Diabetic nephropathy （DN） is a renal disorder induced by prolonged hyperglycemia， with major pathological features including persistent albuminuria， progressive decline in glomerular filtration rate， and elevated arterial blood pressure. As one of the most common and severe microvascular complications of diabetes， the pathogenesis of DN is complex and multifactorial. Without timely and effective treatment， DN may eventually progress to end-stage renal disease （ESRD）. Currently available therapeutic options are often associated with significant adverse effects and high costs， and a large number of patients still progress to ESRD due to delayed treatment. Therefore， there is an urgent need for safer and more effective treatment strategies to improve the living standards and enhance the survival and quality of life of patients with DN. Modern studies have demonstrated that the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway plays a critical role in oxidative stress， inflammatory responses， autophagy， and glycolysis， and is closely associated with the pathophysiological progression of DN. In recent years， traditional Chinese medicine （TCM） has achieved remarkable progress in the prevention and treatment of DN， supported by rich clinical experience and confirmed therapeutic efficacy. With its characteristics of multi-target， multi-component， and multi-pathway actions， along with minimal side effects， TCM can delay the progression of DN and alleviate patient symptoms. Among these mechanisms， the regulation of the PI3K/Akt signaling pathway has gradually become a research hotspot. This paper systematically reviews the role and mechanisms of the PI3K/Akt signaling pathway in the onset and progression of DN based on extensive literature research， summarizes the latest research advances on the precise modulation of the PI3K/Akt pathway by Chinese medicine monomers， active constituents， Chinese patent medicines， and herbal compound formulas in the treatment of DN， aiming to provide a strong theoretical reference for the development of clinically effective agents for DN prevention and treatment.

Diabetic nephropathy （DN） is a renal disorder induced by prolonged hyperglycemia， with major pathological features including persistent albuminuria， progressive decline in glomerular filtration rate， and elevated arterial blood pressure. As one of the most common and severe microvascular complications of diabetes， the pathogenesis of DN is complex and multifactorial. Without timely and effective treatment， DN may eventually progress to end-stage renal disease （ESRD）. Currently available therapeutic options are often associated with significant adverse effects and high costs， and a large number of patients still progress to ESRD due to delayed treatment. Therefore， there is an urgent need for safer and more effective treatment strategies to improve the living standards and enhance the survival and quality of life of patients with DN. Modern studies have demonstrated that the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway plays a critical role in oxidative stress， inflammatory responses， autophagy， and glycolysis， and is closely associated with the pathophysiological progression of DN. In recent years， traditional Chinese medicine （TCM） has achieved remarkable progress in the prevention and treatment of DN， supported by rich clinical experience and confirmed therapeutic efficacy. With its characteristics of multi-target， multi-component， and multi-pathway actions， along with minimal side effects， TCM can delay the progression of DN and alleviate patient symptoms. Among these mechanisms， the regulation of the PI3K/Akt signaling pathway has gradually become a research hotspot. This paper systematically reviews the role and mechanisms of the PI3K/Akt signaling pathway in the onset and progression of DN based on extensive literature research， summarizes the latest research advances on the precise modulation of the PI3K/Akt pathway by Chinese medicine monomers， active constituents， Chinese patent medicines， and herbal compound formulas in the treatment of DN， aiming to provide a strong theoretical reference for the development of clinically effective agents for DN prevention and treatment.

Objective To investigate the expression levels of serum high-mobility group box 1(HMGB1),soluble CD163(sCD163),and prostaglandin E2(PGE2)in patients with hepatitis B virus-related chronic-on-acute liver failure(HBV-ACLF),and to evaluate the value of the three indicators used alone or in combination in predicting prognosis.Methods A total of 76 patients with HBV-ACLF who were hospitalized in Department of Infectious Diseases,The First Affiliated Hospital of Xinxiang Medical University,from July 1,2022 to September 30,2023 were enrolled,and according to the 28-day prognosis,they were divided into survival group with 48 patients and death group with 28 patients.General data were collected,Model for End-Stage Liver Disease(MELD)score was calculated,and ELISA was used to measure the serum levels of HMGB1,sCD163,and PGE2.The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test was used for comparison of categorical data between two groups.The Spearman rank correlation test was used to analyze the correlation of HMGB1,sCD163,and PGE2 with MELD score;the receiver operating characteristic(ROC)curve was used to analyze the value of HMGB1,sCD163,and PGE2 used alone or in combination in predicting the prognosis of HBV-ACLF patients.Results There were significant differences between the two groups in total bilirubin,white blood cell count,the percentage of neutrophils,procalcitonin,serum amyloid A,interleukin-6,serum sodium,and serum creatinine(all P＜0.05).Compared with the survival group,the death group had significantly higher serum levels of HMGB1(Z=-2.997,P=0.003)and sCD163(Z=-2.972,P=0.003),a significantly higher MELD score(t=-6.997,P＜0.001),and a significantly lower serum level of PGE2(Z=-4.909,P＜0.001).The Spearman rank correlation test showed that HMGB1 and sCD163 were positively correlated with MELD score(r=0.431 and 0.319,both P＜0.05),while PGE2 was negatively correlated with MELD score(r=-0.412,P＜0.05).The ROC curve analysis showed that HMGB1,sCD163,and PGE2 used alone had an area under the ROC curve(AUC)of 0.717,0.716,and 0.856,respectively,while the combination of the three indicators had the highest predictive value,with an AUC of 0.930,a sensitivity of 0.778,and a specificity of 0.920.Conclusion Serum HMGB1,sCD163,and PGE2 used alone or in combination have a good reference value in predicting the prognosis of HBV-ACLF patients,and the combination of the three indicators has the highest predictive value,which holds promise for further observation and research.

Objective:To explore the clinical features and genetic variants in three children suspected for β-ketothiolase deficiency (BKTD).Methods:Clinical manifestations, laboratory examination and genetic testing of three children suspected for BKTD at Henan Children′s Hospital between January 2018 and October 2022 were collected, and their clinical and genetic variants were retrospectively analyzed.Results:The children were all males with a age from 7 to 11 months. Their clinical manifestations have included poor spirit, shortness of breath, vomiting, convulsions after traumatic stress and/or infection. All of them had severe metabolic acidosis, elevated ketone bodies in blood and urine, hypoglycemia, with increased isoprenyl-carnitine and 3-hydroxyisovalyl-carnitine in the blood, and 2-methyl-3-hydroxybutyrate and methylprotaroyl glycine in the urine. All of them were found to harbor compound heterozygous variants of the ACAT1 gene, including c. 1183G>T and a large fragment deletion (11q22.3-11q23.1) in child 1, c. 121-3C>G and c. 826+ 5_826+ 9delGTGTT in child 2, and c. 928G>C and c. 1142T>C in child 3. The variants harbored by children 2 and 3 were known to be pathogenic or likely pathogenic. The heterozygous c. 1183G>T variant in child 1 was unreported previously and rated as a variant of unknown significance (PM2_Supporting+ PP3+ PP4) based on guidelines from the American College of Medical Genetics and Genomics. The large segment deletion in 11q22.3-11q23.1 has not been included in the DGV Database and was rated as a pathogenic copy number variation. Conclusion:The variants of the ACAT1 gene probably underlay the pathogenesis of BKTD in these three children.

Objective To investigate the effect of the timing of pronase on the quality of magnetically controlled gastric capsule endoscope(MCE).Methods 225 patients from February 2021 to March 2022 were randomly assigned to 3 groups,40 000 u of oral pronase 40 min before examination in Group A,20 000 u of oral pronase for 60 and 40 min before the examination in Group B,20 000 u of oral pronase for 40 and 20 min before examination in Group C.Gastric cavity cleanliness and gastric mucosa visualisation scores(1 to 4)were recorded for the six regions of the stomach and the sum of the scores was calculated.The detection rate of gastric lesions such as gastric polyps and the time of gastric examination were also recorded.Results 221 patients completed the study.In the mucosal visualization score,group C scored(23.56±1.37)points,which was higher than that in group A's(22.56±1.28)points and group B's(23.00±1.33)points.The difference was statistically significant(P<0.05).In the gastric cavity cleanliness score,group C scored(21.44±2.35)points,which was higher than that in group A's(20.11±2.04)points.The difference was statistically significant(P<0.01).In the total score of cleanliness and mucosal visualization score of the proximal stomach(cardia and fundus),group C was higher than group A and group B,and the difference was statistically significant(P<0.05).In the detection rate of lesions,the detection rates of gastric polyps and erosion in group C were 17.8%and 49.3%,respectively,which were higher than group A's(6.8%and 29.7%)and group B's(9.5%and 31.1%).The differences were statistically significant(P<0.05).The gastric observation time in group C was shorter than that in group A and group B,and the difference was statistically significant(P<0.05).Conclusions Oral administration of 20 000 u of pronase in divided doses 40 and 20 min before the examination can enhance the quality of magnetically controlled gastric capsule endoscope.

Objective To describe and analyze the current situation of the four same type of departments in an hospital in order to provide a reference for the construction of"the most cost-effective medical care".Methods The CN-DRG were used to automatically group and compare the medical capacity and inpatient service efficiency of the hospital department groups,and in the refined analysis,one DRG disease group of in situ cancer and non-malignant disease loss uterine surgery and single species uterine fibroid was included,and the Kruskal-Wallis H test was used to further compare the differences in length of stay and various costs.Results It included a total of 22630 patients,whose weights varied from a maximum of 3948.62 in diagnostic group 1 to a minimum of 133.55 in diagnostic group 11.The cost consumption indexes ranged from a minimum of 0.89 in diagnostic group 5 to a maximum of 1.04 in diagnostic group 2,while the time consumption indexes ranged from a minimum of 0.48 in diagnostic group 11 to a maximum of 0.81 in diagnostic group 5.When comparing the diagnostic groups,there were statistically significant differences(P＜0.05)in hospitalization days,total cost,diagnostic cost,therapeutic cost,and cost of supplies.Specifically,when comparing the diagnostic and treatment groups within departments,the differences in hospitalization days and all costs were statistically significant(P＜0.05)in departments 1 and 2,the differences in diagnostic cost,therapeutic cost,and cost of supplies were statistically significant(P＜0.05)in department 3.Conclusion There exists a notable disparity in the extent to which each diagnostic and treatment group contributes to the hospital's service capacity and cost variability.Consequently,it is necessary to reasonably evaluate the length of hospital stay and medical cost of patients to achieve the highest cost-effective medical treatment.

Objective To establish a method for HPLC fingerprint analysis and determine three main components of Modified Zengye Decoction.Methods The chromatographic column was Shimadzu WondaSil C18 column(250 mm×4.6 mm,5 μm),the mobile phase was acetonitrile-0.3％aqueous phosphoric acid with a gradient elution procedure,the volume flow rate was 1.0 mL/min,the detection wavelengths were 265,203,310 and 290 nm,the column temperature was 25 ℃,and the injection volume was 20 μL.The HPLC fingerprints of the 10 batches of Modified Zengye Decoction were established,and the similarity analysis was performed by using the similarity evaluation system of chromatographic fingerprint of traditional Chinese medicine(version 2012A).The common peaks were identified and assigned,and the contents of the three main components were quantitatively determined.Results There were 17 common peaks in the fingerprints of 10 batches of Modified Zengye Decoction with similarities ranging from 0.872-0.989.The fingerprints recognized peak 9,14 and 17 as ferulic acid,aurantiamarin and harpagoside,respectively.The contents of ferulic acid,aurantiamarin and harpagoside were 0.067 3-0.174 8,0.498 8-1.522 7,0.270 9-0.802 4 mg/g,and the transfer rate were 30.74％-55.63％,11.77％-35.94％,23.15％-68.56％,respectively.Conclusion The established HPLC fingerprint analysis method combined with main components quantitative analysis method can be used for the quality analysis and control of Modified Zengye Decoction with simple analysis method and reliable results.

Objective:To explore the mechanism of hemoperfusion combined with hemofiltration in the treatment of sepsis based on Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway.Methods:One hundred and fifty patients with sepsis treated in the Heze Municipal Hospital from February 2020 to February 2023 were retrospectively selected and they were divided into two groups according to the treatment plan, with 75 cases in each group. Both groups were treated with standard treatment for sepsis, with hemofiltration in the control group and hemoperfusion combined with hemofiltration in the observation group. The TLR4/NF-κB signal pathway-related mRNA expression (TLR4 mRNA, NF-κB mRNA), related inflammatory factors, indicators of vascular endothelial function, the levels of indicators of liver and kidney function were measured between the two groups. The 28-d morbidity and mortality rate was compared between the two groups.Results:Compared with before treatment, the levels of TLR4 mRNA, NF-κB mRNA in two groups were decreased, and the levels of above index in the observation group were lower than those in the control group: 0.34 ± 0.12 vs. 0.63 ± 0.16, 0.30 ± 0.10 vs. 0.59 ± 0.12, there were statistical differences ( P<0.05). Compared with before treatment, the levels of tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-12 and C reactive protein (CRP) in two groups were decreased, and the levels of above index in the observation group were lower than those in the control group: (43.42 ± 7.82) ng/L vs. (56.37 ± 9.41) ng/L, (28.47 ± 6.03) ng/L vs. (39.41 ± 7.02) ng/L, (52.31 ± 5.42) ng/L vs. (70.84 ± 7.08) ng/L, (23.82 ± 7.06) mg/L vs. (38.41 ± 6.83) mg/L, there were statistical differences ( P<0.05). Compared with before treatment, the levels of advanced glycosylation end products (AGEs), soluble intercellular adhesion factor-1 (sICAM-1), homocysteine (Hcy), glutamate transaminase (ALT), glutathione transaminase(AST), blood creatinine (Scr) and blood urea nitrogen (BUN) in two groups were decreased, and the levels of above index in the observation group were lower than those in the control group: (172.37 ± 73.63) mg/L vs. (249.41 ± 80.26) mg/L, (404.26 ± 68.42) ng/L vs. (459.36 ± 70.19) ng/L, (20.27 ± 4.53) μmol/L vs. (28.96 ± 5.02) μmol/L, (62.41 ± 10.69) U/L vs. (78.52 ± 13.41) U/L, (51.47 ± 12.35) U/L vs. (64.17 ± 15.83) U/L, (3.82 ± 0.79) mmol/L vs. (5.57 ± 1.16) mmol/L, (125.16 ± 23.96) μmol/L vs. (163.24 ± 30.12) μmol/L, there were statistical differences ( P<0.05). The 28-d morbidity and mortality rate in the observation group was lower than that in the control group: 12.00%(9/75) vs. 25.33%(19/75), there was statistical difference ( χ2 = 4.39, P<0.05). Conclusions:In the treatment of sepsis, hemoperfusion combined with hemofiltration can effectively alleviate the severity of the disease, reduce the damage of hepatic and renal function, and have a certain effect on the mRNA expression of TLR4/NF-κB signaling pathway and related inflammatory factors.

Objective To investigate correlation between the expression level of multiple cytokine levels in neonatal umbilical cord plasma and early-onset sepsis for screening out the cytokines with good diagnostic value for early-onset neonatal sepsis(EONS).Methods Full-term neonates and preterm neonates(Gestational age ≥ 32 weeks)of 310 cases between September 2021 and June 2023 were selected as study subjects.According to clinical signs,laboratory results and blood culture,these subjects were divided into 3 groups:control group without sepsis,EONS blood culture positive group and EONS blood culture negative group.Umbilical cord blood plasma of all subjects was collected within 72 hours after birth.The expression levels of cytokines IL-2,IL-4,IL-6,IL-9,IL-10,IL-21,IFN-γ and TNF-α were determined,and cytokines with high expression levels(high correlation)were screened out.Receiver operating characteristic(ROC)curve was used to analyze the specificity and sensitivity of the selected cytokines in the diagnosis of neonatal early-onset sepsis.Results Among the 8 cytokines mentioned above,the concentrations of IL-6,IL-9 and IL-21 in cord blood plasma of neonatal early-onset sepsis positive blood culture patients(392.6±258.7pg/ml,11.9±7.5pg/ml,29.1±16.8 pg/ml)and negative blood culture patients(353.8±244.5pg/ml,10.4±6.3pg/ml,27.7±19.2pg/ml)were higher than those of the control group(34.9±25.1pg/ml,5.9±4.5pg/ml,10.8±10.1 pg/ml),with significant differences(t=23.961,20.732;15.174,17.824;22.466,21.193,all P＜0.01),and the increase of IL-6 concentration was the most obvious.ROC curve analysis(the cut-off values of IL-6,IL-9 and IL-21:123.0 pg/ml,3.60 pg/ml,6.00 pg/ml,respectively)showed that the areas under the ROC curve for IL-6,IL-9 and IL-21 alone detection were 0.876(95％CI:0.786～0.955),0.782(95％CI:0.667～0.875)and 0.825(95％CI:0.737～0.913),respectively.The area under the ROC curve for the combined detection of IL-6,IL-9 and IL-21 was 0.930(95％CI:0.875～0.997).The combined detection of IL-6,IL-9 and IL-21 improved the specificity and sensitivity of the test than IL-6,IL-9 and IL-21 alone detection,and the differences were statistically significant(Z=2.137,2.391,2.257,all P＜0.05).There was no significant difference in cytokine expression between positive blood culture and negative blood culture neonates with early-onset sepsis(t=0.276～3.377,all P＞0.05).Conclusion The cytokines expression of IL-6,IL-9 and IL-21 in neonatal umbilical cord plasma of neonatal early-onset sepsis were increased.Combined detection of IL-6,IL-9 and IL-21 has good diagnostic value for early-onset neonatal sepsis.

Objective:To investigate the clinical and molecular characteristics of 11β-hydroxylase deficiency(11β-OHD) to improve the understanding of this disorder.Methods:The clinical manifestation, hormone level, imaging examination, characteristics of gene variation and follow-up of five patients with 11β-OHD diagnosed in Henan Children′s Hospital from 2016 to 2021 were carefully reviewed.Results:Among the 5 children, 3 were male and 2 were female, all without positive family history. The age at diagnosis was 1 year 5 months to 7 years(average 3 years and 9 months), and the bone age was 3 years 6 months to 16 years(average 10 years and 3 months). Two cases were misdiagnosed as 21-hydroxylase deficiency(21-OHD) and treated with long-term mineralocorticoids. Three patients presented with hypertension and one patient had testicular adrenal rest tumor. Adrenal CT showed bilateral adrenal hyperplasia in five patients. ACTH, 17-hydroxyprogesterone, testosterone, and androstenedione levels were increased in 5 children, and hypokalemia occurred in 1 patient. One patient carried homozygous novel missense variant, and four patients had compound heterozygous variants. Four patients carried missence mutations, two patients had deletion and one patient harbored a chimeric CYP11B2 exon1-6/CYP11B1 exon7-9. Three novel CYP11B1 mutations, including c. 1385T>C(p.L462P), c.64C>T(p.Q22*)and c. 1354G>A(p.G452R) were identified. The final height of 2 male children were 164.4 cm and 150.2 cm, respectively, and the related hormone levels of the other 3 children were normal.Conclusion:11β-OHD is easily misdiagnosed, leading to severe impairment of final height. CYP11B1 gene variation is complex and diverse, which requires variety of gene detection methods.