Objective To explore clinical effect of distal tibial tubercle-high tibial osteotomy(DTT-HTO)in treating knee osteoarthritis(KO A)with medial meniscus posterior root tear(MMPRT).Methods A retrospective analysis was performed on 21 patients with varus KOA with MMPRT from May 2020 to December 2021,including 3 males and 18 females,aged from 49 to 75 years old with an average of(63.81±6.56)years old,the courses of disease ranged from 0.5 to 18.0 years with an average of(5.9±4.2)years,and 4 patients with grade Ⅱ,14 patients with grade Ⅲ,and 3 patients with grade Ⅳ according to Kellgren-Lawrence;14 patients with type 1 and 7 patients with type 2 according to MMPRT damage classification.The distance of medi-al meniscusextrusion(MME)and weight-bearing line ratio(WBLR)of lower extremity were compared before and 12 months after operation.Visual analogue scale(V AS),Western Ontarioand and McMaster Universities(WOMAC)osteoarthritis index,and Lysholm knee score were used to evaluate knee pain and functional improvement before operation,1,6 and 12 months after operation,respectively.Results Twenty-one patients were followed up for 12 to 18 months with an average of(13.52±1.72)months.MME distance was improved from(4.99±1.05)mm before operation to(1.87±0.76)mm at 12 months after operation(P＜0.05).WBLR was increased from(15.49±7.04)％before operation to(62.71±2.27)％at 12 months after operation(P＜0.05).VAS was decreased from(7.00±1.14)before operation to(2.04±0.80),(0.90±0.62)and(0.61±0.50)at 1,6 and 12 months after operation.WOMAC were decreased from preoperative(147.90±9.88)to postoperative(103.43±8.52),(74.00±9.54)and(47.62±9.53)at 1,6 and 12 months,and the difference were statistically significant(P＜0.05).Lysholm scores were increased from(46.04±7.34)before oepration to(63.19±8.93),(81.10±6.41)and(89.29±3.04)at 1,6 and 12 months after operation(P＜0.05).Conclusion For the treatment of varus KOA with MMPRT,DTT-HTO could reduce medial meniscus pro-trusion distance,improve the ratio of lower limb force line,and effectively reduce knee pain and improve knee joint function.

Literature regarding the impacts of heavy metal exposure on erectile dysfunction (ED) is scarce. We aimed to evaluate the correlation between 10 urinary metals and ED in a large, nationally representative adult male sample. The dataset was extracted from the National Health and Nutrition Examination Survey (NHANES) during the period of 2001-2002 and 2003-2004. Weighted proportions and multivariable logistic regression analysis adjusted for confounding variables were utilized to determine the relationship between metal exposure and ED. Weighted quantile sum (WQS) regression was utilized to evaluate the impact of a mixture of urinary metals on ED. A total of 1328 participants were included in our study. In multivariable logistic regression analysis, cobalt (Co) and antimony (Sb) were positively associated with ED (odds ratio [OR]: 1.36, 95% confidence interval [CI]: 1.10-1.73, P = 0.020; and OR: 1.41, 95% CI: 1.12-1.77, P = 0.018, respectively) after full adjustment. Men in tertile 4 for Co (OR: 1.49, 95% CI: 1.02-2.41, P for trend = 0.012) and Sb (OR: 1.53, 95% CI: 1.08-2.40, P for trend = 0.041) had significantly higher odds of ED than those in tertile 1. Furthermore, the WQS index was significantly linked with increased odds of ED after full adjustment (OR: 1.31, 95% CI: 1.04-1.72, P < 0.05). Our study expanded on previous literature indicating the possible role of heavy metal exposure in the etiology of ED. The evaluation of heavy metal exposure should be included in the risk assessment of ED.
Adult ; Humans ; Male ; United States ; Erectile Dysfunction/etiology* ; Nutrition Surveys ; Metals, Heavy ; Risk Assessment

OBJECTIVE: To clarify the functional effects of differential expression of ring finger and tryptophan-aspartic acid 2 (RFWD2) on dendritic development and formation of dendritic spines in cerebral cortex neurons of mice. METHODS: Immunofluorescent staining was used to identify the location and global expression profile of RFWD2 in mouse brain and determine the co-localization of RFWD2 with the synaptic proteins in the cortical neurons. We also examined the effects of RFWD2 over-expression (RFWD2-Myc) and RFWD2 knockdown (RFWD2-shRNA) on dendritic development, dendritic spine formation and synaptic function in cultured cortical neurons. RESULTS: RFWD2 is highly expressed in the cerebral cortex and hippocampus of mice, and its expression level was positively correlated with the development of cerebral cortex neurons and dendrites. RFWD2 expression was detected on the presynaptic membrane and postsynaptic membrane of the neurons, and its expression levels were positively correlated with the length, number of branches and complexity of the dendrites. In cultured cortical neurons, RFWD2 overexpression significantly lowered the expressions of the synaptic proteins synaptophysin (P < 0.01) and postsynapic density protein 95 (P < 0.01), while RFWD2 knockdown significantly increased their expressions (both P < 0.05). Compared with the control and RFWD2-overexpressing cells, the neurons with RFWD2 knockdown showed significantly reduced number of dendritic spines (both P < 0.05). CONCLUSION RFWD2 can regulate the expression of the synaptic proteins, the development of the dendrites, the formation of the dendritic spines and synaptic function in mouse cerebral cortex neurons through ubiquitination of Pea3 family members and c-Jun, which may serve as potential treatment targets for neurological diseases.
Animals ; Aspartic Acid/metabolism* ; Cerebral Cortex ; Dendritic Spines/metabolism* ; Mice ; Neurons/metabolism* ; Synapses ; Tryptophan/metabolism*

The rhizome of giant taro (Alocasia macrorrhiza (L.) Schott), which is a highly adaptable wild plant, is a traditional Chinese herbal medicine. In the current study, the antiproliferative constituents of giant taro were investigated and six new (1-6) and four known piperidine alkaloids (7-10) were isolated from its rhizomes. Their chemical structures and absolute configurations were elucidated using various spectroscopic methods and the Mosher ester method. The isolated alkaloids were screened for the antiproliferative activity through MTT assay. The results indicated that piperidine alkaloids exerted potential antiproliferative activity against HepG2, AGS and MCF-7 tumor cells. Further researches showed that compounds 3-5 dose-dependently decreased the colony formation rate and induced the apoptosis of AGS cells, while compound 4 induced AGS cell death via the proapoptotic pathway. This study demonstrates that the piperidine alkaloids isolated from giant taro exhibit significant antitumor activity, which provides phytochemical evidence for further development and utilization.
Alkaloids/pharmacology* ; Alocasia/chemistry* ; Humans ; Piperidines/pharmacology* ; Plants ; Rhizome/chemistry*

A fast and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of prodrug of paclitaxel (Pro-PTX) and paclitaxel (PTX) in rat plasma was developed. The plasma samples were subjected to protein precipitation with acetonitrile (0.1% formic acid), and then separated by LC with an Ultimate AQ-C18 column (50 mm × 3.0 mm, 3 μm) and acetonitrile-1 mmol·L^-1 ammonium formate (containing 0.1% formic acid) as the mobile phase. Multiple reaction monitoring (MRM) scanning mode was used to detect the ion responses m/z 983.4→415.2 (Pro-PTX), m/z 854.4→286.1 (PTX) and m/z 808.3→527.2 (Docetaxel, internal standard) by using a triple quadrupole tandem mass spectrometer with electrospray ionization source and positive ion mode. The method validation results show that the linear ranges of Pro-PTX and PTX in plasma were 2.00-500 ng·mL^-1 (r > 0.99) and 4.00-1 000 ng·mL^-1 (r > 0.99), the lower limit of quantification was 2.00 ng·mL^-1 and 4.00 ng·mL^-1, respectively; the quality control samples with low, medium and high concentrations of Pro-PTX and PTX were within the batch, the relative standard deviation (RSD) between batches were all less than 9%; the relative deviation (RE) was within the range of ± 9%; In the stability test, both Pro-PTX and PTX in plasma were stable under various storage conditions. The method was sensitive, specific, and reproducible, and was suitable for the pharmacokinetic study of Pro-PTX in rats. Animal experiments were approved by the Ethics Committee of Laboratory Animal Management and Animal Welfare, Institute of Materia Medica, Chinese Academy of Medical Sciences (No.: 00003552).

BACKGROUND: Circulating tumor DNA (ctDNA) is a promising biomarker for non-invasive epidermal growth factor receptor mutations (EGFRm) detection in lung cancer patients, but existing methods have limitations in sensitivity and availability. In this study, we used the ΔCt value (mutant cycle threshold [Ct] value-internal control Ct value) generated during the polymerase chain reaction (PCR) assay to convert super-amplification-refractory mutation system (superARMS) from a qualitative method to a semi-quantitative method named reformed-superARMS (R-superARMS), and evaluated its performance in detecting EGFRm in plasma ctDNA in patients with advanced lung adenocarcinoma. METHODS: A total of 41 pairs of tissues and plasma samples were obtained from lung adenocarcinoma patients who had known EGFRm in tumor tissue and were previously untreated. EGFRm in ctDNA was identified by using superARMS. Through making use of ΔCt value generated during the detection process of superARMS, we indirectly transform this qualitative detection method into a semi-quantitative PCR detection method, named R-superARMS. Both qualitative and quantitative analyses of the data were performed. Kaplan-Meier analysis was performed to estimate the progression-free survival (PFS) and overall survival (OS). Fisher exact test was used for categorical variables. RESULTS: The concordance rate of EGFRm in tumor tissues and matched plasma samples was 68.3% (28/41). At baseline, EGFRm-positive patients were divided into two groups according to the cut-off ΔCt value of EGFRm set at 8.11. A significant difference in the median OS (mOS) between the two groups was observed (EGFRm ΔCt ≤8.11 vs. >8.11: not reached vs. 11.0 months; log-rank P = 0.024). Patients were divided into mutation clearance (MC) group and mutation incomplete clearance (MIC) group according to whether the ΔCt value of EGFRm test turned negative after 1 month of treatment. We found that there was also a significant difference in mOS (not reached vs. 10.4 months; log-rank P = 0.021) between MC group and MIC group. Although there was no significant difference in PFS between the two groups, the two curves were separated and the PFS of MC group tended to be higher than the MIC group (not reached vs. 27.5 months; log-rank P = 0.088). Furthermore, EGFRm-positive patients were divided into two groups according to the cut-off of the changes in ΔCt value of EGFRm after 1 month of treatment, which was set at 4.89. A significant difference in the mOS between the two groups was observed (change value of ΔCt >4.89 vs. ≤4.89: not reached vs. 11.0 months; log-rank P = 0.014). CONCLUSIONS Detecting EGFRm in ctDNA using R-superARMS can identify patients who are more likely sensitive to targeted therapy, reflect the molecular load of patients, and predict the therapeutic efficacy and clinical outcomes of patients.
Adenocarcinoma of Lung/genetics* ; Circulating Tumor DNA/genetics* ; ErbB Receptors/genetics* ; Humans ; Lung Neoplasms/genetics* ; Mutation/genetics* ; Protein Kinase Inhibitors

Objective:To apply the B-learning teaching mode into the Medical Statistic course, and to comparatively analyze the students' knowledge, attitude, and practice (KAP). Methods:In this study, undergraduates were investigated by self-designed questionnaires, and the reliability and validity of the questionnaire were evaluated. SAS 9.3 statistical software was used to analyze the KAP evaluation and the influencing factors of online learning with chi-square test, t test and multiple regression analysis. Results:There were significant differences in students' cognitive status in three aspects: the role of online videos ( P=0.012 9), whether to submit assignments ( P=0.040 7), and whether to participate in discussions ( P=0.009 4). In terms of attitude, there were significant differences between the role of B-learning process ( P=0.027 1) and online learning interest ( P=0.013 7). And in the terms of practice, there were significant differences in the time of online learning ( P=0.002 4), weekly login times for online learning ( P=0.015 4) and ways to solve difficulties ( P=0.004 5). Conclusion:The B-learning mode applied to the course of Medical Statistics has greatly improved students' ability in knowledge, attitude and practice (KAP), and achieved good teaching effects.

Background: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. Methods: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Jin Yin-tan Hospital, Wuhan, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. Results: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8–99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6–87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. Conclusion: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

COVID-19 not only affects the physical health of Chinese people, but also their psychological health. This article mainly summarizedthe causes, clinical manifestations and preventive measures of COVID-19 impact on psychology of Chinese people, and presentedtwo representative cases at the same time.

The aim of the present study was to investigate the effects of exercises with different durations and intensities on mitochondrial autophagy and FUNDC1 in rat skeletal muscles. Sixty male Sprague-Dawley rats were randomly divided into 2- and 4-week control groups (Con), moderate-intensity exercise groups (M-ex groups, treadmill exercise, 16 m/min, 1 h/d, 6 d/week), and high-intensity exercise groups (Hi-ex groups, treadmill exercise, 35 m/min, 20 min/d, 6 d/week). The bilateral soleus muscles were separated after the intervention, and paraffin sections were prepared for transmission electron microscopy. ELISA method was used to detect the content of citrate synthase (CS). The co-localizations of microtubule-associated protein 1 light chain 3 (LC3)/cytochrome c oxidase IV (COX-IV), FUNDC1/COX-IV and LC3/FUNDC1 were observed by immunofluorescent staining in frozen sections. The skeletal muscle mitochondria were extracted, and the expression of autophagy-related proteins, including AMPKα, p-AMPKα, Unc-51 like kinase 1 (ULK1), FUNDC1, LC3 and p62, were detected by Western blot. The results showed that exercise increased mitochondrial function, i.e. peroxisome proliferator-activated receptor γ co-activator-1α (PGC-1α), COX-I protein expression levels and CS content. There was no difference of mitochondrial function parameters between 2-week M-ex and 2-week Hi-ex groups, while mitochondrial function of 4-weeks Hi-ex group was significantly lower than that of 4-week M-ex group. Under the same exercise intensity, mitochondrial autophagy activation in skeletal muscle of 4-week exercise was higher than that in 2-week exercise group; Under the same duration of exercise, mitochondrial autophagy activation of Hi-ex group was higher than that in M-ex group. Both 2- and 4-week exercise intervention increased LC3/COX-IV, COX-IV/FUNDC1, and FUNDC1/LC3 co-localizations. Exercise increased LC3-II/LC3-I ratio, down-regulated p62 protein expression level, up-regulated FUNDC1, ULK1 protein expression levels and AMPKα phosphorylation, and the changes of these proteins in 4-week Hi-ex group were significantly greater than those in 4-week M-ex group. These results suggest exercise induces mitochondrial autophagy in skeletal muscles, and the activity of autophagy is related to the duration and intensity of exercise. The induction mechanism of exercise may involve the mediation of FUNDC1 expression through AMPK-ULK1 pathway.
Animals ; Autophagy ; Exercise Therapy ; Humans ; Male ; Membrane Proteins/physiology* ; Mitochondria ; Mitochondrial Proteins/physiology* ; Muscle, Skeletal/metabolism* ; Rats ; Rats, Sprague-Dawley