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.

Objective To evaluate the clinical efficacy of Chevron minimally-invasive osteotomy and internal fixation with ISO intramedullary plate plus traditional Chinese medicine(TCM)bone-setting manipulations for the treatment of moderate hallux valgus.Methods A retrospective study was conducted.A total of 49 patients(62 feet)with moderate hallux valgus were treated with Chevron minimally-invasive osteotomy and internal fixation with ISO intramedullary plate,and were given TCM bone-setting manipulations before the operation,during the operation,and after the operation.The efficacy was evaluated by using the Visual Analogue Scale(VAS)score and the American Orthopedic Foot and Ankle Society(AOFAS)forefoot score after the operation.Before the operation and 12 months after the operation,the hallux valgus angle(HVA),intermetatarsal angle(IMA)between the first and second metatarsal bone,and the distal metatarsal articular angle(DMAA)showed by X-ray imaging in the weight-bearing position of the foot were recorded.Results(1)All of the 49 patients were followed up for 12 to 24 months,with a mean of(20.6±3.1)months.(2)The X-ray imaging assessment showed that 12 months after the operation,the mean HVA,IMA and DMAA values of the 49 patients(62 feet)were significantly lower than those before the operation,and the differences were all statistically significant(P＜0.01).(3)Twelve months after the operation,the pain VAS score of 49 patients was(3.14±1.21)points,which was significantly lower than the preoperative score points(7.26±2.52),and the difference was statistically significant(P＜0.01).(4)The assessment of joint function showed that 12 months after the operation,the scores of various AOFAS items of pain,function and hallux alignment as well as the overall AOFAS scores of 49 patients were significantly higher than those before the operation,and the differences were statistically significant(P＜0.01).(5)For the 62 feet in 49 patients,the excellent efficacy was achieved in 53 feet,good efficacy was achieved in 7 feet,and fair efficacy was achieved in 2 feet,with the fine rate of 96.77%(60/62).Conclusion For the treatment of moderate hallux valgus,the application of Chevron minimally-invasive osteotomy and internal fixation with ISO intramedullary plate plus TCM bone-setting manipulations is effective on promoting the reset of hallux-metatarsophalangeal joint,restoring the balance of the joint,and maintaining the equilibrium state of the joint through postoperative rehabilitation guidance.The combined therapy exerts certain efficacy,reduces the recurrence rate,and eventually achieves the early rehabilitation after the operation.

Objective:To explore the feasibility and effect of applying spherical fitting technology in CT three-dimensional reconstruction in preoperative planning of the resection range of Cam-type femoral acetabular impingement (FAI).Methods:46 Cam-type FAI patients who underwent arthroscopic femoroplasty in the Department of Sports Medicine in the Third Affiliated Hospital of Southern Medical University from July 2020 to June 2022 were enrolled in the spherical fitting group, including 26 females and 20 males, with an average age of 38.4±15.2 years (range of 24-53 years). The preoperative planning was performed using spherical fitting technology in CT three-dimensional reconstruction. Another 42 Cam-type FAI patients who underwent arthroscopic femoroplasty from July 2018 to June 2020 were enrolled in the observation group, including 25 females and 17 males, with an average age of 43.6±18.4 years (range 24-61 years). The preoperative planning was performed using CT three-dimensional reconstruction observation method. This study evaluated the impact of femoroplasty planned by spherical fitting technique on patients' prognosis though comparing the differences of postoperative α angle, femoral head-neck offset ratio, modified Harris hip score (mHHS), and visual analog score (VAS) at 3, 6, 9, and 12 months between two groups.Results:The average follow-up time was 11.8±0.6 months in spherical fitting group and 11.3±0.8 months in observation group. There was no significant difference regarding α angle, femoral head-neck offset ratio, mHHS, and VAS between two groups preoperatively ( P>0.05). The mHHS in two groups increased gradually, while VAS decreased sequentially at 3, 6, 9, and 12 months postoperatively. The postoperative mHHS and VAS were significantly better than those before surgery ( P<0.05). The mHHS was 83.2±14.8 vs. 70.5±11.2 in spherical fitting group and observation group at the followup of 9 months with significant difference ( t=4.471, P=0.007). It was 85.7±13.3 vs. 73.2±12.5 at the followup of 12 months with significant difference ( t=4.596, P=0.008). No significant difference was found in α angle, femoral head-neck offset ratio or mHHS at 3 and 6 months postoperatively ( P>0.05), and no significant difference was found in VAS at 3, 6, 9, and 12 months postoperatively between two groups. Conclusion:The spherical fitting technology in CT three-dimensional reconstruction could assist surgeons with planning of the resection range of Cam deformity preoperatively, and achieve a smooth progress of arthroscopic femoroplasty intraoperatively; after short term follow-up, we found that patients who underwent femoroplasty using this technology achieved satisfactory outcomes.

Objective:To explore the effects of dual task training assisted by a lower limb rehabilitation robot on lower extremity mobility and the walking ability of stroke survivors.Methods:Sixty-one stroke survivors were randomly divided into a control group and an experimental group with 30 in the control group and 31 in the experimental group. In addition to routine exercise training and physical therapy, both groups were given cognitive-motor dual task training 5 times a week for 3 weeks. But only in the experimental group was the dual task training assisted by a lower limb rehabilitation robot. Both groups′ lower limb motor function, walking ability, cognition, balance and ability in the activities of daily living were evaluated before and after the experiment using the Fugl-Meyer lower extremity assessment (FMA-LE), functional ambulation categories (FAC), the digital span test (DST), the Berg Balance Scale (BBS) and the Modified Barthel Index (MBI). Additionally, 6 survivors of a right hemisphere stroke from the experimental group received cognitive-motor dual task training both with and without the robotic assistance alternately. Near-infrared functional brain imaging was applied before and after the intervention, and the functional network connectivity of the resting brains was analyzed.Results:After the intervention the average FMA-LE, FAC, BBS and MBI scores had improved in both groups, with the improvement in the experimental group significantly better than in the control group on average. In terms of cognition there was no significant difference in the DST forward and backward assessment results between the two groups. The analysis of brain network functional connectivity showed that the intensity of functional connectivity between the left prefrontal cortex (PFC) and the left premotor cortex and supplementary motor cortex (PMC/SMA) increased significantly more, on average, after training assisted by the robot.Conclusion:Dual task training with the assistance of a lower limb rehabilitation robot can effectively improve the lower limb motor function, walking, balance and ability in the activities of daily living of stroke survivors. Enhanced functional connection of the PFC and the PMC/SMA in the healthy hemisphere induced by the robot may be the cause.

Objective:To observe the effects of kidney-tonifying and mind-calming acupuncture therapy on sleep,mood,sex hormone levels,and traditional Chinese medicine(TCM)symptoms in patients with perimenopausal insomnia(PMI). Methods:A total of 90 patients with PMI were randomly divided into a treatment group and a control group,with 45 cases in each group.Patients in the treatment group were treated with acupuncture at Shenshu(BL23),Taixi(KI3),Baihui(GV20),and Anmian(Extra).The control group was treated with sham acupuncture.Both groups were treated 3 times a week for 4 weeks.Pittsburgh sleep quality index(PSQI)and insomnia severity index(ISI)were used to evaluate the sleep quality of the subjects before treatment,after treatment,and 1 month after treatment(follow-up).Beck depression inventory(BDI)and Beck anxiety inventory(BAI)were used to evaluate the depression and anxiety of the subjects before treatment,after treatment,and at 1-month follow-up.The TCM symptom scale was used to evaluate the TCM symptoms of the subjects before treatment,after treatment,and 1 month after treatment.Serum levels of estradiol(E2),follicle-stimulating hormone(FSH),and luteinizing hormone(LH)were measured before and after treatment. Results:During the study,2 cases dropped out of the treatment group,and no cases dropped out of the control group.The PSQI scores of the treatment group were significantly lower after treatment and at 1-month follow-up compared with those before treatment(P<0.05),and the difference was statistically significant compared with that of the control group(P<0.05).In the control group,the PSQI score was significantly lower after treatment compared with before treatment(P<0.05),and the difference was not statistically significant at 1-month follow-up compared with before treatment(P>0.05).Compared with the pre-treatment,the ISI,BDI,BAI,and TCM symptom scale scores of the treatment group were lower after treatment and at 1-month follow-up(P<0.05),and the differences with the control group at the same time point were statistically significant(P<0.05).The differences in ISI,BDI,BAI,and TCM symptom scale scores of the control group before treatment,after treatment,and at 1-month follow-up were not statistically significant(P>0.05).After treatment,the serum E2 level in the treatment group was significantly higher than that before treatment(P<0.05),and the difference with the control group was statistically significant(P<0.05).The difference in the serum E2 level before and after treatment in the control group was not statistically significant(P>0.05).The differences in the serum FSH and LH levels between before and after treatment were not statistically significant in either group of subjects(P>0.05). Conclusion:Kidney-tonifying and mind-calming acupuncture therapy can improve sleep quality,relieve anxiety and depression,delay the decrease of serum E2 level,and improve related TCM symptoms in patients with PMI.

Objective:To preliminarily explore the clinical value of three-dimensional ultrasound fusion imaging(3DUS FI) visualization technology in guiding precise needle placement during thermal ablation of hepatocellular carcinoma (HCC).Methods:A total of 56 HCC patients (59 lesions)who underwent 3DUS FI guided thermal ablation were retrospectively analyzed in the First Affiliated Hospital of Sun Yat-sen University from November 2019 to December 2021. All patients were collected with three-dimensional ultrasound volume image before ablation which were fused with real-time two-dimensional ultrasound image for registration, and then the tumor and the safety margin of 5 mm were segmented and marked. Finally, the thermal ablation was performed under three-dimensional visualization. Contrast-enhanced CT/MRI was performed 1 month after thermal ablation to evaluate whether the lesion was completely ablated and measure the ablative margin, and the relationship between ablative margin and the incidence of local tumor progression (LTP) was also analyzed.Results:During the ablation, all lesions could be successfully registered and displayed in three-dimension. Postoperative contrast-enhanced ultrasound showed that all lesions were completely ablated. A total of 37 lesions could be evaluated for ablative efficacy and ablative margin based on contrast-enhanced CT/MRI 1 month after themal ablation, of which 32 (86.5%) lesions achieved complete ablation and obtained at least 5 mm ablative margin. During the follow-up period, LTP was occurred in 4 lesions, 3 of the lesions occurred at the ablative margin< 5 mm. Both 1-year and 2-year cumulative LTP rates were all 7.1%. None of patients had serious complications or deaths associated with thermal ablation.Conclusions:3DUS FI real-time guidance technology is feasible and safe in visually guiding precise needle placement during thermal ablation of HCC.

Objective To observe the clinical effect of ursodeoxycholic acid capsules combined with laparoscopic-assisted choledochoscopic lithotomy in the treatment of intrahepatic and extrahepatic bile duct stones.Methods Patients with intrahepatic and extrahepatic bile duct stones were divided into the control group and the treatment group.The control group was treated with laparoscopic-assisted choledochoscopic lithotomy,and was given general maintenance treatment after operation,such as anti infection,liver protection,and nutritional support.On this basis,the treatment group was treated with ursodeoxycholic acid capsules(0.25 g,tid,orally administration,for 6 months).The symptom disappearance rate,liver function indicators[glutamic-pyruvic transaminase(GPT),glutamic oxalacetic transaminase(GOT),total bilirubin(TBIL)],lipid metabolism indicators[total cholesterol(TC),triglyceride(TG),high density lipoprotein(HDL)]and stone recurrence rate were compared between the two groups.The incidence rates of postoperative complications were calculated.Results Forty-five cases were included in the treatment group and forty-three cases in the control group,respectively.After treatment,the total effective rates in the treatment group and the control group were 95.56％(43 cases/45 cases)and 81.40％(35 cases/43 cases)(P＜0.05).Six months after surgery,the disappearance rates of upper abdominal pain in the treatment group and the control group were 95.56％(43 cases/45 cases)and 81.40％(35 cases/43 cases);the disappearance rates of hepatic tenderness were 100.00％(45 cases/45 cases)and 86.05％(37 cases/43 cases);GPT levels were(31.54±6.27)and(38.29±6.63)U·L-1;GOT levels were(38.75±5.52)and(43.46±5.08)U·L-1;total bilirubin(TBIL)levels were(26.57±6.39)and(32.28±7.61)μmol·L-1;total cholesterol(TC)levels were(5.29±1.06)and(6.12±1.03)mmol·L-1;triglyceride(TG)levels were(1.45±0.43)and(1.69±0.46)mmol·L-1;high density lipoprotein(HDL)levels were(1.69±0.36)and(1.51±0.39)mmol·L-1;stone recurrence rates were 0(0 cases/45 cases)and 11.63％(5 cases/43 cases).The differences between groups were statistically significant(all P＜0.05).The main adverse drug reactions in the treatment group were nausea and diarrhea,while there were no adverse drug reactions in the control group.The total incidence of adverse drug reactions in the treatment group and control group were 6.67％(3 cases/45 cases)and 0(0 cases/43 cases),with no statistically significant difference(P＞0.05).Conclusion The application of ursodeoxycholic acid capsules after laparoscopic-assisted choledochoscopic lithotomy can promote the improvement of clinical symptoms and liver function in patients with intrahepatic and extrahepatic bile duct stones,accelerate lipid metabolism,and prevent stone recurrence.

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

ObjectiveTo screen optimized protocol of acupuncture for post-prostatectomy urinary incontinence （PPUI） patients， and to provide evidence for clinical practice. MethodsMEDLINE， Embase， Cochrane Library， Web of Science， Chinese Biomedical Literature Database， China National Knowledge Infrastructure， WanFang and VIP databases were searched to collect randomized controlled trials of acupuncture for PPUI. The search was conducted from the establishment of the database to February 1， 2024， and the quality of the literature was evaluated to exclude the studies with a high risk of overall bias or modified Jadad ＜3， and constructed acupuncture protocol and performed meta-analysis. We used International Consultation on Urinary Incontinence Short Form （ICI-Q-SF） scores， quality of life scores， overall effective rate， and modified Jadad scores as beneficial indicators， and the number of acupoints selected， stimulation duration， the number of acupuncture， and the duration of the treatment course as costly indicators， to derive the standardized protocol matrix， and used the entropy method to determine the weights of the different decision-making indicators， and finally combined with the Technique for Order Preference by Similarity to Ideal Solution （TOPSIS） for comprehensive evaluation. ResultsNine studies met the criteria， and the acupuncture treatments involved were constructed as six protocols including electrical acupoint stimulation with low-frequency， electroacupuncture at four acupoints of sacral region， replenishing qi and tonifying kidney acupuncture， body acupuncture plus pelvic floor muscle training， auricular acupuncture， and electroacupuncture plus pelvic floor muscle training. The ICI-Q-SF， number of acupuncture sessions， and total effectiveness rate were given higher weights in the decision-making indexes， while the stimulation duration and the duration of treatment course were given lower weights； the entropy method of TOPSIS was used for the evaluation and proved that the best protocol was the electroacupuncture at four acupoints of sacral region which used continuous-wave electroacupuncture with a frequency of 2 Hz for 60 min each time， and required the needle sensation to radiate to the root of the penis， with the advantages of streamlined selection of acupoints， a significant reduction in ICI-Q-SF， and an increase in the effectiveness rate. ConclusionThe final optimized protocol was electroacupuncture at four acupoints of sacral region， which can provide an evidence-based basis for clinical decision-making and guideline development.

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.