ObjectiveTo clarify the differences in the efficacy and mechanism of different processed products of Atractylodes chinensis rhizoma by the pharmacodynamics and metabolomics studies of raw， bran-fried and rice water-processed products on rats with spleen deficiency. MethodSixty male SD rats were randomly divided into blank group， model group， raw product group（3.75 g·kg^-1）， bran-fried product group（3.75 g·kg^-1）， rice water-processed product group（3.75 g·kg^-1） and Shenling Baizhusan group（6.7 g·kg^-1）， with 10 rats in each group. The method of excessive fatigue+improper diet was used to establish a spleen deficiency model in rats. After the end of modeling， except for the blank and model groups， each dosing group was given the corresponding drug suspension， the immune organ coefficients of each group of rats were examined， the levels of interleukin-6（IL-6）， tumor necrosis factor-α（TNF-α）， immunoglobulin G（IgG）， amylase（AMS）， motilin（MTL）， gastrin（GAS）， Na⁺-K⁺-adenosine triphosphatase（ATPase）， aquaporin 2（AQP2）， AQP3 and AQP8 in rats were measured by enzyme-linked immunosorbent assay（ELISA）. Ultra high performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry（UPLC-Q-TOF-MS） combined with orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to search for biomarkers in the plasma samples of spleen-deficient rats by using two criteria［P<0.05 and variable importance in the projection（VIP） value>1］， and to compare the different modulatory effects of the three decoction pieces on the splenic-deficient biomarkers， and metabolic pathway analysis was conducted through the Kyoto Encyclopedia of Genes and Genomes（KEGG） database. ResultCompared with the blank group， the thymus index and spleen index of rats in the model group were significantly decreased（P<0.05）， the levels of IL-6， TNF-α， IgG and AQP2 were significantly increased（P<0.05）， the levels of AMS， GAS， MTL， AQP3， AQP8 and Na⁺-K⁺-ATPase were significantly decreased（P<0.05）. Compared with the model group， raw products， bran-fried products and rice water-processed products all increased thymus index and spleen index（P<0.05）， decreased IL-6， TNF-α， IgG and AQP2 levels（P<0.05）， and increased AMS， GAS， MTL， AQP3， AQP8 and Na⁺-K⁺-ATPase levels to different degrees. A total of 176 differential metabolites were screened in the model group compared with the blank group， of which 75， 72 and 84 biomarkers were called back by the raw products， bran-fried products and rice water-processed products， respectively（P<0.05， P<0.01）. Raw products of A. chinensis rhizoma mainly affected glycine， serine and threonine metabolism. Bran-fried products mainly affected alanine， aspartate and glutamate metabolism， D-arginine and D-ornithine metabolism. Rice water-processed products mainly affected glycine， serine and threonine metabolism， alanine， aspartate and glutamate metabolism， citrate cycle， thiamine metabolism， D-arginine and D-ornithine metabolism. ConclusionRaw products， bran-fried products and rice water-processed products of A. chinensis rhizoma all have good spleen strengthening effects， among which the effects of bran-fried products and rice water-processed products were stronger. Meanwhile， raw products has the strongest dryness， followed by bran-fried products， and the weakest dryness of rice water-processed products. The three decoction pieces are able to significantly modulate metabolic abnormalities in spleen-deficient rats， and the mechanism may be related to amino acid metabolism such as glycine， serine and threonine metabolism as well as alanine， aspartate and glutamate metabolism.

BACKGROUND:Bone mineral density is the clinical gold standard for determining bone strength,but bone mineral density is less sensitive to changes in bone mass,with large changes in bone mineral density only occurring when bone mass is significantly reduced,so bone mineral density has limited ability to predict changes in bone strength and fracture risk. OBJECTIVE:A model of the normal and osteoporotic hip joint was developed to analyze the stresses and deformation in the hip of normal and osteoporotic patients under single-leg standing conditions. METHODS:A healthy adult female volunteer at the age of 36 years was selected as the study subject.The CT data of the hip joint of this volunteer were obtained and saved in DICOM format.The hip joint model was reconstructed in three dimensions,and the material properties were assigned by the gray value assignment method to obtain the normal and osteoporotic hip joint models according to the empirical formula.The same boundary conditions and loads were set to simulate the stresses and deformation in the normal and osteoporotic hip joints in the single-leg standing position. RESULTS AND CONCLUSION:(1)In the finite element model of the normal and osteoporotic hip,the stress distribution was more concentrated in the medial region of the femoral neck.(2)In the hip bone,the stress distribution was mainly concentrated in the upper part of the acetabulum.(3)The stress peaks in the medial femoral neck and upper acetabulum were larger in the normal hip model than in the osteoporotic hip model,probably due to the reduced bone strength of the osteoporotic bone.(4)The peak Von Mises of both normal and osteoporotic hip models were concentrated on the medial femoral neck,and the peak Von Mises of the hip bone was smaller,indicating that the overall effect of osteoporosis on hip bone stresses was relatively small.(5)In terms of deformation in the single-leg standing position,the maximum deformation in the normal hip model was located at the acetabulum and femoral head,and the maximum deformation was located at the upper part of the greater trochanter of the femur.(6)It is suggested that the finite element analysis method to model the values of parameters related to bone tissue in osteoporosis may improve clinical prediction of bone strength changes and fracture risk.It is explained from the biomechanical view that the intertrochanteric femur and femoral neck are good sites for osteoporotic hip fractures.

Objective:To analyze the epidemiological and etiological characteristics of herpes pharyngitis (HA) in three prefectures of Jiangsu Province, and provide evidence for the prevention and control of HA in Jiangsu.Methods:Three surveillance sentinel hospitals in Wuxi, Suzhou and Yancheng were selected from May 2018 to December 2022, and information related to HA visits and hospitalized cases was regularly collected from the hospital inpatient management system by age groups. Enterovirus nucleic acid detection was performed by RT-PCR, and sequencing analysis, identification of genotype subtypes, and phylogenetic analysis were performed on the sequences of the gene encoding the coat protein VP1 of the main prevalent strains.Results:A total of 57 709 HA cases were recorded in the sentinel hospitals in in Wuxi, Suzhou and Yancheng, which was 1.76 times higher than the reported cases of hand, foot and mouth disease during the same period (57 709/32 831).The percentage of HA hospitalizations was 1.35% (781/57 709), and the percentage of hospitalizations showed an increasing trend from year to year ( χ2=62.79, P<0.001 ).The incidence peak of HA was during May-July. The cases were mainly children aged 12-59 months (67.07%, 38 708/57 709), with the highest case number in age group 36-59 months (34.40%, 19 852/57 709). The HA positivity rate was 33.82% (644/1 904); enterovirus A was predominant (54.04%, 348/644); of these, Coxsackievirus (CV)A6 accounted for the highest percentage (52.59%, 183/348), while CVA16 and CVA4 accounted for 24.71% (86/348) and 15.23% (53/348), respectively. All 10 CVA4 HA endemic strains belonged to the C2 gene subtype, and all 6 CVA6 HA endemic strains belonged to the D3a gene subtype; and were genetically closer to and related to the strains in some areas of China (Fujian Province, Guangzhou City, Jiangxi Province, Yunnan Province, Tianjin City, etc.). Conclusions:The disease burden of HA was heavy in 3 areas in Jiangsu, children in age group 12-59-month were mainly affected, and the annual incidence peak of HA was during May-July. The pathogens causing HA varied, but predominated by enterovirus A and had low intra-typical differentiation, and no new evolutionary branches were found, suggesting that it is necessary to include HA in foot and mouth disease surveillance or regarded as a notifiable communicable disease.

Objective It aims to construct an evaluation index system for the development level of intelligent health insurance,which can serve as a reference for health insurance management departments in assessing the develop-ment level of intelligent health insurance and the implementation of health insurance informatization.Methods Key events in intelligent health insurance were identified based on event system theory and text analysis.The evaluation index system was determined through a combination of expert interviews and Delphi expert consultations.The entro-py method was used to calculate the weights of each index,followed by the assessment of the current and ideal de-velopment levels.Results A total of 16 experts were consulted.After two rounds of Delphi expert consultation,two first-level indicators and 18 second-level indicators were finally included in the system.The current development level of intelligent health insurance in China is at the intelligent development stage(2.524 points),while the ideal de-velopment level is at the intelligent improvement stage(4.073 points).The positivity coefficient of both rounds of Del-phi expert consultation was 100%,with an authority coefficient of 0.842,and the degree of expert coordination im-proved with each round.Conclusion The constructed evaluation index system exhibits high scientificity,stability,and generalizability.It can provide an effective evaluation tool for the development of intelligent health insurance in various pooled areas.

A series of chemotherapeutic drugs that induce DNA damage, such as cisplatin (DDP), are standard clinical treatments for ovarian cancer, testicular cancer, and other diseases that lack effective targeted drug therapy. Drug resistance is one of the main factors limiting their application. Sensitizers can overcome the drug resistance of tumor cells, thereby enhancing the antitumor activity of chemotherapeutic drugs. In this study, we aimed to identify marketable drugs that could be potential chemotherapy sensitizers and explore the underlying mechanisms. We found that the alcohol withdrawal drug disulfiram (DSF) could significantly enhance the antitumor activity of DDP. JC-1 staining, propidium iodide (PI) staining, and western blotting confirmed that the combination of DSF and DDP could enhance the apoptosis of tumor cells. Subsequent RNA sequencing combined with Gene Set Enrichment Analysis (GSEA) pathway enrichment analysis and cell biology studies such as immunofluorescence suggested an underlying mechanism: DSF makes cells more vulnerable to DNA damage by inhibiting the Fanconi anemia (FA) repair pathway, exerting a sensitizing effect to DNA damaging agents including platinum chemotherapy drugs. Thus, our study illustrated the potential mechanism of action of DSF in enhancing the antitumor effect of DDP. This might provide an effective and safe solution for combating DDP resistance in clinical treatment.
Female ; Male ; Humans ; Cisplatin/pharmacology* ; Disulfiram/pharmacology* ; Testicular Neoplasms/drug therapy* ; Fanconi Anemia/drug therapy* ; Alcoholism/drug therapy* ; Drug Resistance, Neoplasm ; Cell Line, Tumor ; Substance Withdrawal Syndrome/drug therapy* ; Apoptosis ; Antineoplastic Agents/therapeutic use* ; Cell Proliferation

Objective:To evaluate the strategy and safety of the radiofrequency ablation (RFA) on ventricular arrhythmias (VAs) originating from the pulmonary sinus cusp (PSC) in pediatric patients.Methods:Retrospective study.Fifteen patients with VAs originating from the PSC who were intervened by RFA in the Department of Pediatric Cardiology, Guangdong Provincial People′s Hospital between March 2014 to July 2020 were enrolled.All the patients met the indication criteria for RFA in pediatric patients.The electrocardiogram, ablation method of ablation were analyzed.Different curved catheters were selected for RFA according to the age and weight of the patients.The catheter was then inserted in a " U" or inverted " P" shape to the PSC.The long-term effect of ablation were reviewed.Results:The mean age and body weight of 15 patients with VAs originating from the PSC were (11.6±2.6) (6-15) years and (39.9±12.2) (19-65) kg, respectively.The electrocardiogram recorded during VAs originating from the PSC showed left bundle branch block and inferior axis with monomorphic R pattern, as well as a QS-wave in aVR and aVL.The electrocardiogram characteristics varied in patients with VAs originating from the PSC.The ideal excitation point was not found in the right ventricular outflow tract or the ablation was unsuccessful in all patients, and the earliest target was mapped and RFA was successful.Among the 15 patients, the successful ablation site was in the lower regions of the PSC, involving the right cusp in 11 patients(73.3%), the anterior cusp in 3 patients(20.0%), and the left cusp in 1 patient(6.7%). The earliest potential recorded at the PSC ablation site preceded the QRS complex onset by (27.3±6.0) ms.During the follow-up period for (2.7±2.0) years, no recurrence of VAs or complications were recorded.Conclusions:Under the premise of gentle catheterization procedure and appropriate radiofrequency energy, ablation was effective, safe and with low recurrence rate to eradicate VAs originating from the PSC in children.

Background Liver damage presented in endemic arsenic poisoning is usually serious. Studies have shown that oxidative stress, proteasome beta 5 subunit (PSMB5), regulatory transcription factor EB (TFEB), and lysosomes are associated with liver injury, but their specific links to arsenic-induced liver injury remain unclear. Objective Using a sodium arsenite (NaAsO₂)-induced rat liver injury model established earlier by the research group, the expressions of PSMB5, TFEB, and lysosomal associated membrane protein 1 (LAMP1) in liver tissues were detected. Methods Twenty-four SPF Wistar rats were randomly divided into control group, and low, medium, and high dose groups, with 6 rats in each group, half male and half female. The exposure concentrations were 0, 25, 50, and 100 mg·L⁻¹ NaAsO₂ solutions for 24 weeks. At the end of the experiment, liver was dissected after rats were anesthetized. The levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), total bile acid (TBA), and catalase (CAT) in liver tissues were detected by chemical colorimetry, and the levels of lipid peroxide (LPO), 4-hydroxynonenal (4-HNE), LAMP1, and cathepsin D (CTSD) in liver tissues were detected by enzyme-linked immunosorbent assay (ELISA); the transcriptional expression levels of PSMB5 and TFEB in liver tissues were detected by real-time fluorescence quantitative PCR (RT-qPCR), and the protein expressions of PSMB5, TFEB, and phosphorylated TFEB (p-TFEB) in liver tissues were detected by immunohistochemistry. Results The results of chemical colorimetry and ELISA showed that compared with the control group, the liver homogenate levels of ALP, TBA, and LAMP1 of each arsenic-exposed group, the ALT and LPO in the medium and high concentration groups, the 4-HNE and CTSD in the high concentration group were increased, while the CAT activity of each arsenic-exposed group was decreased (P<0.05). The results of real-time fluorescence quantitative PCR showed that the transcription levels of PSMB5 and TFEB in the liver tissues of each arsenic-exposed group were decreased compared with those of the control group (P<0.05). The results of immunohistochemistry showed that compared with the control group, the expression of PSMB5 of each arsenic-exposed group were decreased, the expression of TFEB in the medium and high concentration groups was decreased, while the expression of p-TFEB of each arsenic-exposed group was increased (P<0.05). The expression of TFEB protein gradually decreased in the nucleus, while the expression of p-TFEB protein gradually increased in the cytoplasm, but no expression of p-TFEB was found in the nucleus. The results of Pearson correlation analysis showed that PSMB5 in liver tissues was positively correlated with CAT (r=0.818, P＜0.05), and negatively correlated with 4-HNE and p-TFEB (r=−0.582, r=−0.899; P＜0.05); TFEB was negatively correlated with CTSD and LAMP1 (r=−0.457, r=−0.564; P＜0.05); CTSD was positively correlated with ALT and ALP (r=0.529, r=0.485; P＜0.05). Conclusion Long-term exposure to NaAsO₂ can induce oxidative stress, inhibit the expression of PSMB5 and TFEB, promote the accumulation of p-TFEB in the cytoplasm, decrease the nuclear entry of active TFEB, damage the lysosome, and cause liver damage.

Background A prominent feature of endemic arsenic poisoning is severe liver damage. Studies have found that liver injury is closely related to oxidative stress, lysosomes, and autophagy. Objective Through establishing a liver injury model of rats by sodium arsenite (NaAsO₂)administration in drinking water, this experiment is designed to explore the roles of oxidative stress, lysosomes, and AMP activated protein kinase (AMPK)/Unc-51 like kinase 1 (ULK1) pathway in this model. Methods Twenty-four Wistar rats were randomly divided into four groups with six rats in each group (half male and half female), including control group and 25, 50, 100 mg·L⁻¹ NaAsO₂ groups. A rat liver injury model was established by drinking water containing NaAsO₂ freely for 24 weeks. Then liver of rats was dissected after sacrificed, and the levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bile acid (TBA), catalase (CAT), lipid peroxidation (LPO), and total antioxidant capacity (T-AOC) in liver tissues were detected by assay kits. The levels of lysosomal-associated membrane protein 2 (LAMP2), cathepsin B (CTSB), and acid phosphatase (ACP2) were determined by enzyme linked immunosorbent assay. The mRNA transcriptional expressions of AMPK, ULK1, microtubule-associated protein light chain 3 (LC3), and sequestosome 1 (p62) were detected by real-time fluorescence quantitative PCR (RT-qPCR). The protein expressions of p-AMPK, p-ULK1, LC3, and p62 were detected by immunohistochemistry. Results Following the NaAsO₂ administration, significant differences were found in the levels of ALT, ALP, and TBA among the designed groups (F=12.09, 72.11, and 23.58, P<0.05). Compared with the control group, the levels of ALT in the 50mg·L⁻¹ and 100 mg·L⁻¹ NaAsO₂ groups were increased (P<0.05); the levels of ALP and TBA in the 25, 50, and 100 mg·L⁻¹ NaAsO₂ groups were increased (P<0.05); the level of LPO in the 100 mg·L⁻¹ group was increased (P<0.05); the levels of CAT and T-AOC in the 25, 50, and 100 mg·L⁻¹ NaAsO₂ groups were decreased (P<0.05). According to the results of enzyme linked immunosorbent assay, the levels of ACP2 in the 25, 50, and 100 mg·L⁻¹ NaAsO₂ groups, the level of CTSB in the 100 mg·L⁻¹ NaAsO₂ group, and the levels of LAMP2 in the 50 and 100 mg·L⁻¹ NaAsO₂ groups were decreased compared with the control group (P<0.05). Based on the results of RT-qPCR and immunohistochemistry, the mRNA transcriptional and protein expressions of AMPK, ULK1, and LC3 in some arsenic groups were elevated to varying degrees compared with the control group, and the increment in the 100 mg·L⁻¹ NaAsO₂ group was significant for all the indicators (P<0.05); the mRNA transcriptional expressions of p62 in the three arsenic groups and the protein expressions of p62 in the 50 and 100mg·L⁻¹ NaAsO₂ groups also increased compared with the control group (P<0.05). Besides, the results of Pearson correlation analysis showed that there was a positive correlation of T-AOC with LAMP2, CTSB, and ACP2 (r=0.651, 0.673, 0.626; P<0.05), a negative correlation of LPO with CTSB and ACP2 (r=−0468, −0.482; P<0.05), a negative correlation of p62 with LAMP2, CTSB, and ACP2 (r=−0.57, −0.626, −0.591; P<0.05), and a positive correlation of p62 with ALT, ALP, and TBA (r=0.709, 0.897, and 0.857, P<0.05). Conclusion Long-term arsenic exposure may induce oxidative stress, damage lysosomes, and activate the AMPK/ULK1 pathway, which can lead to the blockage of autophagy process, and eventually result in liver damage.

, a widely used Chinese herbal medicine, was considered as central nervous system (CNS) drug for years. Both ethanol extracts (EES) and water extracts (WES) of it were applied clinically. Unfortunately, the difference of their efficacy and even effective material foundation of remains obscure. In this study, to explore the active constituents of , we compared pharmacodynamics and chemical profiles / of EES/WES for the first time using multiple chemical analysis, pharmacological and data processing approaches. It was proved that there was no significant difference in the anti-depressive effects between WES and EES. However, the contents of most components and in plasma were higher in EES than those in WES, which was unconvincing for their similar efficacy. Therefore, we further explored components of targeted onto brain and the results showed that 5 lignans were identified with definite absorptivity respectively both in EES and WES caused by the limitation of blood-brain barrier. Moreover, bioinformatic analysis predicted their anti-depressive action. Above all, the systematic strategy screened 5 brain-targeted effective substances of and it was suggested that exploring the components into nidi would promote the studies on herbs effective material basis.

Heart failure is a complex clinical syndrome characterized by the heart losing the function of effective blood-pumping and venous return, which will cause a series of symptoms, and its clinical manifestations vary with the age of children.The main causes of heart failure in children are congenital heart disease and cardiomyopathy.Drug therapy for heart failure in children has gained rapid progression recently with Sacubitril/valsartan being a typical one, which was approved by Food and Drug Administration (FDA) in October 2019 for its effective use in symptomatic left ventricular dysfunction in children aged 1 year and above, marking that the drug therapy for heart failure in children stands at a new starting point.Implantable cardioverter defibrillator and cardiac resynchronization therapy are applicable to some patients with indications.Mechanical circulatory support is essential in the treatment of patients with cardiopulmonary failure, including extracorporeal membrane oxygenation and ventricular assist device, which is used as an important transition of short-term circulatory assisted transplantation.Pediatric heart transplantation is a treatment option for end-stage heart failure.