[Development and validation of a persistent postural-perceptual dizziness screening questionnaire].

Objective: To develop a simple screening questionnaire for persistent postural-perceptual dizziness (PPPD) and evaluate its screening ability. Methods: A convenience sample of 296 individuals who met the inclusion criteria between November 2021 and January 2023 were prospectively selected for three rounds of screening at the Vertigo Specialty Clinic of the Department of Otorhinolaryngology-Head and Neck Surgery in the First Hospital of Shanxi Medical University. In conjunction with expert opinion and statistical analysis, the first and second rounds of screening were used to modify and finalize the questionnaire entries, and the third round of screening was used to evaluate the questionnaire's screening ability. Independent sample t-test was used for inter group comparison, reliability and validity indicators were employed to screen and evaluate questionnaire entries, and the receiver operating characteristic (ROC) curve was plotted to determine the optimal cut-off value and corresponding sensitivity and specificity. Results: The final PPPD screening questionnaire entries included 21 items. In evaluating the reliability of this questionnaire, the Cronbach's alpha coefficient was 0.831, the half folding coefficient was 0.742, the content validity was 0.86, and the Kaiser-Meyer-Olkin (KMO) value in the structural validity was 0.811. Additionally, there were six factors with characteristic root>1 and a cumulative contribution rate of 62.62%. The area under the ROC curve of the screening questionnaire was 0.935 (95%CI: 0.877-0.992), and the optimal cut-off value was 8.5, with a sensitivity of 85.0%, a specificity of 85.5%, and a Kappa value of 0.653. Conclusion: The PPPD simple screening questionnaire designed in this study has a high sensitivity and specificity, making it a useful tool for identifying PPPD patients.

[Randomized controlled study on the application effect of a new type of intravenous radiofrequency closed therapy system made in China and an imported system].

Objective: To compare the application effect of domestic and imported intravenous radiofrequency closure system in the treatment of primary varicose veins of lower extremities. Methods: This single-center prospective, non-inferiority randomized controlled trial was performed in the Department of Vascular Surgery, the Fourth Affiliated Hospital, Zhejiang University School of Medicine from January 2021 to January 2022. Patients with primary varicose veins of lower extremities who met the ataxation criteria were randomly assigned to the experimental group(domestic novel venous radiofrequency closure system) or the control group(imported venous radiofrequency closure system) in a ratio of 1∶1. The two groups of subjects were compared in terms of target vein closure rate, technical success rate, system operation performance, incidence of adverse events and incidence of serious adverse events(SAE) within 6 months after surgery. Quantitative data were compared by Mann-Whitney U test, and categorical data were compared by χ2 test and non-inferiority test. Results: A total of 80 subjects were included in the trial (41 in the experimental group and 39 in the control group), including 27 males and 53 females, aged (M(IQR)) 55(23) years (range:40 to 78 years). There were 48 cases of left lower limb and 32 cases of right lower limb. The technical success rate and system control performance between the groups were 100%.The incidence of adverse events (58.5% (24/41) vs. 61.5% (24/39), χ2=0.075, P=0.784), and the incidence of SAE (7.3% (3/41) vs. 5.1% (2/39), χ2=0.163, P=0.686) within 6 months after surgery in experimental group and control group had no statistical significance. There was one device-related adverse event in each of the two groups. In the experimental group, one patient developed endovenous heat-induced thrombosis after surgery and recovered after taking rivaroxaban tablets. One patient in the control group had pain in the upper right thigh for more than 1 day after operation, which was cured after using analgesic cream. No device-related SAE occurred. The venous closure rate of the experimental group was 100% (38/38) at 6 months after surgery, and that of the control group was 97.4% (37/38). The difference between the two groups was 2.63% (95%CI:-3.19 to 8.45, Z=4.865, P<0.01), and the 95%CI lower limit of the difference in target venous closure rate between two groups was greater than the non-inferiority threshold of -10.00%. Conclusion: The early application effect of the new domestic intravenous radiofrequency closure system in patients with primary varicose veins of lower extremities is in line with expectations, it is not inferior to the imported system.

[Antimicrobials discovery against Staphylococcus aureus by high throughput screening of drug library].

To develop antimicrobials against Staphylococcus aureus by high throughput screening of drug library. The type of this study is experimental research. The clinical isolates of S. aureus were collected from the sputum samples of respiratory inpatient department of the Third Xiangya Hospital of Central South University. The anti-planktonic cells growth inhibition activity of FDA-approved drugs library (including 1 573 molecules) was assessed by building a planktonic cells screening platform; The biofilm inhibitory effect of the FDA-approved drugs was detected by building a biofilm screening platform combined with crystal violet staining; Minimal inhibitory concentrations of the selected hits were determined by broth microdilution assay. Finally, the cytotoxicity of the selected hits was detected by CCK-8 assay. The results showed that 218 hits were exhibited effective growth inhibitory effects against S. aureus by setting the concentrations of the molecules in the FDA-approved library to 100 µmol/L. These selected molecules are mainly anti-infective drugs, accounting for 118 hits; Followed by anti-cancer drugs, anti-inflammatory/-immune drugs, neurological drugs, cardiovascular drugs, endocrine drugs, and metabolic disease drugs, which accounts for 40, 19, 12, 9, 8, and 3 hits; Other unclassified drugs accounts for 9 hits. The top 10 hits exhibiting anti-planktonic cells activity against S. aureus were mainly including antitumor drugs, followed by neurological drugs and unclassified drugs like vitamin K3 with the inhibition rate of 99.65%-100%. Similarly, the top 10 hits showing biofilm inhibitory effects against S. aureus were also mainly including antitumor drugs, followed by neurological drugs and anti-inflammatory/-immune drugs with the inhibition rate of 50.22%-92.95%. The minimal inhibitory concentration (MIC) of the 51 hits by second round screening was determined by micro-dilution assay, which mainly include the antitumor drugs, cardiovascular drugs, endocrine drugs, anti-inflammatory/-immune drugs, metabolic disease drugs, neurological drugs and other unclassified drugs accounted for 22, 5, 3, 9, 2, 5 and 5 hits, respectively, with the MICs of 1.56-50 µmol/L, 6.25-25 µmol/L, 6.25-25 µmol/L, 0.2-50 µmol/L, 25-50 µmol/L, 1.56-50 µmol/L and 0.1-12.5 µmol/L, respectively. In conclusion, the minimum inhibitory concentrations of small molecules screened through high-throughput assay are at the level of micromolar with strong drug development potential and high modifiability. The high effective anti-planktonic cells and anti-biofilm activity by these molecules are expected to provide new ideas for the development of new antimicrobials against S. aureus.

[Perifosine inhibits biofilm formation of Pseudomonas aeruginosa by interacting with PqsE protein].

To explore the biofilm inhibitory efficacy of perifosine against Pseudomonas aeruginosa (P. aeruginos) and its mechanisms. Twenty-fourwell plate was used to form biofilms at the bottom and crystal violet staining was used to determine the biofilm inhibitory effects of perifosine against P. aeruginosa, the wells without perifosine was set as control group. Glass tubes combined with crystal violet staining was used to detect the gas-liqud interface related bioiflm inhibitory effects of perifosine, the wells without perifosine was set as control group. Time-growth curved was used to detect the effects of perifosine on the bacteial planktonic cells growth of P. aeruginosa, the wells without perifosine was set as control group. The interaction model between perifosine and PqsE was assessed by molecular docking assay. The inhibitory effects of perifosine on the catalytic activity of PqsE was determined by detection the production of thiols, the wells without perifosine was set as control group. Binding affinity between perifosine and PqsE was detected by plasma surface resonance. The biofims at the bottom of the microplates and air-liquid interface were effectively inhibited by perifosine at the concentration of 4-8 µg/ml. There was no influence of perifosine on the cells growth of P. aeruginosa. The resuts of molecular docking assay indicates that perifosine could interacted with PqsE with the docking score of -10.67 kcal/mol. Perifosine could inhibit the catalytic activity of PqsE in a dose-dependent manner. The binding affinity between perifosine and PqsE was comfirmed by plasma surface resonance with KD of 6.65×10-5mol/L. Perifosine could inhibited the biofilm formation of P. aeruginosa by interacting with PqsE.

[The exposure of antibiotics on the eradication of bismuth quadruple therapy in H.pylori infection].

Objective: To analyze the impact of previous exposure to macrolide, quinolones and nitroimidazole antibiotics on eradication rate of bismuth quadruple therapy (BQT) in newly diagnosed patients with Helicobacter pylori(H. pylori). Methods: A total of 469 patients with H. pylori initially treated at the Third Hospital of Peking University from September 2017 to August 2020 were retrospectively recruited. The therapeutic regimens were BQT containing clarithromycin/levofloxacin/metronidazole recommended by Chinese guidelines. Clinical data were collected, including general demographic data, exposure history of antibiotics, CYP2C16 metabolic pattern, endoscopic diagnosis, bacterial density, H.pylori resistance, eradication results, etc. Univariate analysis, Chi-square test, Fisher exact probability test, Kruskal-Wallis H test and Logistic regression model were used as statistical methods. Results: Among different eradication therapies, univariate and multivariate analyses suggested that previous exposure to macrolides (OR=3.37,95%CI 1.04-10.98, P<0.05) was relevant to the decreased eradication rate of BQT containing clarithromycin. This may be due to increased resistance to clarithromycin (OR=6.12,95%CI 3.99-9.40, P<0.01).The previous exposure to quinolones (OR=3.65, 95%CI 1.27-10.49, P<0.05) was relevant to the decreased eradication rate of BQT containing levofloxacin, which was probably explained by the increased resistance to levofloxacin (OR=2.50, 95%CI 1.69-3.71, P<0.01). But the previous history of nitroimidazole did not impact the efficacy of BQT containing metronidazole. Conclusions: In patients newly diagnosed with H.pylori infection, the previous exposure to macrolide or quinolones antibiotics is related to lower eradiation rates of H. pylori. Although the exposure to nitroimidazole also indicates drug resistance to metronidazole, the clinical efficacy of BQT with metronidazole 400 mg four times a day is not affected.

Mass Spectrometry Imaging and Its Application in Forensic Toxicology.

ABSTRACT: Mass spectrometry imaging （MSI） is a new imaging technology that can simultaneously detect and record the spatial distribution information of multiple molecules on the sample surface without labeling. The main principle of MSI is to combine mass spectrometry with imaging technology and irradiate the sample slice with ion beam or laser to ionize the molecules on its surface, obtain the mass spectrometry signal through the detector, convert the obtained data into pixel points by the imaging software, and then construct the spatial distribution image of the target compound on the tissue surface. The sample preparation for MSI include： sample collection and storage, tissue section, tissue pretreatment, selection and application of matrix. At present, this technology has been widely used in the fields of biomedicine, new drug development and proteomics, and its application in the field of forensic toxicology has also gradually attracted attention. This article reviews the principles and sample preparation process of MSI, describes the application of MSI in abused substances and metabolites of various material matrices, herbal mixtures, latent fingerprints, hair and animal and plant tissues, and discusses the prospects of the application of this technology in forensic toxicology, in order to provide ideas and references for the application of MSI technology in forensic toxicology.

[Analysis and Application of Seven Common New Psychoactive Substances of Synthetic Cannabinoids in Hair].

ABSTRACT: Objective To establish a detection method for common new psychoactive substances of synthetic cannabinoids in hair with ultra-high performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）. Methods In the 1 mL of internal standard methanol solution, 20 mg hair was added. After cryogenic grinding and ultrasonic extraction, the extract was separated by ACQUITY UPLC HSS T3 column （100 mm×2.1 mm, 1.8 µm）. The mobile phase A was aqueous solution that composed of 20 mmol/L ammonium acetate, 0.1% formic acid, and 5% acetonitrile. The mobile phase B was acetonitrile. Electrospray ionization source in positive ion mode was used for data acquisition in multi-reaction monitoring （MRM） mode. Results The seven common new psychoactive substances of synthetic cannabinoids in hair had a good linear relationship within their respective linear ranges （r>0.99）, the limits of detection were 0.5-2 pg/mg, the limits of quantification were 1-5 pg/mg, the intra-day and inter-day precisions were 0.1%-12.6%, the intra-day and inter-day accuracies were 89.2%-110.7%, the recovery rates were 52.3%-93.3%, and the matrix effects were 19.1%-95.2%. Conclusion The established method has a simple sample preparation process and high sensitivity. It is suitable for qualitative and quantitative analysis of common new psychoactive substances of synthetic cannabinoids in hair.

[Characteristics analysis of early gastric cancer under white light endoscopy].

OBJECTIVE: To investigate endoscopic features of early gastric cancer and clinical features of the patients, which may be helpful to provide reasonable suggestions for physicians to diagnose early gastric cancer during preliminary screening of white light gastroscopy. METHODS: A total of 271 patients who received endoscopic submucosal dissection or surgical operation to confirm early gastric cancer in Peking University Third Hospital from Apr. 2009 to Jun. 2017 were included for the retrospective review. Clinical information was collected, including gender, age, symptoms, family history and physical examination. The endoscopic characteristics of lesions under white light endoscopy were analyzed, including endoscopic long diameter, location, texture, spontaneous bleeding, mucosal color and morphology. The pathologic long diameter, infiltration depth and differentiation degree of early gastric cancer were also summarized. RESULTS: The study included 271 patients and 279 lesions. Among the 271 cases, 190 were male, 81 were female, average age was (63.7±12.4) years. There were 88 cases (32.5%) and 61 cases (22.5%) with the symptom of abdominal pain and discomfort respectively. The patients with family history of gastric cancer were 20 (7.4%). Abdominal physical examinations of the patients were mostly normal, accounting for 86.0% (233/271). Total detection rate of helicobacter pylori (HP) was 34.2% (79/231), with the highest rate 45.5% (10/22) in 2011 and the lowest rate 28.1% (9/32) in 2014. Among the 279 lesions, the mean endoscopic long diameter was (2.01±1.20) cm. The lesions were mainly single, accounting for 97.0% (263/271). There were 114 cases (40.9%), 62 cases (22.2%), 54 cases (19.4%) in the antrum, angular sulcus and cardia of stomach respectively. The lesions were mostly fragile, accounting for 45.5% (56/123). Most lesions had spontaneous bleeding, accounting for 52.3% (146/279). The mucosal color was mostly normal, accounting for 72.8% (203/279). The most common macroscopic morphology was IIa+IIc type (100 cases, 35.8%) and the lesions usually had mucous membrane damage like erosion and shallow ulcer (127 cases,45.5%). Among the 279 lesions, the mean pathologic long diameter was (2.05±1.48) cm. Intramucosal carcinoma accounted for 61.6% (172/279) and moderate differentiated gastric cancers accounted for 52.8% (131/248). CONCLUSION: In order to improve diagnosis of early gastric cancer,superficial elevation and depression of flat lesions as well as mucous membrane damage under white light endoscopy should be taken notice.

[Analysis of factors relevant to primary non-response to infliximab treatment in patients with Crohn's disease].

Objective: To evaluate factors relevant to primary non-response in patients with Crohn's disease undergoing infliximab (IFX) treatment at week 14. Methods: Patients with Crohn's disease in the Third Hospital of Peking University who were subject to IFX treatment more than 3 times and followed-up for more than 14 weeks from October 2015 to October 2018 were reviewed. The response was defined by a decrease of ≥100 points from baseline in the Crohn's Disease Activity Index. The clinical data and laboratory examinations of the two groups were compared, and the treatment outcomes of non-responders were also followed up. Results: A total of 41 patients were enrolled, among which 27(65.9%) were male. The median age at treatment was 25 years, and 8 patients lost primary response (19.5%). There was no significant difference in the sex, age at diagnosis or treatment, Montreal disease type and laboratory examinations [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), hemoglobin, albumin] in the response group and non-response group at baseline phase (P>0.05). Baseline CRP decreased from 17.7 (26.2) mg/L to 2.2 (3.6) mg/L in the response group, but increased from 11.7 (9.5) mg/L to 31.6 (28.4) mg/L in the non-response group at week 14 (P=0.024). The trend of ESR change in the response group [from 23.0 (28.5) mm/h to 7.0 (8.5) mm/h] and the non-response group [from 24.5 (22.5) mm/h to 35.0 (26.5) mm/h] was similar with that of CRP (P=0.036). Hemoglobin and albumin were significantly elevated in the response group, but not in the non-response group at week 14 (P=0.593, P=0.255). Among the non-response patients, 5 were converted to responsive after the treatment protocols had been adjusted. The combined immunosuppressant treatment all obtained clinical response. Conclusions: The elevated CRP and/or ESR may serve as indicators of primary non-response (at week 14) to IFX treatment among Crohn's disease patients, and the combination of immunosuppressive agents may be one of the effective treatments after excluding infection and other causes.

[Effect of A20 gene induced silencing on the biological behaviors of human nasopharyngeal carcinoma cell].

Objective: To observe the effect of knockdown A20 gene expression on the proliferation, invasion and metastasis of human nasopharyngeal carcinoma cell in vivo and in vivo. Methods: Human nasopharyngeal carcinoma cell 5-8F-H3 was transfected with A20-specific shRNA Tet-on inducible plasmid vectors, and A20 silenced cells were screened by Puromycin. Quantitative RT-PCR and Western blot analysis were used to detect the mRNA level and protein of A20. The cell proliferation was detected by cell counting kit-8 (CCK8) and plate colony formation assays. The cell cycle and apoptosis were measured by flow cytometry. And the ability of cell invasion was measured using Boyden chamber assay in vivo. Subcutaneous tumor formation and liver metastasis in vivo were examined with whole-body fluorescence imaging system to observe the influence of silencing A20 gene expression in nude mice. Results: The stable A20 inducible silencing cells line 5-8F-H3/A20-shRNA was established successfully. Down-regulation of A20 mRNA and protein expression were observed in 5-8F-H3/A20-shRNA cells treated with DOX(both P<0.01). The results of CCK-8 assay (F=18.542, P=0.003), clone formation experiment (F=40.080, P<0.001) and flow cytometry analysis (F=7.398, P=0.024) in vivo showed that the cell proliferation of 5-8F-H3 was remarkably inhibited by down-regulation of A20 gene expression. The results of Boyden chamber assay showed that A20 gene silencing could inhibit the cell invasion ability (F=26.157, P<0.001). Silencing of A20 inhibited tumorigenesis and metastasis via subcutaneous tumor formation and liver metastasis experiments in nude mice. Conclusion: A20 gene is closely related to the malignant biological behaviors of nasopharyngeal carcinoma, and it may serve as a potential molecular target for the treatment of nasopharyngeal carcinoma.

Changes of HMGB1 expression on angiogenesis of ovarian cancer and its mechanism.

This study was designed to investigate the changes of high-mobility group box-1 (HMGB1) expression and its effects on regulating the angiogenesis of ovarian cancer. HMGB1 eukaryotic expression plasmid and artificially synthesized small interfering ribose nucleic acid (siRNA) were constructed to transfer SKOV3 cell, respectively. Western blot was adopted to investigate the changes of HMGB1, CXCL12 and vascular endothelial growth factor (VEGF) before and after the transfection and flow cytometry (FCM) was applied to detect SKOV3 apoptosis. Results revealed that the apoptosis rates of SKOV3 cell were 32.8±2.2%, 33.9±1.9% and 11.7±1%, respectively, in the control group, no-load group and transfection group after 2-d cisplatin treatment (10 µg/mL). The apoptosis rate in the transfection group was obviously lower than that in the control group and no-load group (p = 0.00) while no significant difference was found in the apoptosis rate in the other two groups (p = 0.75). Furthermore, the apoptosis rates of SKOV3 cell in the SKOV3 group, negative control group, SKOV3-ribose nucleic acid interfere (RNAi) group were 7.9±0.5%, 8.3±0.8% and 29.5±1.3% respectively. The apoptosis rate was notably higher in SKOV3-RNAi group than in the SKOV3 group and negative control group (p < 0.001) while no significant difference was found in the apoptosis rate in the other two groups (p = 0.89). Thus, it can be concluded that HMGB1 interference can reduce VEGF and CXCL12 expression in ovarian cancer cells, but increase the apoptosis of ovarian cancer cells. Moreover, HMGB1 is highly expressed in cytoplasm and karyon.

Significant impacts of CYP3A4*1G and CYP3A5*3 genetic polymorphisms on the pharmacokinetics of diltiazem and its main metabolites in Chinese adult kidney transplant patients.

WHAT IS KNOWN AND OBJECTIVE: The calcium channel blocker diltiazem has been used widely as a cyclosporine (CsA)/tacrolimus-sparing agent. However, considerable interpatient variability in diltiazem's CsA/tacrolimus-sparing effect has been observed in many clinical studies. This study was carried out to investigate the impacts of the CYP3A4*1G and CYP3A5*3 genetic polymorphisms on the trough concentration/dose ratios and pharmacokinetics of diltiazem and its main metabolites in Chinese adult renal transplant patients. METHODS: Two hundred and twenty-five Chinese renal transplant patients were genotyped for CYP3A4*1G and CYP3A5*3. The predose and post-dose plasma concentrations of diltiazem and its main metabolisms were determined by HPLC. The relationships between the genotypes and pharmacokinetics were investigated. RESULTS AND DISCUSSION: The dose-adjusted concentrations and pharmacokinetics of diltiazem and its main metabolites were significantly affected by CYP3A4 *1G and CYP3A5*3 alleles. Patients with a CYP3A4*1/*1 genotype were found to have a higher dose-adjusted trough concentration and AUC of diltiazem and its main metabolites compared with those with CYP3A4*1G*1G(P<0·05). The dose-adjusted trough levels and AUC of diltiazem and its main metabolites were significantly lower in CYP3A5*1*1 carriers than in CYP3A5*3 carriers (P < 0·05). WHAT IS NEW AND CONCLUSION: The CYP3A4*1G and CYP3A5*3 genetic polymorphisms are closely related to the trough concentration/dose ratios and pharmacokinetics of diltiazem and its main metabolites in Chinese adult renal transplant patients.

[The changes of main upper gastrointestinal diseases and Helicobacter pylori infection status in the past thirty five years].

OBJECTIVE: To study the spectrum of upper gastrointestinal diseases and infection rate of Helicobacter pylori(Hp)in our hospital during the past 35 years. METHODS: Patients who were 16 or older with duodenal ulcer, gastric ulcer, reflux esophagitis, gastric cancer and esophageal cancer diagnosed by gastroscopy and pathology were retrospectively enrolled in our study from January 1980 to December 2014.Patients with chronic superficial gastritis, chronic atrophic gastritis or Hp infection from January 1989 to December 2014 were also included in our study according to the same diagnostic criteria.The incidences of diseases and the infection rates of Hp were studied. RESULTS: A total of 213 495 patients underwent gastroscopy in our department during the past 35 years.The overall diagnostic rates of duodenal ulcer, gastric ulcer, reflux esophagitis, gastric cancer and esophageal cancer were 9.87%, 3.79%, 6.66%, 1.59% and 0.66% respectively.There were 183 426 patients receiving gastroscopy in our department from January 1989 to December 2014. The overall endoscopic diagnosis rates of chronic superficial gastritis and chronic atrophic gastritis were 49.83% and 22.43% respectively.The overall infection rate of Hp was 36.18%, which had a declining trend consistent with peptic ulcer (all P=0.000). Yet, the prevalence of reflux esophagitis, chronic superficial gastritis and chronic atrophic gastritis were increasing (all P=0.000). The diagnostic rates of gastric cancer and esophageal cancer were persistent (P=0.266, P=0.156). CONCLUSIONS: The Hp infection during years has been decreasing, consistent with the declining tendency of peptic ulcer.On the other hand, reflux esophagitis, chronic superficial gastritis and chronic atrophic gastritis show an ascendant trend.The proportion of patients with gastric cancer and esophageal cancer is relatively stable.

Genetic variation and genetic structure of the endangered species Sinowilsonia henryi Hemsi. (Hamamelidaceae) revealed by amplified fragment length polymorphism (AFLP) markers.

Comprehensive research of genetic variation is crucial in designing conservation strategies for endangered and threatened species. Sinowilsonia henryi Hemsi. is a tertiary relic with a limited geographical distribution in the central and western areas of China. It is endangered because of climate change and habitat fragmentation over the last thousands of years. In this study, amplified fragment length polymorphism markers were utilized to estimate genetic diversity and genetic structure in and among S. henryi. In this study, Nei's genetic diversity and Shannon's information index were found to be 0.192 and 0.325 respectively, indicating a moderate-to-high genetic diversity in species. According to analysis of molecular variation results, 32% of the genetic variation was shown to be partitioned among populations, demonstrating a relatively high genetic divergence; this was supported by principal coordinate analysis and unweighted pair-group method with arithmetic average analysis. Moreover, the Mantel test showed that there was no significant correlation between genetic and geographical distances. The above results can be explained by the effects of habitat fragmentation, history traits, and gene drift. Based on the results, several implications were indicated and suggestions proposed for preservation strategies for this species.

Effects of rumen-protected γ-aminobutyric acid on performance and nutrient digestibility in heat-stressed dairy cows.

This experiment was conducted to investigate the effects of rumen-protected γ-aminobutyric acid (GABA) on performance and nutrient digestibility in heat-stressed dairy cows. Sixty Holstein dairy cows (141±15 d in milk, 35.9±4.3kg of milk/d, and parity 2.0±1.1) were randomly assigned to 1 of 4 treatments according to a completely randomized block design. Treatments consisted of 0 (control), 40, 80, or 120mg of true GABA/kg of dry matter (DM). The trial lasted 10wk. The average temperature-humidity indices at 0700, 1400, and 2200h were 78.4, 80.2, and 78.7, respectively. Rectal temperatures decreased linearly at 0700, 1400, and 2200h with increasing GABA concentration. Supplementation of GABA had no effect on respiration rates at any time point. Dry matter intake, energy-corrected milk, 4% fat-corrected milk, and milk fat yield tended to increase linearly with increasing GABA concentration. Supplementation of GABA affected, in a quadratic manner, milk protein and lactose concentrations, and milk protein yield, and the peak values were reached at a dose of 40mg of GABA/kg. Milk urea nitrogen concentration responded quadratically. Total solids content increased linearly with increasing GABA concentration. Supplementation of GABA had no effect on milk yield, lactose production, total solids, milk fat concentration, somatic cell score, or feed efficiency. Apparent total-tract digestibilities of DM, organic matter, crude protein, neutral detergent fiber, and acid detergent fiber were similar among treatments. These results indicate that rumen-protected GABA supplementation to dairy cows can alleviate heat stress by reducing rectal temperature, increase DM intake and milk production, and improve milk composition. The appropriate supplemental GABA level for heat-stressed dairy cows is 40mg/kg of DM.

Significance of SODD expression in childhood acute lymphoblastic leukemia and its influence on chemotherapy.

This study explored the clinical significance of silencer of death domain (SODD) expression in childhood acute lymphoblastic leukemia (ALL) and its influence on chemotherapy as well as the effect of SODD expression on apoptosis of leukemic cells. The expression of SODD proteins in different ALL groups was determined by immunocytochemistry. The SODD RNAi-interfering plasmid was constructed and transferred to Jurkat cells, and the effects of SODD expression on cell proliferation and apoptosis were analyzed using the MTT and FCM methods. The expressions of SODD, Phospho-NF-κB-P65, Bcl-2, and Caspase 3 were detected by Western blot analysis. The expression of SODD proteins was significantly higher in the ALL groups than in the control group (P < 0.05). The positive expression rate of SODD was significantly higher in refractory/relapsed and clinical high-risk groups than in standard-risk, initial treatment, and complete remission groups (P < 0.05). Microtubule-targeting drugs such as vincristine and taxol can notably down-regulate SODD expression during apoptosis, whereas DNR, and Ara-c cannot. The sensitivity of Jurkat cells to chemotherapeutic drugs increased with down-regulated SODD expression induced by SODD-interfering plasmid transfection. The sensitivity of the cells transfected with SODD-cloning genes decreased. SODD expression was high in the ALL children. These findings indicated that SODD over-expression might be correlated with the clinical classification, curative effect, and prognosis of ALL cells. Microtubule-targeting drugs can specifically down-regulate SODD expression in leukemic cells, thereby increasing the sensitivity of leukemic cells to SODD-targeting chemotherapeutics. In contrast, increased SODD expression tends to reduce sensitivity.

Supplementing different ratios of short- and medium-chain fatty acids to long-chain fatty acids in dairy cows: changes of milk fat production and milk fatty acids composition.

Milk fat synthesis might be promoted by the dietary addition of long-chain fatty acids (LCFA) or short- and medium-chain fatty acids (SMCFA). This study evaluated unprotected lipid supplementation with different ratios of SMCFA to LCFA, which had equivalent fatty acid (FA) proportions (by weight) to those in milk, on milk fat production and milk FA composition. Thirty-six Holstein cows (183±46 d in milk) were divided into 3 treatments according to a randomized block design. Cows in 3 treatments received supplements of 80 g/d of SMCFA mixture and 320 g/d of LCFA mixture (ratio of SMCFA to LCFA was 20:80); 400 g/d of butterfat (ratio of SMCFA to LCFA was 40:60); or 240 g/d of SMCFA mixture and 160 g/d of LCFA mixture (ratio of SMCFA to LCFA was 60:40). The FA compositions of the SMCFA mixture and the LCFA mixture were similar to the de novo synthesized FA (except C4:0) and preformed FA (except trans FA) found in the butterfat, respectively. Fatty acid supplements and butterfat were consumed by cows daily before the morning feeding during the 8-wk experimental period. Dry matter intake and milk yield were not different among the treatments. The milk fat percentage and total SMCFA concentration in milk fat tended to increase linearly and the proportion of milk total solids increased linearly with increasing ratios of SMCFA to LCFA in the supplements, whereas milk fat yield was not changed. We suggest that increasing ratios of SMCFA to LCFA in diets has the potential to improve milk fat synthesis.