Hepatolenticular degeneration， also known as Wilson disease （WD）， is a hereditary disease caused by mutations in the ATP7B gene， leading to copper metabolism disorders. Gene mutations result in impaired synthesis of copper-binding protein， and abnormal excretion of copper through bile leads to pathological deposition of copper in various organs， ultimately causing multi-organ damage. The insidious onset and low specificity of symptoms make it difficult to diagnose this disease. On the basis of existing studies and the theory of latent toxin， this paper proposes that latent toxin in kidney collaterals is the main pathogenesis of renal injury in WD. It is pointed out that health Qi deficiency and latent pathogen are the premises for the occurrence of this disease， and the transformation of latent pathogen into toxin is the ley pathological process. Toxin damaging kidney collaterals is the ultimate result. According to the pathogenesis， this paper proposes the treatment principle of reinforcing healthy Qi and resolving toxin and treatment based on syndrome differentiation. This review provides new ideas for the diagnosis and treatment of renal injury in WD with traditional Chinese medicine.

ObjectiveTo observe the clinical efficacy of Gandouling decoction combined with neuromuscular electrical stimulation （NMES） in the treatment of dysphagia in Wilson disease （WD） with combined phlegm and stasis. MethodsA total of 80 WD patients with dysphagia due to combined phlegm and stasis treated in the Department of Encephalopathy， the First Affiliated Hospital of Anhui University of Chinese Medicine were randomized into a control group and an observation group， with 40 patients in each group. In addition， 40 healthy volunteers were recruited as the normal group. The control group was treated with basic copper drainage combined with NMES. The observation group was treated with Gandouling Decoction on the basis of the therapy in the control group. Each course of treatment lasted for 8 days， and the patients were treated for a total of 4 courses. All subjects underwent video fluoroscopic swallowing study （VFSS） before and after treatment. During the examination， contrast agents with 4 different characters were used for the swallowing action， and the passing time was recorded. The TCM syndrome score， water swallow test score， standard swallowing assessment （SSA） score， and 24-h urinary copper level before and after treatment were analyzed. ResultsWhen performing VFSS， the passing time of contrast agents of different characters in the oral stage was longer in the WD group than in the normal group （P<0.01）， while it had no significant difference in the pharyngeal stage. After treatment， the passing time in the oral stage shortened in the control and observation groups （P<0.01）， and the observation group outperformed the control group （P<0.01）. After treatment， both the control and observation groups showed declines in TCM syndrome score and SSA score （P<0.01） and an increase in water swallow test score （P<0.01）， and the changes were more obvious in the observation group than in the control group （P<0.01）. In addition， the treatment in the control and observation groups elevated the 24-h urinary copper level （P<0.01）， and the elevation in the observation group was more obvious than that in the control group （P<0.01）. Neither group showed obvious adverse reaction. ConclusionGandouling decoction combined with NMES can significantly ameliorate dysphagia in WD patients with the syndrome of combined phlegm and stasis regarding the TCM syndrome score， water swallow test score， and SSA score， demonstrating definite clinical efficacy and high safety.

Wilson disease is a copper metabolism disorder caused by mutations in the ATP7B gene， which encodes a copper-transporting ATPase β， and can result in multisystem damage. The kidneys are the third most commonly affected organs after the liver and brain. In recent years， numerous diagnostic and treatment guidelines for Wilson disease have emerged. However， most of these focus primarily on hepatic and neurological manifestations and their management， with limited coverage of renal involvement. The high incidence， low awareness， and lack of clinical specificity of Wilson disease-related renal damage （WDRD） have made early detection and intervention particularly challenging in clinical practice. To further optimize the treatment of patients with WDRD， improve clinical diagnosis and management， and enhance patients' quality of life， the Neurology Committee of the Chinese Association of Integrative Medicine， in April 2024， initiated a revision of the first expert consensus on the integrated diagnosis， treatment， and management of WDRD. This effort brought together experts in hepatology， encephalopathy （neurology）， and nephrology from many tertiary-level grade A hospitals and research institutions across China. Through comprehensive literature review and integration of frontline clinical experience， the expert group jointly developed Chinese Expert Consensus on Integrated Chinese and Western Medicine Management of Wilson Disease-related Renal Damage （hereinafter referred to as the "Consensus"）. This article provides a detailed interpretation of the Consensus in terms of diagnostic criteria， traditional Chinese medicine （TCM） syndrome differentiation and treatment classification， and comprehensive disease management， aiming to better guide clinical application. Regarding diagnostic criteria， the Consensus integrates the latest standards in China and abroad， highlights the importance of biochemical diagnosis， and compensates for the limitations of genetic testing. In the area of TCM syndrome differentiation and treatment， the Consensus refines four major syndrome types， introduces a newly defined syndrome， i.e.， phlegm， blood stasis， and heat accumulation， and elaborates on treatment principles， prescriptions， and clinical modification rules for each syndrome. For comprehensive disease management， the Consensus emphasizes multi-dimensional intervention strategies， including diet， exercise， emotional regulation， medication， and medical care， with the goal of maximally controlling the progression of renal dysfunction and helping patients achieve a better quality of life.

Objective To analyze the changing prevalence and resistance profiles of multiple drug-resistant(MDR)bacteria in Minhang Hospital of Fudan University before and after the onset of COVID-19 pandemic.Methods The resistance profiles of 6 bacterial species were compared before(2017-2019)and after(2020-2022)the onset of COVID-19 pandemic.WHONET 5.6 software was used to statistically analyze the data of antimicrobial susceptibility testing.Results After the onset of COVID-19(2020-2022),the prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKP)was significantly higher than that in the pre-pandemic period(2017-2019)(40.1％vs 27.9％,P＜0.01),while the prevalence of carbapenem-resistant Escherichia coli(CREC)decreased significantly(1.9％vs 3.1％,P＜0.05).The prevalences of carbapenem-resistant Acinetobacter baumannii(CRAB),carbapenem-resistant Pseudomonas aeruginosa(CRPA),methicillin-resistant Staphylococcus aureus(MRSA),and vancomycin-resistant Enterococcus(VRE)did not show significant difference before and after the onset of COVID-19 pandemic.MDR isolates were mainly isolated from respiratory tract samples either before or after COVID-19 pandemic(78.4％vs 78.5％).The prevalence of MDR in the intensive care unit(ICU)was significantly higher during the period from 2020 to 2022 compared to the pre-pandemic period(53.1％vs 35.5％,P＜0.01).The resistance rate of MRSA to methoprim-sulfamethoxazole decreased from 15.7％during 2017-2019 to 3.5％during 2020-2022(P＜0.01).Compared to the pre-pandemic period,the E.faecalis strains showed lower resistance rates to penicillin G,ampicillin,and levofloxacin during 2020-2022.The resistance rate of E.faecium to high-level gentamicin decreased significantly from 50.1％during 2017-2019 to 39.2％during 2020-2022(P＜0.01).The resistance rate of E.coli to imipenem decreased from 2.7％to 1.2％(P＜0.01),while A.baumannii and P.aeruginosa strains showed stable resistance rates to carbapenems(P＞0.05).Conclusions After the onset of COVID-19 pandemic,the prevalence of CREC decreased significantly.The prevalences of CRAB,CRPA,MRSA,and VRE also showed a decreasing trend.However,the prevalence and resistance rates of CRKP significantly increased.It is necessary to strengthen hospital infection control measures to curb the spread of MDR bacteria.

Objective:To explore the value of 18F-fibroblast activation protein inhibitor (FAPI) PET/CT in the assessment of early-stage graft fibrosis (S1-S2) after liver transplantation (LT). Methods:From November 2021 to April 2022, 17 adult liver transplant recipients (12 males and 5 females; age (52.6±7.9) years) in the Affiliated Hospital of Qingdao University were enrolled retrospectively in this study. All 17 patients received laboratory examinations, FibroScan, 18F-FAPI PET/CT and liver biopsy. According to the Scheuer scoring system, hepatic tissue was divided into no fibrosis (S0) and early fibrosis (S1-S2). Independent-sample t test was used to compare SUV max between two groups, and Mann-Whitney U test was used to compare liver stiffness measurement (LSM). ROC curve analysis was used to evaluate the diagnostic efficacy of LSM and SUV max in the early fibrosis of liver grafts. Delong test was used to compare the difference of AUCs. Results:Among 17 adult LT recipients, 11 were in stage S0, 5 were in stage S1, and 1 was in stage S2. There were significant differences in LSM and SUV max between no fibrosis group and early fibrosis group (LSM: 5.4(4.7, 6.6) vs 12.9(5.6, 19.9) kPa, z=-2.01, P=0.044; SUV max: 1.7±0.8 vs 3.9±1.6, t=-3.14, P=0.019). The threshold value of LSM in predicting early-stage graft fibrosis was 8.2 kPa and the AUC was 0.80 (95% CI: 0.54-0.95), which was 2.0 and 0.92 (95% CI: 0.78-1.00) for SUV max respectively. There was no significant difference in AUC between the two tools ( z=0.80, P=0.421). Conclusion:18F-FAPI PET/CT can precisely evaluate the early fibrosis of allografts, with the similar diagnostic efficacy with FibroScan (LSM), which is expected to be a new non-invasive diagnostic tool for predicting the early-stage of graft liver fibrosis.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Objective To explore the action mechanism of tauroursodeoxycholic acid(TUDCA)promoting intracellular clearance of Burkholderia pseudomallei(B.pseudomallei)in RAW264.7 macrophages.Methods After TUDCA of different concentrations were used to treat RAW264.7 cells pre-infected with B.pseudomallei for 8 h or not,flow cytometry was applied to detect the apoptosis of the infected and control cells.In addition,another endoplasmic reticulum stress(ERS)inhibitor 4-PBA was used to detect the apoptosis and proliferation of host cells after B.pseudomallei infection with Annexin-V/PI double staining and MTT cell proliferation assay.Furthermore,after transfected with CHOP siRNA,Western blotting and flow cytometry were employed to detect the effect of TUDCA on the expression levels of Caspase-3 and Caspase-12 and the changes in apoptotic rate after B.pseudomallei infection,respectively.Finally,the effect of TUDCA on intracellular multiplication of infected RAW264.7 cells were observed to estimate the CFU value in the presence and absence of CHOP siRNA.Results Under different concentrations of TUDCA,100 or 200 μmol/L TUDCA significantly reduced B.pseudomallei-induced apoptosis in RAW264.7 cells(P＜0.05).Meanwhile,both TUDCA and 4-PBA treatment could decrease the apoptosis induced by B.pseudomallei infection by ERS(P＜0.05).Further,the expression levels of Caspase-3 and Caspase-12 were obviously increased after B.pseudomallei infection compared with uninfected groups,but their expression levels in the siCHOP group was significantly lower than that in the siC group.Besides,flow cytometry also showed that TUDCA could reduce apoptosis induced by B.pseudomallei infection(P＜0.05),but no significant effect of TUDCA on apoptosis was observed under CHOP knockdown.Finally,intracellular CFU assay indicated that TUDCA treatment promoted the host cell clearance of B.pseudomallei(P＜0.05),but no such effect was observed in siCHOP group.Conclusion In B.pseudomallei infected RAW264.7 cells,TUDCA promotes the intracellular clearance of the bacteria by inhibiting ERS-induced apoptosis.

Excavating the quantitative trait locus (QTL) associated with rice cooking quality, analyzing candidate genes, and improving cooking quality-associated traits of rice varieties by genetic breeding can effectively improve the taste of rice. In this study, we used the indica rice HZ, the japonica rice Nekken2 and 120 recombinant inbred lines (RILs) populations constructed from them as experimental materials to measure the gelatinization temperature (GT), gel consistency (GC) and amylose content (AC) of rice at the maturity stage. We combined the high-density genetic map for QTL mapping. A total of 26 QTLs associated with rice cooking quality (1 QTL associated with GT, 13 QTLs associated with GC, and 12 QTLs associated with AC) were detected, among which the highest likelihood of odd (LOD) value reached 30.24. The expression levels of candidate genes in the localization interval were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), and it was found that the expression levels of six genes were significantly different from that in parents. It was speculated that the high expression of LOC_Os04g20270 and LOC_Os11g40100 may greatly increase the GC of rice, while the high expression of LOC_Os01g04920 and LOC_Os02g17500 and the low expression of LOC_Os03g02650 and LOC_Os05g25840 may reduce the AC. The results lay a molecular foundation for the cultivation of new high-quality rice varieties, and provide important genetic resources for revealing the molecular regulation mechanism of rice cooking quality.
Quantitative Trait Loci ; Oryza/genetics* ; Plant Breeding ; Cooking ; Genetic Association Studies

AIM:To investigate the influence of fat mass and obesity-associated(Fto)gene on the aberrant contraction of aortic smooth muscle in diabetes mellitus(DM)mice,and to explore the mechanism of Fto gene underlying the calcium regulation.METHODS:Smooth muscle-specific Fto gene knockout(FtoSMKO)mice were generated using Cre-loxP technology.The experiment involved 3 groups of mice:wild-type(WT)group,DM model group and FtoSMKO-DM group,with 15 mice in each group.In DM group and FtoSMKO-DM group,type 1 DM was induced by intraperitoneal injec-tion of streptozotocin.The mice in WT group were injected with equal volume of citric acid-sodium citrate buffer solution.The influences of different drugs on the contraction responses of aortic smooth muscle in mice were analyzed using a multi-myograph system.The expression level of FTO protein in the aortic tissues was detected by Western blot.RESULTS:(1)Compared with WT mice,the expression levels of FTO protein in the aortic tissues of DM mice were significantly in-creased(P＜0.01).(2)The expression level of FTO protein in smooth muscle was significantly decreased after knockout of Fto gene(P＜0.01).Compared with WT group,the mice in DM group exhibited a significant decrease in body weight and a marked increase in fasting blood glucose level(P＜0.05).There were no noticeable differences in body weight or fasting blood glucose level between FtoSMKO-DM group and DM group(P＞0.05).(3)The contraction responses of aortic smooth muscle in DM group were substantially increased by phenylephrine compared with WT group.Specifically,vaso-constriction responses mediated by non-L-type calcium channels and store-operated calcium channels(SOCC)were signifi-cantly enhanced in DM group.In addition,the responses mediated by inositol 1,4,5-trisphosphate receptors(IP3R),which facilitate calcium release from the sarcoplasmic reticulum,were significantly enhanced.However,the responses mediated by caffeine-activated ryanodine receptors(RyR),which also facilitate calcium release from the sarcoplasmic re-ticulum,were significantly inhibited(P＜0.05).(4)Compared with DM group,the phenylephrine-induced contraction re-sponses of aortic smooth muscle in FtoSMKO-DM group were greatly weakened(P＜0.05).In particular,the vasoconstriction responses mediated by non-L-type calcium channels and SOCC in FtoSMKO-DM group were greatly suppressed(P＜0.05),while those mediated by caffeine-activated RyR were dramatically boosted(P＜0.05).However,IP3R-mediated responses were not affected(P＞0.05).CONCLUSION:Smooth muscle-specific Fto gene knockout suppresses contractile hyperre-sponsiveness in the aortic smooth muscle of DM mice,which may be attributed to involvement of FTO protein in calcium regulation in the vascular smooth muscle.

Objective To investigate the protective effects and mechanisms of soybean phospholipid powder on nerve cells in vitro and rats neural tissues.Methods In the cell experiments, the cytotoxicity of soybean phospho-lipid powder with different concentrations on mouse microglia cells (BV2) and rat adrenal pheochromocytoma (PC12) cells was observed by cell counting kit-8(CCK-8) assay.The effect of soybean phospholipid powder on the NO level of BV2 cells was analyzed by NO determination experiment, and the synaptic growth of PC12 cells was observed under the microscope.In the animal experiment, the cognitive dysfunction of rat was simulated by scopol-amine rat model.Then the learning and memory abilities of rat were tested by Morris water maze experiment;hipp-ocampal tissue morphology and nerve cell density of scopolamine model mice were observed by hematoxylin-eosin staining (HE) staining.Results Soybean phospholipid powder had no obvious cytotoxicity on BV2 cells and PC12 cells within the concentration of 1000μg/ml.Compared with the control group, the NO secretion of BV2 cells pre-treated with soybean phospholipid powder significantly decreased (P<0.01) , and the neuronal synapse growth of PC12 cells significantly increased (P <0.01) .In comparison to the model group, soybean phospholipid powder significantly improved the learning and memory ability of scopolamine model rats (P<0.05) , reduced the neuronal damage in dentate gyrus (DG), cornu ammonis3 (CA3), cornu ammonis1 (CA1) areas of hippocampus, and in-creased the density of nerve cells (P<0.001).Conclusion Soybean phospholipid powder can play a neuropro-tective role by reducing neuroinflammation and promoting neuronal synapse growth at the cellular level, and im-prove the learning and memory ability of rats with cognitive impairment, reduce hippocampal tissue damage.