ObjectiveTraditional Chinese medicine (TCM) constitutes a valuable cultural heritage and an important source of antitumor compounds. Poria (Poria cocos (Schw.) Wolf), the dried sclerotium of a polyporaceae fungus, was first documented in Shennong’s Classic of Materia Medica and has been used therapeutically and dietarily in China for millennia. Traditionally recognized for its diuretic, spleen-tonifying, and sedative properties, modern pharmacological studies confirm that Poria exhibits antioxidant, anti-inflammatory, antibacterial, and antitumor activities. Pachymic acid (PA; a triterpenoid with the chemical structure 3β-acetyloxy-16α-hydroxy-lanosta-8,24(31)-dien-21-oic acid), isolated from Poria, is a principal bioactive constituent. Emerging evidence indicates PA exerts antitumor effects through multiple mechanisms, though these remain incompletely characterized. Neuroblastoma (NB), a highly malignant pediatric extracranial solid tumor accounting for 15% of childhood cancer deaths, urgently requires safer therapeutics due to the limitations of current treatments. Although PA shows multi-mechanistic antitumor potential, its efficacy against NB remains uncharacterized. This study systematically investigated the potential molecular targets and mechanisms underlying the anti-NB effects of PA by integrating network pharmacology-based target prediction with experimental validation of multi-target interactions through molecular docking, dynamic simulations, and in vitro assays, aimed to establish a novel perspective on PA’s antitumor activity and explore its potential clinical implications for NB treatment by integrating computational predictions with biological assays. MethodsThis study employed network pharmacology to identify potential targets of PA in NB, followed by validation using molecular docking, molecular dynamics (MD) simulations, MM/PBSA free energy analysis, RT-qPCR and Western blot experiments. Network pharmacology analysis included target screening via TCMSP, GeneCards, DisGeNET, SwissTargetPrediction, SuperPred, and PharmMapper. Subsequently, potential targets were predicted by intersecting the results from these databases via Venn analysis. Following target prediction, topological analysis was performed to identify key targets using Cytoscape software. Molecular docking was conducted using AutoDock Vina, with the binding pocket defined based on crystal structures. MD simulations were performed for 100 ns using GROMACS, and RMSD, RMSF, SASA, and hydrogen bonding dynamics were analyzed. MM/PBSA calculations were carried out to estimate the binding free energy of each protein-ligand complex. In vitro validation included RT-qPCR and Western blot, with GAPDH used as an internal control. ResultsThe CCK-8 assay demonstrated a concentration-dependent inhibitory effect of PA on NB cell viability. GO analysis suggested that the anti-NB activity of PA might involve cellular response to chemical stress, vesicle lumen, and protein tyrosine kinase activity. KEGG pathway enrichment analysis suggested that the anti-NB activity of PA might involve the PI3K/AKT, MAPK, and Ras signaling pathways. Molecular docking and MD simulations revealed stable binding interactions between PA and the core target proteins AKT1, EGFR, SRC, and HSP90AA1. RT-qPCR and Western blot analyses further confirmed that PA treatment significantly decreased the mRNA and protein expression of AKT1, EGFR, and SRC while increasing the HSP90AA1 mRNA and protein levels. ConclusionIt was suggested that PA may exert its anti-NB effects by inhibiting AKT1, EGFR, and SRC expression, potentially modulating the PI3K/AKT signaling pathway. These findings provide crucial evidence supporting PA’s development as a therapeutic candidate for NB.

Celastrol and wilforlide A are the main active triterpenoids of the traditional Chinese medicine Lei Gong Teng, which have anti-tumour, anti-inflammatory and immunosuppressive activities, and are the material basis for the clinical efficacy of Lei Gong Teng-related Chinese medicinal preparations. By analysing the biosynthetic pathway of active ingredients, optimizing genetic elements and utilizing "cell factory" to produce triterpenoids heterologously will be an effective way to obtain from Tripterygium wilfordii in the future in a "low-cost and high-efficient" manner. CYP712Ks are the first cytochrome P450s involved in the skeleton modification of friedelane-type and oleanane-type triterpenoids in T. wilfordii, and they can catalyse the generation of polpunonic acid from friedelin and 3-epi-katonic acid from β-amyrin by carboxylation at C-29 position. In this study, four multifunctional TwCYP712K1/2/3/5 were used to clarify the catalytic function and substrate selection preference using in vivo functional characterization in Saccharomyces cerevisiae. The spatial structure of the protein-substrate binding was clarified through homology modeling and molecular docking, and then the differential amino acids in the active pocket of the protein were mutated to clarify the crucial amino acids determining the catalytic function and the selection of substrate structure. A total of 63 mutant elements were constructed, and the amino acid sites affecting the carboxylation function of TwCYP712Ks were analyzed. In particular, the key amino acids affecting the substrate selectivity of TwCYP712K2 towards oleanane-type and friedelane-type triterpenoids were revealed and the TwCYP712K2^F127I and TwCYP712K2^A227T mutants would result in a reversal of the product ratio. In conclusion, four proteins of TwCYP712Ks were semi-rationally designed by homologous protein alignment and mutual mutation to elucidate multiple amino acid sites determining the catalytic function of the proteins, and a series of activity-enhancing or altering mutants were obtained, which provide abundant catalytic elements for the biosynthesis of active triterpenoids from T. wilfordii, and the mechanism of carboxylation in the C-29 position was initially elucidated.

Sustained and controlled release preparation is ideal for reducing the side effects of drugs, improving patient compliance and enhancing efficacy, among which oral sustained-release tablets are the most widely used. The in vitro release of the preparation is closely related to the in vivo absorption of the drug. However, current in vitro release experiments are labor-intensive and destructive, and the lack of big data also makes it difficult to establish good in vivo and in vitro correlations. Computer modeling, as a technical means that can transform objective principles into mathematical models, has great prospects in data prediction. This review explores the existing computer modeling methods that can be used to predict in vitro release profiles of oral sustained-release tablets, and further discusses auxiliary technologies that can improve the accuracy of the models, providing new ideas for drug development.

Objective To understand the consumption of hand hygiene(HH)products and HH compliance in in-tensive care units(ICUs)of secondary and higher grade medical institutions(MIs)in Shanghai,and provide basis for further monitoring of HH among health care workers(HCWs).Methods Through healthcare-associated infec-tion surveillance system,the consumption of HH products and HH compliance in ICUs from secondary and higher grade MIs in Shanghai in 2017-2021 were analyzed.Results 105 ICUs from 74 MIs were included in analysis,the average consumption of HH products was 79.24(44.88-258.63)mL/(bed·day),with statistically significant difference among different types of ICUs(P＜0.001).The average consumption of HH products increased from 65.75 mL/(bed·day)in 2017 to 87.55 mL/(bed·day)in 2021,showing an increasing trend year by year(P＜0.001).HCWs'HH compliance rate was 82.13％,with the highest in nurses(86.59％)and the lowest(48.90％)in medical technicians,HH compliance rates of HCWs of different occupations were statistically significant different(P＜0.001).Among the implementation modes of HH,39.86％used running water for hand washing,42.27％used alcohol-based hand rub to wipe hands,13.22％didn't take HH measures,and 4.65％didn't take HH mea-sures when wearing gloves,with statistically significant differences among different HH implementation modes of HCWs(P＜0.001).There was a positive correlation between the average consumption of HH products per bed·day and HCWs'HH compliance rate(r=0.703,P＜0.05).Conclusion The average consumption of HH products per bed·day and HH compliance rate of HCWs in ICUs in Shanghai presents an increasing trend year by year.There are differences in the average consumption of HH products per bed·day and HH compliance rate among different types of ICUs.The implementation of HH can be evaluated by continuously surveillance on the average consumption of HH products per bed·day.

Objective To analysis the current situation of hospitalized patients seeking medical treatment across different counties and the influencing factors from both the inflow and outflow perspectives.Methods Using the fourth quarter data of 2019 from the medical record index,with Sichuan Province as the research area,it analyzed the spatial flow of patients based on the patient's county of residence,the county where the hospital is located,and the number of mobile patients.By combining information at the individual patient level,healthcare institution level,and county level,it established two-level random intercept logistic regression analysis to explore the influencing factors from the perspectives of inflow and outflow.Results The proportion of patients seeking medical treatment across different counties in Sichuan is 22.90%.The majority of patients,with a population of over one thousand,are concentrated in the eastern region.However,the western region has a higher proportion of patients seeking medical treatment across counties.Chengdu and Mianyang are both the largest sources and recipients of patient flows.Being Han Chinese(49%,P＜0.001),male(2%,P＜0.001),Stable income(6%,P＜0.001)and better medical insurance coverage(16%,P＜0.001)at the patient level,as well as better healthcare resources at the institutional level,and higher economic(20%,P＜0.001)and medical levels(5%,P＜0.001)at the district and county level promote patients seeking medical treatment across counties.Conclusion Hospitalized patients in Sichuan Province tend to seek medical treatment from surrounding counties towards the county centers,as well as flowing to Chengdu from various locations.Promoting hierarchical medical treatment and encouraging patients to seek appropriate medical services can be achieved through strengthening patient health education,improving healthcare service levels,and promoting coordinated development between the economy and medical industry.

Objective:To observe the changes in the nutritional status of pediatric patients after allogeneic hematopoietic stem cell transplantation(allo-HSCT)for one year,and to analyze the risk factors.Methods:We collected data from 88 pediatric patients who underwent allo-HSCT at the Department of Hematology and Oncology in Children's Hospital of Nanjing Medical University between May 2018 and November 2022.All pediatric patients underwent nutritional status analysis before transplantation,at enrollment,3 months,6 months and 1 year after allo-HSCT.Linear regression model was used to analyze the risk factors for growth rate.Results:The body mass index Z score(BMI-Z)before allo-HSCT was(0.096±1.349),and decreased to(-0.258±1.438)、(-0.715±1.432)、(-0.584±1.444)at enrollment,3 months,6 months after allo-HSCT,and(-0.130±1.317)at 1 year after allo-HSCT(P<0.001).There was no significant change in BMI-Z between pre-transplantation and 1 year after transplantation(P=1.000).Height for age Z score(HAZ)before transplantation was(0.137±1.305)and decreased to(-0.083±1.267)、(-0.221±1.299)、(-0.269±1.282)in 3 months,6 months and 1 year after allo-HSCT(P<0.001).Multivariate linear regression showed that age≥10 years old(P=0.015)and chronic graft-versus-host disease(cGVHD)(P=0.005)were independent risk factors for change in HAZ.Conclusion:The BMI-Z of pediatric patients treated with allo-HSCT returned to the pre-transplantation level after one year,while HAZ continued to decrease.Allo-HSCT may cause impaired growth rate in pediatric patients.Attention should be paid to HAZ changes in pediatric patients before and after allo-HSCT,especially in pediatric patients≥10 years old of age and those with cGVHD.Effective nutritional intervention should be provided in time.

Objective To systematically summarize the published literature on the genetic variants associated with nonalcoholic fatty liver disease(NAFLD). Methods Literature from Web of Science,PubMed,and Embase between January 1980 and September 2022 was systematically searched.Meta-analyses of the genetic variants were conducted using at least five data sources.The epidemiologic credibility of the significant associations was graded using the Venice criteria. Results Based on literature screening,399 eligible studies were included,comprising 381 candidate gene association,16 genome-wide association,and 2 whole-exome sequencing studies.We identified 465 genetic variants in 173 genes in candidate gene association studies,and 25 genetic variants in 17 genes were included in the meta-analysis.The meta-analysis identified 11 variants in 10 genes that were significantly associated with NAFLD,with cumulative epidemiological evidence of an association graded as strong for two variants in two genes(HFE,TNF),moderate for four variants in three genes(TM6SF2,GCKR,and ADIPOQ),and weak for five variants in five genes(MBOAT7,PEMT,PNPLA3,LEPR,and MTHFR). Conclusion This study identified six variants in five genes that had moderate to strong evidence of an association with NAFLD,which may help understand the genetic architecture of NAFLD risk.

Objective:To explore the application effect of microsurgical thinning optimized anterolateral thigh flap in the repair of limb tumor wounds.Methods:A retrospective analysis was conducted on the clinical data of patients with limb tumors at the Microsurgery and Reconstruction Department of Xuzhou Renci Hospital from January 2019 to January 2021. All patients underwent surgical resection of the lesions and were repaired with microsurgical thinning optimized anterolateral thigh flap. The outpatient follow-up was conducted after surgery. One year after surgery, limb function and appearance were evaluated using the Musculoskeletal Tumor Society (MSTS) bone tumor limb salvage surgery limb energy scale and efficacy satisfaction score. The total score is 30 points, and a higher score indicates better function. The limb appearance was evaluated using a satisfaction score scale, with a total score of 5-10 points being satisfactory, 0-4 points being average, and -5 to -1 points considered unsatisfactory. Descriptive methods were used for statistical analysis, and normally distributed measurement data were expressed as Mean±SD.Results:A total of 11 patients were included, comprising 7 males and 4 females, aged between 19 and 55 years, with an average age of 31.5 years. Among them, there were 3 cases of dermatofibrosarcoma protuberans, 4 cases of invasive fibroma, 1 case of mucinous fibrosarcoma, 2 cases of malignant fibrous histiocytoma, and 1 case of squamous cell carcinoma of the skin. The tumor lesion ranged from 5.5 cm × 8.0 cm to 9.0 cm × 19.0 cm, and the tumor resection range during surgery was from 6.5 cm × 9.0 cm to 10.0 cm × 20.0 cm. The size of the skin flap ranged from 7.5 cm × 11.0 cm to 10.0 cm × 22.5 cm. The average thickness of the flap before thinning was 2.2 cm (1.6-3.5 cm), and the average thickness after thinning was 1.2 cm (0.9-1.7 cm). One case of superficial necrosis occurred at the edge of the flap measuring 1.5 cm × 2.0 cm after surgery, and the wound healed after dressing changes. One case of arterial crisis occurred 48 hours after surgery, and thrombus formation was detected at the distal end of the anastomosis during exploration. After reanastomosis, blood flow was restored. The remaining flaps survived well, and the incisions healed in one stage. The average postoperative follow-up period was 14.5 months (12-18 months) with no tumor recurrence. The MSTS score for limb function was (25.2±2.1) points, and the satisfaction score for limb appearance efficacy was (7.4±1.6) points, with a satisfaction rate of 10 out of 11.Conclusion:The application of microsurgical thinning optimized anterolateral thigh flap in the plastic surgery of limb tumors can restore satisfactory limb function and appearance, making it an ideal surgical method.

Objective:To explore the application effect of microsurgical thinning optimized anterolateral thigh flap in the repair of limb tumor wounds.Methods:A retrospective analysis was conducted on the clinical data of patients with limb tumors at the Microsurgery and Reconstruction Department of Xuzhou Renci Hospital from January 2019 to January 2021. All patients underwent surgical resection of the lesions and were repaired with microsurgical thinning optimized anterolateral thigh flap. The outpatient follow-up was conducted after surgery. One year after surgery, limb function and appearance were evaluated using the Musculoskeletal Tumor Society (MSTS) bone tumor limb salvage surgery limb energy scale and efficacy satisfaction score. The total score is 30 points, and a higher score indicates better function. The limb appearance was evaluated using a satisfaction score scale, with a total score of 5-10 points being satisfactory, 0-4 points being average, and -5 to -1 points considered unsatisfactory. Descriptive methods were used for statistical analysis, and normally distributed measurement data were expressed as Mean±SD.Results:A total of 11 patients were included, comprising 7 males and 4 females, aged between 19 and 55 years, with an average age of 31.5 years. Among them, there were 3 cases of dermatofibrosarcoma protuberans, 4 cases of invasive fibroma, 1 case of mucinous fibrosarcoma, 2 cases of malignant fibrous histiocytoma, and 1 case of squamous cell carcinoma of the skin. The tumor lesion ranged from 5.5 cm × 8.0 cm to 9.0 cm × 19.0 cm, and the tumor resection range during surgery was from 6.5 cm × 9.0 cm to 10.0 cm × 20.0 cm. The size of the skin flap ranged from 7.5 cm × 11.0 cm to 10.0 cm × 22.5 cm. The average thickness of the flap before thinning was 2.2 cm (1.6-3.5 cm), and the average thickness after thinning was 1.2 cm (0.9-1.7 cm). One case of superficial necrosis occurred at the edge of the flap measuring 1.5 cm × 2.0 cm after surgery, and the wound healed after dressing changes. One case of arterial crisis occurred 48 hours after surgery, and thrombus formation was detected at the distal end of the anastomosis during exploration. After reanastomosis, blood flow was restored. The remaining flaps survived well, and the incisions healed in one stage. The average postoperative follow-up period was 14.5 months (12-18 months) with no tumor recurrence. The MSTS score for limb function was (25.2±2.1) points, and the satisfaction score for limb appearance efficacy was (7.4±1.6) points, with a satisfaction rate of 10 out of 11.Conclusion:The application of microsurgical thinning optimized anterolateral thigh flap in the plastic surgery of limb tumors can restore satisfactory limb function and appearance, making it an ideal surgical method.

Objective To observe the effect of the supine-posture ripple wood training in preventing motion sickness caused by linear acceleration.Methods Totally 61 motion sickness sensitive males were screened by a vertical oscillation simulator and divided into mildly sensitive group(Graybiel score 1-15,n=28)and severely sensitive group(Graybiel score 16,n=33).The participants in the 2 groups received 5-d ripple wood training,30 min/d.The movement frequency of the ripper wood was maintained at 0.25-0.35 Hz,with an acceleration of 0.15-0.25 g.Graybiel score during the training period was recorded.The static balance function test was conducted before and after training on the 1st and 5th day.Results During the training period,the Graybiel scores and motion sickness incidence in the severely sensitive group were decreased with the increase of training days,and all participants achieved complete acclimatization on the 4th day.The Graybiel scores of the mildly sensitive group were low during the whole period,and the complete acclimatization period was 2 d.There was no significant difference in the sway area of the severely sensitive group in static balance function test before and after training(P＞0.05).The mean velocity of the severely sensitive group in static balance function test was significantly increased after training versus before training on the 1st day(P＜0.01),and there was no significant difference before and after training on the 5th day(P＞0.05).There were no significant differences in the sway area or mean velocity of the mildly sensitive group during the whole training period(all P＞0.05).The validation experiment showed that the motion sickness incidence and the symptom severity were significantly decreased in both groups;the motion sickness incidence of the mildly sensitive group decreased from 100.00％(28/28)to 35.71％(10/28);the incidence of severe symptoms in the severely sensitive group decreased from 100.00％(33/33)to 6.06％(2/33)and the vomiting incidence decreased from 96.97％(32/33)to 6.06％(2/33).Conclusion The supine-posture ripple wood training has great effect in preventing motion sickness,with widespread use and simple operation.