Diabetic nephropathy (DN), as one of the most common complications of diabetes, is a primary cause of end-stage renal disease. The pathogenesis of DN encompasses processes such as chronic inflammation, recruitment and activation of immune cells, tubular and glomerular injury, and renal fibrosis. These processes are highly correlated with the activation of the nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome and the resulting pyroptosis it mediates. Previous studies have shown that the release of pro-inflammatory cytokines, leakage of damage-associated molecular patterns (DAMPs), recruitment and activation of immune cells can be reduced by regulating the NLRP3 inflammasome and its mediated pyroptosis, thereby slowing the diffusion of inflammatory responses in adjacentcells, fibrosis, and tissue remodeling processes. Ultimately, these process can improve renal injury and dysfunction caused by diabetic nephropathy. This article summarizes the molecular regulatory mechanisms of the NLRP3 inflammasome and its mediated pyroptosis at different pathological stages of DN, proposes potential targets for regulating their activation, aiming to provide a new direction for personalized treatment of DN.

Elderly breast cancer patients have different characteristics from young breast cancer patients,and their treat-ment faces many challenges.The treatment for elderly patients with breast cancer is often based on retrospective studies or evi-dence of general population lacks Class I clinical evidence.This article summarized the relevant clinical studies of advanced breast cancer with different molecular subtypes,explored the optional treatments and development directions for advanced elderly breast cancer,and provided reference for clinicians.

Objective:To investigate the effect of trastuzumab deruxtecan (T-DXd) in the treatment of metastatic breast cancer (MBC) patients with different expression levels of human epidermal growth factor receptor 2 (HER2) and the influencing factors of prognosis.Methods:The retrospective case series analysis and cohort study were conducted. Clinical data of 20 MBC patients with different expression levels of HER2 treated with T-DXd at Xi'an International Medical Center Hospital from August 2021 to August 2023 were retrospectively collected to analyze the efficacy and safety of T-DXd. The Cox proportional hazards model was used for multivariate analysis of prognostic factors.Results:All 20 patients were female, with a median age [ M ( Q1, Q3)] of 49 years old (40 years old, 58 years old). Of the 20 cases, 12 had low expression of HER2 [immunohistochemistry HER2+, or immunohistochemistry ++ and fluorescence in situ hybridization (FISH)-negative], and 8 had overexpression of HER2 (immunohistochemistry HER2+++, or immunohistochemistry ++ and FISH-positive); median number of lines of treatment with T-DXd was 6 lines (3 lines, 7 lines); 14 patients had partial remission, 3 patients had stable disease, and 3 patients had disease progression, with an objective remission rate (ORR) of 70% (14/20) and a disease control rate of 85% (17/20). Eight patients with overexpression of HER2 had objective remission in 6 cases, and 12 patients with low expression of HER2 had objective remission in 8 cases, and the ORR difference between the two groups was not statistically significant ( P = 1.000). The main adverse reactions of the patients were nausea (14 cases), vomiting (12 cases), leukopenia (10 cases), elevated aspartate aminotransferase (10 cases), elevated alanine aminotransferase (9 cases), anemia (8 cases), fatigue (8 cases), alopecia (8 cases), neutropenia (6 cases), and thrombocytopenia (5 cases); ≥ grade 3 adverse reactions were bone marrow suppression and gastrointestinal reactions, all with an incidence of ≤10%. The median follow-up time was 7.1 months (1.9 months, 11.5 months). The median progression-free survival (PFS) time was 6.5 months (95% CI: 3.9-9.1 months), and the median PFS time of patients with overexpression of HER2 was longer than that of patients with low expression of HER2 [7.0 months (95% CI: 6.4- 7.6 months) vs. 4.0 months (95% CI: 1.7-6.3 months)], and the difference in PFS between the two groups was statistically significant ( P = 0.025). Multivariate Cox regression analysis showed that overexpression of HER2 was an independent protective factor for PFS in MBC patients treated with T-DXd ( HR = 0.265, 95% CI: 0.075-0.945, P = 0.041). Conclusions:MBC patients with overexpression or low expression of HER2 have a good therapeutic effect and safety profile when treated with T-DXd. The overexpression of HER2 may predict good PFS in MBC patients treated with T-DXd, and may serve as a biomarker for predicting PFS in such patients, but it may not affect the ORR.

Objective To investigate the mechanism of Yes-associated protein 1(YAP1)ameliorating aristolochic acid 1(AAI)-induced liver injury in mice based on untargeted metabolomics techniques.Methods There were 83-week-old male hepatocyte-specific Yap1 gene knockout mice(genotyped as Yap1Flox/Flox,Albumin-Cre,aka.Yap1LKO)were randomly selected as the Yap1LKO+AAI group,and 8 Yap1Flox control mice as the Yap1Flox+AAI group.Both groups were injected intraperitoneally with AAI at a dose of 2.5 mg·kg-1·d-1 for 14 consecutive days.Genotypes were identified by tail PCR;serum alanine transaminase(ALT)and aspartate transaminase(AST)activities were determined by microplate assay;histopathological changes of liver tissue were observed by HE staining;and the protein expression of YAP1 in liver tissue was determined by immunohistochemistry.The untargeted metabolomics approach was used to analyze the liver tissue differential metabolites,and the samples were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbit trap high-resolution mass spectrometry,and the differential metabolites were screened by principal component analysis(PCA),Partial least square-discriminant analysis(PLS-DA),and orthogonal partial least squares-discriminant analysis(OPLS-DA);using HMDB database and METLIN database to identify metabolites,and the pathway enrichment of differential metabolites was analyzed by KEGG database.Results(1)After 14 days of AAI induction,the increase of body mass in Yap1LKO mice was lower than that in Yap1Flox mice,but there was no statistical significance(P＞0.05).On day 14,compared with the Yap1Flox+AAI group,the serum ALT and AST enzyme activities in the Yap1LKO+AAI group of mice were significantly increased(P＜0.05),and the histopathological damage of the liver was significantly aggravated.The livers of the Yap1Flox mice had a positive protein expression of YAP1,whereas the Yap1LKO mice did not have a positive protein expression of YAP1.(2)A total of 139 differential metabolites with significant changes(VIP＞1 and P＜0.05)were screened by metabonomic analysis;compared with Yap1LKO+ AAI group,62 liver metabolites in Yap1Flox+AAI group were up-regulated,including choline,taurine,hypotaurine,α-linolenic acid,eleostearic acid,chenodeoxycholic acid and so on.Seventy-seven metabolites were down-regulated including glycerophosphocholine,L-phosphatidylcholine,L-glutamine,L-serine,L-glutathione,5-methionine,phenylalanine,glucose 6-phosphate,lactic acid,uric acid glycosides,etc..KEGG-enriched pathways were mainly choline metabolism,glycerophospholipid metabolism,insulin resistance,glutathione metabolism,etc..Conclusion Hepatocyte-specific Yap1 gene knockout exacerbated AAI-induced liver injury in mice,and YAP1 was involved in the regulation of choline metabolism and glycerophospholipid metabolism through the up-regulation of unsaturated fatty acids,such as choline and taurine,which ameliorated AAI-induced liver injury in mice.

Objective To observe the promoting effect of pulsed shortwave therapy on wound healing in pediatric patients with upper limb burns and explore its underlying mechanisms.Methods A total of 40 children with deep Ⅱ ° upper limb burns treated in our hospital from June 2021 to June 2023 were enrolled,and randomly divided into a control group and an observation group,with 20 cases in each group.The control group received conventional dressings,and the observation group received conventional dressings combined with pulsed shortwave therapy.The wound healing time,first appearance of skin islands on the wound,and initial number of skin islands were observed and recorded using a camera.The proportion of granulation tissue area in the wound was observed using eKare inSight 3D.The positive rate of wound bacteria was detected by collecting wound secretions for bacterial culture examination.Blood flow perfusion on the wound was measured using a blood flow meter.Results The observation group showed significantly faster wound healing and initial appearance of epithelialization(P＜0.05),and obviously higher rate of granulation tissue growth than the control group(P＜0.05).Moreover,the observation group demonstrated better control of bacterial infection in the wounds than the control group(P＜0.05).Blood flow measurement results revealed no significant increase in blood flow perfusion after pulsed shortwave therapy in the observation group(P＞0.05).However,with the elapse of time,both groups exhibited an increasing trend in blood flow perfusion(P＜0.05).Conclusion Pulsed shortwave therapy effectively promotes wound healing in pediatric patients with burns,by facilitating necrotic tissue clearance and granulation tissue regeneration,which may be associated with its non-thermal effects.

The effect of anti-programmed cell death 1 (anti-PD-1) immunotherapy is limited in patients with hepatocellular carcinoma (HCC). Yes-associated protein 1 (YAP1) expression increased in liver tumor cells in early HCC, and Akkermansia muciniphila abundance decreased in the colon. The response to anti-PD-1 treatment is associated with A. muciniphila abundance in many tumors. However, the interaction between A. muciniphila abundance and YAP1 expression remains unclear in HCC. Here, anti-PD-1 treatment decreased A. muciniphila abundance in the colon, but increased YAP1 expression in the tumor cells by mice with liver tumors in situ. Mechanistically, hepatocyte-specific Yap1 knockout (Yap1^LKO) maintained bile acid homeostasis in the liver, resulting in an increased abundance of A. muciniphila in the colon. Yap1 knockout enhanced anti-PD-1 efficacy. Therefore, YAP1 inhibition is a potential target for increasing A. muciniphila abundance to promote anti-PD-1 efficacy in liver tumors. Dihydroartemisinin (DHA), acting as YAP1 inhibitor, increased A. muciniphila abundance to sensitize anti-PD-1 therapy. A. muciniphila by gavage increased the number and activation of CD8⁺ T cells in liver tumor niches during DHA treatment or combination with anti-PD-1. Our findings suggested that the combination anti-PD-1 with DHA is an effective strategy for liver tumor treatment.

Objective:To evaluate the effect of different doses of compound sodium chloride injection combined with norepinephrine on prevention of hypotension after lumbar anesthesia in the patients undergoing caesarean section.Methods:A total of 150 patients with a singleton fetus, aged 18-45 yr, at ≥37 weeks of gestation, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, with height ≥150 cm, weighing ≤100 kg, with body mass index < 40 kg/m 2, scheduled for elective caesarean section under lumbar anesthesia, were divided into 3 groups ( n=50 each) by the random number table method: compound sodium chloride injection 4, 8 and 12 ml·kg -1·h -1 groups (group A, group B, group C). Compound sodium chloride injection 4 ml/kg was intravenously injected for liquid preload before lumbar anesthesia, and 0.5% hyperbaric bupivacaine 12.5 mg was injected to the subarachnoid space for lumbar anesthesia. Norepinephrine was intravenously injected at a dose of 6 μg immediately after intrathecal injection, followed by an infusion of 0.05 μg·kg -1·min -1, and infusion was stopped at 5 min after delivery. Compound sodium chloride injection was intravenously infused simultaneously at a rate of 4, 8 and 12 ml·kg -1·h -1 in A, B and C groups, respectively. The maximum diameter of inferior vena cava (IVCmax) and the minimum diameter of inferior vena cava (IVCmin) were measured by ultrasound, and inferior vena cava collapse index (IVC-CI) was calculated at 1 min before fluid preload (T 1), immediately after fluid preload (T 2), at 5 min after anesthesia (T 3), at 5 min after fetal delivery (T 4) and immediately before leaving the operating room (T 5). The incidence of intraoperative adverse events (hypotension, severe hypotension, bradycardia, hypertension, nausea, and vomiting) and neonatal outcomes (umbilical artery blood gas index and Apgar score at 1 and 5 min after birth) were recorded. Results:Compared with group A, IVCmin was significantly increased and IVC-CI was decreased at T 5 in group B, and IVCmin and IVCmax were significantly increased and IVC-CI was decreased at T 5 in group C ( P<0.05). There was no significant difference in IVCmax, IVCmin and IVC-CI at each time point between group B and group C ( P>0.05). There was no significant difference in the incidence of hypotension, severe hypotension, bradycardia, hypertension, nausea and vomiting among the three groups ( P>0.05). There was no significant difference in the results of blood gas analysis of the umbilical artery and Apgar score at each time point after birth among the three groups ( P>0.05). Conclusions:Compound sodium chloride injection 4, 8 and 12 ml·kg -1·h -1 combined with norepinephrine can effectively prevent the occurrence of hypotension after lumbar anesthesia in the patients undergoing caesarean section without increasing maternal and infant adverse events, and the effect of 8 and 12 ml·kg -1·h -1 for volume supplementation is better than that of 4 ml·kg -1·h -1.

【Objective】 In recent years, granulocyte colony stimulating growth factor (G-CSF) has been proved to be expressed in the posterior capsule of the lens of posterior capsular opacification (PCO), but its specific role remains unclear. The purpose of this study was to explore whether G-CSF plays a role in PCO. 【Methods】 First, human lens epithelial cells (HLEC-B3) were treated with different concentration of recombinant G-CSF protein and screened for effective appropriate concentration. Then, Western blotting was used to detect the effects of extracellular matrix (ECM) synthesis and epithelial mesenchymal transdifferentiation (EMT) marker genes after G-CSF treatment on HLEC-B3 cells. Finally, the effects of G-CSF treatment on the migration and invasion of HLEC-B3 cells were detected by scratch experiment and Transwell test. 【Results】 G-CSF at 80 μg/L could promote the proliferation of HLEC-B3 cells. After G-CSF was treated for 48 h, the expressions of EMT and ECM synthesis marker genes in HLEC-B3 cells were significantly upregulated with time. G-CSF could significantly promote HLEC-B3 cell invasion after 48 h induction. Similarly, G-CSF could also significantly induce cell migration compared to the CTRL group. 【Conclusion】 G-CSF can promote the proliferation, migration and invasion of HLEC-B3 cells, as well as EMT and ECM synthesis, which might be involved in the occurrence of PCO. Inhibiting the expression of G-CSF may be a new strategy for PCO prevention.

Objective To evaluate the effect of labor analgesia on maternal and neonatal outcomes. Methods The medical records of mature puerperas with singleton pregnancy from October 2018 to April 2019 at the General Hospital of Ningxia Medical University were retrospectively reviewed. Puerperas were divided into non-labor analgesia group ( NLA) and labor analgesia group ( LA) according to whether or not puerperas received labor analgesia. Maternal and neonatal outcomes were analyzed. Maternal outcomes in-cluded delivery mode, complications, intrapartum hemorrhage and blood loss at 24 h after birth, duration of the second stage of labor and prolongation, episiotomy and length of hospital stay after birth. Neonatal outcomes included Apgar score at 1, 5 and 10 min after birth, cases of Apgar score＜7 at 5 min after birth, and the proportion and reason of transfer to pediatrics unit. Results A total of 839 puerperas were includ-ed, with 551 cases in NLA group and 288 cases in LA group. Compared with NLA group, the second stage of labor was significantly prolonged ( P＜0. 01) , and no significant change was found in the other maternal or neonatal outcomes in LA group ( P＞0. 05) . Conclusion Labor analgesia can prolong the second stage of labor and exerts no effect on the neonatal outcomes.

Objective To investigate whether capsular polysaccharides of Streptococcus pneumoniae serotypes 6A and 6B contained in 13-valent pneumococcal conjugate vaccine ( PCV13 ) could induce cross- protective antibodies against newly discovered serotypes 6C and 6D and the differences between them. Methods New Zealand rabbits were radomly divided into three groups and respectively muscularly administrated with three doses of PCV13, PCV6A and PCV6B on days 0, 14 and 28. PCV6A and PCV6B were conjugates of capsular polysaccharides of serotypes 6A and 6B chemically coupled with diphtheria toxin mutant CRM197. Serum samples were collected on days 0 and 35. Enzyme-linked immunosorbent assay (ELISA) recommended by World Health Organization (WHO) was used to quantitatively measure serotype-specific antibodies to capsular polysaccharides of serotypes 6A, 6B, 6C and 6D. Opsonophagocytosis assay ( OPA) of WHO pneumococcal serology reference laboratory was used to determine antibody functional activities targeting serotypes 6A, 6B, 6C and 6D. Results Immunization rabbits with PCV13 induced the secretion of antibodies to capsular polysaccharides of serotypes 6A and 6B. These antibodies were able to not only cross-react with capsular polysaccharides of serotypes 6C and 6D but also recognize and bind to target Streptococcus pneumoniae serotypes 6A, 6B, 6C and 6D, resulting in the activation of complements and further phagocytosis of target bacteria by differentiated HL60 cells. Bactericid-al titers were largely even among these serotypes except for serotype 6D which was slightly lower. PCV6A could induce antibody against capsular polysaccharide of serotype 6A, which was able to cross-react with capsular pol-ysaccharides of serotypes 6B, 6C and 6D and showed higher bactericidal titers to serotypes 6A, 6B and 6C over serotype 6D. PCV6B could induce antibody against capsular polysaccharide of serotype 6B, which was able to cross-react with capsular polysaccharides of serotypes 6A, 6C and 6D and showed higher bactericidal titers to se-rotypes 6A, 6B and 6C over serotype 6D. Antibody concentrations and bactericidal titers specific to serotypes 6A, 6B, 6C and 6D were significantly increased following immunization with PCV13, PCV6A or PCV6B (P<0. 01). Conclusion PCV13 containing pneumococcal serotypes 6A and 6B induced antibodies against capsular polysaccharides of serotypes 6A and 6B in New Zealand rabbits, which were able to cross-react with capsular polysaccharides of serotypes 6C and 6D and provide cross-protection to bacteria of serotypes 6C and 6D. Both serotypes of 6A and 6B contained in PCV13 contributed to the induction of cross-protective antibodies, especially to serotype 6C.