Objective:To explore the risk factors of septic acute kidney injury (sAKI) in patients with sepsis, construct a predictive model for sAKI, verify the predictive value of the model, and develop a dynamic nomogram to help clinical doctors identify patients with high-risk sAKI earlier and more easily.Methods:A cross-sectional study was conducted. A total of 245 patients with sepsis admitted to intensive care unit (ICU) of the Affiliated Hospital of Jining Medical University from May 2013 to November 2023 were enrolled as the research subjects. The patients were divided into sAKI group and non-sAKI group based on whether they suffered from sAKI during ICU hospitalization. The differences of the demographic, clinical and laboratory indicators of patients between the two groups were compared. Logistic ordinal regression analysis was performed to analyze the imbalanced variables between the two groups, and to construct a sAKI predictive model. The predictive value of the sAKI predictive model was evaluated through 5-fold cross validation, calibration curve, and decision curve analysis (DCA), and to develop an online dynamic nomogram for the predictive model.Results:A total of 245 patients were enrolled in the final analysis. 110 (44.9%) patients developed sAKI during ICU hospitalization and 135 (55.1%) patients did not develop sAKI. Compared with the non-sAKI group, the patients in the sAKI group had higher ratios of female, hypertension, invasive mechanical ventilation (IMV), renal replacement therapy (RRT), vasopressin usage, and neutrophil count (NEU), aspartate aminotransferase (AST), blood urea nitrogen (BUN), serum creatinine (SCr), uric acid (UA), Na +, K +, procalcitonin (PCT), acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, and sequential organ failure assessment (SOFA) score. Multivariate Logistic ordinal regression analysis showed that female [odd ratio ( OR) = 2.208, 95% confidence interval (95% CI) was 1.073-4.323, P = 0.020], hypertension ( OR = 2.422, 95% CI was 1.255-5.073, P = 0.012), vasopressin usage ( OR = 2.888, 95% CI was 1.380-6.679, P = 0.002), and SCr ( OR = 1.015, 95% CI was 1.009-1.024, P < 0.001) were independent risk factors for sAKI in septic patients, and a sAKI predictive model was constructed: ln[ P/(1+ P)] = -4.665+0.792×female+0.885×hypertension+1.060×vasopressin usage+0.015×SCr. The 5-fold cross validation showed that the average area under the receiver operator characteristic curve (AUC) was 0.860, indicating the sAKI predictive model had a good performance. The calibration curve analysis showed that the calibration degree of the sAKI predictive model was good. DCA showed that the net profit of the sAKI predictive model was relatively high. A static nomogram and an online dynamic nomogram were constructed for the sAKI predictive model. Compared with the static nomogram, the dynamic nomogram allowed for manual selection of corresponding patient characteristics and viewing the corresponding sAKI risk directly. Conclusions:Female, hypertension, vasopressin usage, and SCr are the main risk factors for sAKI in patients with sepsis. The sAKI predictive model constructed based on these factors can help clinical doctors identifying high-risk patients as early as possible, and intervene in a timely manner to provide preventive effects. Compared with the common static nomogram, online dynamic nomogram can make predictive models clearer, more intuitive, and easier.

Objective To analyze the NBS-LRR disease resistance gene family of Codonopsis pilosula(Franch.)Nannf.and explore the disease resistance mechanism,so as to solve the problem of root rot disease of C.pilosula and promote the breeding and industrial development of C.pilosula.Methods Based on the transcriptome data of C.pilosula in response to root rot pathogen,gene structure,phylogeny,gene interaction and expression pattern of C.pilosula NBS-LRR family genes were analyzed by using bioinformatics methods.Results 88 NBS-LRR family genes were successfully identified.Including N,NL,CN,CNL,TN,TNL and PN,there are 50,14,1,14,4,3 and 2 genes respectively.Their physical and chemical properties,gene structure,phylogeny,gene interaction and expression pattern were analyzed.The results showed that CNL subfamily genes of C.pilosula were amplified during evolution;CNL and TNL gene structures ar-relatively conservative;Expression pattern analysis showed that there were differences in temporal expression patterns of C.pilosula NBS-LRR family genes under F.oxysporum infection.The highly expressed genes DN64786c1g6,DN64786c1g5,DN48234c0g2,DN54844c1g2,DN59747c0g3,DN56071c1g8,DN64591c1g1,DN48464c1g1,DN59886c0g1 play an important role in regulating the disease resistance of C.pilosula.The DN54844c1g2 may interact with GLR family,and then participate in immune regulation by regulating Ca2+ influx;DN64786c1g5 may interact with cytc-1 and cytc-2,and then participate in the response of C.pilosula to root rot by participating in redox reaction;DN59747c0g3 may interact with MPK3 and play an important role in the response of C.pilosula to root rot by participating in map signal cascade,phosphorylating WRKY transcription factor and participating in hypersensitivity reaction(HR).Conclusion The identification and expression analysis of NBS-LRR family genes of C.pilosula is of great significance to explore the mechanism of root rot resistance and gene function of C.pilosula..

Objective:To explore the detection of potentially pathogenic bacteria (PPB) in the nasopharynx of children with respiratory syncytial virus (RSV) bronchiolitis and the influence of PPB types on disease severity.Methods:In this retrospective cohort study, clinical data of patients hospitalized for RSV bronchiolitis at Department of Respiratory Medicine, Children′s Hospital of Soochow University between January 1, 2017 and December 31, 2019 were retrospectively analyzed.The virus, Mycoplasma pneumoniae and bacteria in nasopharyngeal secretion of children were detected.They were classified into <3 months group, 3-<6 months group, 6 months-<1 year group and 1-2 years group based on the age.In addition, they were further classified into RSV infection group, RSV+ G + group, RSV+ G - group and RSV+ G + + G - group based on detected PPB in the nasopharynx.Comparison of RSV + PPB frequency between groups was performed by Chi- squared test, clinical characteristics were compared by using Mann- Whitney U test. Results:A total of 280 patients with RSV bronchiolitis were included in the study, involving 113 cases (40.4%) with PPB in the nasopharynx.The most-common detection bacterium was Streptococcus pneumoniae.The detection rate of Streptococcus pneumoniae increased with age ( χ2=12.609, P=0.005), while that of Staphylococcus aureus decreased with age ( χ2=8.387, P=0.034). Compared with RSV group, patients in RSV+ G - group had a longer length of stay, higher rate of fever and shortness of breath, higher oxygen supplement and higher C-reactive protein (CRP) (all P<0.05). Compared with RSV group, patients in RSV+ G + group were older, and they had higher rate of fever, higher percentage of neutrophil, lower percentage of lymphocyte and higher CRP (all P<0.05). Conclusions:PPB in nasopharynx can be detected in about 40% of children hospitalized with RSV bronchiolitis, and nasopharynx complicated with PPB infection may affect the severity of RSV bronchiolitis.

Objective:To evaluate the effects of berberine on necroptosis of non-alcoholic fatty liver disease in mice and its relationship with adenosine monophosphate-activated protein kinase(AMPK)/ signal transducer and activator of transcription 6(STAT6) pathway.Methods:Twenty-five 8-week-old male C57BL/6N mice were divided into control group, steatotic liver group, berberine treatment group(200 mg·kg -1·d -1), AMPK inhibitor Compound C treatment group(0.2 mg·kg -1·d -1), and STAT6 inhibitor AS1517499 treatment group(10 mg·kg -1·d -1). After 12 weeks of intervention, the mice and liver tissue were weighed, and serum aspartate aminotransferase(AST), alanine aminotransferase(ALT), triglyceride, tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) as well as liver malondialdehyde and superoxide dismutase were measured; liver tissue HE, Masson, and oil red O staining were performed. Western blotting was used to detect the expressions of necroptosis related proteins[receptor interaction protein kinase 3(RIPK3), phosphorylated(p-) mixed lineage kinase domain-like(MLKL)], AMPK, p-AMPK, and p-STAT6. Results:Compared with control group, the steatotic liver group had higher quality of liver and liver index, and higher levels of serum AST, ALT, triglyceride, TNF-α, IL-1β, and oxidative stress( P<0.05); Liver tissue was full of cavity changes and inflammatory cell infiltration, widely distributed red lipid droplets and obvious blue fiber dyeing; The expressions of RIPK3 and p-MLKL were up-regulated ( P<0.05), but the levels of p-AMPK and p-STAT6 were relatively reduced ( P<0.05). Compared with the steatotic liver group, berberine intervention decreased liver quality and liver index, improved liver function, reduced blood lipid levels, pro-inflammatory factor expression and oxidative stress level, and significantly alleviated the degree of liver steatosis and fibrosis, the levels of RIPK3 and p-MLKL ( P<0.05), while the expressions of p-AMPK and p-STAT6 were increased significantly ( P<0.05). As compared with the berberine treatment, AMPK and STAT6 inhibitor treatment could offset the protective effect of berberine on steatotic liver, moreover, the expressions of RIPK3 and p-MLKL were increased ( P<0.05). There was no statistical difference in AMPK total protein content among the five groups ( P>0.05). Conclusion:Berberine can activate AMPK/STAT6 pathway to inhibit the necroptosis of hepatocyte, thus plays a protective role on non-alcoholic fatty liver disease in mice.

Objective:To analyze the changes of NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasomes in peripheral blood of patients with diabetic nephropathy (DN) and its clinical significance.Methods:208 patients with type 2 diabetes (T2DM) admitted to our hospital from Feb. 2018 to Dec. 2020 were selected and were divided them into 3 groups according to the urine albumin (UA) /urinary creatinine (UC) ratio (UACR) : simple T2DM group (UACR<30 mg/g) 83 cases, microalbuminuria group (UACR 30-300 mg/g) 70 cases, and massive proteinuria group (UACR>300 mg/g) 55 cases; Fifty healthy volunteers were selected as the control group. General data of each group were collected. Western blot was used to detect the level of NLRP3 in peripheral blood, and enzyme-linked immunosorbent assay (ELISA) kit was used to detect the level of serum interleukin (IL) -1β and IL-18. Logistic regression was employed to analyze the occurrence of DN in T2DM patients. Receiver operating characteristic curve (ROC) curve was used to analyze the value of NLRP3, IL-1β, IL-18 in the diagnosis of DN in peripheral blood.Results:Compared with the control group, the course of disease, FBG, LDL-C, TG, TC, SCr, BUN, HbA1c, NLRP3 protein, IL-1β and IL-18 significant increased in the other 3 groups, and HDL-C, ALB, and eGFR were significant decreased, and the difference was statistically significant ( P<0.05) . The order of their level changes was: massive proteinuria group>microalbuminuria group>pure T2DM group; Pearson test found that peripheral blood NLRP3, IL-1β, IL-18 levels were significantly positively correlated with UACR, LDL-C, TG, and TC ( P<0.001) , while they were significantly negatively correlated with HDL-C ( P<0.001) .The results of unconditional Logistic regression analysis showed that the course of disease, FBG, HDL-C, LDL-C, TG, TC, SCr, BUN, ALB, HbA1c, eGFR, NLRP3 protein, IL-1β and IL-18 may all be related to DN-related in patients with T2DM ( P<0.05) . Multivariate analysis found that high levels of BUN, ALB, HbA1c, EGFR, NLRP3 protein and IL-1 were found β and IL-18 are high risk factors for DN in patients with T2DM ( P<0.05) . The ROC curve showed that the combination of peripheral blood NLRP3, IL-1β, and IL-18 predicted the highest AUC, sensitivity, and specificity of DN in patients with T2DM as 0.918, 93.40%, and 90.13%, respectively. Conclusions:Different stages of DN are often accompanied by increased levels of NLRP3, IL-1β, and IL-18 in peripheral blood. Strengthening the monitoring of NLRP3 inflammasome levels can help assess the renal function of patients and provides a theoretical basis for early diagnosis of DN.

Objective:To enhance understanding of mental retardation autosomal dominant 35 (MRD35) by analyzing the clinical and genetic characteristics of the disease.Methods:Clinical and genetic data of 1 case of MRD35 in Beijing Children′s Hospital in July 2018 were reported, and literature review was conducted.Results:The male proband, 1 year and 3 months old, was admitted with the clinical manifestations including mental retardation, low-grade fever, a large forehead, flat nose, open mouth, and hypomyotonia. The brain magnetic resonance imaging showed enlarged lateral ventricles, cavum septum, cavum verge and cavum velum interpositum cyst. The whole exome sequencing test showed that the proband carried a missense mutation c.1258 G>A, (p.E420K) in the PPP2R5D gene, and the mutation was de novo confirmed by Sanger sequencing. There were ten literatures reported, including a total number of 31 cases. Counting on this case, totally 32 cases were included. Among the 32 patients, 32 cases (100.0%) had mental retardation, 26 cases (81.3%) with motor retardation, 26 cases (81.3%) with macrocephaly, 8 cases (25.0%) with epilepsy. Facial dysmorphic features, ocular abnormalities, skeletal abnormalities, and cardiac malformations were also reported. All reported individuals had missense mutations of PPP2R5D gene and were autosomal dominantly inherited. Conclusions:The main clinical manifestations of MRD35 include growth retardation/mental retardation, severe speech impairment, macrocephaly, hypomyotonia, seizures and dysmorphic facial features. A novel missense mutation in the PPP2R5D gene is the cause of MRD35.

Objective:To explore the clinical efficacy of lenalidomide combined with second-line immunochemotherapy as a salvage regimen in the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL).Methods:The clinical data of 37 relapsed/refractory DLBCL patients receiving lenalidomide combined with second-line immunochemotherapy as a salvage regimen who had recurrence after autologous hematopoietic stem cell transplantation or who were not eligible for transplantation or had no intention to transplant between January 2016 and December 2020 in the First Affiliated Hospital of University of Science and Technology of China were retrospectively analyzed. Among 37 patients, 6 cases with primary central nervous system (CNS) lymphoma and 3 cases with secondary CNS lymphoma. The short-term efficacy after treatment was evaluated. Kaplan-Meier method was used to analyze the overall survival (OS) and progression-free survival (PFS), and log-rank test was used for subgroup comparison.Results:The median follow-up time of 37 patients was 20.4 months (2.7-37.0 months). At the end of treatment, the overall response rate (ORR) of all patients was 64.9% (24/37), the complete response (CR) rate was 45.9% (17/37), and the median duration of response (DOR) of 24 patients who responded to treatment was 17.7 months (3.6-33.6 months). The median PFS time of all patients was 11.2 months, and the 1-year PFS rate was 48.6% (95% CI 32.5%-64.7%). The median OS time of all patients was not reached, and the 1-year OS was 67.6% (95% CI 52.5%-82.7%). Among 24 responding patients, 17 cases who received lenalidomide maintenance therapy after remission tended to have a better response compared with 7 cases who did not receive lenalidomide maintenance therapy after remission, although there was no significant difference in OS and PFS between both groups (both P > 0.05). Additionally, neutropenia was the most common adverse reaction with an incidence of 81.1% (30/37). Conclusions:Lenalidomide combined with the second-line immunochemotherapy may be an effective salvage therapy for patients with relapsed/refractory DLBCL, especially for patients with CNS involvement. The patients achieving remission after salvage therapy continue to receive lenalidomide maintenance therapy and could have a better prognosis.

Objective:To evaluate the role of silencing information regulator 1 (SIRT1)/nuclear factors E2-related factor2 (Nrf2) signaling pathway in berberine-induced reduction of renal ischemia-reperfusion (I/R) injury in mice.Methods:Thirty SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 18-22 g, were divided into 5 groups ( n=6 each) using a random number table method: sham operation group (S group), renal I/R group (RIR group), berberine+ I/R group (B group), berberine+ I/R+ SIRT1 inhibitor EX527 group (BE group) and berberine+ I/R+ Nrf2 inhibitor ATRA group (BA group). After the right kidney was removed, the left renal artery was clamped for 45 min followed by reperfusion to establish the model of renal I/R injury.In B, BE, and BA groups, berberine 100 mg·kg -1·d -1 was given for intragastric administration at 14 days before surgery.In group BE and group BA, EX527 5 mg·kg -1·d -1 and ATRA 10 mg·kg -1·d -1 were injected intraperitoneally at 3 days before surgery, respectively.The equal volume of normal saline was given for 14 consecutive days in group S and group RIR.Blood samples were collected from orbital vein at 24 h of reperfusion for measurement of serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations, for determination of the interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) contents (by enzyme-linked immunosorbent assay) and expression of SIRT1, Nrf2, apoptosis-associated speck-like protein containing CARD (ASC), caspase-1, nucleotide-binding oligomerization domain-like receptor containing pyrin domain (NLRP3) (by Western blot) and for examination of the pathological changes of renal tubules (with a light microscope). The damage to the renal tubules was scored. Results:Compared with group S, the concentrations of serum Cr and BUN, the contents of renal IL-1β and TNF-α and renal tubular injury score were significantly increased in RIR, B, BE and BA groups, the expression of SIRT1, Nrf2, ASC, caspase-1 and NLRP3 was up-regulated in RIR, BE and BA groups, and the expression of SIRT1, Nrf2, caspase-1 and NLRP3 was up-regulated in group B ( P<0.05). Compared with group RIR, the concentrations of serum Cr and BUN, the contents of renal IL-1β and TNF-α and renal tubular injury score were significantly decreased in B, BE and BA groups, the expression of SIRT1 and Nrf2 in group B, Nrf2 and ASC in BE group and SIRT1, ASC and caspase-1 in BA group was up-regulated, and the expression of ASC, caspase-1 and NLRP3 in group B, SIRT1 and NLRP3 in BE group and Nrf2 in BA group was down-regulated ( P<0.05). Compared with group B, the serum concentrations of Cr and BUN, the contents of IL-1β and TNF-α and renal tubular injury score were significantly increased in BE and BA groups, the expression of ASC, caspase-1 and NLRP3 in BE and BA groups was up-regulated, and the expression of SIRT1 in BE and Nrf2 in BA groups was down-regulated ( P<0.05). Conclusion:SIRT1/Nrf2 signaling pathway is involved in the process of berberine-induced reduction of renal I/R, which is related to inhibiting pyroptosis in mice.

Objective:To explore the change trend of patients′ recognition of the medical reform effect and medical staff′s occupation and its relationship with medical experience, since the implementation of the China Healthcare Improvement Initiative(CHII), so as to provide reference for exploring the breakthrough point of consolidating the reform effect.Methods:Four indicators of the third-party assessment of patients were selected, which were " I think the medical reform has benefited patients" , " I think the doctor-patient relationship is improving in the past three years" , " I think medical personnel deserve social respect and recognition" , and " I am willing to let my children join the medical profession" . Descriptive and trend analysis were carried out on the survey results, and correlation analysis was carried out between the survey results and patients′ medical experience.Results:Compared with the baseline evaluation results(76.9% and 69.9%for outpatients, 87.3% and 85.6%for inpatients), the patients′ recognition of the sense of medical reform and the improvement of doctor-patient relationship in the fifth evaluation(86.2% and 89.1%for outpatients, 91.4% and 92.6%for inpatients)were significantly improved. The proportion of patients who thought the medical staff was worthy of respect and willing to let their children work in the hospital in the fifth evaluation(97.4%, 79.1%for outpatients, 98.7%, 85.1%for inpatients)were higher than the baseline evaluation results(92.3%, 71.0%for outpatients, 98.1%, 81.6%for inpatients). The above indicators were positively correlated with the patient′s medical experience.Conclusions:Since the implementation of CHII, patients′ recognition of the sense of medical reform and the improvement of doctor-patient relationship has been continuously improved, and patients′ respect and recognition of professional identity of medical personnel is at a high level and continues to improve. Improving medical experience has a positive effect on the improvement of patients′ sense of medical reform.