Guided by the theory of "fire and original qi are restricted"， it is believed that original qi depletion is the root of the cutaneous immune-related adverse events （cirAEs） related to immune checkpoint inhibitors （ICIs）， and the yin fire exuberance is the branch. Among them， original qi depletion is the internal foundation of the disease， while the drug toxicity of ICIs harming original qi is the initiating factor， and exuberant yin fire is the key pathogenesis. In clinical practice， the general treatment principle advocates banking up original qi to consolidate the root and draining fire to raise yang. Buzhong Yiqi Decoction （补中益气汤） can be used to activate transportation of middle jiao （焦） and promote ascent and dispersion of clear yang， thereby restoring the balance of qi and fire， and medicinals such as Huangqin （Radix Scutellariae）， Huanglian （Rhizoma Coptidis） and Huangbai （Cortex Phellodendri Chinensis） can be supplementetd to clear and drain yin fire. At the same time， considering the accompanying symptoms such as dampness-stasis and fluids depletion， the methods of removing dampness and dispelling stasis， supplementing blood and nourishing yin should be added flexibly. This approach can provide a new perspective and treatment strategy for reducing ICIs-related cirAEs in malignant tumors.

Donors with a serum sodium concentration of >155 mmol/L are extended criteria donors for liver transplantation (LT). Elevated serum sodium of donors leads to an increased incidence of hepatic dysfunction in the early postoperative period of LT; however, the exact mechanism has not been reported. We constructed a Lewis rat model of 70% hepatic parenchymal area subjected to ischemia-reperfusion (I/R) with hypernatremia and a BRL-3A cell model of hypoxia-reoxygenation (H/R) with high-sodium (HS) culture medium precondition. To determine the degree of injury, biochemical analysis, histological analysis, and oxidative stress and apoptosis detection were performed. We applied specific inhibitors of the epithelial sodium channel (ENaC) and Na⁺/Ca²⁺ exchanger (NCX) in vivo and in vitro to verify their roles in injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels and the area of hepatic necrosis were significantly elevated in the HS+I/R group. Increased reactive oxygen species (ROS) production, myeloperoxidase (MPO)‍-positive cells, and aggravated cellular apoptosis were detected in the HS+I/R group. The HS+H/R group of BRL-3A cells showed significantly increased cellular apoptosis and ROS production compared to the H/R group. The application of amiloride (Amil), a specific inhibitor of ENaC, reduced ischemia-reperfusion injury (IRI) aggravated by HS both in vivo and in vitro, as evidenced by decreased serum transaminases, inflammatory cytokines, apoptosis, and oxidative stress. SN-6, a specific inhibitor of NCX, had a similar effect to Amil. In summary, hypernatremia aggravates hepatic IRI, which can be attenuated by pharmacological inhibition of ENaC or NCX.
Animals ; Reperfusion Injury/drug therapy* ; Hypernatremia/complications* ; Rats ; Liver/metabolism* ; Rats, Inbred Lew ; Male ; Apoptosis ; Sodium-Calcium Exchanger/antagonists & inhibitors* ; Reactive Oxygen Species/metabolism* ; Oxidative Stress ; Epithelial Sodium Channel Blockers/pharmacology* ; Epithelial Sodium Channels ; Cell Line ; Liver Transplantation

Objective To investigate the impact of new-onset atrial fibrillation(AF)on all-cause mortality in elderly patients with hypertension having no previous history of AF.Methods A retrospective study was conducted on 1352 elderly hypertensive inpatients who had no history of AF and received long-term follow-up in Chinese PLA General Hospital from January 2014 to June 2017.According to having newly developed AF or not,they were divided into a new-set AF group(191 cases)and a control group(1161 cases).Kaplan-Meier survival curve was plotted for survival analysis and multivariate Cox survival analysis was performed to identify risk factors for all-cause mortality.Results Compared with the control group,the new-onset AF group exhibited significantly advanced age,higher urea level,lower diabetes ratio,and decreased hemoglobin level(P＜0.05,P＜0.01).Kaplan-Meier survival curve analysis showed that the cumulative mortality of the new-onset AF group was significantly higher than that of the control group(P＜0.01).Multivariate Cox regression analysis revealed that age＞75 years(HR=4.562,95％CI:3.104-6.705,P＜0.01),anemia(HR=2.543,95％CI:1.939-3.334,P＜0.01),new-onset AF(HR=1.494,95％CI:1.185-1.884,P＜0.01),eGFR＜60 mL/(min·1.73 m2)(HR=1.729,95％CI:1.389-2.151,P＜0.01),and heart failure(HR=1.539,95％CI:1.173-2.019,P＜0.01)were risk factors for all-cause mortality in elderly hypertensive patients without a history of AF.Conclusions New-onset AF is closely associated with an increased risk of all-cause mortality in elderly hypertensive patients without a previous history of AF.

Malignant pleural effusion(MPE)is a common complication in patients with advanced malignant tumors,which not only significantly reduces their quality of life but also shortens their survival duration.Despite the widespread use of traditional treatment methods such as thoracentesis and pleurodesis,their efficacy is limited accompanied by high recurrence rates.Therefore,exploring novel therapeutic strategies becomes particularly urgent.In recent years,immunotherapy has attracted extensive attention for its potential in cancer treatment.This article systematically reviews the roles of CD4+T cell subsets,including regulatory T cells(Treg),T helper cell(Th)17,Th9,and Th22 cells,within the immunosuppressive microenvironment of MPE.These cell subsets are involved in the formation of the immunosuppressive state of MPE through various mechanisms and play key roles in the occurrence and development of the disease.In addition,the article discusses in detail the role of immune checkpoint molecules,such as programmed death protein 1(PD-1),PD-1 ligand(PD-L1),and cytotoxic T-lymphocyte-associated protein 4(CTLA-4),in the immune evasion of MPE.The abnormal expressions of these molecules provide opportunity for tumor cells to evade immune system surveillance.At the same time,this article also summarizes the application prospects of novel immunotherapy strategies,such as adoptive cell therapy(ACT)and chimeric antigen receptor T cell(CAR-T)therapy,in the treatment of MPE.These innovative therapies offer possibilities for improving the prognosis of MPE patients through activating and enhancing the anti-tumor immune response.

Objective To explore the characteristics of coagulation and immune function and their clinical significance in children with severe adenovirus pneumonia(SAP).Methods A total of 122 children with SAP and 120 children with non-severe adenovirus pneumonia(NSAP)were enrolled and assigned to severe group and non-severe group.The severe group was further subdivided into good prognosis subgroup(n=105)and poor prognosis subgroup(n=17)according to prognosis.Addition-ally,120 healthy children undergoing physical examination during the same period were included as control group.Coagulation function indicators,including prothrombin time(PT),activated partial thromboplastin time(APTT),fibrinogen(FIB),and thrombin time(TT)were measured.Levels of immunoglobulin A(IgA),immunoglobulin G(IgG),and immunoglobulin M(IgM)were determined using the nephelometric immunoassay.Multivariate Cox regression analysis was conducted to explore the influencing factors of poor prognosis.Results Compared with the control group,children in both the non-severe and severe groups exhibited increased levels of white blood cells(WBC),neutrophils(N),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),interleukin-6(IL-6),procalci-tonin(PCT),FIB,and IgG,as well as decreased levels of B lymphocytes,natural killer(NK)cells,PT,APTT,IgA,and IgM(P＜0.05).Compared with the non-severe group,children in the severe group showed increased levels of WBC,N,CRP,ESR,IL-6,PCT,FIB,and IgG,as well as decreased levels of B lymphocytes,NK cells,PT,APTT,IgA,and IgM(P＜0.05).Compared with the good prognosis subgroup,the poor prognosis subgroup exhibited increased levels of CRP,IL-6,PCT,and IgG,as well as decreased levels of APTT,IgM,and IgA(P＜0.05).The results of multivariate Cox regression analysis showed that PCT,APTT,and IgM were influencing factors of poor prognosis in children with SAP(P＜0.05).Conclusion Children with SAP have decreased levels of PT,APTT,IgA,and IgM,as well as increased levels of FIB and IgG.Coagulation and im-mune function indicators are correlated with the prognosis of SAP.

Objective To investigate the relationship between serum C-C motif ligand 23 (CCL23),Stanniocalcin-1 (STC1) levels and prognosis in patients with severe hypertensive intracerebral hemorrhage (HICH). Methods A total of 122 severe HICH patients who visited the Department of Neurosurgery,Hohhot First Hospital from March 2021 to March 2023 were regarded as the study subjects (HICH group),122 patients with mild HICH during the same period (mild group) and 122 healthy individuals who underwent physical examinations were considered healthy. HICH patients were separated into survival group(n=94) and death group(n=28)based on prognosis. ELISA was applied to detect serum levels of CCL23 and STC1. Spearson on method was used to analyze correlations and multivariate COX regression was used to investigate the influencing factors of prognosis in HICH patients,and ROC curve was applied to analyze the predictive value of serum CCL23 and STC1 levels for the prognosis. Kaplan-Meier was applied to analyze the relationship between serum CCL23,STC1 levels and clinical outcomes. Results Serum CCL23(53.32±10.85pg/ml,78.49±11.21pg/ml,112.47±11.53pg/ml)and STC1 (15.12±2.63ng/ml,19.07±2.58ng/ml,22.15±2.75ng/ml)levels in the healthy group,mild disease group and HICH group were increased successively,and the differences was statistically significant (F=856.967,215.043,all P<0.05). The serum levels of CCL23 (108.02±13.51pg/ml) and STC1 (21.06±3.28ng/ml) in the survival group were lower than those in the death group(127.41±13.55 pg/ml,25.83±3.23 ng/ml),the Glasgow coma (GCS) score (8.95±0.92 ) of the survival group was higher than that of the death group(7.61±0.77),and the differences were statistically significant (t=6.663,6.810,7.005,all P<0.001). The serum levels of CCL23 and STC1 were negatively correlated with GCS score (r=-0.481,-0.426,all P<0.001). CCL23[OR(95％CI):1.240(1.091～1.409)],STC[OR(95％CI):1.754(1.215～2.533)]and GCS[OR(95％CI):0.087(0.020～0.382)]score were the influencing factors for poor prognosis in HICH patients . The AUC(95％CI) of CCL23 combined STC1 in the prediction of the prognosis of HICH patients was 0.939 (0.880～0.974) which was higher than that of single diagnosis (Z=1.974,2.040,P=0.048,0.041),the sensitivity and specificity of combined diagnosis were 85.71％ and 94.68％,respectively. The 6-month follow-up survival rate of patients with high expression of CCL23 and STC1 (51.06％ vs 93.33％,56.86％ vs 91.55％) was lower than that of patients with low expression of CCL23 and STC1,and the differences were statistically signrficant (Log rank x2=34.777,23.781,all P<0.05). Conclusion The serum levels of CCL23 and STC1 are high in severe HICH patients,which are closely related to their prognosis. High expression of CCL23 and STC1 may indicate poor clinical outcomes in patients.

Objective To study the diagnostic value of Sysmex UF5000 urine analyzer detection of renal tubular epithelial cells (RTEC) and pathological cast (Path. CAST) in urine to screen for hyperbilirubinemia-induced renal injury. Methods A retrospective analysis was conducted on the urine sediment analysis results of patients with hyperbilirubinemia who visited the Quanzhou First Hospital from February 2023 to January 2024. According to the occurrence of renal injury,they were divided into a non-renal injury group(n=174)and a renal injury group(n=84). Compared the RTEC levels and the positive rate of Path. CAST in urine between two groups. Receiver operating characteristic(ROC) curve analysis was used to evaluate the diagnostic performance of RTEC screening for hyperbilirubinemia-induced renal injury,and further analyzed the sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NPV) of RTEC and Path.CAST single or combined screening. Results The RTEC[5.2(3.2～12.3)/μl]level in the renal injury group,and the positive rate of Path.CAST positivity rate (36.90％),which was significantly higher than that of the non-renal injury group[1.3 (0.7～2.2)/μl,3.45％],the differences were statistically significant (Z/x2=-10.215,51.620,all P<0.001). RTEC could effectively screen patients with renal injury in hyperbilirubinemia,with an AUC (95％CI) of 0.892 (0.846～0.939) and an optimal cut-off value of 3.15/μl for screening. The Youden index was 0.688. When RTEC>3.15/μl or Path.CAST positive was used,its sensitivity and NPV for screening for hyperbilirubinemia-induced renal injury were the highest,with 83.33％ and 91.57％,respectively. When Path.CAST positive was used as the screening condition,its specificity and PPV were the highest,with 96.55％ and 83.78％,respectively. Conclusion Urinary RTEC can effectively screen for renal injury caused by hyperbilirubinemia when RTEC ≤ 3.15/μl or Path.CAST is negative,the possibility of renal injury caused by hyperbilirubinemia can be ruled out.

Objective To evaluate the impact of Jixiong Jiedu decoction on the efficacy of diabetic kidney disease in mice and its influence on intestinal flora and trimethylamine oxide(TMAO)levels.Methods Twelve 7-week-old male db/db mice were randomly assigned to the model group or Jixiong Jiedu decoction group(6 mice per group),while 6 male db/m mice were designated as the control group.Following 8 weeks of continuous gavage,we monitored the body weight and blood glucose levels of the mice at weeks 0,4,and 8.Additionally,we assessed urinary microalbumin,kidney injury molecule-1(KIM-1),creatinine(Scr),and urea nitrogen(BUN)levels in urine.Renal pathology was evaluated using HE and PAS staining.Furthermore,fecal samples underwent 16s RNA sequencing,and the serum TMAO levels were determined.Results Compared with the control group,the blood glucose,body weight,8-hour urinary microalbumin,KIM-1 and Scr in the model group were significantly increased,and the renal pathology showed that glomerular segmental mesangial matrix increased,glomerular volume hypertrophy and renal tubular epithelial cell swelling.The abundance of Lactobacillaceae and Lactobacillus in the model group was significantly increased(P<0.01).The abundance of Lachnospiraceae,Helicobacter and Oscillospira decreased significantly(P<0.01),the abundance of each bacterial group changed,and the serum TMAO content increased significantly.Compared with the model group,the 8h urinary microalbumin,KIM-1(P<0.01)and Scr(P<0.05)in the Jixiong Jiedu decoction group were significantly decreased,and there was no significant difference in BUN(P>0.05),and the renal pathological damage was significantly improved.The abundance of Lactobacillaceae and Lactobacillus in intestinal flora decreased significantly(P<0.01),while the abundance of Lachnospiraceae and Oscillospira increased significantly(P<0.01,P<0.05).The structure of gut microbiota,the abundance of dominant and non-dominant bacteria were positively adjusted,and the serum TMAO content was significantly decreased(P<0.01).Conclusion Jixiong Jiedu decoction effectively ameliorates intestinal flora disorders in db/db mice and regulates serum TMAO levels,thereby exerting a nephroprotective effect.

Objective:To compare the clinical effect of deproteinized calf blood extract (DCBE) eye drops and 0.3% sodium hyaluronate eye drops in the treatment of diabetic cataract patients with dry eye after phacoemulsification.Methods:A randomized controlled study was performed.A total of 112 patients (116 eyes) with type Ⅱ diabetes combined with cataract and dry eye who underwent phacoemulsification in the Eye Hospital of Shandong First Medical University from January 2022 to September 2022 were selected.Patients were divided into DCBE group (49 cases, 51 eyes) and sodium hyaluronate group (63 cases, 65 eyes) by the random number table method.Patients received DCBE eye drops and 0.3% sodium hyaluronate eye drops after surgery according to grouping.Preoperative and postoperative 1 week, 1 month subjective symptoms of dry eye, corneal edema grade, tear film breakup time (TBUT), corneal fluorescein staining (CFS) and Schirmer Ⅰ test (SⅠt) results were recorded and compared.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Eye Hospital of Shandong First Medical University (No.SDSYKYY202112-1).Written informed consent was obtained from each subject.Results:There were significant differences in dry eye symptom score, TBUT and SⅠt at different time points between before and after surgery ( Ftime=323.202, 102.771, 151.876; all P<0.001).Dry eye symptom score decreased and SⅠt increased in the two groups at 1 week and 1 month after surgery compared with before surgery, and the differences were statistically significant (all P<0.017).TBUT was longer at 1 week and 1 month after surgery compared with before surgery in the DCBE group, and TBUT at 1 month after surgery was longer than that before surgery in the sodium hyaluronate group, and the differences were statistically significant (all P<0.017).There were statistically significant differences in CFS scores between the two groups at different time points before and after surgery ( Fgroup=5.391, P=0.022; Ftime=142.402, P<0.001).The CFS scores of both groups at 1 week and 1 month after surgery were lower than those before surgery, and CFS scores in the DCBE group were lower than those in the sodium hyaluronate group, with statistically significant differences (all P<0.017).One week after surgery, the proportion of patients with corneal edema in the DCBE group was 5.9%(3/51), which was significantly lower than 20.0%(13/65) in the sodium hyaluronate group ( χ2=4.790, P=0.029). Conclusions:DCBE eye drops can promote corneal repair, stabilize tear film and improve dry eye discomfort in early postoperative period in diabetic cataract, and its overall effect is better than 0.3% sodium hyaluronate eye drops.

Objective To analyze the clinical data of patients with neurosyphilis(NS)and explore factors influencing their activity of daily living(ADL).Methods The clinical data of 90 patients with NS was retrospectively analyzed,and the ADL scores at admission were assessed by using the Barthel index(BI).The patients were divided into no-dependency,mild-dependency,and moderate-to-severe-dependency groups.The influencing factors of ADL were explored through comparative analysis and multiple linear regression analysis.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of clinical indicators for poor ADL recovery(BI score≤60)at discharge in patients.Results Among the 90 NS patients,the average age was 54.17±12.45 years,with 70 males(77.78%).The most common clinical manifestation was abnormal mental behavior(44.44%),followed by limb sensory or motor disorders(25.56%)and dysarthria(16.67%).Based on the BI scores,41 patients(45.6%)were independent,31 patients(34.4%)had mild dependence,and 18 patients(20.0%)had moderate to severe dependence.The comparison results of the three groups showed that the neutrophil-to-lymphocyte ratio(NLR)was gradually increased[2.80(1.97,4.73)vs.3.80(2.28,4.89)vs.5.37(3.76,7.20)]which was higher in the moderate-to-severe-dependency group than in the independent and the mildly-dependent group(P<0.05);cerebrospinal fluid protein concentration[427(341,644)mg/L vs.553(425,830)mg/L vs.933(641,1706.5)mg/L]was gradually increased and there were significant differences in pairwise comparisons(P<0.05).Multiple linear regression analysis showed that NLR(β=-0.242,P=0.018)and cerebrospinal fluid protein concentration(β=-0.461,P<0.001)were negatively correlated with ADL at admission.The area under curve(AUC)for cerebrospinal fluid protein concentration in predicting poor ADL recovery at discharge was 0.806(95%CI:0.708-0.883,P<0.001),with an optimal cutoff value of 620 mg/L,sensitivity of 86.7%,and specificity of 69.4%.Conclusion The main clinical manifestations of NS patients are psychiatric/behavioral abnormalities.Elevated NLR and cerebrospinal fluid protein concentration may be associated with the decreased ADL.Early active intervention of inflammatory response and cerebrospinal fluid protein abnormalities may provide a new way to improve the prognosis of patients.