Objective To investigate the effect of p53-gene expression on renal function in rat with low birth weight ( LBW) .Methods Fifteen pregnant rats were randomly assigned into normal group, LBW group, and L-arginine ( L-Arg)-treated group.For normal group, pregnant rats were fed with 21% protein diet during pregnancy.For LBW and L-Arg treated groups, rats were fed with 10%protein diet.After de-livery, all rats were fed with 21%protein diet.For L-Arg-treated group, rats were given a supplementation with L-Arg (200 mg/kg) drinking water during 21 d lactation, other rats were given running water.At the age of 2m, the ultrastructural change in mesangial cell and podocyte was observed with electron microscope. At the age of 7 d, 21 d, 2 m, and 3 m old, the p53 mRNA expression in renal tissues was observed with re-verse transcription polymerase chain reaction ( RT-PCR) , blood and urine were collected to detect biochem-ical indicators of renal function and 24 h-urine protein.Results ⑴At the age of 3 m,the blood urea nitro-gen ( BUN) and urine cretinine ( UCr) in normal group were significantly lower than those in LBW group ( P <0.01).Compared to normal group, the Ucr of LBW group was significantly lower at the age of 2 m ( P<0.05).At the age of 3 m,the Ucr of L-Arg treated group and LBW group was significantly lower ( P <0.05), the level of 24 h-Urine protein was notably increased in LBW group and L-Arg treated group than that in normal group ( P <0.01, P <0.05) .⑵At the age of 3 m,the expression of p53 mRNA in LBW group was higher obviously than that in normal group.There is a significantly negative correlation between the expression of p53 mRNA and the level of Ucr in LBW group ( r =-0.91, P <0.05).⑶ There were mesangial cell proliferation with matrix increase, filtration membrane podocyte reduction, and partially dis-solved in LBW group, the mesangial cell proliferation of L-Arg treated group was decreased compared to that in LBW group.Conclusions The higher expression of p53 gene in LBW group might be one of reasons for the decreased renal function in LBW rats.

Objective To study the effect of renal p53 protein expression on kidney development in rats with intrauterine growth restriction ( IUGR) . Methods Pregnant rats were randomly assigned into normal group, IUGR group and L-Arg treated group. Normal group were fed with normal diet (21％protein). IUGR group and L-Arg treated group were fed with low-protein diet (10％ protein). During lactation, maternal rats in the three groups were all fed with normal diet. Maternal rats in L-Arg treated group were given additional special drinking water ( L-Arg:200 mg/kg) , while maternal rats in normal and IUGR group were given normal drinking water. Offspring weaned after 21 d and had free access to normal rodent diet and water. When the pups grew up to 2 m, the number of glomeruli was counted using acid digestion method, the proliferation and apoptosis of glomerular and tubular cells were studied using TUNEL and Ki-67 immunohistochemistry, and the ultrastructure of epithelial cells was determined by electron microscopy. At 7 d, 21 d, 2 m and 3 m, p53 protein expression in renal tissue was measured by Western blot, respectively. Results At 2 m, the number of glomerulus ( right kidney) in IUGR group was significantly lower than normal group [(23 647±541) vs. (27 689±492), P＜0. 01]; the index of renal cell apoptosis in IUGR group was higher than normal group [(21. 9 ± 2. 0) vs. (16. 7 ± 2. 5), P＜0. 05];however, IUGR group and normal group had no statistically significant difference (P＞0. 05). The proliferation of mesangial cells was found in IUGR and L-Arg treated group, but not in normal group. And the extent of proliferation in L-Arg treated group was lesser than IUGR group. A reduction of foot process and partial fusion of foot process could be observed in IUGR group and L-Arg treated group while the foot process morphology in normal group was normal. At 2 m and 3 m, p53 protein level in IUGR group and L-Arg treated group were higher than normal group [ 2 m: ( 0. 28 ± 0. 03 ) and ( 0. 21 ± 0. 01 ) vs. (0. 10±0. 02);3 m:(0. 39±0. 04) and (0. 26±0. 02) vs. (0. 17±0. 03);P＜0. 01], while IUGR group higher than L-Arg treated group ( P＜0. 05 ) . Conclusions The kidney of IUGR rats showed reduced glomerular number, increased renal cell apoptosis, enhanced p53 protein expression, increased proliferation of glomerular mesangial cells, decreased foot process, and partial fusion of foot process. And L-Arg could to some extent improve the organizational structure of the kidney in IUGR rats.

Objective To discuss the relationship between the substype of peripheral blood CD8 lymphocyte in patients with chronic hepatitis virus B and clinic condition and the replication of HBV. Methods CD45RO, CD45RA and CD28 of peripheral blood CD8 lymphocyte were detected by flow cytometry with multicolor fluorescence technology in 107 patients with chronic hepatitis virus B and 20 healthy volunteers. Results The total quantity of CD8 lymphocyte in patientswith chronic hepatitis virus B was not different from that in controls. The percent of CD3+ CD8+/CD45R0+ cells in patients with chronic active hepatitis was significantly higher than that of the control (15.7?3. 35)% vs( 8. 56?1. 12)% , P

Objective To investigate the predominant genotypes of β-lactamase in Klebsiella pneu-moniae isolates and the mechanism of antibiotic and histidine kinase inhibitor in affecting β-lactamase gene expression .Methods Tube dilution method and E-test were used to detect the susceptibility of K.pneumon-iae isolates to β-lactam antibiotics .The major genotypes of β-lactamase in β-lactam antibiotic-resistant iso-lates were identified by PCR and sequencing method .Disk diffusion test was performed to analyze the activity ofβ-lactamase .The effects of cefotaxime and histidine kinase inhibitor closantel on the expression of β-lac-tamase gene were evaluated by real-time fluorescent quantitative RT-PCR.Results All of the 118 β-lactam antibiotic-resistant K.pneumoniae isolates expressed β-lactamase, 90.7%(107/118) of which were KPC-2, TEM-1, CTX-M-14, SHV-11 and/or OXA-1 gene positive.The positive rates of TEM-1 (71.0%) and SHV-11 (64.5%) were significantly higher than that of the other three genotypes ( P<0.05).68.2%(73/107) of the isolates possessed two or more than two β-lactamase genotypes, and 30.8%(33/107) iso-lates were identified as TEM-1+SHV-11 genotype.Except for KPC-2 mRNA, the levels of TEM-1, SHV-11, CTX-M-14 and OXA-1 mRNA were significantly up-regulated by cefotaxime at MIC/4 (P<0.05), but were inhibited by 100μmol/L closantel (P<0.05).Conclusion TEM-1 and SHV-11 are the majorβ-lactamase genotypes carried by K.pneumoniae strains isolated from Zhejiang area , and TEM-1 plus SHV-11 ( TEM-1+SHV-11) is the predominant carrying mode of the β-lactamase genotypes .Sublethal dose of cefotaxime can enhance the expression of β-lactamase genes in K.pneumoniae, while the histidine kinase inhibitor , closan-tel, can block the increased expression of β-lactamase genes induced by cefotaxime .

To study the changes in skeletal muscle structure and insulin resistance of low birth weight rats.The low birth weight filial rat model was established by feeding low protein diet to the pregnant rat during gestation.At 7 d,21 d,and 2 months,blood glucose and serum insulin were measured,and the structure of skeletal muscle was observed.From 7 d to 2 months,the muscle fibers of low birth weight rat were atrophic and arranged in disorder.The ultrastructure of skeletal muscle was also abnormal distinctly at 2 months.No differences of blood glucose and rerum insulin were found between the two groups.

Objective To observe the influence of L-Arg supplementation during early postnatal life on renal function of rats with intrauterine growth retardation(IUGR).Mehod Afer establishment of IUGR model with 10% protein diet,rats were divided randomly into 2 groups: IUGR group and L-Arg treated group(LT group).Normal control group(NC group) rats were fed with 20% protein diet.The level of NO,Cr in serum were measured from 1 w to 3 months and UCr,24 h-proteinuria were measured from 3 w to 3 months.Results(1)The levels of serum NO reduced significantly in group IUGR at every stage,not significantly different between group LT and NC,but more in group LT than in group IUGR.(2)The levels of 24h-proteinuria had no significant difference among three groups at 3 w and 2 month,but was significantly higher in group IUGR than group LT and group NC.(3)The Cr levels had no significant difference at every stage among three groups.The UCr level was decreased in group IUGR than group NC at 2 month and than group NC and LT at 3 month.(4)The level of CCr in group IUGR was decreased significantly at 3 w,2 month and 3 month than group LT and group NC.Conclusion L-Arg can increase serum NO and CCr levels and decrease the level of 24h-proteinuria in rats with IUGR.It is one of the important reasons to increase 24h-proteinuria and reduce CCr level for low NO value.

Objective To explore the clinical features and causes of misdiagnosis of the patients with acquired deficiency of vitamin K-dependent coagulation factors (ADVKDCF). Methods Retrospective analysis was performed with the data from 62 patients with ADVKDCF for etiological factors, clinical manifestations,laboratory examinations, diagnosis and treatments. Results Among the 62 patients, 51 patients were with unknown causes( subgroup A) and 11 were with clear histories of anticoagulant rodenticide poisoning( subgroup B). The presentations of hemorrhage of the patients varied with hematuria as the most common first symptom,followed by skin, mucosa, muscle, internal organs bleeding (28/62). The most common hemorrhage symptom is hematuria. 35 of the 62 patients had hemoglobin(Hb) levels less than 100 g/L due to blood loss( the lowest level was 32 g/L). Thirty-eight patients were misdiagnosed at the first visit and the median time from hemorrhage manifestation to definite diagnosis was 8 days (range,2 to 192 days). ADVKDCF was mostly misdiagnosed as the urinary system diseases (23/38), followed by hemophilia (8/38). Laboratory examinations showed normal platelet count , throm bin time (TT) and normal fibrinogen(Fg) concentration, but prolonged plasma prothrombin time (PT), activated partial prothrombin time (APTT) and international normalized ration (INR). All of patients received high dose vitamin K ( intravenous vitamin K1 with a initial dose of 20 to 240 mg/d and then oral vitamin K4 maintenance) . The bleeding symptoms disappeared 1 day after treatment and the Hb levels increased dramatically. There were significant differences in PT, APTT and INR of the patients before and after treatment( P ＜0. 01 ). Followed by a median follow - up of 8 months , no patient had severe adverse effects or recurrence. Conclusion The hemorrhage presentations of the patients with ADVKDCF are various. The most common hemorrhage symptom is hematuria. The misdiagnosis rate of ADVKDCF is high with urinary systems disorders as the most common misdiagnosis. Sequential treatment with vitamin K is an effective and safe method to prevent recurrence. Early detection of coagulation function is helpful to reduce misdiagnosis possibility.

Objective To investigate the relationship between D-dimer and platelet to lymphocyte ratio(PLR)and prognosis of breast cancer(BC).Methods The clinical data of 67 BC patients hospitalized in the First Affiliated Hospital of Nanjing Medical University from September 2018 to March 2020 were retrospectively analyzed.Thirty healthy individuals during the same period were enrolled as controls.Their plasma D-dimer levels,blood platelet count,and lymphocyte count were detected and PLR was calculated.The D-dimer and PLR levels in BC patients and their correlations with clinical characteristics and prognosis were analyzed.Results The preopera-tive levels of D-dimer(1.13[0.62,2.18]mg/L)and PLR(135.2[106.6,166.5])in BC patients were significantly higher than that(D-dimer:0.35[0.16,0.59]mg/L;PLR:102.9[88.4,115.8])in healthy controls(P<0.001).The preoperative levels of D-dimer(1.39[0.78,2.33]mg/L)and PLR(152.2[118.0,169.3])in the postoperative recurrence group were significantly higher than that(D-dimer:0.35[0.16,0.59]mg/L;PLR:102.9[88.4,115.8])in the postoperative non-recurrence group(P<0.001).The areas under the receiver operating characteristics(ROC)curve(AUCROC)of D-dimer for the diagnosis and recurrence of BC were 0.891 and 0.724,respectively.The AUCROC of PLR for the diagnosis and recurrence of BC were 0.735 and 0.689,respectively.The AUCROC of the combination of D-dimer and PLR were 0.907 and 0.762,respectively.Plasma D-dimer levels were significantly positively correlated with lymph node metastasis(P=0.02)and distant metastasis(P=0.03)of BC,while PLR was significantly associated with lymph node metastasis of BC(P<0.001).The disease-free survival(DFS)rate of the combination group with high D-dimer and PLR levels was significantly lower than that with low D-dimer and PLR levels(Median survival time:24.8 months vs 30.5 months,P=0.048).Conclusion The preoperative levels of D-dimer and PLR are significantly correlated with lymph node metastasis and distant metastasis of BC,which may predict the surgical prognosis of BC.

Objective:To establish a quick and convenient method for detecting human adenoviruses (Human adenoviruses, HAdV) based on immunochromatographic assay (ICA).Methods:Two antibody clones, 3C11 and 7E6 were found to bind to all tested HAdVs and then subsequently processed into ICA. The specificity and sensitivity were evaluated using representative strains of the respiratory HAdV types, including HAdV-1, 2, 3, 4, 5, 6, 7, 10 and a gastroenteric type HAdV-41 together with the original throat swabs of 10 HAdV patients confirmed by nuclear acid testing (NAT).Results:The ICA exhibited high specificity to HAdVs and its detection limitation ranged from 0.16 to 10 3 half tissue culture infectious dose (TCID 50)/ml for different types of HAdVs. All clinic samples with successful virus isolation tested by this ICA showed positive result . Conclusions:The ICA developed in the present study will be suitable for HAdVs screening in clinic setting, especially for those of respiratory types.

The clinical application of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of hepatocellular carcinoma (HCC) patients. With the widespread applica-tion of ICIs in HCC, the management of immune-related adverse events (irAE) gained more and more attention. However, the complicated disease characteristics and various combination therapies in HCC throw out challenges to irAE management. Therefore, the editorial board of the 'Chinese expert consensus on the management of immune-related adverse events of hepatocellular carcinoma treated with immune checkpoint inhibitors (2021 edition)' organizes multidisciplinary experts to discuss and formulate this consensus. The consensus focuses on issues related to HCC irAE manage-ment, and puts forward suggestions, in order to improve standardized and safety clinical medication, so as to maximize the benefits of immunotherapy for patients.