Acute kidney injury (AKI) is one of the common critical illnesses characterized by a higher incidence, poor prognosis and limited effective therapeutics in clinical practice. Early diagnosis, etiologic differentiation and prognostic evaluation are crucial for improving outcomes and key components of integrated AKI management. However, the lack of ideal markers and intervention targets poses significant challenges in these aspects. Klotho, a protein predominantly synthesizes and secretes by renal tubular epithelial cells, has been shown to exert various protective effects on the kidney. Recent evidence suggests that abnormal Klotho levels are implicated in the pathogenesis and development of AKI, and hold promise for application in early diagnosis, etiologic recognition, and prognostic evaluation of AKI. Additionally, administration of exogenous Klotho protein or upregulation of endogenous Klotho expression has demonstrated preventive and therapeutic efficacy against AKI caused by a variety of etiologies. This paper reviewed the alterations in Klotho levels during AKI and evaluated its potential role in enhancing the integrated diagnosis and treatment of AKI.

Acute kidney injury (AKI) is one of the common critical illnesses characterized by a higher incidence, poor prognosis and limited effective therapeutics in clinical practice. Early diagnosis, etiologic differentiation and prognostic evaluation are crucial for improving outcomes and key components of integrated AKI management. However, the lack of ideal markers and intervention targets poses significant challenges in these aspects. Klotho, a protein predominantly synthesizes and secretes by renal tubular epithelial cells, has been shown to exert various protective effects on the kidney. Recent evidence suggests that abnormal Klotho levels are implicated in the pathogenesis and development of AKI, and hold promise for application in early diagnosis, etiologic recognition, and prognostic evaluation of AKI. Additionally, administration of exogenous Klotho protein or upregulation of endogenous Klotho expression has demonstrated preventive and therapeutic efficacy against AKI caused by a variety of etiologies. This paper reviewed the alterations in Klotho levels during AKI and evaluated its potential role in enhancing the integrated diagnosis and treatment of AKI.

Objective To explore the effect of respiratory care bundle combined with management by objectives(MBO)on postoperative pulmonary function,pulmonary complications and postoperative quality of recovery of respiratory risky patients undergone gastrointestinal surgeries.Methods A total of 80 patients with respiratory risk underwent elective surgery in a ward of gastrointestinal surgery from April to November 2021 were selected.Based on the order of the surgery,48 patients with surgeries between April to July were selected into control group and received routine respiratory care,while 32 patients with surgeries between August to November were selected into trial group and received the respiratory care bundle combined with MBO.The pulmonary function,postoperative pulmonary complications and postoperative quality of recovery were analyzed and compared on the 7th postoperative day.Results There was no significant difference between two groups in preoperative general data,preoperative lung function,preoperative quality of recovery(QoR-15)and other baseline data,as well as the surgery data.On the 7th postoperative day,the decrease of pulmonary function indexes,FVC(t=3.173,P=0.002)and FEV1(t=2.883,P=0.005)in the trial group was less than that in the control group,and the degree of percutaneous oxygen saturation in the trial group was higher than that in the control group(Z=-2.454,P=0.014).There was no significant difference in the incidence of postoperative pulmonary complications.As with the QoR-15,the score of trial group was higher than that in the control group in 3 items including"moderate pain"(Z=-2.738,P=0.006),"feeling nervous or anxious"(Z=-2.593,P=0.010)and"feeling sad and depressed"(Z=-2.945,P=0.003).There was no significant difference in other items between the two groups.Conclusion The respiratory care bundle combined with MBO is beneficial to the recovery of postoperative pulmonary function and postoperative quality of recovery of gastrointestinal surgical patients with respiratory risk.

Objective To explore the effect of respiratory care bundle combined with management by objectives(MBO)on postoperative pulmonary function,pulmonary complications and postoperative quality of recovery of respiratory risky patients undergone gastrointestinal surgeries.Methods A total of 80 patients with respiratory risk underwent elective surgery in a ward of gastrointestinal surgery from April to November 2021 were selected.Based on the order of the surgery,48 patients with surgeries between April to July were selected into control group and received routine respiratory care,while 32 patients with surgeries between August to November were selected into trial group and received the respiratory care bundle combined with MBO.The pulmonary function,postoperative pulmonary complications and postoperative quality of recovery were analyzed and compared on the 7th postoperative day.Results There was no significant difference between two groups in preoperative general data,preoperative lung function,preoperative quality of recovery(QoR-15)and other baseline data,as well as the surgery data.On the 7th postoperative day,the decrease of pulmonary function indexes,FVC(t=3.173,P=0.002)and FEV1(t=2.883,P=0.005)in the trial group was less than that in the control group,and the degree of percutaneous oxygen saturation in the trial group was higher than that in the control group(Z=-2.454,P=0.014).There was no significant difference in the incidence of postoperative pulmonary complications.As with the QoR-15,the score of trial group was higher than that in the control group in 3 items including"moderate pain"(Z=-2.738,P=0.006),"feeling nervous or anxious"(Z=-2.593,P=0.010)and"feeling sad and depressed"(Z=-2.945,P=0.003).There was no significant difference in other items between the two groups.Conclusion The respiratory care bundle combined with MBO is beneficial to the recovery of postoperative pulmonary function and postoperative quality of recovery of gastrointestinal surgical patients with respiratory risk.

Objective:To explore the risk factors of bortezomib-related peripheral neuropathy (BIPN) and the clinical and electrophysiological characteristics of patients in treatment of multiple myeloma (MM).Methods:The clinical data of 71 newly diagnosed MM patients treated with BD (bortezomib + dexamethasone) regimen in Yancheng First People's Hospital from March 2016 to December 2019 were retrospectively analyzed. The bone marrow morphology, immunology, cytogenetics, molecular biology (MICM), routine electrophysiological examination before and after treatment were performed. All patients were divided into the peripheral neuropathy (PN) group and the non-PN group according to the presence or not of BIPN, and the clinicopathological differences of both groups were also compared; a binary logistic regression model was used to analyze the factors affecting the occurrence of PN. The electrophysiological characteristics were summarized and fluorescence in situ hybridization (FISH) was used to detect karyotype of BIPN patients.Results:Among 71 MM patients, there were 40 cases (56.3%) of PN and 31 cases (43.7%) of non-PN. The proportion of patients at international staging system (ISS) staging Ⅲ, and the levels of IgA, IgG, IgM, serum creatinine, β 2-microglobulin (β 2-MG) in the PN group were higher than those in the non-PN group, and hemoglobin (Hb) level in the PN group was lower than that in the non-PN group, and the differences were statistically significant (both P < 0.05). Binary logistic regression analysis showed that increased IgA ( OR = 1.151, 95% CI 1.012-1.309, P = 0.033), increased IgG ( OR = 1.055, 95% CI 1.000~1.112, P = 0.049), increased IgM ( OR = 1.010, 95% CI 1.001-1.018, P = 0.022), increased serum creatinine ( OR = 1.037, 95% CI 1.011~1.065, P = 0.005), increased β 2-MG ( OR = 1.564, 95% CI 1.039-2.354, P = 0.032) were risk factors for BIPN. Among 40 patients with BIPN, 33 cases (82.5%) of sensory nerve conduction velocity (SCV) were abnormal, 23 cases (57.5%) of motor nerve conduction velocity (MCV) were abnormal; 31 cases (77.5%) showed demyelination damage, 9 cases (22.5%) had axonal damage. Among 40 patients with BIPN, 24 cases underwent FISH detection, including 19 cases (79.2%) with chromosomal mutations, of which 12 cases (50.0%) were mixed subtype abnormal. Conclusions:MM patients with high levels of β 2-MG, IgA, IgG, IgM and serum creatinine are more prone to PN when treated with bortezomib. The electrophysiology of patients with BIPN is mainly characterized by demyelination of sensory nerves.

Objective:To investigate the familial inheritances, clinical features, treatments and outcomes of familial Waldenstrom macroglobulinemia (WM) patients.Methods:The clinical manifestations, laboratory examinations, diagnosis and treatments, and follow-up data of 6 familial WM patients who were admitted to Yancheng No.1 People's Hospital from June 2002 to July 2019 were retrospectively analyzed, and the literature was reviewed.Results:Among 6 WM patients, 4 patients had dizziness and fatigue at the onset, 1 patient had recurrent low-grade fever and abnormal sweating as the first manifestations, 1 patient was hospitalized due to pulmonary infection, and WM was found later. Two brothers of the patients were diagnosed with WM, another 2 brothers of the patients had IgM-type monoclonal gammopathy of undetermined significance (MGUS) during the physical examination. All the 6 patients were middle-aged/elderly men, with a median age of 63 years old (51-70 years old). The median follow-up time were 71.5 months (4-217 months), and by the end of the follow-up (June 2020), 2 cases died of pulmonary infection, and 1 of them developed acute myeloid leukemia; the other 4 cases were in regular chemotherapy. Two IgM-MGUS patients were followed up without symptoms.Conclusions:WM patients have familial aggregation, and their clinical manifestations are highly heterogeneous. Patients with family history may have poor prognosis. It is necessary to strengthen the awareness of WM and family history screening.

Objective:To investigate the expression of Toll-like receptor 8 (TLR8) in diffuse large B-cell lymphoma (DLBCL) and its correlation with clinicopathological characteristics and prognosis of patients.Methods:The data in the Oncomine database was used to analyze the difference of TLR8 mRNA expression between DLBCL tumor tissues and normal lymphocytes, and the result was verified in two independent subsets GSE 25638 and GSE 32018 of the NCBI-GEO database. The OSDLBCL online survival analysis tool was used to analyze the correlation of TLR8 mRNA relative expression level with overall survival (OS) and progression-free survival (PFS) of DLBCL patients. Gene ontology bioprocess (GO_BP) enrichment analysis was performed by using GSEA software. The correlation of TLR8 mRNA expression with tumor immune cell infiltration degree and immune checkpoint-related molecule expression was analyzed by TIMER online tool website. A total of 53 DLBCL patients who underwent lymph node biopsy in Yancheng No. 1 People's Hospital from June 2020 to June 2021 were selected. Immunohistochemistry was used to detect the expression of TLR8 protein, and its relationship with the clinicopathological characteristics of patients was analyzed.Results:The analysis result of data from Oncomine and GEO databases showed that the relative expression levels of TLR8 mRNA in tumor tissues of patients with DLBCL or activated B cell-like DLCBL were higher than those in normal lymphocytes (all P < 0.001). The results of OSDLBCL online survival analysis indicated that the OS ( P = 0.020) and PFS ( P = 0.004) in DLBCL patients with high TLR8 mRNA expression were worse than those in patients with low TLR8 mRNA expression. The level of TLR8 was related to the abnormal function of immune response, cytokine metabolism and DNA damage monitoring; the result of TIMER online analysis showed that the expression level of TLR8 mRNA was positively related to the degree of neutrophil infiltration ( r = 0.78, P < 0.001) and the expression of immunosuppressive molecules [HAVCR2 ( r = 0.85, P < 0.001), LAG3 ( r = 0.63, P < 0.001), CD274 ( r = 0.77, P < 0.001), TIGIT ( r = 0.32, P = 0.037), and C10ORF54 ( r = 0.34, P = 0.029)]. Among 53 DLBCL patients, 29 patients (54.7%) had low expression of TLR8 protein and 24 patients (45.3%) had high expression of TLR8 protein. There were statistical differences in the expressions of TLR8 protein in DLBCL patients with different serum lactate dehydrogenase and β 2-microglobulin levels (both P < 0.05). Conclusions:TLR8 is highly expressed in DLBCL patients, and TLR8 may be a prognostic marker of DLBCL.

Objective:To investigate the clinicopathological features, diagnosis, differential diagnosis and treatment of nodal marginal zone lymphoma (NMZL) with elevated monoclonal IgM.Methods:The clinical data of one NMZL patient with elevated monoclonal IgM treated at Yancheng No.1 People's Hospital in July 2020 were retrospectively analyzed, and the related literature was analyzed.Results:The patient was a 57-year-old female and the main clinical manifestations were fatigue and bone pain in left rib. Serum immunofixation electrophoresis showed IgM-κ type M proteinemia, bone marrow cytology showed a few plasmacytoid lymphocytes, bone marrow biopsy and immunohistochemistry showed B-cell non-Hodgkin lymphoma, bone marrow genetic testing showed MYD88 L265p and CXCR4 were both negative, postoperative pathology result of retroperitoneal lymph node biopsy was marginal zone lymphoma (mature small B type, prone to NMZL),and immunohistochemistry results: CD3, CD5, CD138, κ, λ, CD10, Cyclin D1 were negative, CD20, Pax-5, CD23 (FDC), bcl-2 were positive; Ki-67 positive index < 5%. The final diagnosis was NMZL with elevated monoclonal IgM. Partial remission was achieved after 8 cycles of reduced-dose CHOP regimen; thalidomide was used in the maintenance treatment, the disease condition was stable until August in 2021 and the follow-up was continuing.Conclusions:NMZL with elevated monoclonal IgM is relatively rare. Its diagnosis should be differentiated from Waldenstr?m macroglobulinemia and other inert B-cell lymphomas. Currently, there is no standard treatment and following the principle of individualized treatment can improve the prognosis of patients.

Objective To evaluate the therapeutic effect of antibiotics combined with recombinant tuberculosis vaccine AEC/BC02 on Mycobacterium tuberculosis infection in guinea pigs. Methods Two weeks after guinea pigs were challenged subcutaneously with a high dose of Mycobacterium tuberculosis,the guinea pigs with the positive skin test responses to the recombinant ESAT6-CFP10 allergen were randomly di-vided into four groups:normal saline (NS),AEC/BC02,antibiotics and antibiotics+AEC/BC02. In antibiotics+AEC/BC02 group,guinea pigs firstly received isoniazid ( INH) and rifapentine ( RFT) treatment once a week for a total of three times,and then were immunized with a single dose of AEC/BC02 vaccine six times at 10-day intervals. Guinea pigs in AEC/BC02 and antibiotics groups were respectively vaccinated with AEC/BC02 vaccine and given INH and RFT treatment at the same dose and frequency as given to antibiotics+ AEC/BC02 group. Thirteen weeks after challenge,all guinea pigs were sacrificed for necropsy. Results The gross pathological scores of NS,AEC/BC02,antibiotics and antibiotics+AEC/BC02 groups were 83±8,77± 22,45±28 and 19±14,respectively. Antibiotics+AEC/BC02 group had a significantly lower gross pathological score than antibiotics,AEC/BC02 and NS groups (P<0. 05,P<0. 01,P<0. 01,respectively). Moreover,the gross pathological scores of antibiotics and AEC/BC02 groups were significantly decreased as compared with that of NS group (both P<0. 01). However,there was no significant difference between AEC/BC02 and NS groups. The spleen bacterial load of antibiotics+AEC/BC02 group was (2. 50±1. 26) lg CFU,which was sig-nificantly lower than those of NS [(4. 92+0. 52) lg CFU],AEC/BC02 [(4. 78+0. 84) lg CFU] and antibi-otics [(4. 39+0. 50) lg CFU] groups (P<0. 01). Compared with NS group,antibiotic and AEC/BC02 groups showed no significant difference in spleen bacterial load. Histopathological changes indicated different levels of granulomatous lesions appeared in lung tissues of all groups and the most severe change was ob-served in AEC/BC02 group,followed by that in NS,antibiotics and antibiotics+AEC/BC02 groups. Conclu-sion INH and RFT treatment in combination with AEC/BC02 vaccine in the treatment of guinea pigs with Mycobacterium tuberculosis infection was superior to either treatment alone as it significantly alleviated organ lesions and lowered the bacterial loads in spleen and lung.

Objective To investigate the effect of occipitocervical fusion in patients with craniovertebral junction deformity combined with atlantoaxial instability. Methods The clinical data of 59 patients with craniovertebral junction deformity combined with atlantoaxial instability from March 2013 to June 2017 were retrospectively analyzed. The patients were treated with occipitocervical fusion. The atlantoaxial distance (ADI), distance between the odontoid and Chamberlain line and cervicomedullary angle (CMA) were used to evaluate atlantoaxial dislocation, vertical displacement and spinal cord compression, and the Japan Orthopedic Association (JOA) score was used to evaluate the effect before operation and 7 days after operation. Results The operation time was 109 to 214 (148.5 ± 20.1) min, the transoperative bleeding was 55 to 210 (122.0 ± 16.7) ml, and no injury of spinal cord nerve and vertebral artery occurred during operation. The CMA and JOA score 7 d after operation were significantly higher than that before operation: (153.8 ± 5.4)° vs. (131.2 ± 7.1) ° and (12.7 ± 1.8) scores vs. (10.6 ± 1.4) scores, and the ADI and distance between the odontoid and Chamberlain line 7 d after operation were significantly lower than that before operation: (2.9 ± 0.7) mm vs. (8.3 ± 2.7) mm and (3.2 ± 1.4) mm vs. (8.2 ± 2.3) mm, and there were statistical difference (P＜0.05). One case (1.7%, 1/59) died of massive brainstem infarction 1 d after operation; 2 patients (3.4%, 2/59) had undergone a revision operation due to fusion failure 3 months after operation; other 56 patients in reduction, internal fixation and bone graft fusion. The patients were followed up for 6 to 38 (15.9 ± 7.2) months, and the symptom relief was in 56 cases. The rate of symptom relief was 94.9% (56/59). The JOA score at last follow-up was significantly higher than that before operation: (13.3 ± 1.8) scores vs. (10.6 ± 1.4) scores, and there was statistical difference (P＜0.05). Conclusions The occipitocervical fusion can effectively relieve spinal cord compression and atlantoaxial instability in patients with craniovertebral junction deformity combined with atlantoaxial instability.