Diabetic kidney disease（DKD） is a chronic kidney structural and functional disorder caused by diabetes. With the global prevalence of diabetes continuing to rise， DKD has gradually become a major cause of chronic kidney disease and end-stage renal disease（ESRD）， posing a serious threat to patients' quality of life and long-term health outcomes. Studies have shown that apoptosis plays a pivotal role in the development and progression of DKD， with its mechanisms involving abnormal activation of multiple signaling pathways such as Toll-like receptor 4（TLR4）/nuclear transcription factor-κB（NF-κB）/B-cell lymphoma-2（Bcl-2）/cysteinyl aspartate-specific proteinase（Caspase）-3， protein kinase R-like endoplasmic reticulum kinase（PERK）/eukaryotic initiation factor 2α（eIF2α）/activating transcript factor 4（ATF4）/CCAAT enhancer-binding protein homologous protein（CHOP）， phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β）， Janus kinase 2（JAK2）/signal transducer and activator of transcription 3（STAT3）， adenosine monophosphate-activated protein kinase（AMPK）/mammalian target of rapamycin（mTOR） and silent information regulator 1（SIRT1）/tumor suppressor protein 53（p53）， thereby accelerating renal pathological damage in DKD. Extensive evidence-based medical studies have confirmed that traditional Chinese medicine（TCM）， leveraging its unique therapeutic advantages of multi-target， multi-component and multi-pathway approaches， has demonstrated remarkable efficacy and favorable safety profiles in treating DKD. Recent studies have demonstrated that active components of TCM can specifically target and modulate key effectors in apoptotic signaling pathways. Meanwhile， traditional compound formulations exert synergistic effects through multiple approaches such as replenishing deficiency and activating blood circulation， detoxifying and dredging collaterals， tonifying kidney essence， and removing stasis and purging turbidity， thereby comprehensively regulating critical pathological processes including endoplasmic reticulum stress and mitochondrial apoptosis pathways. This combined therapeutic approach of molecular targeting and holistic regulation provides novel strategies for delaying the progression of DKD. Based on this， this paper provides an in-depth analysis of key apoptotic signaling pathways and their regulatory mechanisms， while systematically summarizing recent research advances regarding the therapeutic effects of TCM active components， compound formulations， and proprietary Chinese medicines on DKD through modulation of these pathways， with particular emphasis on their underlying molecular mechanisms. These findings not only elucidate the modern scientific connotation and theoretical basis of TCM in treating DKD but also establish a solid theoretical and practical foundation for promoting the wider clinical application and further research of TCM in the field of DKD treatment.

OBJECTIVE To investigate the effect of plasma trough concentration of venetoclax and its influencing factors in patients with acute myeloid leukemia （AML）. METHODS After 5 days of venetoclax administration， venous blood samples were collected from AML patients before the next dose. Plasma trough concentrations of venetoclax were determined using high-performance liquid chromatography-tandem mass spectrometry. Spearman correlation was used to assess the correlations between venetoclax plasma trough concentration and various parameters （including patients’ general information， venetoclax-related indicators， liver function indicators， kidney function indicators， and blood routine indicators）. Multiple linear regression analysis was performed to identify independent factors influencing plasma trough concentration of venetoclax. Using efficacy as dependent variable [complete remission （CR）+partial remission （PR） vs. no remission （NR）]， univariate and multivariate binary Logistic regression analyses were conducted to identify factors affecting efficacy. The receiver operating characteristic （ROC） curve was used to evaluate the predictive value of venetoclax plasma trough concentration for clinical efficacy （assessed as CR）. RESULTS A total of 172 venetoclax plasma trough concentration measurements from 101 patients were included in this study. The median plasma trough concentration of venetoclax was 2.38 （1.18， 3.85） μg/mL； the median sampling time for plasma trough concentration of venetoclax was 10 （7， 15） d； the duration of venetoclax use was （34±12） d. Multiple linear regression analysis showed that alkaline phosphatase （ B ＝14.65， 95%CI： 5.35-23.95， P ＝0.002）， total bilirubin （ B ＝－101.71， 95%CI： －197.16 to －6.25， P ＝0.037）， and white blood cell count （ B ＝－106.84， 95%CI： －187.61 to －26.07， P ＝0.010） were independent factors influencing plasma trough concentration of venetoclax. Due to patient attrition during treatment， 114 venetoclax plasma trough concentration measurements from 69 patients were included for efficacy evaluation. The results showed that 46 patients （66.7%） achieved CR， 11 patients （15.9%） achieved PR， and 12 patients （17.4%） were NR. Multivariate binary Logistic regression analysis showed that age， hemoglobin， venetoclax plasma trough concentration， hematocrit， and mean corpuscular hemoglobin were independent factors affecting patient efficacy （ P ＜0.05）. ROC curve analysis showed that the cut-off value of plasma trough concentration of venetoclax for predicting patient efficacy （assessed as CR） was 1.68 μg/mL （AUC＝0.66， 95%CI： 0.54-0.78， P ＝0.014）. CONCLUSIONS There is considerable inter-individual variability in plasma trough concentration of venetoclax among AML patients. Plasma trough concentration of venetoclax is significantly correlated with alkaline phosphatase， total bilirubin， and white blood cell count. Plasma trough concentration of venetoclax is an independent factor affecting patient’s efficacy， and when the cut-off value for predicting CR is above 1.68 μg/mL， better effects may be achieved.

Objective:To explore the clinical characteristics of hydrocephalus patients with delayed intracranial hemorrhage (DICH) after ventriculo-peritoneal shunt (VPS) and independent influencing factors for DICH after VPS, and construct a nomogram model for predicting the incidence of DICH after VPS.Methods:A retrospective analysis was performed; clinical data of 168 patients with hydrocephalus who underwent VPS at Department of Neurosurgery, Lihuili Hospital Affiliated to Ningbo University from January 2016 to December 2023 were collected. Based on the postoperative DICH occurrence, these patients were categorized into a non-DICH group and a DICH group. Clinical characteristics of patients from the DICH group were analyzed. Differences in clinical data between patients from the non-DICH group and DICH group were compared. Multivariate Logistic regression analysis was performed to screen the independent influencing factors for DICH after VPS, and a nomogram model for predicting DICH incidence after VPS was constructed. Receiver operating characteristic (ROC) curve, calibration curve, Hosmer-Lemeshow test and Bootstrap resampling method were used to evaluate the predictive efficiency and stability of the nomogram model.Results:(1) Among the 168 patients, 36 (21.43%) developed DICH, which occurred (6.06±2.77) days after VPS (ranged 2-13 days). Seven patients presented with symptoms as vomiting, epilepsy, and decreased consciousness, while 29 patients had no hemorrhage-related complication. The hemorrhage volume in these 36 DICH patients was 0.85(0.30, 3.54) mL. Regarding the hemorrhage sites, 12 patients had simple puncture tract hemorrhage, 14 had simple intraventricular hemorrhage, 7 had both puncture tract hemorrhage and intraventricular hemorrhage, and 3 had puncture tract hemorrhage combined with hemorrhage in other sites. At discharge, 8 patients had a good prognosis, and 28 had a poor prognosis. (2) Compared with the non-DICH group, the DICH group had statistically older age, higher proportion of patients with hypertension or craniotomy history, lower preoperative neutrophil-to-lymphocyte ratio (NLR), higher postoperative NLR, and higher ratio of postoperative to preoperative NLR (NLRR), with significant differences ( P<0.05). Results of multivariate Logistic regression analysis indicated that age ( OR=1.077, 95% CI: 1.022-1.135, P=0.005), history of craniotomy ( OR=3.547, 95% CI: 1.384-9.092, P=0.008), and NLRR ( OR=1.744, 95% CI: 1.179-2.581, P=0.005) were independent influencing factors for DICH in hydrocephalus patients after VPS ( P<0.05). (3) A nomogram model for predicting DICH in hydrocephalus patients after VPS was constructed based on age, history of craniotomy and NLRR. ROC curve analysis showed that area under the curve (AUC) of the nomogram model for predicting DICH in hydrocephalus patients after VPS was 0.812 (95% CI: 0.735-0.890, P<0.001); Hosmer-Lemeshow test indicated that the model had good calibration, and no significant difference was noted between the predicted probabilities and actual probabilities ( χ2=10.487, P=0.233); decision curve analysis results showed that the nomogram model could generate good clinical net benefits with risk threshold of 0%-60%; AUC of the internal validation ROC curve was 0.805 (95% CI: 0.785-0.816) and the C-index was 0.82 by Bootstrap resampling method, suggesting good stability of the model. Conclusion:Hydrocephalus patients with advanced age, history of craniotomy, and elevated NLRR trend to have DICH following VPS; the nomogram model constructed based on age, history of craniotomy and NLRR has good predictive performance and clinical practicability.

Objective·To investigate the effect of plasma exchange combined with classical chemotherapy on renal function in patients with multiple myeloma(MM).Methods·A retrospective analysis was conducted on data from patients newly diagnosed with MM in the Department of Hematology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,between October 2021 and September 2023.Sixty-eight MM patients admitted from October 2021 to September 2022 served as the control group,and 41 patients admitted from October 2022 to September 2023 comprised the experimental group.The control group received classical chemotherapy for MM[PAD(bortezomib+adriamycin+dexamethasone)or PCD(bortezomib+cyclophosphamide+dexamethasone)],and the experimental group underwent plasma exchange before classic chemotherapy.The frequency of plasma exchange was determined according to the clearance rate of M-protein in patients,with the criterion being a reduction of more than 40%in plasma M-protein levels after exchange,and the total number of exchanges ranged from 1 to 3 sessions.After 2 chemotherapy courses,the free light chain difference(dFLC),serum creatinine(Scr),and other renal function indexes were compared between the two groups.Results·Compared with the control group,the experimental group showed no statistically significant difference in dFLC levels.The Scr level decreased[67.00(54.00,75.00)μmol/L vs 77.50(63.00,94.00)μmol/L,P=0.011],and the estimated glomerular filtration rate(eGFR)increased[97.80(92.80,101.30)mL/(min·1.73 m2)vs 85.80(61.35,95.35)mL/(min·1.73 m2),P<0.001]after treatment.Before treatment,the numbers of patients with MM-related severe renal injury[eGFR<50 mL/(min·1.73 m2)]were 41 in the control group and 28 in the experimental group.After treatment,8 patients(19.51%)in the control group achieved complete renal response[eGFR≥60 mL/(min·1.73 m2)],while 12 patients(42.86%)in the experimental group achieved the same,with the difference being statistically significant(P=0.036).After two courses of treatment,the overall response rates(ORR)of the control group and the experimental group were 76.47%and 92.68%,respectively,and the difference in overall therapeutic efficacy was statistically significant(P=0.031).Conclusion·Plasma exchange combined with classical chemotherapy can significantly reduce the Scr levels and increase eGFR in MM patients within a short period,ameliorating the MM-related renal impairment to some extent and improving clinical treatment outcomes.

Objective·To investigate the effect of plasma exchange combined with classical chemotherapy on renal function in patients with multiple myeloma(MM).Methods·A retrospective analysis was conducted on data from patients newly diagnosed with MM in the Department of Hematology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,between October 2021 and September 2023.Sixty-eight MM patients admitted from October 2021 to September 2022 served as the control group,and 41 patients admitted from October 2022 to September 2023 comprised the experimental group.The control group received classical chemotherapy for MM[PAD(bortezomib+adriamycin+dexamethasone)or PCD(bortezomib+cyclophosphamide+dexamethasone)],and the experimental group underwent plasma exchange before classic chemotherapy.The frequency of plasma exchange was determined according to the clearance rate of M-protein in patients,with the criterion being a reduction of more than 40%in plasma M-protein levels after exchange,and the total number of exchanges ranged from 1 to 3 sessions.After 2 chemotherapy courses,the free light chain difference(dFLC),serum creatinine(Scr),and other renal function indexes were compared between the two groups.Results·Compared with the control group,the experimental group showed no statistically significant difference in dFLC levels.The Scr level decreased[67.00(54.00,75.00)μmol/L vs 77.50(63.00,94.00)μmol/L,P=0.011],and the estimated glomerular filtration rate(eGFR)increased[97.80(92.80,101.30)mL/(min·1.73 m2)vs 85.80(61.35,95.35)mL/(min·1.73 m2),P<0.001]after treatment.Before treatment,the numbers of patients with MM-related severe renal injury[eGFR<50 mL/(min·1.73 m2)]were 41 in the control group and 28 in the experimental group.After treatment,8 patients(19.51%)in the control group achieved complete renal response[eGFR≥60 mL/(min·1.73 m2)],while 12 patients(42.86%)in the experimental group achieved the same,with the difference being statistically significant(P=0.036).After two courses of treatment,the overall response rates(ORR)of the control group and the experimental group were 76.47%and 92.68%,respectively,and the difference in overall therapeutic efficacy was statistically significant(P=0.031).Conclusion·Plasma exchange combined with classical chemotherapy can significantly reduce the Scr levels and increase eGFR in MM patients within a short period,ameliorating the MM-related renal impairment to some extent and improving clinical treatment outcomes.

Objective:To explore the clinical characteristics of hydrocephalus patients with delayed intracranial hemorrhage (DICH) after ventriculo-peritoneal shunt (VPS) and independent influencing factors for DICH after VPS, and construct a nomogram model for predicting the incidence of DICH after VPS.Methods:A retrospective analysis was performed; clinical data of 168 patients with hydrocephalus who underwent VPS at Department of Neurosurgery, Lihuili Hospital Affiliated to Ningbo University from January 2016 to December 2023 were collected. Based on the postoperative DICH occurrence, these patients were categorized into a non-DICH group and a DICH group. Clinical characteristics of patients from the DICH group were analyzed. Differences in clinical data between patients from the non-DICH group and DICH group were compared. Multivariate Logistic regression analysis was performed to screen the independent influencing factors for DICH after VPS, and a nomogram model for predicting DICH incidence after VPS was constructed. Receiver operating characteristic (ROC) curve, calibration curve, Hosmer-Lemeshow test and Bootstrap resampling method were used to evaluate the predictive efficiency and stability of the nomogram model.Results:(1) Among the 168 patients, 36 (21.43%) developed DICH, which occurred (6.06±2.77) days after VPS (ranged 2-13 days). Seven patients presented with symptoms as vomiting, epilepsy, and decreased consciousness, while 29 patients had no hemorrhage-related complication. The hemorrhage volume in these 36 DICH patients was 0.85(0.30, 3.54) mL. Regarding the hemorrhage sites, 12 patients had simple puncture tract hemorrhage, 14 had simple intraventricular hemorrhage, 7 had both puncture tract hemorrhage and intraventricular hemorrhage, and 3 had puncture tract hemorrhage combined with hemorrhage in other sites. At discharge, 8 patients had a good prognosis, and 28 had a poor prognosis. (2) Compared with the non-DICH group, the DICH group had statistically older age, higher proportion of patients with hypertension or craniotomy history, lower preoperative neutrophil-to-lymphocyte ratio (NLR), higher postoperative NLR, and higher ratio of postoperative to preoperative NLR (NLRR), with significant differences ( P<0.05). Results of multivariate Logistic regression analysis indicated that age ( OR=1.077, 95% CI: 1.022-1.135, P=0.005), history of craniotomy ( OR=3.547, 95% CI: 1.384-9.092, P=0.008), and NLRR ( OR=1.744, 95% CI: 1.179-2.581, P=0.005) were independent influencing factors for DICH in hydrocephalus patients after VPS ( P<0.05). (3) A nomogram model for predicting DICH in hydrocephalus patients after VPS was constructed based on age, history of craniotomy and NLRR. ROC curve analysis showed that area under the curve (AUC) of the nomogram model for predicting DICH in hydrocephalus patients after VPS was 0.812 (95% CI: 0.735-0.890, P<0.001); Hosmer-Lemeshow test indicated that the model had good calibration, and no significant difference was noted between the predicted probabilities and actual probabilities ( χ2=10.487, P=0.233); decision curve analysis results showed that the nomogram model could generate good clinical net benefits with risk threshold of 0%-60%; AUC of the internal validation ROC curve was 0.805 (95% CI: 0.785-0.816) and the C-index was 0.82 by Bootstrap resampling method, suggesting good stability of the model. Conclusion:Hydrocephalus patients with advanced age, history of craniotomy, and elevated NLRR trend to have DICH following VPS; the nomogram model constructed based on age, history of craniotomy and NLRR has good predictive performance and clinical practicability.

Objective:To investigate the value of 3D CT reconstruction in diagnosis of chronic lateral ankle instability (CLAI) combined with syndesmotic diastasis (SD).Methods:A retrospective study was conducted to analyze the clinical data of 160 patients with CLAI who had been examined by arthroscopy from January 2018 to September 2022 at Department of Foot and Ankle Surgery, Wuhan Fourth Hospital. There were 64 males and 96 females with an age of (39.8±12.6) years. Eighty-one left and 79 right feet were affected; the time from injury to surgery was (27.3±11.6) months. The patients were divided into a widened interval group and a normal interval group according to the syndesmotic width measured, with 2 mm as a critical value. After preoperative 3D CT reconstruction, the differences in anterior tibiofibular distance, posterior tibiofibular distance, the narrowest tibiofibular distance, fibular translation, fibular rotation, and syndesmotic area (SA) were compared between the 2 groups. Univariate and multivariate analyses were performed successively to identify the risk factors. The receiver operating characteristic (ROC) curve was used to identify the best predictive factor and critical value. According to the findings of previous research, the above analyses were repeated to determine the best predictive factor and critical value respectively in the sex subgroup, fibular morphology subgroup and incisura feature subgroup.Results:The binary logistic regression showed that SA was a risk factor for CLAI combined with SD ( OR=1.196, 95% CI: 1.122 to 1.275, P < 0.001). The ROC curve revealed an area under curve of 0.847 and the difference critical value of 22.06 mm 2 that indicated a sensitivity of 80.4% and a specificity of 78.9%, respectively. Subgroup analyses showed that SA was suitable for male and female patients and patients with different fibular morphologies and incisura features but the difference critical values were different. Conclusion:In 3D CT reconstruction, measurement of SA may help the diagnosis of CLAI combined with SD.

Objective:To explore the clinical manifestations and characteristics of serum adrenal cortex hormone spectrum in patients with adrenocortical hypercortisolism with different pathological types of adrenal adenoma.Methods:A retrospective analysis was conducted on 68 patients with adrenal Cushing's syndrome who underwent surgical treatment in the Department of Endocrinology and/or Urology, Peking University First Hospital from January 2018 to June 2022. Among them, 12 patients had obvious eosinophilic changes in pathology(eosinophilic group), and 56 patients had no obvious eosinophilic changes(non-eosinophilic group). Among eosinophilic group, one male and 11 females, age(49.83±9.87) years old, body mass index (BMI)(25.86±3.21) kg/m 2, systolic blood pressure (140.25±20.72)mmHg(1 mmHg=0.133 kPa), diastolic blood pressure(91.00±14.87)mmHg, 7 cases were overt Cushing's syndrome. Among non-eosinophilic group, 14 males and 32 females, age(52.91±10.82) years old, BMI (26.06 ± 3.57) kg/m 2; ystolic blood pressure (142.13±16.71) mmHg, diastolic blood pressure (83.63±11.41) mmHg; 16 cases of overt Cushing's syndrome. There was no statistically significant difference in the above indicators between the two groups ( P>0.05).In terms of laboratory tests, 0: 00 cortisol levels in the eosinophilic group and non-eosinophilic groups were 14.95(5.93, 23.2) ng/dl and 6.69(4.07, 11.35) ng/dl ( P=0.044), the cortisol levels after 1mg dexamethasone inhibition test were 20.19(11.29, 26.92) ng/dl and 5.94(2.68, 12.90) ng/dl ( P=0.005), and 8: 00, 16: 00, and 0: 00, ACTH levels were 2.08 (1.02, 2.90) pg/ml and 8.37(2.30, 11.67) pg/ml ( P=0.006), 1.22(1.00, 3.20) pg/ml, and 4.22(1.80, 6.33) pg/ml ( P=0.012), 0.65 (0, 2.63) pg/ml, and 2.76(1.44, 5.57) pg/ml( P=0.023), serum triglyceride were 1.92(1.31, 2.50) mmol/L and 1.31(1.04, 1.80) mmol/L ( P=0.026), and the differences were statistically significant. In terms of target organ damage, there were 6 cases and 10 cases ( P=0.017) in the eosinophilic group and non eosinophilic group with ventricular wall hypertrophy, 1 case and 0 cases( P=0.030) in the aortic dissection group, and 4 cases and 5 cases ( P=0.024) with four or more types of target organ damage, respectively, with statistically significant differences. Two groups of preoperative serum adrenal cortex hormone profiles were detected by liquid chromatography tandem mass spectrometry. The differences in adrenal cortex hormone profiles and hormone ratios between the two groups were compared. Age, gender, and statistically significant indicators were included in a multivariate logistic regression model to analyze the correlation between each indicator and eosinophilic changes. Results:Adrenal cortical hormone profile of the two groups showed that the serum estrone levels in the eosinophilic group and non-eosinophilic group were 20.27(13.49, 39.81) pg/ml and 12.59(8.08, 21.18) pg/ml ( P=0.034), and 11-hydroxyandrostenedione levels were 692.34(536.19, 1 049.66) pg/ml and 1 157.60(710.78, 1 539.30) pg/ml( P=0.026), with statistically significant differences; There were no statistically significant difference in the expression levels of other hormones ( P>0.05). In terms of hormone ratio, the estradiol/testosterone ratios in the eosinophilic and non eosinophilic groups were 0.14(0.08, 0.62) and 0.04(0.01, 0.09)( P=0.008), the estrone/androstenedione ratios were 0.06(0.05, 0.12) and 0.04(0.03, 0.06)( P=0.007), the 11-hydroxyandrostenedione/androstenedione ratios were 2.26(1.30, 2.69) and 4.03(2.48, 5.25)( P=0.008), the estriol/estrone ratios were 0.10(0.03, 0.29) and 0.25(0.12, 0.51)( P=0.016), the estriol/estradiol were 0.22(0.03, 0.30) and 0.33(0.12, 0.73)( P=0.032), and the differences were statistically significant. The results of multivariate analysis showed that estrone ( OR=1.04, 95% CI 1.01-1.07, P=0.009) and estrone/androstenedione ( OR=25 008 670.29, 95% CI 8.45-74 015 852 572 024.10, P=0.025) were independently associated with eosinophilic pathology. Conclusions:Adrenocortical hypercortisolism patients with eosinophilic pathology have higher levels of serum cortisol secretion, more pronounced inhibition of the hypothalamic pituitary adrenal axis, more significant metabolic disorders and target organ damage, and higher production of estrone.

HBV/HCV dual infection is not uncommon, especially in highly endemic areas and among individuals at elevated risk of infection, because of the common transmission mode of hepatitis B virus (HBV) and hepatitis C virus (HCV) and may be underestimated due to the presence of occult HBV infection. HBV/HCV dual infection is associated with more rapid progression to advanced severe liver disease, severely increased fibrosis or cirrhosis, liver decompensation, and the development of hepatocellular carcinoma, thus requiring effective antiviral treatment. However, the intracellular interaction between HBV and HCV has not been fully elucidated at present. This paper summarizes the recent research on HBV/HCV dual infection and the current status of treatment and emphasizes the aspects that need further clarification in order to provide a basis for exploring treatment strategies for dual infection.