Objective:To investigate the interventional effects of the Fuzheng Huayu (FZHY) formula and its partial mechanistic role on cholestatic liver fibrosis in mice.Methods:Mdr2 gene knockout (Mdr2－/ －) mice were randomly divided into a model group, FZHY group, and Obeticholic acid group. Wild-type C57BL/6J mice of the same age served as the control group. Mdr2－/ －mice were given the corresponding drugs starting from the first day of 9 weeks of age by oral gavage in each group. The control and model groups were administered 0.3% sodium carboxymethylcellulose by oral gavage and were sacrificed at 12 weeks of age for specimen collection. High-speed biochemistry analyzer was used to detect serum alkaline phosphatase and alanine aminotransferase activity in mice. Hematoxylin-eosin staining and Sirius red staining were used to observe pathological changes in liver tissues. Hydroxyproline content was measured to assess collagen in liver tissues. Immunohistochemical staining, Western blotting, and real-time fluorescence quantitative PCR were used to detect the expression of fibrosis markers Col-I and alpha-smooth muscle actin in liver tissues. The expressional condition of cholangiocyte response markers Epcam, CK7, CK19, as well as Pcna, Mki67, and Ccnd1, inflammatory related factors Ccl2, Ccl5, Tnf-α, Il10, and Cxcl4, phosphorylated peroxisome proliferator-activated receptor alpha (PPARα) and nuclear factor kappa-B (NF-κB) were determined. Comparative analysis among multiple groups was performed using one-way ANOVA. The LSD method was used for comparisons between groups. Two-tailed statistical tests were used.Results:Compared with wild-type mice, Mdr2 －/ － mice had a significant increase in serum alanine aminotransferase and alkaline phosphatase activity ( P<0.001). The percentage of Sirius red-positive staining areas and hydroxyproline content in liver tissues was significantly increased ( P<0.01). The expression of Col-I, α-smooth muscle actin, Epcam, CK7, CK19, Pcna, Mki67, and Ccnd1, and the expression of Ccl2, Ccl5, Tnf-α, Il10, and Cxcl4 were significantly increased ( P<0.01); however, both FZHY and Obeticholic acid significantly reversed the increases in these indicators ( P<0.05; P<0.01). Further results showed that compared to wild-type mice, the expression of PPARα was significantly reduced in liver tissues of Mdr2 －/ － mice, while NF-κB was significantly enhanced ( P<0.01). In contrast, compared to Mdr2-/- mice, the expression of PPARα in the liver tissues of FZHY group mice was significantly increased ( P<0.05), while NF-κB was significantly inhibited ( P<0.05). Conclusion:FZHY can significantly improve liver fibrosis, cholangiocyte response, and inflammation in Mdr2 －/ － mice with spontaneously occurring cholestatic liver fibrosis, and its mechanistic role is related to the regulation of the PPARα/NF-κB pathway.

Objective:To investigate the interventional effects of the Fuzheng Huayu (FZHY) formula and its partial mechanistic role on cholestatic liver fibrosis in mice.Methods:Mdr2 gene knockout (Mdr2－/ －) mice were randomly divided into a model group, FZHY group, and Obeticholic acid group. Wild-type C57BL/6J mice of the same age served as the control group. Mdr2－/ －mice were given the corresponding drugs starting from the first day of 9 weeks of age by oral gavage in each group. The control and model groups were administered 0.3% sodium carboxymethylcellulose by oral gavage and were sacrificed at 12 weeks of age for specimen collection. High-speed biochemistry analyzer was used to detect serum alkaline phosphatase and alanine aminotransferase activity in mice. Hematoxylin-eosin staining and Sirius red staining were used to observe pathological changes in liver tissues. Hydroxyproline content was measured to assess collagen in liver tissues. Immunohistochemical staining, Western blotting, and real-time fluorescence quantitative PCR were used to detect the expression of fibrosis markers Col-I and alpha-smooth muscle actin in liver tissues. The expressional condition of cholangiocyte response markers Epcam, CK7, CK19, as well as Pcna, Mki67, and Ccnd1, inflammatory related factors Ccl2, Ccl5, Tnf-α, Il10, and Cxcl4, phosphorylated peroxisome proliferator-activated receptor alpha (PPARα) and nuclear factor kappa-B (NF-κB) were determined. Comparative analysis among multiple groups was performed using one-way ANOVA. The LSD method was used for comparisons between groups. Two-tailed statistical tests were used.Results:Compared with wild-type mice, Mdr2 －/ － mice had a significant increase in serum alanine aminotransferase and alkaline phosphatase activity ( P<0.001). The percentage of Sirius red-positive staining areas and hydroxyproline content in liver tissues was significantly increased ( P<0.01). The expression of Col-I, α-smooth muscle actin, Epcam, CK7, CK19, Pcna, Mki67, and Ccnd1, and the expression of Ccl2, Ccl5, Tnf-α, Il10, and Cxcl4 were significantly increased ( P<0.01); however, both FZHY and Obeticholic acid significantly reversed the increases in these indicators ( P<0.05; P<0.01). Further results showed that compared to wild-type mice, the expression of PPARα was significantly reduced in liver tissues of Mdr2 －/ － mice, while NF-κB was significantly enhanced ( P<0.01). In contrast, compared to Mdr2-/- mice, the expression of PPARα in the liver tissues of FZHY group mice was significantly increased ( P<0.05), while NF-κB was significantly inhibited ( P<0.05). Conclusion:FZHY can significantly improve liver fibrosis, cholangiocyte response, and inflammation in Mdr2 －/ － mice with spontaneously occurring cholestatic liver fibrosis, and its mechanistic role is related to the regulation of the PPARα/NF-κB pathway.

The performance appraisal of public hospitals is the most official and authoritative assessment and evaluation of tertiary public hospitals in China,and it is an important measure to guide hospitals to improve their internal management level and achieve high-quality development.In this study,a data monitoring management system based on the performance appraisal indicators of national tertiary public hospitals was developed and constructed through intelligent collection and reporting,report in-tegration,visual analysis,data drilling,etc.,which realized the one-stop dynamic management of indicators,optimized the data filling process of national examination indicators,improved the data quality and credibility,and promoted the integration of na-tional assessment and hospital assessment.the intelligent management level of the hospital has been improved,which provides strong support for the hospital's refined operation management and scientific decision-making.

Objective To establish a simultaneous detection approach for 34 emerging contaminants(ECs)in tap water by liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).Human health risk assessment was performed according to the detection results from 43 tap water samples.Methods Tap water samples were concentrated and extracted by solid phase extraction,and then blown to near dry by nitrogen at 40℃.The sample extracts were dissolved in methanol-water solution(95:5,VN)to 0.5 mL for analyzing.Agilent Jet Stream Electrospray Ionization(AJS ESI)and the multiple reaction monitoring(MRM)mode were performed for MS to acquire the data of 34 ECs.A database including precursor ion,product ion and retention times was established accordingly.Results The average linear correlation coefficients(r)of 34 kinds of ECs was 0.995 9.The limits of detection were 0.01～0.60 ng/L and the recoveries were between 60.7％and 119.8％.The intra-group precisions were between 0.05％～9.89％and the intra-day precisions were between 0.20％～14.40％for the spiked samples.The method was applied to analyze 43 tap water samples and a total of 15 ECs were detected.According to the results,the detection rate of caffeine was the highest(84％),and the concentration range was ND～74.42 ng/L.Among all the ECs detected,1,2,3-benzotriazole had the highest concentration(ND～361.15 ng/L),where detection rate was 44％.Humans may be exposed to these ECs by drinking the tap water.The human health risk assessments of 12 kinds of ECs were carried out,however,the estimated risk was negligible(risk quotient＜0.01).Conclusion The method is simple,highly sensitive and selective,and could meet the detection needs of ECs at trace level in tap water.There was no human health risk posed for ECs identified in 43 tap water samples analyzed by this method.

Objective:To explore the clinical outcome and applicability of the comb flap technique and stepwise design concept in plastic aesthetic and reconstructive surgery.Methods:The clinical data of patients who underwent plastic aesthetic and reconstructive surgery with the comb flap technique in Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2018 to December 2022 were retrospectively analyzed. The application of the comb flap technique follows the concept of stepwise design, that was, preoperative and intraoperative design and adjustment were carried out step by step and in sequence, and the design was combined with the surgical procedure. Its main operations included: an incision was designed along the edge of the target area, the tissue flap was widely separated at the base of the target area. The tissue flap was cut in sequence perpendicular to the cutting edge and temporarily sutured and fixed, the edge was cut and fixed. During the operation, the tension of the incision and the local appearance could be adjusted. The incisal edge was finely sutured, and the temporary suture was finally removed. The healing of surgical incision and complications were observed after the operation, and the facial recovery and surgical effect were followed up.Results:Six patients were enrolled, including 3 males and 3 females, aged from 2 to 58 years. One patient underwent upper eyelid tightening and lower eyelid blepharoplasty through subeyebrow incision. One patient underwent middle and lower face rhytidectomy. One patient underwent thick lip thinning and right facial liposuction. One patient underwent facial congenital melanocytic nevi resection. One patient underwent eyebrow congenital melanocytic nevus resection. One patient underwent facial flap repair. All patients had primary healing of incision, and no surgery-related complications occurred. All patients were followed up for 3 to 18 months, and all patients were satisfied with the surgical effect.Conclusion:The application of comb flap technique and stepwise design concept in plastic aesthetic and reconstructive surgery can delicately adjust the alignment of the incision margin, make the tension evenly distributed, and reduce the risk of scar formation and deformity after the operation. It has a wide range of clinical applications and good applicability.

Objective:To explore the clinical outcome and applicability of the comb flap technique and stepwise design concept in plastic aesthetic and reconstructive surgery.Methods:The clinical data of patients who underwent plastic aesthetic and reconstructive surgery with the comb flap technique in Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2018 to December 2022 were retrospectively analyzed. The application of the comb flap technique follows the concept of stepwise design, that was, preoperative and intraoperative design and adjustment were carried out step by step and in sequence, and the design was combined with the surgical procedure. Its main operations included: an incision was designed along the edge of the target area, the tissue flap was widely separated at the base of the target area. The tissue flap was cut in sequence perpendicular to the cutting edge and temporarily sutured and fixed, the edge was cut and fixed. During the operation, the tension of the incision and the local appearance could be adjusted. The incisal edge was finely sutured, and the temporary suture was finally removed. The healing of surgical incision and complications were observed after the operation, and the facial recovery and surgical effect were followed up.Results:Six patients were enrolled, including 3 males and 3 females, aged from 2 to 58 years. One patient underwent upper eyelid tightening and lower eyelid blepharoplasty through subeyebrow incision. One patient underwent middle and lower face rhytidectomy. One patient underwent thick lip thinning and right facial liposuction. One patient underwent facial congenital melanocytic nevi resection. One patient underwent eyebrow congenital melanocytic nevus resection. One patient underwent facial flap repair. All patients had primary healing of incision, and no surgery-related complications occurred. All patients were followed up for 3 to 18 months, and all patients were satisfied with the surgical effect.Conclusion:The application of comb flap technique and stepwise design concept in plastic aesthetic and reconstructive surgery can delicately adjust the alignment of the incision margin, make the tension evenly distributed, and reduce the risk of scar formation and deformity after the operation. It has a wide range of clinical applications and good applicability.

Objective Based on ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-QTOF-MS/MS),a nontarget screening strategy was adopted in analyzing and identifying emerging pollutants(EPs)in tap water across the country,and studying its spatial and temporal distribution characteristics.Methods After extracting tap water samples by solid phase extraction,mobile phases(0.1%aqueous formic acid and methanol solutions)was used to elute the sample on a C18 chromatographic column.The nontarget screening strategy was used to acquire the MS information in full scan mode.We extracted and analyzed the chromatographic and mass spectral peaks,then searched the spectral library to compare the exact mass numbers,and the secondary MS/MS spectra fragment ion information was compared one by one.Finally,the retention time and the mass spectrum data of candidate EPs were identified and analyzed with the data of standard samples.then quantified by the internal standard method.Results A total of 135 EPs were initially screened from tap water across the country and 24 with high chromatographic peak response were finally selected and verified by standard products,including 6 pharmaceuticals,13 pesticides,3 industrial compounds and 2 food additives.Nine of them showed detection rates of more than 60%,such as canrenone,medroxyprogesterone,hydrocortisone acetate,etc.The concentrations of detected pollutants range from ND 422.63 ng/L.And the four contaminants with higher average concentrations were canrenone,medroxyprogesterone,hydrocortisone acetate and tris(2-butoxyethyl)phosphate.Conclusion In this study,a nontarget strategy based on UPLC-QTOF-MS/MS was adopted to screen potential unknown pollutants with no-standards,and explored the overall contamination status of tap water samples.This contributed to more comprehensive understanding of the EPs distribution,and provided technical support for monitoring the EPs in tap water.

Objective Based on ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-QTOF-MS/MS),a nontarget screening strategy was adopted in analyzing and identifying emerging pollutants(EPs)in tap water across the country,and studying its spatial and temporal distribution characteristics.Methods After extracting tap water samples by solid phase extraction,mobile phases(0.1%aqueous formic acid and methanol solutions)was used to elute the sample on a C18 chromatographic column.The nontarget screening strategy was used to acquire the MS information in full scan mode.We extracted and analyzed the chromatographic and mass spectral peaks,then searched the spectral library to compare the exact mass numbers,and the secondary MS/MS spectra fragment ion information was compared one by one.Finally,the retention time and the mass spectrum data of candidate EPs were identified and analyzed with the data of standard samples.then quantified by the internal standard method.Results A total of 135 EPs were initially screened from tap water across the country and 24 with high chromatographic peak response were finally selected and verified by standard products,including 6 pharmaceuticals,13 pesticides,3 industrial compounds and 2 food additives.Nine of them showed detection rates of more than 60%,such as canrenone,medroxyprogesterone,hydrocortisone acetate,etc.The concentrations of detected pollutants range from ND 422.63 ng/L.And the four contaminants with higher average concentrations were canrenone,medroxyprogesterone,hydrocortisone acetate and tris(2-butoxyethyl)phosphate.Conclusion In this study,a nontarget strategy based on UPLC-QTOF-MS/MS was adopted to screen potential unknown pollutants with no-standards,and explored the overall contamination status of tap water samples.This contributed to more comprehensive understanding of the EPs distribution,and provided technical support for monitoring the EPs in tap water.

Objective To evaluate the association between short-term exposure to air pollutants of end-stage renal disease(ESRD)patients on maintenance hemodialysis and the number of daily hospital admissions.Methods The data on hospitalizations were obtained from the database of the municipal Urban Employees'Basic Medical Insurance and Urban Residents'Basic Medical Insurance of a city in Southwest China.Single and multiple pollutant generalized additive models were utilized to estimate the effect of air pollutants(CO,NO2,O3,PM10,PM25,and SO2)on patient admissions after the lag time of different numbers of days.In addition,subgroup analyses stratified by sex,age,PM25 and PM10 concentration thresholds,seasonality,and comorbidity status for cardiovascular diseases and hypertension were conducted.Results In the single pollutant models,the pollutants significantly associated with patient admissions and the corresponding lag time of the strongest association were as follows,every time CO increased by 0.1 mg/m3,there was a 2.39％increase(95％confidence interval[CI]:0.96％-3.83％)in patient admissions after 7 days of lag time;every time NO2,O3,PM2.5,PM10,and SO2 increased by 10 μg/m3,patient admissions increased by 4.02％(95％CI:1.21％-6.91％)after 7 days of lag time,3.57％(95％CI:0.78％-6.44％)after 0-4 days of lag time,2.00％(95％CI:1.07％-2.93％)after 6 days of lag time,1.19％(95％CI:0.51％-1.88％)after 7 days of lag time,and 8.37％(95％CI:3.08％-13.93％)after 7 days of lag time,respectively.In the multiple pollutant model,every time O3 and PM2.5 increased by 10 μg/m3,there was an increase of 3.18％(95％CI:0.34％-6.09％)in daily patient admissions after 0-4 days of lag time and an increase of 1.85％(95％CI:0.44％-3.28％)after 7 days of lag time.Furthermore,subgroup analyses showed that seasonality,the severity of air pollution,and patients'comorbidities might be the effect modifiers for the association between ambient air pollution and hospital admissions in ESRD patients receiving maintenance hemodialysis.Conclusion Air pollution is closely associated with hospital admissions in ESRD patients undergoing maintenance hemodialysis and the strength of this association varies according to seasonality,the severity of air pollution,and patients'status of comorbidities.

The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury-repair process following lung injury. Pulmonary fibrosis (PF) is a fibrotic lung disorder characterized by cell senescence in lung alveolar epithelial cells. In this study, we report that P21 expression was increased in alveolar epithelial type 2 cells (AEC2s) in a time-dependent manner following multiple bleomycin-induced PF. Repeated injury of AEC2s resulted in telomere shortening and triggered P21-dependent cell senescence. AEC2s with elevated expression of P21 lost their self-renewal and differentiation abilities. In particular, elevated P21 not only induced cell cycle arrest in AEC2s but also bound to P300 and β-catenin and inhibited AEC2 differentiation by disturbing the P300-β-catenin interaction. Meanwhile, senescent AEC2s triggered myofibroblast activation by releasing profibrotic cytokines. Knockdown of P21 restored AEC2-mediated lung alveolar regeneration in mice with chronic PF. The results of our study reveal a mechanism of P21-mediated lung regeneration failure during PF development, which suggests a potential strategy for the treatment of fibrotic lung diseases.