AIM: To study the changes of K + channels of outer hair cells in guinea pig cochlea with streptomycin ototoxicity. METHODS: Auditory brainstem responses (ABR) and whole-cell patch clamp techniques were used.RESULTS: (1) The body weight of guinea pigs with streptomycin ototoxicity decreased significantly; (2) The ABR threshold markedly increased in streptomycin group (Ⅱ,Ⅲ);(3)The number of dissociated outer hair cells of guinea pigs (Ⅱ,Ⅲ) was lower than that of control (Ⅰ); (4) Streptomycin decreased the Ca 2+ -sensitive K + currents and delayed outward K + currents distinctly; (5) There was no significant difference of K + currents between Ⅰ and Ⅱ/Ⅲ. CONCLUSION: These results suggest that the inhibition of K + channels is the basis of streptomycin ototoxicity, but not the direct reason for cell death.

Objective To observe the effect of tetraethylplyrazine(TMP) on outward K~+ channel of outer hair cells in guinea pig cochlea.Methods 60 guinea pigs were divided into 6 groups randomly in the experiment.Auditory brainstem response was used to monitor the change of ABR thresholds and patch clamp techniques to observe the effect of TMP on outward K~+ channel.Results TMP decreased the elevated ABR threshold caused by streptomycin. The TMP increased the amplitudes of calcium sensitive potassium channels (I_ K(Ca) ) and delayed outward potassium channels (IK) of outer hair cells of guinea pig cochlea.Conclusion The study indicates that TMP may act as a protective agent against ototoxicity of streptomycin. The amplitudes of I_ K(Ca) and IK of outer hair cells are increased by the TMP,suggesting the possible mechanisms of reducing ototoxicity.

Objective To explore any protective effect of hyperbaric oxygen in traumatic brain injury and its effect on the expression of silent information regulator 1 ( SIRT1) . Methods Sixty mice were randomly divided into a control group (n=20), a brain injury group (TBI, n=20) and a hyperbaric oxygen therapy group (TBI+HBO, n=20) . The mice in the TBI and TBI + HBO groups were given massive blows to establish closed brain injuries, while in the control group the scalp was incised and a bone window was removed without brain damage. The mice in the TBI + HBO group were given hyperbaric oxygen treatment twice per day for five days, while those in the TBI and control groups were put in the hyperbaric chamber but not given HBO treatment. At one hour after the trauma and on 5 days afterward, the neurological functioning of the mice was measured to generate neurological severity scores. Brain tissue was resected for triphenyl tetrazolium staining to measure the infarct area. Cortical neurons were isolated to eval-uate the SIRT1 expression using immunofluorescence and Western blotting. Results No significant difference in the average NSS score was observed between the TBI and TBI+HBO groups one hour after modeling. The average NSS score in the TBI group subsequently increased and then decreased gradually until the fifth day. The average NSS score of the TBI+HBO group was significantly lower than that of the TBI group after the onset of the treatment at the differ-ent time points, decreasing to (2.11±0.43) on the 5thday compared with (4.06±0.54) in the TBI+HBO group. On the 2nd day after the trauma, the cerebral infarction areas of the TBI and TBI+HBO groups were significantly larger than in the control group. During the treatment, the infarction area of the TBI+HBO group decreased gradually until on the 5th day it was significantly smaller than that of the TBI group. Traumatic brain injury significantly down-regula-ted SIRT1 protein compared with the control group, but the hyperbaric oxygen therapy significantly increased the ex-pression of SIRT1 compared with the TBI group. Conclusion Hyperbaric oxygen therapy can significantly relieve traumatic brain injury, reducing NSS scores and the infarcted area and enhancing SIRT1 expression, at least in mice.

Objective To analyze the status quo of the diagnosis and treatments of primary gastro-intestinal lymphoma (PGIL) in order to improve it. Methods Eighty-one patients with PGIL were ana-lyzed retrospectively including clinical manifestations, endoscopic features, pathological features, HP in-fection, treatment, and prognosis. Results The age of patients with gastric lymphoma was (52.84±15.33) years. The age of patients with intestinal lymphoma was (42.09±15.28) years. Common symp-toms included abdominal pain (76.5%), gastrointestinal bleeding (55.6%), anemia (54.3%), abdominal mass (25.9%), hypoproteinemia (40.7%), bowel obstruction (11.1%), abdominal dis-tension, vomiting, and other non-specific gastrointestinal symptoms (32.1%), weight loss (33.3%); fever (8.6%), diarrhea (7.4%), digestive tract perforation (1.2%), constipation (1.2%), and dysphagia (1.2%). Endoscopic appearances were as follows: tumor type (67.7%), ulcer type (27.7%), and diffuse type (4.6%). Clinical diagnosis rate and endoscopic biopsy confirmation rate were 30.9% and 73.8%. MALT lymphoma accounted for 61.7% of the patients. HP detection rate was 39.5 % and positive rate was 37.5 %. A total of 69 patients received surgeries: 3 had preoperative chem-otherapy, and 34 had postoperative chemotherapy. Twelve patients had non-surgical treatment, 6 patients of whom had simple chemotherapy and HP eradication therapy, and the other 6 gave up during the treat-ment. There was no significant difference in the survival rate of Stage Ⅰ～Ⅱ patients in the surgery alone group, surgery plus chemotherapy group, and chemotherapy and HP eradication therapy group (P>0.05). The survival rate of Stage IIIⅢ～Ⅳ patients in the surgery alone group was lower than that in the other 2 groups (P<0.05). The 5-year, 3-year, and 1-year survival rate was 55.87%, 70.96%, and 96.39%, respectively. Conclusion There are no specific clinical and endoscopic features in PGIL, so the misdiagnosis rate is high. Multi-site biopsy or repeated biopsies and immunohistochemical methods can be used to raise the pathological diagnosis rate. Chemotherapy and HP eradication are recommended.

OBJECTIVE:To improve the quality standard of Jianpi zhixiening granules. METHODS:TLC was applied for qual-itative identification of Scutellaria baicalensis,Crategi Fructus,Lonicerae japonicae,Codonopsis Radix,Nelumbo nucifera,Copti-dis Rhizoma. The contents of berberine hydrochloride and baicalin were determined by HPLC. The determination was performed on Shimadzu VP-ODS column with mobile phase consisted of methanol-acetonitrile-water (46:30:42,V/V/V,berberine hydrochlo-ride))(0.1% sodium dodecylsulphate,0.1% phosphoric acid,methanol-0.4% phosphoric acid(50:50,V/V,baicalin)at the flow rate of 1.0 mL/min. The detection wavelengths were set at 265 nm (berberine hydrochloride) and 280 nm (baicalin). The column temperature was 30 ℃,and sample size was 10 μL. RESULTS:TLC spots of S. baicalensis,Crategi Fructus,L. Japonicae,Co-donopsis Radix,N. nucifera,Coptidis Rhizoma were clear and well-separated without negative interference. The linear ranges of berberine hydrochloride and baicalin were 6.67-33.34 μg/mL(r=0.9998)and 7.7-38.7 μg/mL(r=0.9999). RSDs of precision,sta-bility and reproducibility tests were all lower than 1.0% . The recoveries were 96.5% -99.9%(RSD=1.2% ,n=6)and 101.1%-102.9%(RSD=0.6%,n=6). CONCLUSIONS:Improved standard can be used for quality control of Jianpi zhixiening granules.

The pathogenesis of stroke is complex, with genetic risk factors as one of the main factors. The genetic variants of phosphodiesterase 4D (PDE4D) was significantly associated with the susceptibility to ischemic stroke (IS) in Caucasian population, but its association with the susceptibility to stroke in Chinese population is unclear. This article is intended to review the research on the association between PDE4D genetic variants and stroke susceptibility in Chinese population, aiming to further optimize the relevant research programs and provide reference for the prevention and treatment of stroke in China.
Humans ; Brain Ischemia/genetics* ; Genetic Predisposition to Disease ; East Asian People ; Cyclic Nucleotide Phosphodiesterases, Type 4/genetics* ; Stroke/genetics* ; Polymorphism, Single Nucleotide ; Risk Factors

OBJECTIVETo investigate whether ascorbic acid could enhance the efficacy of arsenic trioxide (As(2)O(3)) combined with 2, 3-dimethoxy-1, 4-naphthoquinone (DMNQ) in inducing the apoptosis of leukemia cell line U937 and its possible mechanism.

METHODSFlow cytometry and electron microscopy were applied to detect apoptosis of U937 cells after treatment with various combinations of As(2)O(3), DMNQ and ascorbic acid for 24 hours.

RESULTSAs(2)O(3) and DMNQ induced-apoptosis of U937 cells was enhanced (35.24%-->61.20%) upon cotreatment with ascorbic acid. Catalase could reverse this effect of DMNQ. Ascorbic acid had no effect on DMNQ-induced apoptosis of U937 cells.

CONCLUSIONAscorbic acid enhanced the apoptosis of U937 cells via reactive oxygen species-dependent pathway in the presence of As(2)O(3).

Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Ascorbic Acid ; pharmacology ; Drug Synergism ; Flow Cytometry ; Humans ; Naphthoquinones ; pharmacology ; Oxides ; pharmacology ; U937 Cells

OBJECTIVETo explore the association of inherent cellular reactive oxygen species (ROS) levels with susceptibility of the tumor cells to apoptosis induction by arsenic trioxide (As(2)O(3)).

METHODSLow concentration (2 micromol/L) of As(2)O(3) was administered to two cultured leukemic cell lines, NB4 and U937, and two esophageal carcinoma cell lines, EC1.71 (also named EC/CUHK1) and EC1867, to confirm the difference in apoptosis susceptibility of NB4 versus U937 and of EC1.71 versus EC1867. Dihydrogenrhodamine 123 (DHR123), used as a ROS capture agent, was incubated with cells in the absence of As(2)O(3). Fluorescence intensity of rhodamine 123, the product of cellular oxidation of DHR123, was detected by flow cytometry and ROS was measured.

RESULTSLow concentration of As(2)O(3) induced apoptosis was more likely to occur in NB4 and EC1.71 cells than in U937 and EC1867 cells, or NB4 was more sensitive than U937, and EC1.71 more sensitive than EC1867 to As(2)O(3). The inherent cellular ROS level is higher in NB4 than in U937, and also higher in EC1.71 than in EC1867.

CONCLUSIONSThe difference in cellular ROS level is positively associated with cellular susceptibility to apoptosis induction by As(2)O(3). The inherent ROS level might be important in defining apoptotic susceptibility to As(2)O(3).

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; genetics ; Arsenicals ; pharmacology ; DNA, Neoplasm ; genetics ; Flow Cytometry ; Fluorescent Dyes ; Humans ; Oxides ; pharmacology ; Reactive Oxygen Species ; metabolism ; Rhodamine 123 ; Tumor Cells, Cultured ; drug effects ; metabolism

Objective:To analyze clinical characteristics and high-frequency ultrasound features of localized scleroderma, and to construct and validate a non-invasive prediction model for staging of skin lesions based on the high-frequency ultrasound features.Methods:Patients with localized scleroderma were retrospectively collected from the Department of Dermatology and Venereology, Second Xiangya Hospital of Central South University from February 1, 2021 to February 28, 2023, and clinical data as well as high-frequency ultrasound and pathologic features of 85 lesions from these patients were analyzed. Lesions were divided into modeling cohort and validation cohort according to the chronological order of patient enrollment. The univariate analysis and multivariable logistic regression models were used to analyze the independent influential factors in the staging of localized scleroderma lesions in the modeling cohort, construct the regression equation, and to build a nomogram prediction model. The Bootstrap validation method was used for internal validation, and the predictive performance of the nomogram model in the modeling cohort and validation cohort was further evaluated by the calibration curve and receiver operating characteristic (ROC) curve.Results:In the modeling cohort, 60 patients with localized scleroderma, including 16 males and 44 females, were enrolled, with the age [ M ( Q1, Q3) ] being 22.0 (10.0, 39.2) years, and there were 28 lesions in the oedematous phase and 32 lesions in the fibrotic and atrophic phase; in the validation cohort, 25 patients with localized scleroderma, including 8 males and 17 females, were enrolled, with the age being 18.0 (7.0, 30.0) years, and there were 9 lesions in the oedematous phase and 16 lesions in the fibrotic and atrophic phase. Univariate analysis in the modeling cohort showed no significant differences in the age and gender of patients or the location of lesions between the oedematous phase group and the fibrotic and atrophic phase group (all P > 0.05) ; compared with the oedematous phase group, the fibrotic and atrophic phase group showed an increased proportion of patients with disease duration ≥ 2 years (20/32 cases vs. 10/28 cases, χ2 = 4.29, P = 0.038), decreased thicknesses of the subcutaneous fat layer in skin lesions (1.4 [0.0, 26.0] mm vs. 1.8 [0.1, 14.3] mm, Z = -2.14, P = 0.032), increased decrements in the subcutaneous fat layer thickness in the lesional sites compared with non-lesional control sites (1.8 [0.5, 11.0] vs. 0.3 [-1.9, 8.0] mm, Z = -4.72, P < 0.001), increased ratios of the lesional elasticity values to control elasticity values (2.9 [1.8, 6.9] vs. 1.8 [1.1, 5.9], Z = -4.34, P < 0.001), and increased ultrasound-based lesional activity scores (5.0 [3.0, 8.0] points vs. 3.0 [0.0, 5.0] points, Z = -4.76, P < 0.001). Multivariable logistic stepwise regression analysis showed that the disease duration ≥ 2 years ( P = 0.032), increased ratios of the lesional elasticity values to control elasticity values ( P = 0.019), increased ultrasound-based lesional activity scores ( P = 0.013), and increased decrements in the subcutaneous fat layer thickness in the lesions compared with the controls ( P = 0.013) helped to confirm localized scleroderma lesions in the fibrotic and atrophic phase. Based on the results of regression analysis, a total of 4 factors were included in the nomogram prediction model, including the disease duration, the decrement in the subcutaneous fat layer thickness in lesions compared with controls, the ratio of the lesional elasticity values to control elasticity values, and the ultrasound-based lesional activity score; additionally, the constructed logistic regression model formula for predicting the probability (p) of skin lesions in fibrotic and atrophic phase was "ln (p/[1 - p]) = -9.595 + 2.204 × the disease duration + 0.784 × the decrement in the subcutaneous fat layer thickness in the lesions compared with the controls (mm) + 0.887 × the ratio of the lesional elasticity values to control elasticity values + 1.374 × the ultrasound-based lesional activity score". The calibration curve showed a good predictive performance of the model through the Bootstrap validation method, and the ROC curve demonstrated good discrimination and accuracy (modeling cohort: area under the curve = 0.936, 95% CI: 0.879 - 0.994; validation cohort: area under the curve = 0.889, 95% CI: 0.748 - 1.000) . Conclusions:High-frequency ultrasound could provide essential details for staging the localized scleroderma lesions. Based on the disease duration, subcutaneous fat layer thickness, skin elasticity values, and ultrasound-based lesional activity scores, the constructed prediction model could predict the stages of localized scleroderma lesions with excellent discrimination, accuracy, and predictive performance.