Effect of quercetin's anti-breast cancer depending on presence of estrogen receptor via down-regulating long non-coding RNA MALAT-1 and its mechanism / 中国药理学通报

Aim To investigate the molecular mechanism by which quercetin inhibits the malignant behavior of breast cancer cells. Methods Breast cancer cell lines MCF-7 and MB231 were used as the research models. Lentiviral transfection was employed to establish tumor cells with high expression of ERa and MAL-AT-1. The expression of MALAT-1 was assessed using RT-qPCR,and ERa expression was determined through Western blot. Subsequently, CCK-8 assay and colony formation assay were conducted to evaluate cell proliferation. PI staining and adenovirus transfection were performed to observe the inhibitory effects of quercetin on breast cancer cell proliferation. Results 17|3-es-tradiol ( E2 ) promoted the proliferation of MCF-7 breast cancer cells, while 5 jjunol L quercetin reversed the promoting effect of E2 on proliferation ( P 0. 05 ) . Quercetin had no effect on MB231 breast cancer cells. Overexpression of ERa significantly inhibited the pro-proliferative effect of E2 on MB231-ERa cells, and quercetin further suppressed this effect. Additionally , quercetin inhibited the expression of MALAT-1. However,this inhibitory effect was reversed by overexpression of MALAT-1, leading to enhanced cell proliferation , cell cycle progression, and clonal formation a-bility. Conclusions Quercetin exerts its anti-tumor effects on breast cancer cells by regulating MALAT-1, dependent on the presence of estrogen receptor. Quercetin shows potential as a therapeutic drug for breast cancer targeting the estrogen receptor.

Long-term evaluation and physical and mental effects of residual tinnitus following treatment of sudden hearing loss / 中华耳鼻咽喉头颈外科杂志

Objective: To clarify the long-term characteristics of tinnitus following treatment of sudden deafness and its long-term physical and mental effects on patients. Methods: A retrospective analysis was performed on 88 patients (46 males and 42 females; Age from 11 to 89 years) with sudden deafness treated in Department of Otoscope Surgery of Peoples's Libration Army General Hospital in Beijing from April 2020 to January 2021, and the occurrence of tinnitus and treatment effect of all patients were analyzed. Follow-up was conducted for patients with residual tinnitus after treatment for more than 1 year by the investigation and filling in the survey information collection form, Tinnitus Evaluation Questionnaire (TEQ) and Tinnitus Handicap Inventory (THI). Descriptive statistics and SPSS 22.0 software were used for statistical data analysis. Results: In this study, 93.2% (82/88) of patients with sudden deafness were accompanied by tinnitus at the onset, and the proportion of long-term tinnitus after treatment was 90.2% (74/82). After 1 year of treatment for sudden deafness, the improvement of tinnitus was significant in low-frequency sudden deafness compared with those of high-frequency, flat and total deafness sudden deafness (χ2 value was 6.801, 4.568 and 4.038, all P<0.05). In patients with residual tinnitus, 9 (12.2%) patients felt minimal loudness or even no loudness, 34 (46.0%) patients felt slight loudness, 28 (37.8%) patients felt tinnitus was relatively loud, and 3 (4.1%) patients felt tinnitus was loud or noisy. Nine (12.2%) patients's sleep was often affected, 41 (55.4%) patients's sleep was sometimes affected, 9 (12.2%) patients's sleep was rarely affected, 15 (20.3%) patients's sleep was almost not affected. Twenty-eight (37.8%) patients basically completely adapted to tinnitus and 46 (62.2%) patients did not completely adapted to residual tinnitus. Eight (10.8%) patients had no impact on life, 39 (52.7%) patients had slight impact, 22 (29.7%) patients had moderate impact, and the other 5 (6.8%) patients had greater impact. According to tinnitus evaluation questionnaire(TEQ), there were 12 cases (16.2%) of grade Ⅰ, 26 cases (35.1%) of grade Ⅱ, 28 cases (37.8%) of grade Ⅲ, 7 cases (9.5%) of grade Ⅳ and 1 case (1.4%) of grade Ⅴ. According to tinnitus handicap inventory(THI), tinnitus disability was classified into grade Ⅰ, 22 cases (29.7%), grade Ⅱ, 14 cases (18.9%), Grade Ⅲ, 27 cases (36.5%) and grade Ⅳ, 11 cases (14.9%). Conclusion: The rate of residual tinnitus following treatment of sudden deafness is high. Some of the patients can completely adapt residual tinnitus after one year, but some of them will be affected when sleep, work and study. Residual tinnitus can lead to tinnitus disability in different degrees.

Clinical Observation on Orthopedics No.1 Prescription Combined with Celecoxib in Treating Knee Osteoarthritis with Middle Stage of Cold-dampness Syndrome / 中国实验方剂学杂志

Objective:To study the clinical efficacy of orthopedics No.1 prescription combined with celecoxib in the treatment of knee osteoarthritis （KOA） with middle stage of cold-dampness syndrome and investigate its effect on serum cytokines levels. Method:The 72 patients were randomly divided into control group and observation group， with 36 cases each. Patients in both groups were given basic treatment with oral celecoxib capsules （0.2 g/ time， 1 time/day）. On the basis of western medicine treatment， patients in observation group were treated with orthopedics No.1 prescription decoction-free granules by fumigation， 1 bag/time， 1 time/day， 5 times/week. Both groups received treatment for 4 weeks. The visual analog pain score （VAS）， American knee society knee score （KSS）， serum interleukin-1<italic>β </italic>（IL-1<italic>β</italic>）， tumor necrosis factor-<italic>α </italic>（TNF-<italic>α</italic>）， and transforming growth factor-<italic>β</italic>₁（TGF-<italic>β</italic>₁） levels were observed before and after treatment， and their clinical efficacy was evaluated. Result:After treatment， VAS score significantly decreased in both groups （<italic>P</italic><0.01）， and KSS score significantly increased （<italic>P</italic><0.01）， with better clinical effect in observation group. After treatment， serum IL-1<italic>β</italic> and TNF-<italic>α</italic> levels decreased significantly in both groups （<italic>P</italic><0.01）， and the levels in observation group were lower than those in control group after treatment （<italic>P</italic><0.05）. TGF<italic>-β</italic>₁content was significantly higher than that before treatment in two groups （<italic>P</italic><0.01）. Conclusion:Orthopedics No.1 prescription combined with celecoxib for the treatment of KOA with middle stage of cold-dampness syndrome can effectively relieve the clinical symptoms of patients with KOA， improve joint function， improve quality of life， reduce the contents of inflammatory factors IL-1<italic>β</italic> and TNF-<italic>α</italic> in serum， and increase the expression of TGF-<italic>β</italic>₁ level.

Liquid biopsy biomarkers of renal interstitial fibrosis based on urinary exosome.

Renal interstitial fibrosis (RIF) is difficult to diagnose. This paper explored liquid biopsy markers in urinary exosomes derived from RIF patients. Urine samples from 32 patients with various degrees of RIF and 20 non-RIF patients were collected. The size and morphology of urinary exosomes isolated by polyethylene glycol were observed with electron microscopy. Protein biomakers of exosomes were analyzed by Western blot. qRT-PCR was used to detect the levels of biomarkers (miR-29c, miR-21, E-cadherin, and vimentin) of epithelial mesenchymal transition in urinary exosomes. The diagnostic value was detected with ROC curves. Results displayed successfully isolated urinary exosomes. The examined miRNAs and mRNAs were checked from all urinary exosomes samples, except for two cases of RIF which lacked E-cadherin mRNA. RNA levels were different in patients with diverse degrees of RIF. Urinary miR-29c was decreased with the progress of fibrosis. Levels of E-cadherin mRNA were first decreased and then increased. The contents of miR-21 and vimentin mRNA were also depended on the degrees of RIF. ROC curve analysis showed that the area under the curve (AUC) of miR-29c was 0.8621, statistically significant compared with the non-RIF group (P < 0.05). The miR-29c level within the urinary exosomes is a promising marker for the diagnosis of RIF.

Effect of different doses of adipose-derived stem cells on early renal fibrosis / 中国组织工程研究

BACKGROUND:Our preliminary findings have shown that stem cells have a certain effect on early formation of renal fibrosis and delay the occurrence of renal interstitial fibrosis.OBJECTIVE:To investigate the effect of exogenous adipose-derived stem cell transplantation on the formation of renal interstitial fibrosis in rats,and to explore the dose-effect relationship.METHODS:Fifty Sprague-Dawley rats were randomly divided into five groups.Rats in sham operation group were injected with PBS;and those in the other four groups were ligated to establish the model of renal fibrosis.After successful modeling,the model group was injected with PBS,while low dose group,middle dose group and high dose group were injected with 1 ×107/L,2x107/L,3x107/L adipose-derived stem cell suspension (0.1 mL),respectively.Rats were killed 14 days after injection.Hematoxylin-eosin staining and Masson staining were used to observe the degree of renal tubular interstitial injury and the relative area of the renal interstitium.Expression of alpha smooth muscle actin and transforming growth factor beta1 was detected by immunohistochemistry.RESULTS AND CONCLUSION:(1) Hematoxylin eosin staining:The model group showed typical glomerular and tubulointerstitial changes;the low,middle and high dose groups had a certain degree of glomerular and tubulointerstitial changes,but the severity of injury in these three groups,especially in the high dose group,was significantly milder than that in the model group.(2) Masson staining:In the model group,the renal interstitium was widened and the collagen fibers were deposited;in the low,middle and high dose groups,the degree of renal interstitial expansion was lower than that in the model group,and moreover,the degree of renal interstitial expansion in the middle and high dose groups was lower than that in the low dose group (P ＜ 0.05).(3) Immunohistochemical staining:Compared with the sham operation group,the expression of alpha smooth muscle actin and transforming growth factor beta1 in the model group was higher than that in the sham operation group (P ＜ 0.05).Compared with the model group,significantly decreased expression of alphasmooth muscle actin was found in the high dose group (P ＜ 0.05) and significantly reduced transforming growth factor beta1 expression was observed in the high,middle,and low dose groups (P ＜ 0.05),especially in the middle and high dose groups.To conclude,exogenous adipose-derived stem cell transplantation can delay the formation of early renal fibrosis in a dose-effect manner,which may be realized by changing the signal pathway state induced by transforming growth factor beta1.

Application of intraoperative electrophysiological monitoring in lumbosacral selective posterior rhizotomy for spastic cerebral palsy / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the clinical application of intraoperative electrophysiological monitoring in lumbosacral selective posterior rhizotomy for spastic cerebral palsy.</p><p><b>METHODS</b>Total 372 dorsal roots of 89 patients underwent selective posterior rhizotomy at a single medical center. The dorsal roots from L3 to S1 were divided into rootlets and stimulated with a 1-second 50 Hz train. Motor responses were recorded by electromyography. Rootlets were assigned according to the extent of abnormal electrophysiological propagation, and grades of 3+ to 4+ were cut. If no electrical response was observed, the second criterion is the behavioral response (that is, muscle contraction in the legs or toes) assessed by the physical therapist, when rootlets were stimulated at the lowest threshold with a 1-second 50 Hz train.</p><p><b>RESULTS</b>The rootlets of 340 dorsal roots were assigned according to the extent of abnormal electrophysiological propagation, 324 (83.5%) roots were assigned the maximally abnormal response of grade 3+ (76, 22.4%) or 4+ (248, 72.9%) in EMG monitoring and were cut. For no electrical response was observed, according to the second criterion, 48 roots were partially cut. It was also be found that free running EMG occurred earlier than stimulus triggered EMG, and identified "abnormal" rootlets on free running EMG monitoring was more easily and quickly than on stimulus triggered EMG. During the postoperative 2 weeks in hospital, there was a significant decrease in lower-limb spasticity and an increase in range of movement in all patients, and no one case occurred obvious loss of muscle strength, abnormity of sensory, or deterioration of bladder/bowel control.</p><p><b>CONCLUSIONS</b>The spread of electromyography response to the contra lateral limb and/or upper extremity remains a valid criterion to define a "abnormal" posterior nerve rootlet that feeds into a disinhibited spinal circuit involved in uncontrolled spasticity. Intraoperative electrophysiological monitoring is reproducible and reliable for selection of "abnormal" rootlets.</p>

Multicenter phase II study of modified FOLFIRI regimen in the advanced colorectal cancer patient refractory to fluoropyrimidine and oxaliplatin / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of modified FOLFIRI regimen in advanced colorectal cancer (CRC) patients refractory to fluoropyrimidine and oxaliplatin.</p><p><b>METHODS</b>The modified FOLFIRI regimen consisted of intravenous infusion of irinotecan 180 mg/m2 d1 + LV 200 mg/m2 dl + 5-Fu 400 mg/m2 bolus dl plus 46-hour intravenous infusion of 5-Fu 2.4 g/m2, every 2 weeks as one cycle. The main selection criterion for this study was the advanced CRC refractory to fluoropyrimidine and oxaliplatin.</p><p><b>RESULTS</b>Of the 80 evaluable patients for efficacy: 10 (12.5%) had a partial response, 51 (63.7%) stable disease, and 19 (23.8%) progressive disease. The median time to progression was 96 days. Safety analysis was based on the data of 83 evaluable patients. The most frequently observed grade 3 or 4 toxicities were neutropenia (24.1%), nausea/vomiting (8.4%), and diarrhea (2.4%).</p><p><b>CONCLUSION</b>Modified FOLFIRI regimen is effective and well tolerated in patients with advanced colorectal cancer refractory to fluoropyrimidine and oxaliplatin.</p>

Research on chondrogenic differentiation and immunologic response of allogeneic mesenchymal stem cells implanted into joint cavity / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the cartilage formation ability of allogeneic mesenchymal stem cells implanted into sheep joint cavity without the use of immunosuppressive therapy.</p><p><b>METHODS</b>Allogeneic mesenchymal stem cells (MSCs) loaded onto porous beta-tricalcium phosphate ceramic (beta-TCP) were implanted into normal sheep joint cavity. A complete mismatch between donor stem cells and recipient sheep was confirmed by mixed lymphocyte reaction assays prior to implantation. Eight weeks after implantation, the implants were taken out for histological and immunohistochemical analysis. The histological results were compared with data derived from joint cavity implantation of autologous MSCs-ceramic composites and cell-free ceramics. The systemic immune response was evaluated by the analysis of recipient serum for production of antibodies against allogeneic cells.</p><p><b>RESULTS</b>For implantation with allogeneic MSCs, no sign of adverse immune response was detected. Histologically, few inflammation cells infiltration occurred and no antibodies against allogeneic cells were detected. Neocartilage formation in implants loaded with either allogeneic or autologous mesenchymal stem cells was revealed by histochemical and immunohistochemical analysis. In implants without stem cells, no cartilage formation was detected.</p><p><b>CONCLUSIONS</b>Allogeneic mesenchymal stem cells are capable of forming cartilage under the effect of joint cavity environment. Without the use of immunosuppressive therapy, allogeneic MSCs do not provoke an adverse immune response in vivo.</p>

Epidemiology of SEN virus infection among patients with hepatitis B and C in China.

China is highly endemic for viral hepatitis. In the present study, we investigated the clinical significance and molecular analysis of SEN virus (SEN-V) infection in patients with chronic hepatitis B and C in YanBian city, China. Serum samples were obtained from 71 patients with hepatitis B and C who visited YanBian hospital in the north-east of China. Detection of SEN-V DNA was performed by nested polymerase chain reaction (PCR) using primer pairs in the 5'-untranslated region. SEN-V DNA was present in 14/23 (63.9%), 12/15 (80.0%), 5/7 (71.4%), 13/18 (72.2%), 7/8 (87.5%), 1/1 (100%) of the patients with type B (B)-chronic hepatitis (CH), B-liver cirrhosis (LC), B-hepatocellular carcinoma (HCC), type C (C)-CH, C-LC, C-HCC, respectively. The highest prevalence of SEN-V DNA was seen in the various age groups over 40 years old. There was no significant correlation of clinical parameters between SEN-V DNA-positive and -negative patients with type B and C liver diseases. The YanBian isolates showed 71.4-95.0% homology to isolates reported previously. In conclusion, the prevalence of SEN-V infection in YanBian City was high but SEN-V coinfection did not seem to modify the serological features of chronic hepatitis B and C in China.

TT virus infection does not affect the clinical profiles of patients with hepatitis B and C in Yanbian City, China.

China is an area of high endemicity for viral hepatitis, and the molecular epidemiological investigation of TT virus (TTV) infection is of interest. In the present study, we investigated the epidemiology, clinical significance and molecular characteristics of TTV infection in patients with chronic hepatitis B and C in Yanbian City, China. Serum samples obtained from 74 patients with hepatitis B and hepatitis C who visited Yanbian Hospital, located in northeast China, were analyzed in this study. The study group included 22 cases of chronic hepatitis B (B-CH), 17 cases of liver cirrhosis B (B-LC), 7 cases of hepatocellular carcinoma (B-HCC), 16 cases of chronic hepatitis C (C-CH), 11 cases of liver cirrhosis C (C-LC) and 1 case of hepatocellular carcinoma (C-HCC). Detection of TTV DNA was performed as described by Nishizawa et al. The second-round PCR products from 7 subjects were sequenced, followed by investigation of nucleotide homology and phylogenetic analysis. TTV DNA was present in 18.2, 5.9, 28.6, 6.3, 9.1 and 0% of the patients with B-CH, B-LC, B-HCC, C-CH, C-LC and C-HCC, respectively. The highest prevalence of TTV infection was seen in the groups aged 40-50 and over 60 years. There was no significant correlation between the presence of TTV DNA and the clinical parameters in patients with hepatitis B and C. The various isolates showed 97.9-100% with isolates reported previously from Japan and 98.4-100% with isolates reported previously from China. Nucleotide sequence analysis revealed that the Yanbian isolates could be classified in the same group as the Japan and China isolates. We concluded that chronic coinfection with TTV did not affect the serological features of chronic hepatitis B and C in China, as found in Tokyo, Japan.

Clinico-epidemiological study of GBV-C/HGV infection in Tokyo metropolitan, and Nanjing and Yanbian cities in the People's Republic of China.

In the present study, we compared the molecular epidemiology of GBV-C/HGV co-infection and the clinical profiles in patients diagnosed with either type B or type C hepatitis virus infection from Nanjing in Southeast China and Yanbian in Northeast China, with those at the Nihon University Hospital in Tokyo. The patients included 97 men in Nanjing, 66 men and women in Yanbian, and 249 men and women at the Nihon University Hospital. GBV-C/HGV RNA was detected using reverse transcriptase polymerase chain reaction as described by Abe et al. The prevalence of GBV-C/HGV co-infection in Nanjing, Yanbian, and Tokyo was 18.8, 23.3, and 3.5% in type B liver diseases, respectively, and 3.6, 11.1, 7.3% in type C liver diseases, respectively. A comparison of background factors between GBV-C/HGV RNA-positive and -negative patients revealed no significant differences in any parameter between Nanjing, Yanbian, and Tokyo. A phylogenic tree analysis of nucleotide sequences showed that the Nanjing strain was closely related to the Shanghai, Hong Kong, and Tokyo isolates, while the Yanbian isolate was closely related to the Korean, Mongolia, and Tokyo strains. These isolates were classified to the East Asian type of genotype 3. The results of the phylogenic tree analysis suggests that the GBV-C/HGV isolates from China and Japan have a common origin. Therefore, the prevalence of GBV-C/HGV infection may be geographically determined, irrespective of racial differences.