Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Gene therapy, harnessing the power of CRISPR-Cas9 and/or DNAzyme systems, stands as a pivotal approach in cancer therapy, enabling the meticulous manipulation of genes pivotal to tumorigenesis and immunity. However, the pursuit of precise gene therapy encounters formidable hurdles. Herein, a near-infrared upconversion theranostic nanomachine is devised and tailors for CRISPR-Cas9/DNAzyme systems mediate precise gene therapy. An ingenious logic DNAzyme system consists of Chain 1 (C1)/Chain 2 (C2) and endogenous lncRNA is designed. We employ manganese modified upconversion nanoparticles for carrying ultraviolet-responsive C1-PC linker-C2 (C₂P) chain and Cas9 ribonucleoprotein (RNP), with outermost coats with hyaluronic acid. Upon reaching tumor microenvironment (TME), the released Mn²⁺ ions orchestrate a trifecta: facilitating endosomal escape, activating cGAS-STING signaling, and enabling T1-magnetic resonance imaging. Under near-infrared irradiation, Cas9 RNP/C₂P complex dissociates, releasing Cas9 RNP into the nucleus to perform gene editing of Ptpn2, while C1/C2 chains self-assemble with endogenous lncRNA to form a functional DNAzyme system, targeting PD-L1 mRNA for gene silencing. This strategy remodels the TME by activating cGAS-STING signaling and dual immune checkpoints blockade, thus realizing tumor elimination. Our theranostic nanomachine armed with the CRISPR-Cas9/DNAzyme logic systems, represents a resourceful and promising strategy for advancing cancer systemic immunotherapy and precise gene therapy.

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized by chronic hyperglycemia, hyperlipidemia, and peripheral insulin resistance. Endoplasmic reticulum stress (ERS), a response to cellular stress, is activated across various tissues during the progression of T2DM, leading to disruptions in protein synthesis. Notably, epithelial and endocrine cells with hormone-secreting functions are particularly vulnerable to functional impairments induced by ERS. The gut-pancreas axis is essential for regulating metabolism and the progression of T2DM. Intestinal epithelial L cells, integral to the intestinal barrier, can secrete the glucagon-like peptide-1 (GLP-1). This hormone promotes insulin secretion from pancreatic β-cells and plays a critical role in glucose metabolism. Importantly, ERS plays a critical role in regulating glucolipid-induced dysfunction of gut-pancreas axis. For instance, ERS is involved in regulating the intestinal barrier and the secretion of GLP-1 as well as insulin. Therefore, ERS can be a potential target for T2DM treatment. In this paper, we review the regulatory roles of ERS in the gut-pancreas axis during the development of T2DM, and summarize the therapeutic drugs and strategies targeting ERS for T2DM treatment.

Objective:To investigate the application value of metagenomic next-genera-tion sequencing (mNGS) in pathogenic diagnosis of suspected infected severe acute pancreatitis (SAP).Methods:The prospective study was conducted. The clinical data of 25 patients with suspected infected SAP who were admitted to the Xiangya Hospital of Central South University from May to September 2023 were collected. Upper limb venous blood samples of all the patients were collected for both of mNGS and routine pathogen microbial culture. Observation indicators: (1) grouping situations of the enrolled patients; (2) comparison of the diagnostic efficiency of mNGS and routine pathogen microbial culture; (3) results of peripheral blood pathogen microbial testing and peri-pancreatic effusion microbial culture; (4) testing time and cost. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3). Count data were expressed as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Results:(1) Grouping situations of the enrolled patients. A total of 25 patients were selected for eligibility. There were 18 males and 7 females, aged 48(40,59)years. The duration of hospital stay of 25 patients was 30(20,50)days. The etiologies of 25 patients included 14 cases of hyperlipidemic pancreatitis, 8 cases of biliary pancreatitis, 1 case of alcohol-induced acute pancreatitis, and 2 cases of pancreatitis caused by other causes. Of the 25 patients, there were 17 cases with infected pancreatic necrosis (IPN) including 7 cases of death, and 8 cases with sterile pancreatic necrosis including no death. (2) Comparison of the diagnostic efficiency of mNGS and routine pathogen microbial culture. The positive rates of mNGS and routine pathogen microbial culture in diagnosis of suspected infected SAP were 72.0%(18/25) and 32.0%(8/25), respectively, showing a significant difference between them ( χ2=8.01, P<0.05). The sensitivity and negative predic-tive value of mNGS and routine pathogen microbial culture in diagnosis of IPN were 94.1%(16/17), 35.3%(6/17) and 85.7%(6/7), 35.3%(6/17), showing significant differences between them ( χ2=12.88, 5.04, P<0.05). The specificity and positive predictive value of mNGS and routine pathogen microbial culture in diagnosis of IPN were 75.0%(6/8), 75.0%(6/8) and 88.9%(16/18), 75.0%(6/8), showing no significant difference between them ( χ2=0, 0.82, P>0.05). (3) Results of peripheral blood pathogen microbial testing and peripancreatic effusion microbial culture. Of the 17 patients with IPN, 36 strains of pathogenic bacteria were detected by mNGS, and 6 strains were detected by routine pathogen microbial culture. There were 16 of 17 patients with IPN showing positive mNGS pathogenic testing, of which 13 cases were consistent with the pathogenic testing results of peri-pancreatic effusion microbial culture, showing a consistency rate of 76.5%(13/17). There were 6 pati-ents with IPN showing positive routine pathogen microbial culture, with a consistency rate of 35.3%(6/17) to peripancreatic effusion microbial culture. (4) Testing time and cost. Testing time of mNGS and routine pathogen microbial culture were (43±17)hours and (111±36)hours, showing a signifi-cant difference between them ( t=9.31, P<0.05). Testing cost of mNGS was (2 267±0)yuan/case, accoun-ting for 1.7% of the hospitalization expenses of (133 759±120 744)yuan/case. Testing cost of routine pathogen microbial culture was (240±0)yuan/case, accounting of 0.2% of the hospitalization expenses. Conclusion:mNGS has important value for early pathogenic diagnosis of suspected infected SAP, and has a high timeliness.

Objective To study the clinical characteristics of children with anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV).Methods A retrospective analysis was conducted on the clinical data of 25 children diagnosed with AAV at the Second Xiangya Hospital of Central South University from January 2010 to June 2022.Results Among the AAV children,there were 5 males and 20 females,with a median age of onset of 11.0 years.Involvement of the urinary system was seen in 18 cases(72%);respiratory system involvement in 10 cases(40%);skin involvement in 6 cases(24%);eye,ear,and nose involvement in 5 cases(20%);joint involvement in 4 cases(16%);digestive system involvement in 2 cases(8%).Eleven cases underwent kidney biopsy,with 5 cases(46%)showing focal type,2 cases(18%)showing crescentic type,2 cases(18%)showing mixed type,and 2 cases(18%)showing sclerotic type.Immune complex deposits were present in 5 cases(45%).Seven cases reached chronic kidney disease(CKD)stage Ⅴ,with 2 cases resulting in death.Two cases underwent kidney transplantation.At the end of the follow-up period,2 cases were at CKD stage Ⅱ,and 1 case was at CKD stage Ⅲ.Of the 16 cases of microscopic polyangiitis(MPA)group,13(81%)involved the urinary system.Of the 9 cases of granulomatosis with polyangiitis(GPA),6 cases(66%)had sinusitis.Serum creatinine and uric acid levels were higher in the MPA group than in the GPA group(P<0.05),while red blood cell count and glomerular filtration rate were lower in the MPA group(P<0.05).Conclusions AAV is more common in school-age female children,with MPA being the most common clinical subtype.The onset of AAV in children is mainly characterized by renal involvement,followed by respiratory system involvement.The renal pathology often presents as focal type with possible immune complex deposits.Children with MPA often have renal involvement,while those with GPA commonly have sinusitis.The prognosis of children with AAV is poor,often accompanied by renal insufficiency.

Objective To study the correlation of anti-C1q antibodies with active systemic lupus erythematosus(SLE)and lupus nephritis(LN)in children,as well as their diagnostic value for active SLE and LN.Methods A retrospective selection of 90 hospitalized children with SLE at the Children's Medical Center of Second Xiangya Hospital,Central South University from January 2016 to March 2019 as the SLE group,all of whom were tested for anti-C1q antibodies.A control group was formed by collecting 70 hospitalized children with other autoimmune diseases(OAD)during the same period.The differences in anti-C1q antibody levels were compared between two groups.The correlation of anti-C1q antibodies with various indicators of SLE and LN was analyzed,and the diagnostic value of anti-C1q in SLE and LN was evaluated.Results The serum levels of anti-C1q antibodies in the SLE group were higher than those in the OAD group(P<0.05).The SLE disease activity index score was positively correlated with anti-C1q antibodies(rs=0.371,P<0.001)and positively correlated with anti-double-stranded DNA antibodies(rs=0.370,P<0.001).The sensitivity and specificity of anti-C1q antibodies for diagnosing active SLE were 89.90%and 53.90%,respectively,with an area under the curve of 0.720(P<0.05)and a critical value of 5.45 U/mL.The sensitivity and specificity of anti-C1q antibody levels for diagnosing active LN were 58.50%and 85.00%,respectively,with an area under the curve of 0.675(P<0.05)and a critical value of 22.05 U/mL.Conclusions Anti-C1q antibodies can serve as non-invasive biomarkers for evaluating the activity of SLE or predicting the activity of LN in children.

Objective To observe the safety and effectiveness of single dose intravenous infusion of tranexamic acid(TX-A)in dual level posterior lumbar interbody fusion(PLIF),and to explore the changes and trends in perioperative white blood cell(WBC),erythrocyte sedimentation rate(ESR),and C-reactive protein(CRP).Methods Between October 2020 and September 2022,46 patients with lumbar degenerative disease were treated with dual level PLIF,including 18 males and 28 females,with an average age of(60.24±10.68)years old,from 34 to 80 years old.They were divided into observation group and control group according to different treatment methods.There were 28 patients in the observation group,including 12 males and 16 females,with an average age of(61.04±9.03)years old.There were 3 cases with lumbar disc herniation(LDH),lumbar spinal stenosis(LSS)18 cases,lumbar spondylolisthesis(LS)7 cases.TXA(1 g/100 ml)was administered intravenously 15 min before skin incision after general anesthesia.The control group consisted of 18 patients,including 6 males and 12 females,with an average age of(59.00±13.04)years old.There were 5 cases with LDH,LSS 9 cases,LS 4 cases,and TXA was not used.The operation time,intraoperative bleeding volume,postoperative drainage volume,postoperative deep vein thrombosis(DVT),postoperative hospital stay,postoperative activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen(FIB),platelet(PLT),red blood cell(RBC),hemoglobin(HB),hematocrit(HCT),the first day,the fourth day,the seventh day and the last tested after operation WBC,ESR and CRP were recorded.Results The postop-erative wounds of the patients healed well and there was no DVT.46 patients were followed up from 3 to 6 months.The intraop-erative blood loss was 400.0(300.0,500.0)ml and the postoperative drainage was 260.0(220.0,450.0)ml in the observation group,which were lower than the control group[600.0(400.0,1000.0)ml,395.0(300.0,450.0)ml],P＜0.05.There was no significant difference between the two groups in operation time,postoperative hospital stay,postoperative APTT,PT,TT,FIB,PLT,RBC,HB,HCT,and postoperative WBC,ESR and CRP at different times(P＞0.05).Conclusion Single dose intravenous infusion of TXA can reduce the blood loss of bi-segmental PLIF,and has no significant effect on WBC,ESR and CRP after op-eration.

Background and Aims:Accurate early pathogen diagnosis is a breakthrough for improving the prognosis of infectious pancreatic necrosis(IPN)patients.However,there is currently a lack of efficient methods for early identification of IPN in clinical settings.This study was performed to assess the application value of next-generation sequencing technology based on metagenomic capture(MetaCAP)in the pathogen diagnosis of IPN. Methods:A prospective study was conducted on 29 patients suspected of having acute necrotizing pancreatitis at Xiangya Hospital of Central South University between January and July 2024.Blood samples were tested using MetaCAP and conventional pathogen culture.The results of peritoneal fluid pathogen culture were used as the gold standard to compare the diagnostic efficacy of the two methods. Results:Due to three cases lacking peritoneal fluid culture results,a total of 26 cases were included in the final analysis.The overall mortality rate was 23.1％(6/26).During hospitalization,9 cases(34.6％)were diagnosed with IPN.The sensitivity and negative predictive value of MetaCAP for diagnosing IPN were significantly higher than those of conventional pathogen culture(77.8％vs.11.1％,P=0.031;86.7％vs.65.2％,P=0.032),while the differences in specificity(76.5％vs.88.2％,P=0.689)and positive predictive value(63.6％vs.33.3％,P=0.347)between the two methods were not statistically significant.The average detection time for MetaCAP was 33(20-49)h,while microbial culture took 125(45-142)h,with a significant difference(P＜0.001).The average cost for blood MetaCAP testing was 2 500 yuan per case,but it accounted for only 1.19％of the average hospitalization cost. Conclusion:MetaCAP has significant value in the early pathogen diagnosis of IPN,with a shorter detection time,good testing efficacy,and health-economic value,demonstrating a promising clinical application prospect.

Objective:To explore the clinicopathological and genetic characteristics of sporadic medullary thyroid carcinoma (MTC) and new therapeutic targets for sporadic MTC.Methods:Based on family and personal disease history, we identified 32 sporadic MTC who underwent surgical resection from Jan 2010 to Dec 2022. Clinicopathological and immunohistochemical features were analyzed in all patients, while 6 of them were subject to the whole exome sequencing (WES).Results:Compared with those of low-grade sporadic MTC, patients with high-grade tumors were more likely to have lymph node metastasis at presentation ( χ2=4.428, P=0.040); less likely to be cured by biochemical treatment ( χ2=4.072, P=0.044). Pathological grading scheme, biochemical cure, and TNM stage were independent risk factors of disease free survival. WES was performed on 6 pairs of normal tissues. We screened RET and RAS as driver mutations, and the mutation ratio was 3/6 respectively. Patients with RET or RAS mutations had no recurrence. In addition, we detected PDGFRA somatic mutation, with a mutation ratio of 1/6. Conclusions:For sporadic MTC cases, the pathological grading system has important prognostic value, and RET and RAS somatic mutations are the main driver mutations. PDGFRA are potential therapeutic targets for sporadic MTC.

Objective:To survey the perceived social support status and influencing factors of medical staffs working in community health service institutions in Shanghai Minhang District .Methods:The study was a cross-sectional study. From September 2022 to January 2023, a survey on the status of perceived social support was conducted among 181 medical staffs working in community health service institutions in Shanghai Minhang District. The self-designed general information questionnaire, perceived social support scale, general self-efficacy scale, quality of professional life scale, and trait coping style scale were used in the survey. The effects of demographic characteristics, general self-efficacy, empathy fatigue and trait coping style on perceived social support status of community medical workers were analyzed.Results:A total of 181 questionnairs were distributed and 178 valid ones returned with a valid recovery rate of 98.3%. In three dimensions of perceived social support, family support scored (17.11±8.87), friend support scored (17.08±8.41), other support scored (19.89±4.09), and the total score of understanding social support was (60.99±11.71). There were 2 cases of low support status (1.12%), 81 cases of intermediate support status (45.51%), and 95 cases of high support status (53.37%). Univariate analysis showed that there were significant differences in perceived social support among participants with different ages, marriage status, majors, professional titles, job satisfaction, positive or negative coping styles, general self-efficacy, and empathy fatigue ( P<0.05). Multivariate logistic regression analysis showed that people aged 40 and above had a higher degree of perceived social support than those under 40 ( OR=2.792, 95% CI: 1.051-7.418, P<0.05); compared with public health professionals, clinical medicine, nursing and other medical technique professionals had a higher degree of perceived social support ( OR=4.024, 95% CI: 1.479-10.953; OR=2.941, 95% CI: 1.031-8.393; OR=3.996, 95% CI: 0.543-29.409, all P<0.05); compared with those who were less satisfied with their self-assessment work, participants who were more satisfied or generally satisfied with their self-assessment work had lower perceived social support ( OR=0.200, 95% CI: 0.051-0.781; OR=0.320, 95% CI: 0.146-0.701, all P<0.05); compared with those with mild and moderate empathy fatigue, participants with high empathy fatigue had lower perceived social support ( OR=0.406, 95% CI: 0.182-0.909, P<0.05). Except supporting primary and secondary traumatic stress, the total score of perceived social support and its dimensions were positively correlated with empathy satisfaction; and negatively correlated with job burnout and secondary traumatic stress. Regression analysis shows that empathy satisfaction had a positive predictive effect on overall scores of perceived social support and its dimensions of friend support and other support capacity. Conclusions:The social support status of community healthcare workers in Shanghai Minhang district is generally acceptable. However, it is important to pay special attention to the social support status of those who are under 40 years old, have a background in public health, are satisfied with their work, and experience a high level of empathy fatigue. Measures should be implemented to specifically enhance empathy satisfaction among healthcare workers; timely guidance and intervention should be provided accordingly.