Objective To investigate the potential mechanism of nicotinamide combined with amphotericin B against Candida albicans based on metabolomics. Methods The intracellular metabolites of C. albicans intervened by different drugs including NAM, AmB, and their combination with a proper concentration were analyzed by gas chromatography-mass spectrometry. The differential metabolites were screened by multivariate statistical analysis and identified by searching the NIST database. Results Compared with the control group, the NAM intervention group was hardly separated from it, while the AmB group and NAM+AmB group showed a clear trend of separation. Under the intervention of AmB, 23 metabolites significantly changed compared with the control group, and 28 metabolites remarkably changed after NAM+AmB intervention, including amino acids, organic acids, sugars and other components. Conclusion NAM, as an endogenous metabolite of C. albicans, combined with AmB could enhance the effects of AmB in the original metabolic pathway and changed it to a certain extent. It was speculated that AmB combined with NAM may pose more antifungal effect on Candida albicans by regulating the tricarboxylic acid cycle，interfering with amino acid metabolism and influencing polyamine synthesis.

Objective: To develop a RHCE genotyping assay based on kompetitive allele-specific PCR (KASP) and assess its clinical accuracy for RhCE blood group determination. Methods: KASP primers were designed to interrogate three RHCE loci: the 109 bp insertion/deletion in intron 2, c. 307T>C, and c. 676C>G. A total of 1 194 RhD-positive inpatients from Chengdu were typed by both KASP genotyping and manual tube serology. Discordant samples (n=10) were retested by both methods and further resolved by Sanger sequencing. An additional 377 cases were tested for the c. 48C>G locus to evaluate the predictive accuracy of individual loci and combined locus testing for RhC antigen. Results: Genotyping concordance with serology was 100.0% for both the c. 676C>G locus (RhE/Rhe) and the c. 307T>C locus (Rhc). For RhC prediction using the 109 bp insertion, overall accuracy was 99.7% (1 191/1 194); the 3 discordant cases were confirmed by Sanger sequencing to be false negatives attributable to 109 bp deletion in intron 2. Testing the c. 48C>G allele for RhC prediction yielded 7 false positives, with an accuracy of 98.1% (370/377). RhC antigen status was determined by combining the 109 bp insertion and the c. 48C allele. After excluding 10 samples with inconsistent results between the two loci, the accuracy reached 100% in the remaining 367 samples. When both loci were applied in combination, accuracy reached 100% in the 367 cases with concordant results. Among the 1 194 patients, CCee (45.8%) and CcEe (31.7%) were the most common RhCE phenotypes. The e antigen had the highest positivity rate (92.2%), and the Ce haplotype was the most frequent (66.9%). Conclusion: The KASP-based RHCE genotyping method achieves high accuracy for clinical RhCE typing. Combining the 109 bp insertion/deletion with the c. 48C allele significantly improves RhC antigen prediction compared with either locus alone. This method was applied to RhCE genotyping of 1 194 RhD-positive inpatients in Chengdu, providing local RhCE phenotype and haplotype distribution data to support RhCE-matched transfusion practice.

Objective To evaluate the impact of an integrated management mode of prenatal diagnosis-postnatal treatment for congenital heart disease (CHD) on perioperative and long-term outcomes of the arterial switch operation (ASO), and to analyze the efficacy of ASO in a single center. Methods This retrospective study analyzed the clinical data of 183 children who underwent ASO at Guangdong Provincial People’s Hospital from 2018 to 2024. The cohort included 106 (57.9%) patients of transposition of the great arteries with intact ventricular septum (TGA/IVS), 61 (33.3%) patients of transposition of the great arteries with ventricular septal defect (TGA/VSD), and 16 (8.7%) patients of Taussig-bing anomaly (TBA). Perioperative indicators were compared between 91 patients in the prenatal-postnatal integrated management group (an integrated group) and 92 patients in the traditional management group (a non-integrated group). Long-term survival and reoperation rates were analyzed using Kaplan-Meier curves. Results The overall perioperative mortality rate was 4.9% (9/183), showing a downward trend year by year. The primary cause of perioperative mortality was low cardiac output syndrome (LCOS), which occurred in 12 patients (6.6% incidence) with a mortality rate of 75.0%. The integrated group had a higher proportion of males (89.0% vs. 72.8%, P<0.05) and lower body weight [3.1 (2.7, 3.3) kg vs. 3.3 (3.0, 3.7) kg, P<0.05] compared to the non-integrated group. The age at surgery was significantly earlier in the integrated group [7 (3, 10) d vs. 14 (9, 48) d, P<0.05], and all children in the integrated group underwent ASO within the optimal surgical window (100.0% vs. 82.6%, P<0.05). Intraoperatively, cardiopulmonary bypass time [173 (150, 207) min vs. 186 (159, 237) min, P<0.05] and aortic cross-clamp time [100 (90, 117) min vs. 116 (97, 142) min, P<0.05] were significantly shorter in the integrated group. Although the integrated group had longer postoperative mechanical ventilation time [145 (98, 214) h vs. 116 (77, 147) h, P<0.05] and higher 48-hour maximum vasoactive inotropic score [15 (10, 21) points vs. 12 (8, 16) points, P<0.05], there was no statistically significant difference in the incidence of severe complications (LCOS, necrotizing enterocolitis, extracorporeal membrane oxygenation) or mortality rate (3.3% vs. 6.5%, P=0.51) between the two groups, despite earlier surgical intervention and a higher proportion of critically ill cases in the integrated group. The length of hospital stay in the emergency surgery group was significantly shorter than that in the elective surgery group [20 (15, 28) d vs. 25 (21, 30) d, P<0.05], suggesting that early surgery may be of potential benefit. A total of 163 patients were successfully followed up for a median of 4.7 years, with a 5-year survival rate of 95.1% and a freedom from reintervention survival rate of 95.1%. There were no late deaths, and the most common postoperative complication was pulmonary artery stenosis. Conclusion The integrated management model allowed critically ill children with lower body weights to safely undergo surgery, significantly optimizing the timing of surgery and shortening intraoperative times. The long-term risk of reoperation after ASO is primarily concentrated on pulmonary artery stenosis, necessitating long-term follow-up and monitoring.

Background Lead is a typical persistent environmental pollutant that can accumulate in bones for decades. During pregnancy, alterations in calcium metabolism promote the mobilization of bone lead, resulting in secondary exposure; however, the mechanisms by which pregnancy-associated bone lead mobilization affects maternal renal function remain unclear. Objective To investigate the role of mitochondrial dysfunction in pregnancy-related bone lead mobilization-induced renal injury. Methods Newly weaned female Wistar rats were randomly assigned to a control or a lead-exposed group administered either 0.05% sodium acetate or 0.05% lead acetate in drinking water. Following a 4-week lead exposure and a 4-week washout period, the females were co-housed with healthy age-matched males for mating. Rats were sacrificed at early (gestational day 3) and late (gestational day 17) pregnancystages, respectively. Renal histopathology was assessed using hematoxylin and eosin staining staining. Mitochondria-related indicators, including oxidative stress, inflammatory responses, and energy metabolism, were measured. Differential metabolites were identified using serum metabolomics. Results Renal injury in the lead-exposed pregnant rats progressed in a time-dependent manner, characterized by degeneration of proximal tubular epithelial cells, glomerular hyaline changes, and interstitial inflammatory cell infiltration. Repeated measures ANOVA indicated a significant interaction between the treatment factor (lead exposure) and the temporal factor (gestational stage) on renal injury (P<0.001). Further analysis of mitochondrial function-related indicators in late-pregnancy renal tissue revealed that the lead exposure group exhibited significantly increased levels of malondialdehyde (MDA) and reactive oxygen species (ROS) (P<0.05), accompanied by a reduction in superoxide dismutase (SOD) and reduced glutathione (GSH) activities (P<0.05); regarding inflammatory markers, levels of interleukin-18 (IL-18) and interleukin-1β (IL-1β) were elevated (P<0.01), whereas interleukin-33 (IL-33) was decreased in the lead-exposed group (P<0.05); energy metabolism-related indicators, including adenosine triphosphate (ATP) level, Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase activities, and mitochondrial respiratory chain complexes I, III, and V activities, were significantly reduced (P<0.05) in the lead-exposed gorup. The typical differential metabolite N-methylisoleucine, identified through serum metabolomics analysis, was negatively correlated with blood lead levels, kidney injury scores, and IL-1β, while positively correlated with catalase (CAT) activity and Ca²⁺-Mg²⁺-ATPase. Conclusions Mitochondrial dysfunction may play a critical role in renal injury induced by bone lead mobilization during late gestation.

AIM:To evaluate the optimal timing of preoperative intravitreal anti vascular endothelial growth factor(VEGF)therapy in proliferative diabetic retinopathy(PDR)using intraoperative fluorescein angiography(IOFA).METHODS:A retrospective case series study was conducted on patients who underwent vitrectomy for PDR with vitreous hemorrhage(VH)at Sichuan Provincial People's Hospital from January 2023 to February 2025. Patients were divided into three groups according to the interval between intravitreal conbercept injection and surgery: Group A(3 d before surgery), Group B(7 d before surgery), and Group C(14 d before surgery). IOFA was used to assess the number and size of retinal neovascularization(NV). Additional data were collected including preoperative best corrected visual acuity(BCVA), vitreous hemorrhage grading, operative time, frequency of intraoperative endodiathermy, duration of high perfusion pressure, vitreoretinal adhesion grade, postoperative BCVA, and central macular thickness(CMT). Multidimensional analyses were performed.RESULTS:This study enrolled a total of 91 patients(94 eyes)with PDR accompanied by vitreous hemorrhage. Among them, Group A consisted of 31 patients(31 eyes; 18 males, 13 females; mean age 53.26±12.38 y), Group B consisted of 34 patients(37 eyes; 21 males, 13 females; mean age 51.61±14.16 y), and Group C consisted of 26 patients(26 eyes; 18 males, 8 females; mean age 51.00±12.02 y), with baseline characteristics comparable among the three groups(all P>0.05). Comparative analysis of NV visualized via IOFA revealed that both the number and size of NVs were significantly lower in Groups B and C than in Group A(all P<0.0167), while no statistically significant differences were observed between Groups B and C(both P>0.05). No significant differences were found among the three groups regarding other intraoperative parameters, including operation time, frequency of electrocoagulation application, duration of high perfusion pressure, or grading of vitreoretinal adhesion(all P>0.05).CONCLUSION:IOFA confirms that preoperative anti-VEGF therapy administered 7 or 14 d before surgery is more effective than a 3 d interval in suppressing retinal NV activity in PDR patients.

ObjectiveTo explore the effect of oral sodium butyrate on skeletal muscle atrophy in CT26 tumor mice through the gut microbiota-skeletal muscle axis and its potential mechanism. MethodsSixty SPF BALB/c male mice aged 8 weeks were randomly divided into a normal control group (NC, n=18) and a ABX-depleted group (ABX, n=42). The ABX mice were pretreated with a quadruple antibiotic cocktail via oral gavage (0.2 ml per administration, once daily, 6 d per week, for 2 weeks), whereas NC received an equal volume of sterile water. The quadruple antibiotic cocktail consisted of metronidazole (1 g/L), vancomycin (0.5 g/L), ampicillin (1 g/L), and gentamicin (1 g/L). Following successful pretreatment, six mice from each group were randomly selected for gut microbiota sequencing analysis and designated as the Abx group and the NC0 group, respectively. Theremaining mice in ABX were subcutaneously inoculated in the dorsum with 0.2 ml of CT26 cell suspension (at a cell density of 1×10⁷/ml). Then these mice were randomly allocated into three subgroups: a control tumor bearing model group (0_NaB, n=12), a tumor-bearing model group receiving low-dose oral sodium butyrate (L_NaB, n=12), a tumor-bearing model group receiving high-dose oral sodium butyrate (H_NaB, n=12). And mice in NC were inoculated at the same site with 0.2 ml of normal saline. The administration dose for L_NaB was 0.3 g/(kg·d), that for H_NaB was 0.5 g/(kg·d), while NC and 0_NaB were given the same volume of normal saline (0.2ml per time, once daily, 6 d per week, for 4 weeks). The general condition of mice was monitored, and forelimb grip strength gastrocnemius muscle mass and its muscle fiber cross-sectional area were measured for each group. The structural changes in gut microbiota were assessed by 16S rRNA sequencing of cecal contents. Pathological alterations in the intestinal wall were examined via HE staining. Serum and gastrocnemius muscle levels of TNF‑α, IL-6, IL-1β, and LPS were quantified using ELISA. The protein expression of ZO-1 and occludin in the small intestine, as well as proteins associated with the TLR4/MyD88/NF-κB signaling pathway in the gastrocnemius muscle, were detected by Western blot analysis. Results(1) The alpha-diversity in Abx was significantly lower than that in NC0 (P<0.01), a significant decrease of the mass and muscle fiber cross-sectional area of the gastrocnemius (P<0.01), with the majority of gut microbiota being effectively depleted. (2) Compared with NC, the subcutaneous tumors of mice in 0_NaB were prominent, a significant increase of the mass and muscle fiber cross-sectional area of the gastrocnemius, accompanied by a significant decrease in body weight at the end of the 3th and 4th week (P<0.05), and a significant weakening of the forelimb grasping strength at the 5th and 6th week (P<0.01). Compared with 0_NaB, the tumor mass of mice in L_NaB and H_NaB showed a significant decreasing trend, and the grip strength of the forelimbs significantly increased at the 5th and 6th week (P<0.05, P<0.01). (3) Compared with 0_NaB, the Shannon and Observed species indices in α diversity of L_NaB and H_NaB were significantly increased (P<0.05). At the genus level, compared with 0_NaB, L_NaB exhibited a significant decrease in the relative abundance of Parasutterella (P< 0.01), while H_NaB showed significant reductions in the relative abundances of both Escherichia-Shigella and Parasutterella (P < 0.01). (4) Compared with 0_NaB, the small intestinal tissue structure in L_NaB and H_NaB was more intact, the infiltration of inflammatory cells was significantly reduced, and the capillaries were slightly dilated. The expression levels of ZO-1 and occludin proteins in L_NaB were significantly increased (P<0.01). (5) The LPS concentration in the gastrocnemius muscle and the protein expression levels of TLR4, MyD88, p-IκBα, and p-NF‑κB p65 in L_NaB and H_NaB were significantly lower than those in 0_NaB (P<0.05). The serum TNF‑α concentration in H_NaB and TNF-α concentration in the gastrocnemius muscle of the L_NaB and H_NaB were significantly lower than those in 0_NaB (P<0.05, P<0.01, P<0.01). ConclusionOral administration of NaB can improve gut microbiota α diversity, adjusting its composition, improving intestinal mucosal barrier function, reducing the LPS-induced pro-inflammatory response, and delaying skeletal muscle atrophy. The underlying mechanism may involve down regulation of TLR4/MyD88/NF-κB signaling in skeletal muscle.

Ten-eleven translocation 2 （TET2）， as a core enzyme in epigenetic regulation， dynamically regulates the differentiation and function of CD4⁺ T cells by mediating DNA demethylation. Recent studies have shown that TET2 deficiency can promote the progression of autoimmune hepatitis （AIH） by disrupting the Th17/Treg balance and activating inflammatory signals along the gut-liver axis. This article systematically reviews the bridging role of TET2 between CD4⁺ T cells and gut microbiota， explores the molecular mechanisms by which it drives AIH through the gut microbiota-epigenetics-immunity network， and discusses the potential intervention strategies targeting the TET2-microbiota axis.

This paper systematically reviews the core concepts and lines of theoretical inheritance of major spleen-stomach theories in traditional Chinese medicine （TCM）， including spleen deficiency theory， spleen-stomach damp-heat theory， and liver-spleen disharmony theory. It is found that these theories have all undergone a developmental trajectory characterized by classical foundation， refinement of therapeutic methods， systematization of pathogenesis， and modern innovation. The evolution of spleen-stomach theory has achieved a shift from a singular focus on tonifying the spleen to regulating dynamic middle-jiao （焦） balance， and from localized spleen-stomach regulation to the circular movement of qi involving all five zang organs. In terms of modern disease-syndrome integrative research， spleen deficiency syndrome is shown to be closely associated with impairment of the gastrointestinal mucosal barrier， metabolic disorders， and gene polymorphisms related to Helicobacter pylori-associated gastric diseases. Spleen-stomach damp-heat syndrome is closely linked to hyperactive energy metabolism， inflammatory cytokines， and abnormal expression of aquaporins. Liver-spleen disharmony syndrome is mainly associated with dysregulation of the brain-gut axis and microbiota-related metabolic disorders. It is proposed that future research on spleen-stomach diseases and syndromes should further elucidate their potential multidimensional differential biological characteristics， thereby promoting the modernization of the TCM discipline of spleen-stomach studies.

OBJECTIVE To evaluate the efficacy and safety of total glucosides of paeonia （TGP） in the treatment of systemic lupus erythematosus （SLE）. METHODS Randomized controlled trial （RCT） about TGP combined with western medicine versus western medicine alone for SLE treatment were retrieved from PubMed， Embase， Cochrane Library， Web of Science， CNKI， VIP， Wanfang Data， and CBM. The search period spanned from the inception of each database to June 1， 2025. After literature screening， data extraction， and quality assessment of the included studies， Meta-analysis was performed using RevMan 5.4 software. RESULTS Fifteen RCTs， involving 1 318 patients， were included. Meta-analysis results showed that compared with western medicine alone， TGP combined with western medicine significantly improved clinical efficacy [OR＝4.96， 95%CI（3.41， 7.23）， P＜0.000 01]， complement 3 [MD＝0.18， 95%CI （0.13， 0.23）， P＜0.000 01] and complement 4[MD＝0.08， 般021） 95%CI （0.04， 0.11）， P＜0.000 01]， and reduced the levels of immunoglobulin G （IgG） [MD＝－3.10， 95%CI （－3.59，－2.62）， P＜0.000 01]， IgA [MD＝－0.68， 95%CI （－0.78， －0.58）， P＜0.000 01]， IgM [MD＝－0.43， 95%CI （－0.53，－0.34）， P＜0.000 01]， systemic lupus erythematosus disease activity index （SLEDAI） [MD＝－1.59， 95%CI （－2.20， －0.99）， P＜0.000 01]， recurrence rate [OR＝0.23， 95%CI （0.13， 0.42）， P＜0.000 01] and the incidence of adverse drug reactions [OR＝ 0.54， 95%CI （0.36， 0.82）， P＝0.004]. CONCLUSIONS TGP therapy can improve clinical efficacy of SLE patients， promote the restoration of immunoglobulins and complements， reduce SLEDAI and recurrence rate and has good safety.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.