It is believed that "deficiency qi retention and stagnation" is the fundamental pathogenesis of coronary microvascular dysfunction （CMD） after percutaneous coronary intervention （PCI）. Patients often have severe coronary vessel congestion before PCI， leading to emptiness in the heart's collaterals， which results in deficiency of healthy qi， poor movement of blood and body fluids， so the heart collaterals are susceptible to stagnation and stasis，then phlegm and stasis generate； after PCI， it is easy to damage the healthy qi then lead to qi deficiency， causing qi， blood， and body fluids fail to transport， thereby leading to blood stasis and phlegm turbidity retention， generating heat and wind to damage the heart and body. It is proposed that the prevention before PCI should replenish qi and collaterals， expel blood stasis and resolve phlegm， to support "deficient qi" in heart collaterals and prevent "stagnation" after PCI. Postoperative management should focus on replenishing qi and protecting the collaterals， eliminating pathogen and controlling development， so as to avoid exacerbating deficiency and stagnation by damaging healthy qi， and eliminate pathogen and unblock the collaterals to interrupt the pathogenesis， which prevent "retention and stagnation" from changes.

Based on a letrozole-induced rat model of polycystic ovary syndrome (PCOS), serum metabolomics was employed to characterize metabolic abnormalities, identify potential biomarkers, and investigate their roles in the pathogenesis and progression of PCOS. Metabolomic analyses revealed significantly decreased levels of cholesterol, pregnenolone, leucine, and citrate in the serum of model rats, accompanied by elevated levels of androsterone glucuronide (ADTG) and linoleic acid, indicating dysregulation of key pathways including steroid biosynthesis, branched-chain amino acid metabolism, tricarboxylic acid (TCA) cycle, and lipid metabolism. To elucidate the tissue origins and molecular mechanisms underlying these metabolic alterations, ovarian proteomics and qRT-PCR analyses were further integrated. The results confirmed the upregulation of key enzymes involved in the related metabolic pathways, such as 17α-hydroxylase (CYP17A1), 11β-hydroxysteroid dehydrogenase (HSD11B1), branched-chain amino acid aminotransferase (BCAT2), fatty acid desaturase 2 (FADS2), and oxoglutarate dehydrogenase (OGDH). These findings suggest that both “cholesterol precursor depletion-androgen accumulation” and “energy/lipid metabolic reprogramming” constitute core features of metabolic disturbances in PCOS. Through multi-omic cross-validation, six serum metabolites with high stability and clinical translational potential were identified as promising combinational biomarkers for the auxiliary diagnosis of PCOS. This study employed a metabolomics-guided strategy, supported by proteomic and transcriptomic validation, which has not only deepened our understanding of PCOS metabolic mechanisms but also provided us with a theoretical foundation for its auxiliary diagnosis.

OBJECTIVE To investigate the effect and mechanism of gracillin from Reineckia carnea on autophagy in non- small cell lung cancer A549 cells. METHODS Using A549 cells as subjects， the effects of different concentrations of gracillin （0.25， 0.5， 1， 2， 4 μmol/L） on the proliferation of cells were detected by CCK-8 after being treated for different time （12， 24， 48 h）. Compared with the control group without medication， the effect of gracillin （2 μmol/L） on the formation of autophagosomes in cells was observed by transmission electron microscope after 24 h of exposure. The aggregation of GFP-LC3 on autophagosome membrane was detected by GFP-LC3 plasmid transfection after being treated with gracillin （0.25， 0.5， 1， 2 μmol/L） for 24 h. Quantitative real-time PCR and Western blot assay were used to detect the mRNA and protein expressions of family with sequence similarity 102 member A（FAM102A）， the expressions of autophagy-related proteins [p62， Beclin-1， microtubule-associated protein 1 light chain 3B （LC3B）]， and the expressions of phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway-related proteins in A549 cells after being treated with gracillin （0.25， 0.5， 1 and 2 μmol/L） for 24 h. RESULTS Gracillin significantly inhibited the proliferation of A549 cells in a concentration- and time-dependent manner. The IC50 was 2.55 μmol/L at 24 h. After 24 h of gracillin treatment， autophagosomes with bilayer membrane structure were found in the cell cytoplasm， and GFP-LC3 green fluorescent spots on autophagosome membrane were obvious， representing an increasing trend as drug concentration. Compared with the control group， mRNA and protein expressions of FAM102A （0.5， 1， 2 μmol/L groups）， protein expression of Beclin-1 （1， 2 μmol/L groups） and LC3B-Ⅱ/LC3B-Ⅰ ratio （2 μmol/L group） were significantly increased in different concentrations of gracillin groups， while the protein expression of p62 （1， 2 μmol/L groups）， and the protein phosphorylations of Akt （1， 2 μmol/L groups） and PI3K （2 μmol/L group） were all decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Gracillin can promote excessive autophagy in A549 cells by up-regulating mRNA and protein expressions of FAM102A and inhibiting PI3K/Akt signaling pathway， thus inhibiting cell proliferation.

Glioblastoma is a common malignant tumor in the central nervous system,often exhibiting radiation resistance.Drug delivery systems can help to overcome the blood-brain barrier and targeted delivery of radiation sensitizers to glioblastoma,thereby enhancing the efficacy of radiation therapy,which has received increasing attention.This review focuses on the relationship between radiation resistance and the intrinsic DNA damage repair mechanism,the clearance of reactive oxygen species with DNA and membrane attack,and the rapid proliferation of glioblastoma stem cells.It also discusses the performance of inorganic nanomaterials,organic composite materials,and bionic drug delivery systems in solving the problem of trans-barrier delivery,and summarizes the design method of drug delivery systems for crossing the blood-brain barrier and targeted delivery of radiation sensitizers to glioblastoma,to provide some possible direction for solving the clinical translation problems of nano delivery systems.

The aim of this study is to investigate the effect of Dahuang Fuzi decoction(DHFZT)on the killing effect of natural killer(NK)cells and the growth of lung cancer xenografts in mice.Lewis lung cancer xenograft model was constructed,and the mice were randomly divided to the normal saline group,low and high concentrations of DHFZT groups.The growth of lung cancer xenografts in mice in the control group,low and high concentration of DHFZT treatment groups was detected.The levels of IFN-y,IL-2 and IL-10 were detected by ELISA.The killing effect of NK cells was detected by calcein release assay.The release of CD107α was detected by flow cytometry.The expression of activated receptors and the tumor cell surface ligands were detected in the con-trol group and DHFZT treatment groups.The results showed that the xenografts of Lewis mice in the DHFZT treatment groups were grown slower than that in the control group in a dose depend-ent manner(P＜0.05).Compared with the control groups,the levels of IL-2 and IFN-y in tumor tissues were increased in DHFZT treatment groups(P＜0.05),but no significant changes in IL-10.Calcein release assay showed that the killing efficiency of NK cells in the DHFZT treatment groups was increased(P＜0.05).The secretion level of IFN-y in the culture supernatant was increased by DHFZT treatment(P＜0.05).DHFZT treatment increased the expression level of CD107α of NK cells.The expression of MIC A/B on the surface of A549 and H1299 cells was up-regulated by DHFZT treatment,but not the expression of inhibitory ligand HLA-ABC.The results showed that DHFZT enhanced the killing effect of NK cells on mouse lung cancer cells by up-reg-ulating the expression of MIC A/B,increasing the secretion of IFN-y and CD107α.Hence,these re-sults indicated that DHFZT suppresses the lung cancer growth potential through regulating the killing effect of NK cells.

Objective:To explore the overall efficacy of pediatric liver transplantation (LT) and the risk factors affecting the long-term outcomes.Methods:From October 2006 to December 2022, clinical profiles, intraoperative findings, perioperative managements and long-term follow-ups were retrospectively reviewed for 3004 cases (including 40 cases of retransplantation) of children with end-stage liver disease undergoing LT. Overall patient and graft survival rates after transplantation were explored by Kaplan-Meier survival curve. The survival rates of recipients receiving living donor liver transplantation and deceased donor liver transplantation, recipients with body weight ≤5 kg and >5 kg at the time of transplantation, recipients with age ≤5 months and >5 months, graft recipient weight ratio (GRWR) ≤5% and >5 %, and recipients with compatible and incompatible blood types were compared, as well as the survival rates of recipients from 2006 to 2011, 2012 to 2017, and 2018 to 2022. The occurrence of complications was analyzed. Cox regression was used to analyze the risk factors of long-term mortality, and those with <0.05 were included in the LASSO regression model to identify the independent risk factors.Results:As of December 2022, overall survivals at 1/5/10-year were 95.1 %(2 819/2 964), 93.1 % (2 759/2 964) and 91.8% (2 721/2 964) and 1/5/10-year graft survival rate 94.5 % (2 839/3 004), 92.0 % (2 764/3 004) and 86.2 % (2 589/3 004 ). The 5-year survival rate improved : Five-year survival rate at pediatric LT centers were 71.6 % (63/88, from 2006 to 2011), 91.6 % (1 009/1 101 ,from 2012 to 2017) and 95.5 % (1 695/1 775, from 2018 to 2022 ). Survival rates were lower in recipients with body weight ≤5 kg [83.7 % (41 /49) vs 94.4 % (2 746/2 915), P=0.001) ] and GRWR >5 % [90.0 % (378/420) vs 94.6 % (2 046/2 544), P=0.007 ] compared to those >5 kg and ≤5 %. Difference in surgical age and blood type compatibility were not statistically ( P=0.26 and 0.4 ). Infection [35.3 % (70/198) ]and surgical complications [24.2 % (48/198) ]were the main causes of mortality after transplantation. While infection [35.7% (25/70) ] ,portal vein complications [18.6%(13/70) ]and lung injury [15.7 % (11/70) ]were the main reasons of death within 1 month after transplantation. The incidence of postoperative infection and acute rejection decreased from 86.5 %(76/88) and 38.2% (34/88) in 2006-2011 to 75.5% (1 340/1 775) and 22.2% (394/1 775). Post-transplantation surgery-related complications included portal veinous complications (3.1 %, 92/3 004), hemorrhage (2.3 %, 68/3 004) ,hepatic arterial complications (1.7 %, 50/3 004) and hepatic venous complications (1.1 %, 33/3 004). Univariate analysis revealed that risk factors related to postoperative mortality included preoperative anemia ( P=0.012), high preoperative leucocyte count ( P=0.026), preoperative renal insufficiency ( P=0.008), hypoproteinemia ( P=0.001), coagulation dysfunction ( P= 0.005), low body weight ( P=0.007), GRWR>5% ( P=0.001), intraoperative volume of blood loss and transfusion ( P<0.001) ,postoperative intensive care unit (ICU) time ( P<0.001), hospital length post-LT ( P=0.045) ,postoperative lung infection ( P<0.001), abdominal infection ( P=0.029), postoperative hemorrhage ( P<0.001), intestinal perforation ( P<0.001), acute rejection ( P<0.001) Epstein-Barr virus (EBV) infection ( P<0.001) and post-transplant lymphoproliferative disorder (PTLD) ( P=0.018). Multivariable analysis revealed that preoperative creatinine ( HR=1.015, 95% CI: 1.002-1.028, P=0.024), GRWR ( HR=2.082, 95% CI: 0.473-9.157, P=0.031) ,pulmonary infection ( HR=4.389, 95% CI: 2.248-8.569, P<0.001) ,postoperative abdominal hemorrhage ( HR= 6.922, 95% CI:1.871-25.610, P=0.004), intestinal perforation ( HR=9.154, 95% CI: 2.307-36.323, P=0.002) and acute rejection ( HR=0.452, 95% CI: 0.210-0.971, P=0.042) were important influencing factors of long-term survival post-LT. Conclusions:LT is currently the most effective treatment for end-stage liver disease in children. Improving preoperative organ function, optimizing surgical techniques, minimizing intraoperative hemorrhage and preventing postoperative complications can effectively enhance the long-term outcomes of LT recipients.

Objective:To compare improved microbial assay (IMA) and electrochemiluminescence (ECL) for measuring serum folate, and to investigate the linear or non-linear correlation between the results of the two methods.Methods:This comparative study was conducted in National Health Commission Key Laboratory of Reproductive Health from October 2020 to February 2021, in which the folate concentration of 251 serum samples were measured by IMA and ECL. According to the serum folate concentration, the folate status was divided into sufficient (≥13.5 nmol/L), marginal deficiency (6.8≤serum folate<13.5 nmol/L), and deficiency (<6.8 nmol/L). Pearson correlation analysis and multivariate fractional polynomial (MFP) model were used to evaluate the correlation between the results measured by the two methods. The sensitivity of ECL for detecting folate status were calculated based on the IMA results as the golden standard.Results:The average folate concentrations in serum samples measured by ECL and IMA were (19.8±8.2) nmol/L and (23.0±9.7) nmol/L, respectively ( P<0.001). The Pearson correlation coefficient ( r) of the two methods was 0.894 ( P<0.001), yet the MFP model demonstrated non-linear correlation between the two methods. When the IMA results were≤9.1 nmol/L, the r was 0.070 ( P>0.05); when the IMA results were>9.1 nmol/L, the r was 0.867 ( P<0.001); for non-hemolytic serum samples ( n=221), the r was 0.902 ( P<0.001). Additionally, the sensitivity of ECL detecting folate deficiency was 27.78%, and the sensitivity of ECL detecting folate insufficiency (deficiency and marginal deficiency) was 93.33%. Conclusion:When folate concentrations was>9.1 nmol/L), the results of ECL and IMA were highly correlated; yet the correlation between the two methods was weak at lower folate concentrations, indicating that ECL was not applicable for serum folate measurement among folate insufficiency population.

Background A large amount of iron deposition in the brain can cause neuronal damage by inducing oxidative stress, neuroinflammation, and abnormal mitochondrial function. In addition, iron deposition is also reported to be closely related to the pathogenesis of Alzheimer's disease (AD). The neurofibrillary tangles aggregated by tau hyperphosphorylation are one of the important pathological features of AD. Objective To investigate potential effect of exogenous trivalent iron ions on neuronal activity in human neuroblastoma (SH-SY5Y) cells and tau hyperphosphorylation and aggregation. Methods SH-SY5Y cells were treated with ferric chloride (FeCl₃) at four concentrations (10, 100, 200, and 400 mg·L⁻¹). Cell survival rate was then detected by CCK8 assay. Intracellular iron content was determined prussian blue (Perl's) by iron staining after 24 h exposure to FeCl₃ at 10 or 200 mg·L⁻¹. Transfection of tau-P301L plasmid was conducted to construct an AD-like cell model for tau overexpression. The differences in the expression of the phosphorylated tau (p-tau) protein in SH-SY5Y cells and SH-SY5Y cells with tau overexpression were detected by Western blotting after 24 h exposure to FeCl₃ at 10 and 200 mg·L⁻¹. After dilution with phosphate buffered saline (PBS), FeCl₃, human tauR3, and FeCl₃ + tauR3 were incubated at 37℃, and the fluorescence intensity reflecting tau aggregation level was measured by thioflavin T(ThT) method at 12, 24, 36, 48, 60, 72, 84, and 96 h, respectively. Meanwhile, after 96 h coincubation of FeCl₃ and tauR3, the fibers formed by tau aggregation were observed under a transmission electron microscope (TEM). Results After 24 h of FeCl₃ exposure, the cell survival rate of SH-SY5Y cells among all groups was statistically different (F=8.63, P<0.01). The cell survival rates in the 200 and 400 mg·L⁻¹ groups were 80.1% and 68.7% of the control group, respectively (P<0.05). Compared with the control group, the nuclei of the 200 mg·L⁻¹ FeCl₃ group were mainly yellowish-brown after iron staining and the positive cell rate was up-regulated by 12.9% (P<0.01). After 24 h of FeCl₃ exposure , the p-tau (Ser396) protein expression was statistically different among all groups (F=11.6, P<0.01). Compared with the control group, the p-tau protein expression level of SH-SY5Y cells in the 200 mg·L⁻¹ group was up-regulated by 72.7% (P<0.01). After FeCl₃-treated SH-SY5Y cells with tau overexpression for 24 h, the p-tau (Ser396) protein expression was statistically different among all groups (F=27.8, P<0.01). Compared with the tau group, the p-tau (Ser396) protein expression level of SH-SY5Y cells in the tau + 200 mg·L⁻¹ group was up-regulated by 44.6% (P<0.05). Compared with the tauR3 group, the fluorescence intensities in the 84 and 96 h tauR3 + FeCl₃ groups were up-regulated by 49.9% and 53.7% (P<0.01) respectively. After 96 h of coincubation, compared with the tauR3 group, FeCl₃ + tauR3 aggravated tau aggregation and formed fiber deposition under TEM. Conclusion Exogenous trivalent iron ions may inhibit SH-SY5Y cell viability, promote the phosphorylation of tau in SH-SY5Y cells transfected with tau-P301L plasmid, and aggravate tauR3 aggregation and fiber production.

“Stasis generating deficiency” is considered to be an important pathogenesis of recurrence after catheter ablation of atrial fibrillation （AF）. Blood stasis is commonly seen after ablation together with various pathogens such as phlegm-fire， qi stagnation and retained fluid， and will lead to depletion of zang-fu （脏腑） organs and then the failure of the nourishment of the heart. Therefore， it is advised to emphasize on the importance of considering zang-fu organs depletion caused by blood stasis and various excess pathogens in dealing with the recurrence after catheter ablation. The method of dissolving stasis and supplementing deficiency simultaneously has been proposed before catheter ablation， and it is critical to calm heart and dissolve stasis， regulate and supplement internal deficiency so as to prevent the postoperative recurrence of AF. For recurrence of AF after ablation， attention should be paid to dissolving stasis and dispelling pathogens， regulating vessels and supplementing deficiency， as well as the excess pathogens such as stasis binding and phlegm fire， stasis binding and qi stagnation， stasis binding and retained fluid， and the depletion of zang-fu organs should be considered. Accordingly， the method of dissolving stasis and dispelling phlegm， subduing fire and unblocking vessels， regulating and supplementing heart and spleen； dissolving stasis and move stagnation， unblocking qi and blood， supplementing lung and boosting qi； dispelling stasis and dissolving rheum， warming yang and activating blood， consolidating the root and nourishing heart can be used respectively， so as to treat both the root and the branch simultaneously.

ObjectiveIn the treatment of acute gouty arthritis （AGA）， western medicine is mostly used for anti-inflammatory and analgesic purposes to control the blood uric acid level， but some patients are still at risk of poor control and recurrent attacks. Chinese medicinal prescriptions， potent in resisting inflammation and relieving pain， are able to stabilize the blood uric acid level， reduce acute attacks， and improve the clinical efficacy of western medicine. However， there is a lack of evidence to support their use as evidence-based medicine. This study employed network Meta-analysis （NMA） to evaluate the efficacy and safety of common Chinese medicinal prescriptions in the treatment of AGA， aiming to provide evidence-based medical evidence for the clinical use of Chinese medicinal prescriptions in the treatment of AGA. MethodChinese and English databases were searched for prospective cohort studies and randomized controlled trials （RCTs） on Chinese medicinal prescriptions against AGA from database inception to December 1， 2022. Stata software and Review Manager were used for statistical analysis. ResultForty-four papers with 3 564 cases involved were included in the current NMA. In terms of reducing blood uric acid， the cumulative probability results showed that Mahuang Lianyao Chixiaodou Tang showed optimal efficacy （87.60%）. In terms of relieving joint pain， Danggui Niantongtang and Guizhi Shaoyao Zhimutang showed optimal efficacy （92.00% and 82.30%）. In terms of improving erythrocyte sedimentation rate （ESR）， Simiaowan was superior to other prescriptions （87.00%）. In terms of reducing C-reactive protein （CRP）， Simiaowan and Baihutang modified with Guizhitang showed superior efficacy （76.00% and 66.10%）. In terms of safety， except for the basic treatment group， Mahuang Lianyao Chixiaodou Tang had the lowest probability of adverse events， and Danggui Niantongtang had the highest probability of adverse reactions during treatment. According to the results of cluster analysis， Mahuang Lianyao Chixiaodou Tang and Simiaowan are effective and safe. ConclusionAccording to the results of NMA， Chinese medicinal prescriptions can assist in the treatment of AGA and improve the effectiveness of western medicine. For patients with AGA， clinicians can choose Mahuang Lianyao Chixiaodou Tang or Simiaowan as an auxiliary drug for routine western medicine treatment.