The Huangdi Neijing proposes the " using bitter herbs to nourish or purge" theory to guide clinical prescription and formulation of herbal remedies based on the physiological characteristics and functions of the five zang viscera, along with the properties and flavors of medicinal herbs. This study explored diabetic kidney disease pathogenesis and treatment based on the " using bitter herbs to nourish or purge" theory. Kidney dryness is a key pathological factor in diabetic kidney disease, and the disharmony of kidney dryness is an essential aspect of its pathogenesis. Strengthening is the primary therapeutic principle, and kidney dryness is a persistent factor throughout the occurrence and progression of diabetic kidney disease. In the early stage, the pathogenesis involves heat-consuming qi and injuring yin, leading to kidney dryness. In the middle stage, the pathogenesis manifests as qi deficiency and blood stasis in the collaterals, resulting in turbidity owing to kidney dryness. In the late stage, the pathogenesis involves yin and yang deficiency, with kidney dryness and disharmony. This study proposes the staging-based treatment based on the " need for firmness" characteristic of the kidney. The aim is to provide new insights for clinical diagnosis and treatment in traditional Chinese medicine by rationally using pungent, bitter, and salty medicinal herbs to nourish and moisturize the kidney. This approach seeks to promote precise syndrome differentiation and personalized treatment for different stages of diabetic kidney disease, thereby enhancing clinical efficacy.

Obesity usually exacerbates the immunosuppressive tumor microenvironment (ITME), hindering CD8⁺ T cell infiltration and function, which further represents a significant barrier to the efficacy of immunotherapy. Herein, a multifunctional liposomal system (CR-Lip) for encapsulating celastrol (CEL) was utilized to remodel obesity-related ITME and improve cancer immunotherapy, wherein Ginsenoside Rg3 (Rg3) was detected interspersed in the phospholipid bilayer and its glycosyl exposed on the surface of the liposome. CR-Lip had a relatively uniform size (116.5 nm), facilitating favorable tumor tissue accumulation through the interaction between Rg3 and glucose transporter 1 overexpressed in obese tumor cells. Upon reaching the tumor region, CR-Lip was found to induce the immunogenic cell death (ICD) of HFD tumor cells. Notably, the level of PHD3 in HFD tumor cells was effectively boosted by CR-Lip to effectively block metabolic reprogramming and increase the availability of major free fatty acids fuel sources. In vivo, experiments studies revealed that the easy-obtained nano platform stimulated enhanced the production of various cytokines in tumor tissues, DC maturation, CD8⁺ T-cell infiltration, and synergistic anticancer therapeutic potency with aPD-1 (tumor inhibition rate = 82.1%) towards obesity-related melanoma. Consequently, this study presented an efficacious approach to tumor immunotherapy in obese mice by encompassing tumor eradication, inducing ICD, and reprogramming metabolism. Furthermore, it offered a unique insight into a valuable attempt at the immunotherapy of obesity-associated related tumors.

Objective To explore the mechanism underlying the protective effect of α2-macroglobulin (A2M) against glucocorticoid-induced femoral head necrosis. Methods In a human umbilical vein endothelial cell (HUVEC) model with injuries induced by gradient concentrations of dexamethasone (DEX;10-8-10-5 mol/L), the protective effects of A2M at 0.05 and 0.1 mg/mL were assessed by examining the changes in cell viability, migration, and capacity of angiogenesis using CCK-8 assay, Transwell and scratch healing assays and angiogenesis assay. The expressions of CD31 and VEGF-A proteins in the treated cells were detected using Western blotting. In BALB/c mouse models of avascular necrosis of the femoral head induced by intramuscular injections of methylprednisolone, the effects of intervention with A2M on femoral trabecular structure, histopathological characteristics, and CD31 expression were examined with Micro-CT, HE staining and immunohistochemical staining. Results In cultured HUVECs, DEX treatment significantly reduced cell viability, migration and angiogenic ability in a concentration- and time-dependent manner (P<0.05), and these changes were obviously reversed by treatment with A2M in positive correlation with A2M concentration (P<0.05). DEX significantly reduced the expression of CD31 and VEGF-A proteins in HUVECs, while treatment with A2M restored CD31 and VEGF-A expressions in the cells (P<0.05). The mouse models of femoral head necrosis showed obvious trabecular damages in the femoral head, where a large number of empty lacunae and hypertrophic fat cells could be seen and CD31 expression was significantly decreased (P<0.05). A2M treatment of the mouse models significantly improved trabecular damages, maintained normal bone tissue structures, and increased CD31 expression in the femoral head (P<0.05). Conclusion A2M promotes proliferation, migration, and angiogenesis of DEX-treated HUVECs and alleviates methylprednisolone-induced femoral head necrosis by improving microcirculation damages and maintaining microcirculation stability in the femoral head.

Objective To explore the mechanism underlying the protective effect of α2-macroglobulin (A2M) against glucocorticoid-induced femoral head necrosis. Methods In a human umbilical vein endothelial cell (HUVEC) model with injuries induced by gradient concentrations of dexamethasone (DEX;10-8-10-5 mol/L), the protective effects of A2M at 0.05 and 0.1 mg/mL were assessed by examining the changes in cell viability, migration, and capacity of angiogenesis using CCK-8 assay, Transwell and scratch healing assays and angiogenesis assay. The expressions of CD31 and VEGF-A proteins in the treated cells were detected using Western blotting. In BALB/c mouse models of avascular necrosis of the femoral head induced by intramuscular injections of methylprednisolone, the effects of intervention with A2M on femoral trabecular structure, histopathological characteristics, and CD31 expression were examined with Micro-CT, HE staining and immunohistochemical staining. Results In cultured HUVECs, DEX treatment significantly reduced cell viability, migration and angiogenic ability in a concentration- and time-dependent manner (P<0.05), and these changes were obviously reversed by treatment with A2M in positive correlation with A2M concentration (P<0.05). DEX significantly reduced the expression of CD31 and VEGF-A proteins in HUVECs, while treatment with A2M restored CD31 and VEGF-A expressions in the cells (P<0.05). The mouse models of femoral head necrosis showed obvious trabecular damages in the femoral head, where a large number of empty lacunae and hypertrophic fat cells could be seen and CD31 expression was significantly decreased (P<0.05). A2M treatment of the mouse models significantly improved trabecular damages, maintained normal bone tissue structures, and increased CD31 expression in the femoral head (P<0.05). Conclusion A2M promotes proliferation, migration, and angiogenesis of DEX-treated HUVECs and alleviates methylprednisolone-induced femoral head necrosis by improving microcirculation damages and maintaining microcirculation stability in the femoral head.

Mitophagy is a process by which cells selectively eliminate damaged or dysfunctional mitochondria through the autophagy-lysosomal pathway under the regulation of mitophagy-related proteins to maintain mitochondrial quality and cellular homeostasis,and it is closely related to the occurrence and development of a variety of tumors.Increasing studies have shown that mitophagy plays a dual role in breast cancer progression.① Mitophagy promotes breast cancer cell survival and invasion by triggering energy metabolic reprogramming,reducing ROS accumulation and maintaining mitochondrial homeostasis.②Mitophagy leads to death or apoptosis of breast cancer cells by attenuating inflamma-tory responses and triggering mitochondrial damage.The relevant mechanisms include①PTEN induced kinase 1,PINK1(PINK1)/Parkin pathway;② autophagy receptor-associated protein pathway(including BNIP3,BNIP3L and FUNDC1);③ mitochondrial division pathway.This review summarizes the role and mechanism of mitophagy in the hopes of providing reference for research and treatment of breast cancer.

Objective:To investigate the application value of Th1/Th2 cytokines,interleukin-17(IL-17)and serum tumor markers in the diagnosis,prognosis and recurrence of breast cancer.Methods:A total of 200 patients with breast cancer admitted to Inner Mongolia Hospital of Peking University Cancer Hospital from December 2021 to December 2022 were selected,and they were divided into negative group(60 cases),weakly positive(80 cases)group and positive group(60 cases)according to immunohistochemistry indicators.In addition,another 60 persons who underwent physical examination were selected as healthy control group.The changes of the Th1/Th2,IL-17,CA125,CYFRA21-1,CA153 and CEA levels were observed,and the clinical value of the combined detection of the 6 indicators in predicting the prognosis and recurrence of breast cancer was investigated.Results:The results of comparative analysis indicated that the clinical pathological features related to recurrence,histological grading,tumor diameter and lymph node metastasis(x2=7.552,12.037,12.063,8.543,P＜0.05),respectively.Multivariate analysis showed that tumor recurrence,tissue grading,tumor diameter and lymph node metastasis were the important factors for the prognosis of patients with breast cancer(OR=3.096,3.050,3.425,3.031,P＜0.05).Compared with the single prediction of Th1/Th2,IL-17,CA125,CYFRA21-1,CA153 and CEA,the combined prediction of 6 indicators had higher clinical value for prognosis and recurrence of patients with breast cancer,which sensitivity,accuracy and specificity were respectively 96%,93.46%and 85%.Conclusion:The observation on the changes of the combined predictive levels of 6 items,which include Th1/Th2,IL-17,CA125,CYFRA21-1,CA153 and CEA of patients,indicates that the combined detection has high sensitivity and accuracy.This highly efficient and convenient detection method can provide references for improving the prognosis,reducing the recurrence and enhancing the accuracy of assessment.

Objective:To investigate the efficacy and safety of the application of microwave ablation assisted clamp-less suture-less nephron sparing surgery technique in the management of cystic renal cell carcinoma.Methods:The data of 21 consecutive patients with cystic renal cell carcinoma who underwent microwave ablation assisted clamp-less suture-less laparoscopic nephron sparing surgery (MACS-LNSS) in Renji Hospital, Shanghai Jiaotong University School of Medicine from January 2017 to December 2020, were retrospectively analyzed. There were 17 males and 4 females with a mean age of (58.0±2.6) years old. There were 19 cases with Eastern Cooperative Oncology Group (ECOG) score 0 and 2 with score 1. The mean diameter of the tumor was (3.6±0.4) cm, and the mean distance from the collecting system was (10.7±0.9) mm with 12 located on the left and 9 on the right side. There were 5 cases of Bosniak Ⅲ with mean CT value (27.6±4.6) HU and 16 of Bosniak Ⅳ and the mean estimated glomerular filtration rate(eGFR) was (84.1±4.1 ) ml/(min·1.73 m 2). The American Society of Anesthesiology (ASA) graded 17 cas as grade 1, 3 cases as grade 2 and 1 cases as grade 3. MACS-LNSS was performed for all patients. The microwave ablation probe was introduced via the laparoscopic trocar and inserted into the tumor. Then all tumors were resected after microwave ablation was performed for 1 to 3 cycles lasting 2 to 5 minutes for each tumour with a power output of 60 to 100 W using an MTC-3C microwave ablation system. Results:MACS-LNSS was successfully performed in 20 cases. Another one converted to conventional laparoscopic partial nephrectomy because of intraoperative bleeding with 14 min renal artery branch clamped. No case converted to open surgery or radical nephrectomy. The mean operative time was (92.0±6.3) min, with a mean estimated blood loss of (60.0±7.2) ml. The mean length of postoperative hospital stay was (2.7±0.1) d. No case required perioperative transfusion. One case with fever and one case with urine leakage were observed postoperatively and recovered after conservative treatment. Pathologic results revealed 18 cases of clear cell carcinoma, 3 of low grade malignant potential multilocular cystic renal cell tumors. The median eGFR at 6 months postoperative was (82.9±3.8) ml/(min·1.73 m 2).No local recurrence and distant metastasis was observed with a mean follow-up of (41.3±1.5)(range from 32 to 58) months. Conclusions:MACS-LNSS which has the advantages of controllable complications is an alternative, safe and feasible technique for cystic renal cell carcinoma less than 7 cm, with regular tumor base, and the distance from the collecting system more than 5 mm.

The safety and efficacy of laparoscopic surgery for colorectal cancer has been confirmed by several large-scale clinical studies.Laparoscopy has become the main modality of surgical treatment for colorectal cancer in China.Based on evidence-based medicine and the experience accumulated in clinical practice,laparoscopic colorectal surgical techniques are still being continuously optimised and improved.The key techniques mainly revolve around the following three aspects:①complete surgical excision extension;②appropriate lymph node dissection area;③safe digestive tract reconstruction.Prioritizing the standardization of laparoscopic colorectal cancer surgery,promoting the consistent implementation of these procedures,establishing a scientific evaluation system,thoroughly assessing surgical outcomes,and conducting high-quality clinical research are essential for enhancing the standardization of laparoscopic colorectal cancer surgery in China.

Objective:To study the effects and the related molecular mechanisms of miR-148a-3p on the proliferation,invasion and migration of salivary adenoid cystic carcinoma SACC-LM cells.Methods:miR-148a-3p mimics and inhibitors,siRNA targeting EG-FR and their corresponding controls were transfected into SACC-LM cells.Bioinformatics was used to predict the potential target genes of miR-148a-3p.EGFR and miR-148a-3p mRNA expression levels were examined by qRT-PCR and the protein levels of EG-FR were detected by Western blotting.CCK-8,scratch,and Transwell assays were used to study the proliferation,migration,and invasion of SACC-LM cells,respectively.The direct targeting relationship between miR-148a-3p and EGFR was examined by using the double luciferase reporter gene assay.Statistical analysis of the data was performed by SPSS 22.0 software.Results:Overexpres-sion or inhibition of miR-148a-3p significantly inhibited or promoted the proliferation,invasion and metastasis of SACC-LM cells re-spectively(P＜0.05).Bioinformatics and double luciferase assay showed that miR-148a-3p directly targeted and regulated the expres-sion of EGFR(P＜0.001).Downregulation of EGFR inhibited the proliferation,migration and invasion of SACC-LM cells(P＜0.05)and partially reversed the promoting effect of miR-148a-3p inhibition(P＜0.05).Conclusion:The downregulation of miR-148a-3p leads to the abnormally high expression of its target gene EGFR,and promotes the proliferation,invasion,and migration of salivary adenoid cystic carcinoma cells.

Objective To explore the relationship between serum lipoxygenin A4(LXA4)and S100 calc-binding protein A4(S100A4)levels and disease and disease outcome in children with primary nephrotic syn-drome(PNS).Methods A total of 168 children with PNS admitted to Nanjing Mingji Hospital from March 2020 to March 2022 were selected as the study objects,and 150 healthy children who came to Nanjing Mingji Hospital for physical examination were selected as the control group.The children with PNS were divided into remission group(n=73)and attack group(n=95)according to disease activity.Serum LXA4 and S100A4 levels were detected by enzyme-linked immunosorbent assay.The patients were followed up for 1 year after discharge and were divided into good prognosis group(n=138)and poor prognosis group(n=30)according to the prognosis.Spearman correlation analysis was used to investigate the relationship between serum LXA4,S100A4 levels and disease activity.The predictive value of serum LXA4 and S100A4 in the prognosis of PNS children was evaluated by receiver operating characteristic(ROC)curve.Multivariate Logistic regression was used to analyze the prognostic factors of PNS children.Results The serum levels of LXA4 and S100A4 in the remission group and the attack group were higher than those in the control group,and the serum levels of LXA4 and S100A4 in the attack group were higher than those in the remission group(P＜0.05).The serum levels of LXA4 and S100A4 were positively correlated with disease activity in children with PNS(r=0.593,0.546,P＜0.05).The good prognosis group had significantly lower serum levels of LXA4 and S100A4 than the poor prognosis group(P＜0.05).The area under the curve(95％CI)of serum LXA4 and S100A4 for pre-dicting the outcome of PNS in children was 0.767(0.756-0.888)and 0.846(0.824-0.863),respectively.The area under the curve of the joint(95％CI)was 0.905(0.879-0.924).Compared with the good progno-sis group,the poor prognosis group had significantly higher proportion of nephritis type,24 h urinary protein,hematuria,and urine protein clearance time,and significantly lower proportion of simple type,total protein,and IgM levels(P＜0.05).The multivariate Logistic regression analysis showed that hematuria(OR=2.300,95％CI 1.598-3.312),24 h urinary protein 121.25 mg/24 h(OR=2.098,95％CI 1.489-2.956),LXA4≥95.64 ng/L(OR=2.627,95％CI 1.737-3.973),and S100A4≥248.15 ng/L(OR=2.729,95％CI 1.777-4.192)were risk factors for poor prognosis in children with PNS(P＜0.05).Conclusion The serum levels of S100A4 and LXA4 are increased in children with PNS,and are related to disease activity and progno-sis,which may be used as potential markers for evaluating the condition and prognosis of PNS.