Objective To observe the changes in serum a proliferation inducing ligand(a proliferation inducing ligand,APRIL)and N-myc downstream regulated gene 1(N-myc downstream regulated gene 1,NDRG1)levels,and analyze their diagnostic value for ovarian endometrioma(OEM).Methods From July 2021 to July 2022,132 patients with OEM who visited Zigong First People's Hospital were regarded as the observation group,and regular follow-up was conducted.According to the prognosis of these patients,they were grouped into the recurrence group(n=50)and the non recurrence group(n=82).Meanwhile,78 healthy individuals who had their medical checkups at the hospital during the same period were the control group.Enzyme linked immunosorbent assay(ELISA)was applied to detect serum APRIL and NDRG1 levels,and the general data of the recurrent and non recurrent groups were compared.Logistic regression analysis was applied to analyze the relevant factors affecting the prognosis of OEM.Pearson analysis was applied to explore the correlation between serum APRIL and NDRG1 levels in patients with OEM.Receiver operating characteristic(ROC)curve was applied to evaluate the diagnostic value of serum APRIL,NDRG1 levels and their combination for OEM.Results Compared with the control group,APRIL level(35.28±6.81ng/ml vs 26.37±3.19ng/ml)and NDRG1 level(124.39±15.67μg/L vs 9.67±10.82μg/L)in observation group were increased,and the differences were significant(t=10.864,17.278,all P<0.05).Compared with the non recurrence group,the serum levels of APRIL(40.38±7.88ng/ml vs 32.16±6.18ng/ml)and NDRG1(132.04±19.83μg/L vs 119.73±13.16μg/L)in the recurrence group were increased,and the differences were significant(t=6.668,4.287,all P<0.05).Logistic regression analysis showed that serum APRIL and NDRG1 levels were risk factors for the prognosis of patients with OEM(Waldχ2=11.839,28.437,all P＜0.001).Pearson method analysis results showed a positive correlation between serum APRIL level and NDRG1 level in patients with OEM(r=0.439,P<0.001).The area under the curve(AUC)of combined diagnosis of serum APRIL and NDRG1 levels in patients with OEM was 0.849,with a sensitivity and specificity of 73.95%and 85.37%,respectively,which was better than the single prediction of APRIL and NDRG1(Z =2.644,2.094,P=0.008,0.036).Conclusion The serum levels of APRIL and NDRG1 were increased in patients with OEM.The combination of the two has high clinical value in the diagnosis of OEM,which may be closely related to the prognosis of patients with OEM.

Objective:To understand the relationship between the RNA shedding time of SARS-CoV-2 infected persons and the single nucleotide mutation of the virus, the population of infected persons, underlying diseases and other factors, so as to provide more clues for the study of SARS-CoV-2 infection dynamics.Methods:The data of epidemiology, clinical manifestations, and underlying diseases of infected persons in a cluster epidemic of COVID-19 in Jiangsu province from July to September 2021 were collected. Nasopharyngeal swab samples of cases were collected, and the whole genome of the virus was sequenced by second-generation sequencing technology. The online analysis platform was used to judge the virus type and analyze the mutation site, and Cox proportional risk model was used to analyze the relationship between the RNA shedding time of SARS-CoV-2 and various research factors.Results:There were 350 persons who finally obtained the whole genome sequence of the virus in this COVID-19 outbreak, of which 60.3% were female, the median age was 49 years old (interquartile range, IQR: 37-65 years old)), and the median time of virus shedding was 33 days ( IQR, 26-44 days). The whole-genome sequencing analysis showed that compared with the Wuhan reference strain sequence, the infected persons’ sequence had 34~41 nucleotide mutation sites, belonging to VOC/Delta variant (B.1.617.2 evolutionary branch), and C346T, C1060T, T2803C, T7513C, A29681C were the main single nucleotide polymorphisms (SNPs) of this epidemic. Cox regression analysis showed that age, underlying disease, clinical classification, vaccination, SNP T2803C and T7513C had an impact on the RNA shedding time of SARS-CoV-2. The adjusted multivariate Cox regression result showed that age [ HR=0.73, 95% CI (0.55, 0.95)] and T7513C [ HR=0.37, 95% CI (0.18, 0.77)] were still the risk factors for the extension of SARS-CoV-2 RNA shedding time. Conclusions:This study analyzed the effects of the individual factors and viral single nucleotide variations on the time of viral RNA shedding. Those who were older, suffered from hypertension, had more severe clinical symptoms, were not vaccinated or incompletely vaccinated, and had T7513C mutation in the infected virus, had a risk of a long RNA shedding time of SARS-CoV-2, which should be given special attention and follow-up after rehabilitation.

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
Animals ; Coronavirus Papain-Like Proteases/antagonists & inhibitors* ; Cricetinae ; Humans ; Mice ; Pandemics ; SARS-CoV-2/enzymology* ; COVID-19 Drug Treatment

Objective To explore the efficacy and safety of two antibody induction therapies during donor after cardiac death (DCD) kidney transplantation .Methods Retrospective analysis was performed for the clinical data of DCD kidney patients in 2016 .Patients using basiliximab monoclonal or thymoglobulin (ATG ) polyclonal antibody were divided into two groups . Early postoperative biopsy proven ,acute rejection rate ,creatinine level and patient/graft survival rate were compared between two groups at 1 ,3 or 6 month post-operation .Results Basiliximab (n=44) and ATG (n=60) was used as induction .No significant inter-group difference existed in donor age ,primary disease , creatinine pre-donation , recipient age or cause of renal failure . And recipient male ratio and body weight were greater in ATG group than those in basiliximab group [87％ vs .55％ ;(70 ± 13) vs .(64 ± 12) kg] .Outcomes of basiliximab group showed acute rejection rate was 9％ ,average creatinine 112 .4 at 1 month ,127 .0 at 3 months and 107 .8 at 6 months and total infection rate 16％ .Graft/patient 6-month survival rates were 95％ (42/44)and 98％ (43/44) .Outcomes of ATG group showed that acute rejection rate was 3％ ,average creatinine 135 .6 at 1 month ,119 .0 at 3 months and 118 .0 at 6 months and total infection rate 22％ .Graft/patient 6-month survival rates were both 100％ (60/60) .Conclusions During DCD kidney transplantation ,both induction therapies may prevent acute rejection immediately post-operation .No difference exists in acute rejection rate ,infection rate ,graft/recipient 6-month survival rate or graft function . These two inductions have an excellent early prognosis .

Objective To investigate the clinical effect of donor kidneys in rhabdomyolysis(RM) combined with acute kidney injury(AKI).Methods A retrospective analysis was made on the clinical data of 10 donors with RM and 14 cases of renal transplantation from March 2017 to May 2018.Results AKI was caused by RM in 10 donors.Before harvesting the donor kidneys,blood creatine kinase (CK) level was (14 005.19 ± 11 894.27) U/L in 10 donors,plasma myoglobin level was ＞3 000 μg/L in 7 cases,and that was (2 288 ± 680) μg/L in 3 cases.LDH level was 883 ± 453 IU/L and serum creatinine (Cr) value was (216.55 ± 125) μmol/L.6 donors received continuous renal replacement therapy.Six patients with delayed renal function recovery (DGF) were treated with CRRT.The duration of GDF was 3-20 days,with an average of 10 ± 6.6 days.All the patients were followed up for 3-15 months.The glomerular filtration rate was (40.19 ± 19.55) ml·min· 1.73 m-2 and (55.01 ± 15.94) ml · min· 1.73 m-2 at 1st and 3rd month after operation,respectively.Conclusion The incidence of DGF in donor kidneys with RM and AKI is high,and the short-term effect is satisfactory.The long-term effect needs to be further observed.

Although still in its infant stage, synthetic biology has achieved remarkable development and progress during the past decade. Synthetic biology applies engineering principles to design and construct gene circuits uploaded into living cells or organisms to perform novel or improved functions, and it has been widely used in many fields. In this review, we describe the recent advances of mammalian synthetic biology for the treatment of diseases. We introduce common tools and design principles of synthetic gene circuits, and then we demonstrate open-loop gene circuits induced by different trigger molecules used in disease diagnosis and close-loop gene circuits used for biomedical applications. Finally, we discuss the perspectives and potential challenges of synthetic biology for clinical applications.

Objective:To study the curative efficacy of metformin combined with Jinlida granules in the treatment of gestational diabetes mellitus and its effects on the serum vascular endothelial growth factor (VEGF),adiponectin (APN) and homocysteine(Hcy) levels.Methods:94 patients of gestational diabetes mellitus who were treated from July 2014 to July 2016 in our hospital were selected.According to random number table,those patients were divided into the observation group (n=47) and the control group (n=47).On the basis of routine treatment,such as control diet,reasonable exercise and healthy diet,etc,the control group was treated with metformin,while the observation group was combined with Jinlida granules on the basis of the control group.The changes of blood glucose,blood lipid and serum VEGF,APN and Hcy before and after treatment were compared between the two groups,the incidence of maternal complications and neonatal adverse outcomes were compared.Results:Compared with before treatment,the blood glucose,blood lipid of both groups after treatment were significantly improved (P ＜0.05),the fasting plasma glucose (FBG),postprandial 2h blood glucose (2hPG),glycosylated hemoglobin (HbAlc),total cholesterol (TC),triacylglycerol (TG),low density lipoprotein cholesterol(LDL-C) of observation group were significantly lower than those of the control group,the serum high density lipoprotein cholesterol (HDL-C) level was significantly higher than that of the control group(P＜0.05);after treatment,the serum VEGF,APN and Hcy levels were significantly improved than those before treatment in both groups (P＜0.05),and the serum VEGF,and Hcy levels of observation group were lower than those of the control group,the serum APN level was higher than that of the control group (P ＜ 0.05);the incidence of gestational hypertension,hydramnios,cesarean section and premature delivery of observation group was significantly lower than that of the control group (P ＜0.05);the incidence of giant child,neonatal Jaundice and neonatal respiratory distress in the observation group was significantly lower than that of the control group (P＜0.05).Conclusion:Metformin combined with Jinlida granules was effective for the gestational diabetes mellitus,which could effectively control the blood glucose,blood lipid levels and might be related to the regulation of serum VEGF,APN and Hey levels.

Objective 17β-estradiol is known to have a neuroprotective effect.The aim of this study was to investigate the effects of 17β-estradiol on propofol-induced neuroapoptosis in primarily cultured cortical neurons. Methods Rat cortical neurons were primarily cultured for 7 days and randomly divided into groups A ( vehicle control) , B, and C, treated with equal volume of 20%intralipid, 500 μmol/L propofol, and 500 μmol/L propofol +0.1 μmol/L 17β-estradiol, respectively.At 12 hours after treatment, the morphology of the neurons was observed under the microscope, their survival rate calculated by MTT, their apoptosis was deter-mined by FCM assay, and their mitochondrial membrane potential measured by fluorescent dye rhodamine 123. Results Compared with group A, group B showed a significantly reduced number of neurons, lack of 3-dimensional appearance, unclear contour, and fractured neuron axons, but a remarkable improvement was observed in the propofol-induced morphological damage in group C.The survival rate of the neurons and the mitochondrial membrane potential were markedly decreased in group B ([52.3 ±5.2]% and [59.1 ± 5.3]%) as compared with groups A ( [99.9 ±3.6]%and [99.6 ± 5.8]%) and C ([90.1 ±7.2]%and [89.2 ±7.1]%) (both P<0.01 ) , while the rate of neuroapoptosis significantly increased in group B ([43.4 ±4.6]%) in comparison with A ([3.1 ±0.2]%) and C ([22.3 ±3.2]%) (both P<0.01). Conclusion 17β-es-tradiol can protect against propofol-induced apoptosis of primarily cul-tured neurons by inhibiting the reduction of their mitochondrial membrane potential.

Objective To prepare dual?modality single?photon emission computed tomography (SPECT)?MRI molecular nanoprobes targeting HAb18G/CD147 expressed on breast cancer cell membranes and investigate the physicochemical and biological properties in vitro. Methods Superparamagnetic iron oxide nanoparticles (SPIOs) were prepared by one?pot reaction method as described. The single?chain antibody fragments HAb18F(ab')2 were conjugated to SPIOs via chemical method and then labeled with 125I using Iodogen method. The final 125I?SPIO?HAbF18(ab')2 nanoprobes were purified. SPIOs or 125I?HAb18F(ab')2 were used as control. We carried preliminary evaluation on their physicochemical properties and biological characteristics in vitro: transmission electron microscope (TEM) and dynamic light scattering (DLS) were used to measure these nanoparticle sizes and the hydrodynamic diameters. The MRI T2 transverse relaxation efficiency of these nanoprobes at different Fe2+concentrations were measured with 1.5 T clinical MR scanner. The 125I?SPIO?HAb18F(ab')2 and 125I?HAb18F(ab')2 radiochemical purity were measured by thin layer chromatography and the radio chemical yield was calculated. We also conducted stability tests in vitro and octanol/water partition coefficient experiments. Two breast tumor cell lines, MDA?MB?231 (HAb18G?overexpressing cells,experimental group) and MDA?MB?468 (control), were used for assessment of cells viability at different Fe2 + concentrations (1, 5, 10, 20, 40 μg/ml) by methyl thiazolyl tetrazolium assay. Specific binding experiments in vitro included two parts:magnetic resonance imaging and radionuclide tests, the above?mentioned breast cancer cell lines were incubated with 125I?SPIO?HAb18F(ab')2 nanoprobes respectively and took MDA?MB?231 cells which were not treated as blank group. First comparing the MR signal intensity differences among experimental group, the control group and blank group, then calculated the rate of MRI signal changes;Two breast tumor cell lines, MDA?MB?231 and MDA?MB?468 were incubated with 125I?SPIO?HAb18F(ab')2 nanoprobes too, then measured radioactivity counting byγcounter at different time and calculated the cell binding rates, and did statistical analysis by using one?way ANOVA. Results The SPIOs were fairly homogeneous with an average core size of (10.32±1.30) nm;the SPIO and 125I?SPIO?HAb18F(ab')2 hydrodynamic diameter of 44.80 and 52.64 nm, and MRI scanning showed that the transverse relaxation efficiency of SPIO and 125I?SPIO?HAb18F(ab')2 were 38.79 and 106.73 mM-1 · s-1, respectively. The radio chemical yield of 125I?SPIO?HAbF18(ab')2 and 125I?HAb18F(ab')2 were 41.90% and 85.50%, respectively. The radio chemical yield of the two groups were >95%, suggesting well stability in vitro. The lipo?hydro partition coefficient values were -0.99 ± 0.03 and-1.49 ± 0.08, respectively, which demonstrated that they were both water?soluble substances. Different Fe2+concentrations (1,5,10,20,40μg/ml) of 125I?SPIO?HAb18F(ab')2 on breast cancer cell lines MDA?MB?231 and MDA?MB?468 showed no significant inhibition of cell proliferation (F values were 0.78, 0.66; P values were 0.58, 0.66). The cell?specific binding experiment showed: MRI signal intensity values on experimental group, the control group and the blank group were (1 670 ± 5), (1 930 ± 8), (2 349 ± 14), respectively, significant differences existed among these groups (F=4 408.48,P=0.000), the rate of signal intensity change of experimental group and the control group were 28.87%,17.78%. SPECT:MDA?MB?231 could uptake 125I?SPIO?HAb18F(ab')2, the cell binding rates were (6.52 ± 0.60)% and (10.52 ± 2.04)% in 20 min and 4 h, respectively.Conclusions Our results suggested that the dual?modality SPECT?MRI nanoprobes 125I?SPIO?HAb18F(ab')2 were prepared successfully with good physicochemical properties and biological characteristics in vitro. These dual?modality molecular imaging nano?probes may have potential to improvearly detection and diagnosis of HAb18G/CD147?expressing cancers and to facilitate the development of HAb18G/CD147?directed interventions.

Objective To investigate the mechanisms of the protective effects of dexmedetomidine against the propofol-induced neuroapoptosis in primary cultured cortical neurons.Methods The neurons were cultured 7days and then divided into four groups: vehicle-control group (treated with equal volume of intralipid), propofoltreated group (treated with 500 μmol/L propofol), propofol plus dexmedetomidine treated group (treated with 500 μmol/L propofol and 0.1 μmol/L dexmedetomidine), and LY294002 pretreated group (treated with 500 μmol/L propofol ,0.1 μ mol/L dexmedetomidine and 10 μmol/L LY294002).12 hours after different treatments, neuron viability was measured by MTT assay,neuroapoptosis was detected by Hoechst33258 staining, and the levels of pAkt and Bcl-2 protein were detected by Western blot.Results Compared with the vehicle-reduced group,propofol reduced neuron viability greatly((53.4±4.2)％ vs (99.9±6.3)％;P＜0.01), but increased neuroapoptosis greatly((44.6±4.3)％ vs (5.8±0.4)％;P＜0.01).The levels of pAkt((0.41±0.03) vs (0.86±0.07))and Bcl-2 ((0.15±0.02) vs (0.72±0.03)) were decreased greatly (both P＜0.01).Compared with propofol treatment group, the neuron viability of propofol plus dexmedetomidine group were increased greatly((86.4±5.3) ％ , P＜0.01) ,the neu roapoptosis was decreased greatly ((23.1 ± 3.5) ％, P＜ 0.01), and the levels of pA kt (0.8 ± 0.03) and Bc1-2 (0.52 ±0.05) were increased greatly (both P＜0.01).Compared with propofol plus dexmedetomidine treated group,LY294002 inhibited the protective effects of dexmedetomidine, decreased neuron viability greatly ((64.3±5.1) ％ ,P＜0.01), increased the number of apoptotic neurons((38.8±4.9) ％, P＜0.01), and reduced the levels of pAkt (0.52±0.04) and Bcl-2(0.31±0.02) significantly (P＜0.01).Conclusion Dexmedetomidine exerts the neuroprotective effects against propofol-induced neuroapoptosis by activating the PI3K-Akt-Bcl-2 signalling pathway.