In recent years many reports on the progress of mammary tumors treated by traditional Chinese medicine ( TCM) have appeared in the literature.In this article, progress of clinical and experimental study between human and canine mammary tumors was compared.Ways and methods of how TCM treat mammary tumors were exhibited such as Chinese medicinal formulae, herbal extracts and active ingredients.Meanwhile, mechanisms of TCM treating mammary tumors were pointed out.The purpose of this article is to provide idea about TCM clinical therapy methods for canine mammary tumors, and to provide research foundation and important models for study of human mammary tumors.

Fear memories are temporarily suppressed after repeated retrieval, a phenomenon known as memory extinction.How to reduce or even eliminate fear memory is the key to the treatment of fear related diseases such as post-traumatic stress disorder(PTSD). A single extinction training based on Pavlov's fear regulation task could only inhibit the expression of conditioned fear memory traces, but it could not eliminate the acquired conditioned fear memory. However, according to the reconsolidation theory based on memory, the retrieval-extinction paradigm has a more lasting effect on the erasure and rewriting of fear memory, and can effectively prevent the return of fear memory. Studies have shown that extraction-regression is closely related to a variety of neurotransmitter receptors such as glutamate receptor(GluR), dopamine receptor(DAR), L-type voltage-gated calcium channels(LVGCs) and cannabinoid. Moreover, its effect is closely related with factors such as retrieval-extinction memory stage. At present, most of the researches on extracted boundary conditions only stay at the level of behavior, with little understanding and exploration on the level of molecular mechanism. From the perspective of molecular neurobiology, with different stages of memory and different types of receptors and molecular mechanisms, this research reviewed the mechanisms of retrieval-extinction in recent years.It provided valuable signaling pathways, molecular targets and research directions for the treatment of fear-related diseases such as PTSD.

Objective To investigate the effect of micro RNA (miR)-125a-3p on proliferation and apoptosis of glioma cells and its role in MAPK signaling pathway. Methods (1) The miR-microarray data from the Cancer Genome Atlas (TCGA, https:// cancergenome.nih.gov/) database were downloaded, and the miR-125a-3p expressions in 565 gliomas tissues and 10 normal brain tissues were compared. (2) Clinical collection of 30 glioma specimens surgically resected in our hospital from April 2015 to April 2018, was performed, including 7 of low-grade glioma and 23 of high-grade glioma;8 normal brain tissues needed craniocerebral trauma excision were collected at the same time period;reverse transcription (RT)-real-time quantitative (q) PCR was used to detect the miR-125a-3p expressions in glioma tissues and normal brain tissues. (3) The normal brain glial cells HA1800 and glioma cells (U251, U138, U87, U373, and T98G) were routinely cultured in vitro; RT-qPCR was used to detect the miR-125a-3p expression in normal brain glial cells and glioma cell lines. (4) The cultured glioma cell lines U251 and U373 at logarithmic phase were divided into miR-125a-3p group and negative control group;and miR-125a-3p mimic or nonsense sequence were transfected using LipofectamineTM 2000;72 h after transfection, the miR-125a-3p expression was detected by RT-qPCR; the proliferation rate was detected by clone formation after transfection; the apoptosis rate was detected by flow cytometry 72 h after transfection; the cleaved-caspase-3, cleaved-caspase-9, cleaved-caspase-7, P38 and P-P38/MAPK protein expressions were detected by Western blotting. Results (1) In TCGA database, the miR-125a-3p expression in glioma brain tissues was statistically lower as compared with that in normal brain tissues (P<0.05). (2) The miR-125a-3p expressions in clinically collected normal brain tissues, low-grade glioma specimens and high-grade glioma specimens were decreased successively, enjoying statistically significant differences (P<0.05). (3) As compared with normal glial cells, the miR-125a-3p expressions in glioma cell lines were significantly lower (P<0.05), of which, U251 and U373 enjoyed the most obvious decrement. (4) As compared with the blank control group, the miR-125a-3p group had significantly increased miR-125a-3p expression, significantly decreased colony forming efficiency, significantly increased proliferation rate, significantly increased expressions of apoptosis-related proteins cleaved-caspase-3, cleaved-caspase-9, and cleaved-caspase-7, and statistically increased phosphorylated-P38/MAPK expressions (P<0.05). Conclusion The miR-125a-3p expression is low in glioma tissues and cells; miR-125a-3p over-expression can inhibit the proliferation of glioma cells and promote apoptosis through MAPK signaling pathway, which may provide a new potential target for treatment of glioma.

By measuring the relative expression level of miR-1825 in serum of pre-operative and post-operative patients with breast cancer and healthy subjects, the clincal value of miR-1825 for pre-operative and post-operative breast cancer patients was evaluated.The serum of pre-operative breast cancer patients( n=92), post-operative breast cancer patients( n=64) and healthy subjects( n=60) were collected from General Hospital of Southern Theatre Command of PLA from October 2018 to March 2021. Real-time quantitative PCR was used to detect the relative expression of miR-1825 in the serum of breast cancer patients and healthy controls. The clinicopathological data were used to analyze the correlation between the expression level of miR-1825 and serum tumor markers level. The receiver operating characteristic curve (ROC) was used to evaluate the diagnosis value of breast cancer with miR-1825, CA15-3. Mann-Whitney U test was used for comparisons between two groups,and Kruskal-Wallis H test was used for multiple group comparisons. The correlation between miR-1825 and CEA, CA15-3, CA-125 expression were analyzed using Spearman correlation test.The relative expression level of miR-1825 in serum of pre-operative patients with breast cancer 1.290(0.705, 1.793) was significantly higher than that of healthy controls 0.18(-0.876, 0.725), but decreased after surgery and chemotherapy -0.080(-0474, 0.405). The analysis of clinicopathological characteristics found that the expression level of miR-1825 was higher in patients with stage Ⅲ-Ⅳ, low degree of tissue differentiation, and tumor larger than 2 cm[stageⅠ-Ⅱ:0.975(0.458, 1.380), stageⅢ-Ⅳ: 1.955(1.663, 2.535), U=98.000, P<0.001;low degree of tissue differentiation:1.685(1.448, 2.143), high/medium degree of tissue differentiation:0.700(0.395, 0.898), U=15.500, P<0.001; tumor smaller than 2 cm:0.935(0.438, 1.370), tumor larger than 2 cm:1.915(1.580, 2.288), U=215.500, P<0.001].Spearman analysis result showed that the expression of serum miR-1825 in breast cancer patients was linearly correlated with the expression of CEA ( r=0.274, P=0.008) and CA15-3 ( r=0.587, P<0.001); ROC curve result showed that miR-1825 was able to distinguish preoperative breast cancer patients from healthy people and postoperative patients. When using one biomarker to discriminate pre-operation and post-operation patients,miR-1825 had the best diagnostic efficiency,with an area under the ROC curve(AUC) of 0.914(95 %CI: 0.872-0.956). miR-1825 may become a potential serum marker for the diagnosis of breast cancer and monitoring of therapeutic efficacy.

By measuring the relative expression level of miR-1825 in serum of pre-operative and post-operative patients with breast cancer and healthy subjects, the clincal value of miR-1825 for pre-operative and post-operative breast cancer patients was evaluated.The serum of pre-operative breast cancer patients( n=92), post-operative breast cancer patients( n=64) and healthy subjects( n=60) were collected from General Hospital of Southern Theatre Command of PLA from October 2018 to March 2021. Real-time quantitative PCR was used to detect the relative expression of miR-1825 in the serum of breast cancer patients and healthy controls. The clinicopathological data were used to analyze the correlation between the expression level of miR-1825 and serum tumor markers level. The receiver operating characteristic curve (ROC) was used to evaluate the diagnosis value of breast cancer with miR-1825, CA15-3. Mann-Whitney U test was used for comparisons between two groups,and Kruskal-Wallis H test was used for multiple group comparisons. The correlation between miR-1825 and CEA, CA15-3, CA-125 expression were analyzed using Spearman correlation test.The relative expression level of miR-1825 in serum of pre-operative patients with breast cancer 1.290(0.705, 1.793) was significantly higher than that of healthy controls 0.18(-0.876, 0.725), but decreased after surgery and chemotherapy -0.080(-0474, 0.405). The analysis of clinicopathological characteristics found that the expression level of miR-1825 was higher in patients with stage Ⅲ-Ⅳ, low degree of tissue differentiation, and tumor larger than 2 cm[stageⅠ-Ⅱ:0.975(0.458, 1.380), stageⅢ-Ⅳ: 1.955(1.663, 2.535), U=98.000, P<0.001;low degree of tissue differentiation:1.685(1.448, 2.143), high/medium degree of tissue differentiation:0.700(0.395, 0.898), U=15.500, P<0.001; tumor smaller than 2 cm:0.935(0.438, 1.370), tumor larger than 2 cm:1.915(1.580, 2.288), U=215.500, P<0.001].Spearman analysis result showed that the expression of serum miR-1825 in breast cancer patients was linearly correlated with the expression of CEA ( r=0.274, P=0.008) and CA15-3 ( r=0.587, P<0.001); ROC curve result showed that miR-1825 was able to distinguish preoperative breast cancer patients from healthy people and postoperative patients. When using one biomarker to discriminate pre-operation and post-operation patients,miR-1825 had the best diagnostic efficiency,with an area under the ROC curve(AUC) of 0.914(95 %CI: 0.872-0.956). miR-1825 may become a potential serum marker for the diagnosis of breast cancer and monitoring of therapeutic efficacy.

BACKGROUND:Icariin,with antiinflammatory,antioxygenatory and immunoregulatory effects,can be a potential drug for preventing and treating acute liver injury. OBJECTIVE:To investigate the protective effect and possible mechanism of icariin in mice with acute liver injury induced by carbon tetrachloride. METHODS:Thirty-two Kunming mice were equally and randomly divided into the following groups:normal,model,low-dose icariin and high-dose icariin groups.The low-and high-dose icariin groups were continuously gavaged with icariin(100 and 200 mg/kg,respectively)once a day for 7 continuous days.The normal group and model group were injected with physiological saline(10 mL/kg)at the same time point.After the last administration,all the groups except for the normal group were injected with carbon tetrachloride to induce acute liver injury.The mice were killed 24 hours later,and the liver index was detected.Serum levels of alanine aminotransferase and aspartate aminotransferase were detected by automated biochemical analysis.Tumor necrosis factor α and interleukin 6 levels in serum were detected using ELISA.The levels of superoxide dismutase,glutathione peroxidase and malondialdehyde in liver tissue were detected through a reagent kit.The histopathology changes of the liver were observed by hematoxylin-eosin staining.TUNEL method was used to detect the apoptosis in hepatocytes.Western blot was performed to detect the expression levels of glucose-regulated protein 78 kDa,endoplasmic reticulum stress-related protein(C/-EBP homologous protein),mixed lineage kinase domain-like protein and Caspase-3 in liver tissue. RESULTS AND CONCLUSION:Compared with the normal group,the liver index and serum levels of alanine aminotransferase,aspartate aminotransferase,tumor necrosis factor α and interleukin 6 were increased in the model group(P＜0.05).Compared with the model group,the above indexes were decreased in the low-dose and high-dose icariin groups(P＜0.05).Compared with the normal group,the activities of superoxide dismutase and glutathione peroxidase in the liver tissue of mice were decreased in the model group(P＜0.05)and the level of malondialdehyde was increased(P＜0.05).Compared with the model group,the activities of superoxide dismutase and glutathione peroxidase were increased in the low-and high-dose icariin groups(P＜0.05)and the level of malondialdehyde was decreased(P＜0.05).Hematoxylin-eosin and TUNEL staining showed that mice in the model group had severe structural destruction of liver tissue,extensive necrosis of hepatocytes and high apoptotic rate of hepatocytes,while the structural destruction of liver tissue and the area of necrosis of hepatocytes in the low-and high-dose icariin groups were significantly milder than those in the model group,and the apoptotic rate of hepatocytes was lower than that in the model group(P＜0.05).Western blot assay showed that the protein expression of glucose-regulated protein 78 kDa,C/-EBP homologous protein,mixed lineage kinase domain-like protein and Caspase-3 in liver tissue of mice in the model group was increased compared with that in the normal group(P＜0.05),while the expression levels of these proteins in liver tissue of mice were significantly reduced after low-and high-dose icariin intervention(P＜0.05).To conclude,icariin can produce a protective effect against carbon tetrachloride-induced acute liver injury,and its mechanism may be related to the regulation of endoplasmic reticulum stress and reduction of programmed necrosis.

Objective To evaluate the effectiveness of non-operative treatment for the acute intra-synovial sheath anterior cruciate ligament (ACL) rupture.Methods Twenty-eight patients diagnosed as the acute intra-synovial sheath ACL rupture at outpatient clinic between May 2014 and July 2016 were included.All patients were immobilized with knee braces for 6 weeks,followed by range of motion (ROM) training and partial to full weight-bearing of knees.All patients returned 3 months later for MRI scanning and those with the side-to-side difference of the anterior-posterior laxity less than 5 mm continued with non-operative treatment,followed up for MRI examination and clinical assessments 6 and 12 months later.Results Four patients dropped out because they didn't meet the stability criteria at 3 months after the treatment,3 of whom received surgical reconstruction and 1 with muscle strengthening training.Another patient received surgical reconstruction at 5 months due to re-injury.The remaining 23 patients achieved satisfactory results at 12 months after the treatment,with the average side-to-side difference of the anterior-posterior laxity of 2.1mm (0-4 mm),MRI good-to-excellent rate of 85.2％ (8 of Grade 1 and 15 of Grade 2),subjective IKDC (International Knee Documentation Committee) score of 92.71 (89.7-98.9),Lysholm score of 91.6 (86-95),and modified Larson score 96.4 (92-99).Conclusions Patients with the acute intra-synovial sheath anterior cruciate ligament (ACL) rupture showed satisfactory functional scores and objective stability and healing on MRI after the non-operative treatment.

Objective : To analyze the status and influencing factors of the intention of people aged 18 to 25 years to primary medical institutions and their satisfaction for health services in Zhejiang Province, so as to provide basis for the improvement of health services in primary medical institutions. Methods: During November and December in 2019,the 18-25 year-old people in Zhejiang Province were recruited to investigate the general information, intention to seek medical advice and satisfaction for health services in primary medical institutions through WeChat. Logistic regression was performed to analyze the influencing factors of the intention and the satisfaction. Importance matrix was used to analyze the key drivers of the satisfaction. Results: Among the 620 people surveyed, with a response rate of 93.37%, 142 (22.90%) chose primary medical institutions for advice. Actually 516 (83.23%) people went to primary medical institutions last year, and 384 ( 74.42% ) of them were satisfied with the health services. The results of multivariate logistic regression analysis showed that the people aged 18-25 years who were under the new rural cooperative medical care system ( OR=3.062, 95%CI: 1.745-5.373 ) and who had records in community health centers ( OR=0.547, 95%CI: 0.308-0.970 ) were more likely to go to primary medical institutions for medical advice; the ability of doctors ( OR=1.478, 95%CI:1.168-1.871 ) ,the drug notification by medical staff ( OR=1.308, 95%CI: 1.065-1.606 ) , routine examination items ( OR=1.523, 95%CI: 1.227-1.889 ) , the ways of payment ( OR=1.168, 95%CI: 1.017-1.340 ) , the comfort of environment ( OR=1.785, 95%CI: 1.437-2.219 ) and the bulletin boards of health knowledge ( OR=1.302, 95%CI: 1.086-1.561 ) were associated with the satisfaction. The results of importance matrix analysis showed that the ability of doctors and routine examination items were the priorities to improve, followed by the drug notification by medical staff; the comfort of environment had competitive advantages; the ways of payment and the bulletin boards of health knowledge needed to be further analyzed. Conclusions The 18-25-year-old people in Zhejiang Province were less intended to seek medical advice in primary medical institutions, which was associated with the type of medical insurance and records in community health centers. They were satisfied with the health services, the ability of doctors and routine examination items were the key drivers.

Objective:To investigate the characteristics and the risk factors of coronavirus disease 2019 (COVID-19) associated acute kidney injury (AKI).Methods:A retrospective cohort study was performed to examine the basic data, clinical characteristics and prognosis of patients with COVID-19 in Zhongnan Hospital of Wuhan University and Wuhan Fourth Hospital from January 1st to February 1st in 2020. According to the diagnostic criteria of Kidney Disease: Improving Global Outcomes (KDIGO), patients with AKI were included in AKI group and those without AKI were included in non-AKI group. The differences of each index between the two groups were compared. The prognostic value of AKI for COVID-19 was analyzed by Kaplan-Meier survival curve and Cox regression.Results:A total of 394 COVID-19 patients were included, with a total mortality of 5.6%; 37 (9.4%) of them developed AKI. The mortality of patients with COVID-19 associated AKI was 18.9%. There were significant differences in age, gender, smoking history, hypertension history, malignancy history, cardiovascular disease history and cerebrovascular disease history between the two groups. In addition to the difference of serum creatinine (SCr) and blood urea nitrogen (BUN), white blood cell count (WBC), neutrophil count (NEU), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), D-dimer, procalcitonin (PCT) and C-reaction protein (CRP) in AKI group were significantly higher than those in non-AKI group [WBC (×10 9/L): 5.75 (4.13, 7.83) vs. 4.52 (3.35, 5.90), NEU (×10 9/L): 4.55 (2.81, 6.11) vs. 3.06 (2.03, 4.50), AST (U/L): 40.0 (24.5, 69.5) vs. 30.0 (23.0, 42.5), LDH (μmol·s -1·L -1): 5.21 (3.68, 7.57) vs. 4.24 (3.05, 5.53), D-dimer (μg/L): 456 (266, 2 172) vs. 290 (152, 610), PCT (μg/L): 0.33 (0.03, 1.52) vs. 0.01 (0.01, 0.11), CRP (mg/L): 53.80 (26.00, 100.90) vs. 23.60 (9.25, 51.10), all P < 0.05], while lymphocyte count (LYM) and platelet count (PLT) were decreased [LYM (×10 9/L): 0.68 (0.47, 1.05) vs. 0.91 (0.63, 1.25), PLT (×10 9/L): 142.0 (118.0, 190.0) vs. 171.0 (130.0, 2 190.0), both P < 0.05]. The mortality of AKI group was significantly higher than that of non-AKI group [18.9% (7/37) vs. 4.2% (15/357), P < 0.01]. Kaplan-Meier survival curve showed that the 30-day cumulative survival of AKI group was lower than that of non-AKI group (log-rank: P = 0.003). Cox analysis also showed that AKI increased the odds of patients with COVID-19 mortality by 3.2-fold [hazard ratio ( HR) = 3.208, 95% confidence interval (95% CI) was 1.076-9.566, P = 0.037]. Conclusions:The risk of AKI is higher in patients with COVID-19. Early intervention to prevent AKI in patients with COVID-19 is of great significance to improve the prognosis of patients.

Scleroderma is a rare disease which requires multidisciplinary treatment. Drug-based therapy can partially alleviate or end the progression of the disease, but cannot reverse the lesions that have occurred. Scleroderma patients who seek care in plastic surgery has gradually increased in recent years. With the understanding of the regenerative role of fat and adipose stem cells, physicians have found that surgical treatment of scleroderma can improve morphology while reversing the state of the diseased tissue, acting as a local treatment or slowing progression. This paper briefly described the etiology and classification of scleroderma, analyzed the current status of scleroderma treatment and focused on the surgical treatment strategy of scleroderma, providing guidelines for the surgical management of scleroderma.