related Adverse Events Caused by Immune Checkpoint Inhibitors in Cancer: A Pooled Analysis of 23 Clinical Trials and 8,436 Patients / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The occurrence pattern of immune-related adverse events (irAEs) induced by immune checkpoint inhibitor (ICI) in cancer treatment remains unclear. @*Materials and Methods@#Phase II-III clinical trials that evaluated ICI-based treatments in cancer and were published between January 2007 and December 2019 were retrieved from public electronic databases. The pooled median time to onset (PMT-O), resolution (PMT-R), and immune-modulation resolution (PMT-IMR) of irAEs were generated using the metamedian package of R software. @*Results@#Twenty-two eligible studies involving 23 clinical trials and 8,436 patients were included. The PMT-O of all-grade irAEs ranged from 2.2 to 14.8 weeks, with the longest in renal events. The PMT-O of grade ≥ 3 irAEs was significantly longer than that of all-grade irAEs induced by programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) inhibitors (27.5 weeks vs. 8.4 weeks, p < 0.001) and treatment of nivolumab (NIV) plus ipilimumab (IPI) (7.9 weeks vs. 6.0 weeks, p < 0.001). The PMT-R of all-grade irAEs ranged from 0.1 to 54.3 weeks, with the shortest and longest in hypersensitivity/infusion reaction and endocrine events, respectively. The PMT-IMR of grade ≥ 3 irAEs was significantly shorter than that of all-grade irAEs caused by PD-1/PD-L1 blockade (6.9 weeks vs. 40.6 weeks, p=0.002) and NIV+IPI treatment (3.1 weeks vs. 5.9 weeks, p=0.031). @*Conclusion@#This study revealed the general and specific occurrence pattern of ICI-induced irAEs in pan-cancers, which was deemed to aid the comprehensive understanding, timely detection, and effective management of ICI-induced irAEs.

Value of chitinase-like protein YKL-40 in bronchoalveolar lavage fluid for predicting refractory / 中国当代儿科杂志

OBJECTIVE@#To evaluate the value of chitinase-like protein YKL-40 in bronchoalveolar lavage fluid (BALF) for predicting refractory @*METHODS@#A total of 50 children with common @*RESULTS@#Compared with the common MPP group, the RMPP group had significantly higher incidence rates of fever, shortness of breath, lung consolidation, and pleural effusion (@*CONCLUSIONS@#There is an increase in the level of YKL-40 in BALF in children with RMPP, and the level of YKL-40 in BALF has a certain value for predicting RMPP.

The evolution of the nasopharyngeal carcinoma staging system over a 10-year period: implications for future revisions / 中华医学杂志(英文版)

BACKGROUND@#The classification criteria and staging groups for nasopharyngeal carcinoma described in the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system have been revised over time. This study assessed the proportion of patients whose staging and treatment strategy have changed due to revisions of the UICC/AJCC staging system over the past 10 years (ie, from the sixth edition to the eighth edition), to provide information for further refinement.@*METHODS@#We retrospectively reviewed 1901 patients with non-metastatic nasopharyngeal carcinoma treated in our cancer center between November 2009 and June 2012. The Akaike information criterion and Harrell concordance index were applied to evaluate the performance of the staging system.@*RESULTS@#In total, 25 (1.3%) of the 1901 patients who were staged as T2a according to the sixth edition system were downgraded to T1 in the eighth edition; 430 (22.6%) staged as N0 in the sixth edition were upgraded to N1 in the eighth edition; 106 (5.6%) staged as N1/2 in the sixth edition were upgraded to N3 in the eighth edition. In addition, 51 (2.7%) and 25 (1.3%) of the study population were upstaged from stage I to stage II and stage II to stage IVa, respectively; 10 (0.5%) was downgraded from stage II to stage I. The survival curves of adjacent N categories and staging groups defined by eighth classification system were well-separated. However, there was no significant difference in the locoregional failure-free survival (P = 0.730) and disease-free survival (P = 0.690) rates between the T2 and T3 categories in the eighth edition classification system.@*CONCLUSIONS@#Modifications to the tumor-node-metastasis staging system over the past 10 years have resulted in N classification changes in numerous cases. Although the eighth edition tumor-node-metastasis staging system better predicts survival outcomes, the T classification could be simplified in future revisions.

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.

Ultrasound monitoring of diaphragm thickness fraction in evaluating extubation outcome in patients undergoing mechanical ventilation / 中国医学影像技术

Objective: To observe the predictive value of diaphragmatic ultrasound for extubation outcomes in patients undergoing mechanical ventilation(MV). Methods: Totally 54 patients were ventilated mechanically more than 48 hours and ready to extubate when admitted to ICU were enrolled. During the T-tube spontaneous breathing trial (SBT), the diaphragm thickening fraction (DTF) and diaphragm thickening rapid shallow breathing index (DTF-RSBI) were measured and calculated using bedside ultrasound. Rapid shallow breathing index (RSBI) and other physiological indexes were recorded. ROC curve was used to evaluate the predictive value of DTF and DTF-RSBI for extubation. Results: There were 36 patients underwent successful (successful group) and 18 underwent failed extubation (failure group). DTF in successful group was significantly higher than that in failure group, while RBSI and DTF-RBSI in successful group were significantly lower than those in failure group (both P<0.05). Taken 28.50% as the cut-off value of DTF, the AUC for DTF was 0.702, and the sensitivity and specificity was 78.80% and 61.10%, respectively. When the cut-off value of DTF-RSBI was 72.6 breaths/(min•mm), AUC for DTF-RSBI was 0.903, the sensitivity and specificity was 100% and 72.20%, respectively. Conclusion: DTF-RSBI is more accurate than DTF and traditional RSBI, having better practical value for predicting extubation outcomes.

Accuracy of respiratory variation of different vein diameters in predicting fluid responsiveness in patients with septic shock complicated with myocardial injury / 中华麻醉学杂志

Objective@#To evaluate the accuracy of trans-xiphoid inferior vena cava diameter variation (v-IVCTX), trans-liver inferior vena cava diameter variation (v-IVCTL), internal jugular vein diameter variation (v-IJV) and femoral vein diameter variation (v-FV) in predicting the fluid responsiveness in the patients with septic shock complicated with myocardial injury.@*Methods@#Fifty patients with septic shock complicated with myocardial depression admitted to intensive care unit of our hospital, aged ≥18 yr, were selected.The hemodynamics was monitored by PiCCO.Cardiac output (CO) and stroke volume were measured, and v-IVCTX, v-IVCTL, v-IJV and v-FV were measured by ultrasound and then calculated.Fluid replacement test was performed after meeting the standard of fluid resuscitation, and positive fluid responsiveness was defined as increase in CO after volume expansion>10%.Patients were divided into positive fluid responsiveness group and negative fluid responsiveness group.The receiver operating characteristic curve was drawn to evaluate the accuracy of the respiratory variation of each vein diameter in predicting fluid responsiveness.@*Results@#Compared with negative fluid responsiveness group, v-IVCTX, v-IVCTL and v-IJV were significantly increased (P<0.05), and no significant change was found in v-FV, CO or stroke volume in positive fluid responsiveness group (P>0.05). The cutoff value of v-IVCTX, v-IVCTL and v-IJV in predicting fluid responsiveness was 16.5%, 14.5% and 12%, respectively, the sensitivity was 80%, 76% and 84%, respectively, and the specificity was 72%, 64% and 44%, respectively.The area under the curve (95% confidence interval) of v-IVCTX, v-IVCTL and v-IJV was 0.777 (0.642-0.911), 0.741 (0.605-0.876), and 0.694 (0.549-0.838), respectively.@*Conclusion@#v-IVCTX and v-IVCTL both can predict the fluid responsiveness in the patients with septic shock complicated with myocardial injury.

Accuracy of different indicators in predicting volume responsiveness in septic shock patients with myocardial depression: a comparison between lung ultrasound and PiCCO / 中华麻醉学杂志

Objective To compare the accuracy of the lung ultrasound and pulse indicator continuous cardiac output (PiCCO) in predicting volume responsiveness in septic shock patients with myocardial suppression.Methods Fifty patients of both sexes with septic shock complicated with myocardial depression,aged ≥ 18 yr,were enrolled in the study.The method for fluid replacement test was as follows:0.9％ sodium chloride injection or lactated Ringer's solution 500 ml was rapidly infused intravenously.PiCCO was used to monitor cardiac output,stroke volume,extravascular lung water index (EVLWI),pulmonary vascular penetration index (PVPI),intra-thoracic blood volume index and global end-diastolic volume index.The chest wall was scanned by ultrasound and the lung ultrasound score (LUS) was assessed.Positive fluid responsiveness was defined as an increase in PiCCO-monitored cardiac output＞ 10％ after fluid replacement.Patients were divided into positive fluid responsiveness group and negative fluid responsiveness group according to the results of fluid resuscitation test.The receiver operating characteristic (ROC) curve was drawn to evaluate the accuracy of each index in predicting fluid responsiveness.Results Compared with negative fluid responsiveness group,EVLWI,PVPI and LUS were significantly decreased,the number of patients in whom the bilateral anterior chest wall presented as B-line was increased in positive fluid responsiveness group (P＜0.01).The area under the ROC curve and 95％ confidence interval of LUS in predicting volume responsiveness was 0.836 (0.720-0.952),the cutoff value was 14.5 points,sensitivity 88％,and specificity 72％.The area under the ROC curve and 95％ confidence interval of EVLWI in predicting volume responsiveness was 0.818 (0.701-0.936),the cutoff value was 9.6 ml/kg,sensitivity 84％,and specificity 72％.The area under the ROC curve and 95％ confidence interval of PVPI in predicting volume responsiveness was 0.720 (0.575-0.865),the cutoff value was 1.55,sensitivity 92％,and specificity 52％.Conclusion The lung ultrasound and PiCCO produce higher accuracy in predicting volume responsiveness in septic shock patients with myocardial suppression;LUS has more advantages due to non-invasive examination.

Hypoglycemic Mechanism of Ziya Biti Tablet Based on LC-MS Metabolomics Technique / 中国实验方剂学杂志

Objective: To observe the hypoglycemic effect of Uygur medicine Ziya Biti tablet on the type 2 diabetic rats, and analyze the hypoglycemic mechanism based on metabolomic techniques. Method: According to the results of clinical research about different origins of Ziya Biti tablet, the optimal composition was screened out; type 2 diabetic rats were taken as an experimental object in the pharmacodynamic experiments;the control group and model group were given the same dose of normal saline, Ziya Biti bablet group was given 300 mg·kg-1, the metformin group was given 300 mg·kg-1 metformin hydrochloride. The fasting blood and weight changes of the experimental group after the treatment were recorded and compared with normal group; ultra-high performance liquid chromatography-linear ion trap/electrostatic field orbit trap combined-type high resolution mass spectrometry (UHPLC-LTQ/Orbitrap MS) technology was used to conduct the metabolomics analysis on the rat serum, and principal component analysis (PCA), partial least squares discriminant analysis (OPLS-DA) on different groups of rat serum metabolites were performed to identify potential biomarkers. Result:Compared with the model group, the rats in the Uygur medicine Ziya Biti tablet showed a healthy states, and the blood glucose were decreased(PPPConclusion:The experimental results showed that Uygur medicine Ziya Biti tablet can reduce the blood glucose of type 2 diabetic rats and allivate general physiological characteristics. The mechanism of action may be related to the improvement of amino acid metabolism and lipid metabolism.