Objective To investigate the effect of FEZ family zinc finger 1-antisense RNA 1(LncRNA FEZF1-AS1)targeting regulation of miR-200c-3p expression on biological behaviors of human lung fibroblasts(HLF).Methods Transforming growth factor β1(TGF-β1)was used to induce the transformation of HLF into myofibroblasts,which were divided into the Blank group and the model group(HLF+TGF-β1 group).According to different transfection plasmid,cells were divided into the Blank group,the TGF-β1+Si LncRNA FEZF1-AS1 NC group and the TGF-β1+Si LncRNA FEZF1-AS1 group.The protein expressions of α-SMA,Collagen Ⅰ and Vimentin were detected by Western blot assay.The expressions of LncRNA FEZF1-AS1 and miR-200c-3p were detected by quantitative real-time PCR(qRT-PCR).Cell proliferation ability was detected by CCK-8 method,migration ability was detected by cell scratch experiment and invasion ability was detected by Transwell assay.The targeting relationship between FEZF1-AS1 and miR-200c-3p was detected by dual-luciferase reporter assay.Results Compared with the Blank group,protein expressions of α-SMA,Collagen Ⅰ,Vimentin and the expression of LncRNA FEZF1-AS1 were increased in the HLF+TGF-β1 group(P＜0.05),and the expression of miR-200c-3p was decreased(P＜0.05).Compared with the TGF-β1+Si LncRNA FEZF1-AS1 NC group,cell proliferation,migration,invasion ability,LncRNA FEZF1-AS1 expression,protein expressions of α-SMA,Collagen Ⅰ and Vimentin were decreased in the TGF-β1+Si LncRNA FEZF1-AS1 group(P＜0.05),and the expression of miR-200c-3p was increased(P＜0.05).There were binding sites between miR-200c-3p and FEZF1-AS1 gene sequence.Conclusion LncRNA FEZF1-AS1 promotes the formation and progression of idiopathic pulmonary interstitial fibrosis by inhibiting miR-200c-3p.

Objective To evaluate the microbial contamination levels of 10 kinds of Chinese herbal pieces,and explore the diversity of fungi and heat-resistant bacteria.Methods The total aerobic microbial count(TAMC),total yeast and mould count(TYMC),total heat-resistant microbial count(THRC)and 3 types control bacteria were detected according to the microbial limit inspection method of Chinese Pharmacopoeia 2020.Besides,the community characteristics of contaminated fungi and heat-resistant bacteria on prepared slices were analysed based on internal transcribed spacer(ITS)and 16S ribosomal DNA(16SrDNA)high-throughput sequencing method.Results The TAMC of 28％(14/50)samples exceeded 106 cfu/g,the TYMC of 20％(10/50)samples exceeded 104 cfu/g,the THRC of 68％(34/50)samples were higher than 10 cfu/g,and the bile-tolerant gram-negitive bacteria were detected in 40％(20/50)of the samples.Escherichia coli were found in 2 batches of the Pogostemon cablin,but Salmonella was not found in any sample.High throughput sequencing results showed that the fungi contaminated distributed in 12 phylums,777 genera and 1 467 species;the heat-resistant bacteria were mainly distributed in 5 phylums,57 genera and 74 species.The decoction pieces contained Aspergillus flavus and heat-resistant pathogens such as Bacillus amyloliquefaciens,Staphylococcus lentus,and Staphylococcus warneri.Conclusion The 10 kinds of decoction pieces are generally contaminated by microorganisms,and some of them contain toxic fungi and pathogenic heat-resistant bacteria,which poses a potential risk of microbial pathogenicity for patients.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective:To examine the feasibility and safety of endoscopic subcutaneous mastectomy and immediate reconstruction via a small skin incision approach without gas and mesh for early breast carcinomas.Methods:We analyzed 7 patients diagnosed with breast cancer who underwent an endoscopic subcutaneous mastectomy and immediate reconstruction from Jun. to Nov. 2021 using a gasless and meshless small skin incision approach at the Department of Thyroid and Breast Surgery, the First Affiliated Hospital of USTC. Mean age was 44.9 (29-63) years. Clinical stage, postoperative complications and other data of patients were collected. Patients were required to fill in BREAST-Q scale anonymously before and during postoperative follow-up. The difference was considered significant for P < 0.05. Results:The tumors were all unilateral and solitary lesions, with a mean diameter of 1.74 (0-5) cm. The average distance of mass from the nipple on imaging was 2.11cm (range 0 to 4) . Postoperative pathological clinical stage,1 patient was in Tis, 3 patients were in stage I, 2 patients were in stage II and a pathological complete response was achieved in one patient (ypT0pN0cM0 CR) . The mean operative time was 245.3 (195-316) min, the mean intraoperative bleeding volume was 37.1ml, the mean postoperative hospital stay was 5.1 d, and the median follow-up time was 8.8 (6-11.2) months. All the 7 patients had incision healing at the first stage, and no complications such as infection, incision complications, capsular contracture, nipple-areola complex or skin flap necrosis, removal or displacement of breast implant occurred. No local recurrence or metastasis was detected during the follow-up period. Compared with preoperative, the scores of postoperative psychosocial status, chest wall status were lower ( P<0.05) , but still ideal, while breast satisfaction and sexual satisfaction scores were not significantly different from preoperative baseline ( P>0.05) . Conclusion:This study indicates that endoscope-assisted breast reconstruction with gasless and meshless is a safe and feasible surgical intervention method for early breast cancer, with good cosmetic effects, and can be promoted as a new type of breast reconstruction.

The COVID-19 outbreak is a global pandemic that has had caused a profound impact on social stability, economic development and national security, and has further evolved into a major public health crisis. The rapid research and development and efficient deployment of vaccines is one of the effective means to prevent and control the epidemic. This article reviews the primary features of current COVID-19 vaccines, simultaneously focus the clinical features of liver injury post-vaccination and explore its possible pathogenesis.

Objective:To evaluate the safety of two inactivated COVID-19 vaccines in a large-scale emergency use.Methods:Based on the "Vaccination Information Collection System", the incidence data of adverse reactions in the population vaccinated with the inactivated COVID-19 vaccines developed by Beijing Institute of Biological Products Co., Ltd and Wuhan Institute of Biological Products Co., Ltd, respectively, in emergency use were collected, and the relevant information were analyzed with descriptive epidemiological and statistical methods.Results:By December 1, 2020, the vaccination information of 519 543 individuals had been collected. The overall incidence rate of adverse reactions was 1.06%, the incidence rate of systemic adverse reactions was 0.69% and the incidence rate of local adverse reactions was 0.37%. The main systemic adverse reactions included fatigue, headache, fever, cough and loss of appetite with the incidence rates of 0.21%, 0.14%, 0.06%, 0.05% and 0.05%, respectively; the main local adverse reactions were injection site pain and injection site swelling with the incidence rates of 0.24% and 0.05%, respectively.Conclusion:The two inactivated COVID-19 vaccines by Beijing Institute of Biological Products Co., Ltd and Wuhan Institute of Biological Products Co., Ltd showed that in the large-scale emergency use, the incidence rate of general reactions was low and no serious adverse reactions were observed after the vaccinations, demonstrating that the vaccines have good safety.

Objective:To observe the dynamic changes of serum RANTES during the treatment with nucleos(t)ide analogues combined with pegylated interferon alpha (peginterferon-α), and further analyze the predictive effect of RANTES on HBsAg clearance in patients with chronic hepatitis B.Methods:98 cases of chronic hepatitis B with quantitative HBsAg < 3 000 IU/ml and HBV DNA < 20 IU/ml after≥1 year NAs treatment were enrolled. Among them, 26 cases continued to receive NAs monotherapy, 72 cases received NAs combined with pegylated interferon alpha therapy. The changes in RANTES during treatment were observed. The receiver operating characteristic curve was used to analyze the early changes of RANTES to predict the HBsAg clearance during 48 weeks.Results:During 48 weeks, 15 cases (20.83%) had achieved HBsAg clearance in combination group, while no patient had achieved HBsAg clearance in NAs group. The overall serum RANTES level had decreased from baseline in NAs and combination group. At week 48, in the combination group, the serum RANTES level was decreased more significantly in patients with HBsAg clearance than patients without. Further analysis showed that, in combination group, HBsAg clearance rate of patients with serum RANTES decreased at week 12 and 24 was higher than patients with elevated (29.17% vs. 4.17%, P = 0.014; 28.00% vs. 4.55%, P = 0.052), and quantitative HBsAg reduction was larger significantly [(1.49 ± 1.26) log 10IU/ml vs. (0.73 ± 0.81) log 10IU/ml, P = 0.017; (1.54 ± 1.27) log 10IU/ml vs. (0.57 ± 0.56) log 10IU/ml, P = 0.004]. Receiver operating characteristic curve analysis showed that the baseline quantitative HBsAg and the reduction in quantitative HBsAg and serum RANTES during the early period were predictors of HBsAg clearance after 48-week combination therapy. Furthermore, the combination of baseline quantitative HBsAg and 12 - or 24-week reduction of serum RANTES were better predictors of HBsAg clearance than that of baseline quantitative HBsAg combined with HBsAg decrease at week 12 or 24. The area under the receiver operating characteristic curve of the former was 0.925 and 0.939, while that of the latter was 0.909 and 0.929, respectively. Conclusion:Early reduction of serum RANTES at week 12 and 24 can predict HBsAg loss in CHB patients receiving addition of peginterferon-α to ongoing NAs Therapy, so serum RANTES could be one of the key immunological markers for predicting HBsAg clearance.

OBJECTIVE： To observe neuroprotective effects of low-molecular-weight chondroitin sulfate （CS） on dopaminergic neurons in Parkinson’s disease （PD） mice model induced by 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP）. METHODS： C57BL/6 mice were randomly divided into control group， MPTP injury group， low-molecular-weight CS low-dose and high-dose groups （100， 400 mg/kg）. Control group and MPTP injury group were given constant volume of normal saline intragstrically， administration groups were given relevant medicine intragastrically， once a day， for consecutive 17 d. Since 11th day after medication， except for control group， other groups were given MPTP solution （20 mg/kg） intraperitoneally to induce PD model， once a day， consecutive 5 d. After last medication， behavioral changes of mice （10 mice in each group） were evaluated by rotary rod fatigue tester. The damage of dopamine neurons （the percentage of TH positive cell and the percentage of fluorescence intensity） in substantia nigra of mice （3 mice in each group） was detected by immunohistochemistry and immunofluorescence. The content of dopamine in striatum was determined by HPLC （6 mice in each group）. The changes of oxidant stress indexes （SOD， GSH-Px， MDA） in substantia nigra of mice were determined by chemical colorimetry （6 mice in each group）. RESULTS： Compared with control group， retention time of mice on rotating rods was shortened significantly in MPTP injury group； TH positive cells of substantia nigra were decreased significantly， fluorescence intensity was obviously weakened； the percentage of positive cells and fluorescence intensity， the content of dopamine in striatum， the activities of SOD and GSH-Px in substantia nigra were decreased significantly， while the content of MDA was increased significantly （P＜0.01）. Compared with MPTP injury group， retention time of mice on the rotating rods was prolonged significantly in low-molecular-weight CS groups， the number of TH positive cells was increased significantly in substantia nigra and fluorescence intensity was increased significantly； the percentage of positive cells， the percentage of fluorescence intensity and the content of dopamine in striatum were increased significantly， while above indexes of high-dose group were significantly longer or higher than those of low-dose group （P＜0.05 or P＜0.01）. The activities of SOD and GSH-Px in substantia nigra were increased significantly in low-molecular-weight CS groups， while the content of MDA in substantia nigra was decreased significantly in low-molecular-weight CS high-dose group （P＜0.05 or P＜0.01）. CONCLUSIONS： Prophylactic administration of low-molecular-weight CS can relieve the damage of dopaminergic neurons in substantia nigra of PD model mice induced by MPTP in a dose-dependent manner， and increase the secretion of dopamine in striatum. The effect may be related to the inhibition of lipid peroxidation and the enhancement of antioxidant capacity of tissues.

PURPOSE: Breast cancer has become a major public health threat in the current society. Anthracycline doxorubicin (DOX) is a widely used drug in breast cancer chemotherapy. We aimed to investigate the immunogenic death of breast tumor cells caused by DOX, and detect the effects of combination of DOX and a small molecule inhibitor in tumor engrafted mouse model. METHODS: We used 4T1 breast cancer cells to examine the anthracycline DOX-mediated immunogenic death of breast tumor cells by assessing the calreticulin exposure and adenosine triphosphate and high mobility group box 1 release. Using 4T1 tumor cell-engrafted mouse model, we also detected the expression of indoleamine 2,3-dioxygenase (IDO) in tumor tissues after DOX treatment and further explored whether the specific small molecule IDO1 inhibitor NLG919 combined with DOX, can exhibit better therapeutic effects on breast cancer. RESULTS: DOX induced immunogenic cell death of murine breast cancer cells 4T1 as well as the upregulation of IDO1. We also found that treatment with NLG919 enhanced kynurenine inhibition in a dose-dependent manner. IDO1 inhibition reversed CD8+ T cell suppression mediated by IDO-expressing 4T1 murine breast cancer cells. Compared to the single agent or control, combination of DOX and NLG919 significantly inhibited the tumor growth, indicating that the 2 drugs exhibit synergistic effect. The combination therapy also increased the expression of transforming growth factor-β, while lowering the expressions of interleukin-12p70 and interferon-γ. CONCLUSION: Compared to single agent therapy, combination of NLG919 with DOX demonstrated better therapeutic effects in 4T1 murine breast tumor model. IDO inhibition by NLG919 enhanced the therapeutic efficacy of DOX in breast cancer, achieving synergistic effect.
Adenosine Triphosphate ; Animals ; Breast Neoplasms ; Breast ; Calreticulin ; Cell Death ; Doxorubicin ; Drug Therapy ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; Kynurenine ; Mice ; Public Health ; Therapeutic Uses ; Up-Regulation

Objective To compare the stereotactic hematoma drainage and conservative therapy in the treatment of a small amount of bleeding in patients with hypertensive cerebral,and analyze its effects on serum matrix metalloproteinase 9(MMP-9),tumor necrosis factor alpha (TNF-alpha) effect.Methods 60 cases of patients with hypertensive cerebral small as the research object from January 2014 to 2016 10 in our hospital were bleeding,according to treatment methods are divided into operation group and non operation group,30 cases in each group,operation group by stereotactic hematoma drainage treatment,non operative group by con-servative therapy,changes of comparative analysis of the efficacy of the two groups and serum MMP-9,TNF-alpha.Results the operation of hematoma clearance time was (3.4 ± 0.9)d,which was significantly lower than the surgery group hematoma time (12.2 ± 2.5)d(P<0.05);surgery hospitalization time was (16.7 ± 4.5)d,which was significantly lower than the surgery group hospitalization time (23.6 ± 5.1)d(P<0.05). Before treatment,there was no significant difference in NIHSS score between the two groups (P>0.05).Af-ter 2 weeks and 1 months treatment,the NIHSS score of the operation group was significantly lower than that of the non operation group (P<0.05).Before treatment,the serum MMP-9 and TNF-alpha levels were not significantly different between the two groups (P>0.05).1 month after treatment,the serum levels of MMP-9 and TNF-in the operation group were significantly lower than those in the non operation group (P<0.05). The complication rate of the operation group was 13.3%,which was lower than that of the non operation group,and the complication rate was 26.7% (P<0.05).Conclusion stereotactic hematoma drainage is supe-rior to conservative therapy in the treatment of hypertensive intracerebral hemorrhage.It can shorten the time of hospitalization,reduce complications,and reduce the levels of serum MMP-9 and TNF-alpha.