OBJECTIVE: To observe the effect of moxibustion on small intestinal mucosal immune barrier in rats with diarrhea-predominant irritable bowel syndrome (IBS-D) and explore its underlying mechanisms. METHODS: Of 38 newborn rats from 4 healthy SPF pregnant rats, 12 neonatal rats were randomly selected in a normal group. IBS-D model was prepared by the combined measures for the rest rats, including neonatal maternal separation, acetic acid enema and chronic restraint stress. Twenty-four successfully-modeled rats were randomized into a model group and a moxibustion group, 12 rats in each one. In the moxibustion group, suspending moxibustion was delivered at bilateral "Tianshu" (ST25) and "Shangjuxu" (ST37), 20 min each time, once daily and for 7 consecutive days. Separately, before acetic acid enema (aged 35 days), after modeling (aged 45 days) and after intervention (aged 53 days), the body mass, loose stool rate (LSR) and and the minimum volume threshold when abdominal withdrawal reflex (AWR) scored 3 were observed in the rats of each group. After intervention (aged 53 days), using HE and PAS staining, the morphology of duodenum was observed, the length of villus and the depth of crypt were measured, the ratio of the length of villus to the depth of crypt was calculated; and the numbers of mucosal intraepithelial lymphocytes (IELs) and goblet cells were counted. With ELISA adopted, the contents of γ-interferon (IFN-γ), interleukin-4 (IL-4) and secretory immunoglobulin A (sIgA) in duodenal mucosa of rats were detected. The proportion of T cell subsets in duodenal mucosa was detected using flow cytometry. The microvilli and tight junctions of duodenal mucosal epithelial cells were observed by transmission electron microscopy, and the integrity of duodenal mucosa observed by scanning electron microscopy. RESULTS: Compared with the normal group, for the rats in the model group, the body mass, the minimum volume threshold when AWR scored 3, the length of duodenal villus and the the ratio of the length of villus to the depth of crypt, as well as the proportion of CD₈⁺ T subset were all reduced (P<0.01, P<0.05), the counts of goblet cells in duodenal mucosa decreased (P<0.01); LRS, the proportion of CD₄⁺ T subset and CD₄⁺/CD₈⁺, as well as the contents of IFN-γ, IL-4 and sIgA in duodenal mucosa and IFN-γ/IL-4 were all elevated (P<0.01); and the numbers of IELs rose (P<0.01). The morphology of duodenal mucosa was irregular, the villi got shorter, sparse and scattered, with uneven density. The morphology of epithelial cells was destroyed and the tight junctions damaged, with larger spaces. When compared with the model group, in the moxibustion group, the body mass, the minimum volume threshold when AWR scored 3, the length of duodenal villus and the ratio of the length of villus to the depth of crypt, as well as the counts of goblet cells in duodenal mucosa increased (P<0.01); LRS, the proportion of CD₄⁺ T subset, and CD₄⁺/CD₈⁺, as well as the contents of IFN-γ, IL-4 and sIgA in duodenal mucosa and IFN-γ/IL-4 were reduced (P<0.01); and the numbers of IELs was dropped (P<0.01). The morphology of duodenal mucosa was more regular, the villi were grew, got longer and arranged regularly, with even density. The morphology of epithelial cells was slightly destroyed, and the tight junctions partially damaged. CONCLUSION Moxibustion at "Tianshu" (ST25) and "Shangjuxu" (ST37) can reduce visceral hypersensitivity in IBS-D rats and relieve abdominal pain, diarrhea and other symptoms. Its effect mechanism may be related to the repair of small intestinal mucosal immune barrier and the improvement in the immune function in IBS-D.
Animals ; Irritable Bowel Syndrome/immunology* ; Rats ; Moxibustion ; Intestinal Mucosa/immunology* ; Female ; Diarrhea/therapy* ; Intestine, Small/immunology* ; Male ; Humans ; Rats, Sprague-Dawley ; Disease Models, Animal

The gut microbiota regulates intestinal nutrient absorption, participates in modulating host glucolipid metabolism, and contributes to ameliorating glucolipid metabolism disorder. Dysbiosis of the gut microbiota can compromise the integrity of the intestinal mucosal barrier, induce inflammatory responses, and exacerbate insulin resistance and abnormal lipid metabolism in the host. Dangua Humai Oral Liquid, a hospital-developed formulation for regulating glucolipid metabolism, has been granted a national invention patent and demonstrates significant clinical efficacy. This study aimed to investigate the effects of Dangua Humai Oral Liquid on gut microbiota and the intestinal mucosal barrier in a mouse model with glucolipid metabolism disorder. A glucolipid metabolism disorder model was established by feeding mice a high-glucose and high-fat diet. The mice were divided into a normal group, a model group, and a treatment group, with eight mice in each group. The treatment group received a daily gavage of Dangua Humai Oral Liquid(20 g·kg~(-1)), while the normal group and model group were given an equivalent volume of sterile water. After 15 weeks of intervention, glucolipid metabolism, intestinal mucosal barrier function, and inflammatory responses were evaluated. Metagenomics and untargeted metabolomics were employed to analyze changes in gut microbiota and associated metabolic pathways. Significant differences were observed between the indicators of the normal group and the model group. Compared with the model group, the treatment group exhibited marked improvements in glucolipid metabolism disorder, alleviated pathological damage in the liver and small intestine tissue, elevated expression of recombinant claudin 1(CLDN1), occluding(OCLN), and zonula occludens 1(ZO-1) in the small intestine tissue, and reduced serum levels of inflammatory factors lipopolysaccharides(LPS), lipopolysaccharide-binding protein(LBP), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α). At the phylum level, the relative abundance of Bacteroidota decreased, while that of Firmicutes increased. Lipid-related metabolic pathways were significantly altered. In conclusion, based on the successful establishment of the mouse model of glucolipid metabolism disorder, this study confirmed that Dangua Humai Oral Liquid effectively modulates gut microbiota and mucosal barrier function, reduces serum inflammatory factor levels, and regulates lipid-related metabolic pathways, thereby ameliorating glucolipid metabolism disorder.
Animals ; Gastrointestinal Microbiome/drug effects* ; Mice ; Intestinal Mucosa/microbiology* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred C57BL ; Humans ; Glycolipids/metabolism* ; Lipid Metabolism/drug effects* ; Administration, Oral ; Disease Models, Animal

OBJECTIVES: To assess the preliminary efficacy and safety of a dose-intensified C5VD regimen (cisplatin, 5-fluorouracil, vincristine, and doxorubicin) in children with locally advanced hepatoblastoma. METHODS: This prospective study enrolled 24 children with newly diagnosed, locally advanced hepatoblastoma who received the dose-intensified C5VD regimen at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children's Hospital between January 2020 and December 2023. Clinical characteristics, treatment outcomes, and chemotherapy-related toxicities were analyzed. RESULTS: Of the 24 patients, 13 were male and 11 were female, with a median age at diagnosis of 18.7 months (range: 3.5-79.4 months). All patients achieved complete macroscopic resection of hepatic lesions without liver transplantation. Serum alpha-fetoprotein levels decreased significantly after two chemotherapy cycles. During a median follow-up of 38.4 months (range: 15.8-50.7 months), all patients maintained continuous complete remission, with 3-year event-free survival and overall survival rates of 100%. Across 144 chemotherapy cycles, the incidence rates of grade 3-4 neutropenia, thrombocytopenia, and infections were 97%, 77%, and 71%, respectively; no treatment-related deaths occurred. Notably, 5 patients (21%) developed Brock grade ≥3 hearing loss, of whom 1 required a hearing aid. CONCLUSIONS The dose-intensified C5VD regimen demonstrates significant efficacy with an overall favorable safety profile in the treatment of newly diagnosed, locally advanced pediatric hepatoblastoma. Grade 3-4 myelosuppression and infection are the predominant toxicities. However, high‑dose cisplatin-induced ototoxicity remains a concern, highlighting the need for improved otoprotective strategies.
Humans ; Hepatoblastoma/pathology* ; Male ; Female ; Infant ; Liver Neoplasms/pathology* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child, Preschool ; Prospective Studies ; Doxorubicin/adverse effects* ; Child ; Cisplatin/adverse effects* ; Vincristine/adverse effects* ; Fluorouracil/adverse effects*

Objective:To evaluate the impact of donor characteristics on the prognosis of myelodysplastic syndrome (MDS) patients undergoing haplo-identical transplantation (HIDT) .Methods:A retrospective analysis of 203 MDS patients who received HIDT was conducted to evaluate how donor factors influenced transplant outcomes.Results:In MDS patients undergoing haploidentical transplantation, donors over 50 years were associated with higher EBV reactivation (2-year cumulative incidence 42.9% vs 22.0% for <50 years old; P=0.010). Female donors were linked to increased severe chronic GVHD compared with male donors (2-year incidence 11.9% vs 4.0% ; P=0.017). Additionally, 2-year overall survival (OS) was slightly lower with female donors than male donors (56.6% vs 69.7% ), but the difference was not statistically significant ( P=0.073). Donor-recipient blood type did not affect post-transplant OS or cumulative relapse rates. Donor-recipient kinship analysis revealed that child donors, compared to haploidentical sibling or parent donors, had lower rates of grade Ⅱ–Ⅳ acute GVHD (27.2% vs 45.7% vs 53.5%, P=0.007) and 2-year EBV reactivation (13.9% vs 29.3% vs 38.9%, P=0.001). For donors under 20 years, donor gender did not significantly affect 2-year OS ( P=0.913), relapse-free survival ( P=0.716), or 100-day incidence of grade Ⅱ–Ⅳ acute GVHD ( P=0.359) . Conclusion:For MDS patients undergoing HIDT, donors over 50 should be avoided. Male and child donors are preferred, while donor gender does not significantly affect outcomes if the donor is under 20 years old.

OBJECTIVE: To summarize research progress on enhanced recovery after posterior cruciate ligament (PCL) reconstruction, clarify the core contradictions, effective intervention methods, and evaluation shortcomings in current clinical practice, and provide theoretical support for optimizing clinical rehabilitation strategies. METHODS: Relevant domestic and international literature in recent years was systematically searched. The key technologies and challenges for enhanced recovery after PCL reconstruction were analyzed from three aspects: the core issues of enhanced recovery after PCL reconstruction, treatment strategies, and the post-reconstruction effectiveness evaluation system. RESULTS: Enhanced recovery after PCL reconstruction mainly faces two core problems. First, there is a balance dilemma between graft tendon protection and knee joint function recovery: the tensile capacity of the graft tendon is weak in the early postoperative period, so excessive weight-bearing easily leads to relaxation, while overly conservative immobilization causes muscle atrophy and joint adhesion. Second, the return-to-sport rate is significantly affected by injury type and treatment method: patients with combined multiple ligament or meniscus injuries have a much lower return-to-sport rate than those with isolated PCL injury, and the risk of return-to-sport failure is higher. Current research mainly promotes rehabilitation from two aspects: physical therapy and surgical technology. Physical therapy runs through the perioperative period: preoperatively, muscle strength training, swelling control, and maintenance of joint range of motion are used to optimize surgical conditions; postoperatively, phased intervention is implemented. Surgical technology focuses on minimally invasive and anatomical approaches: arthroscopic surgery reduces injury, double-bundle reconstruction and internal tension-relief technology improve stability, and modified tunnel positioning and special surgical methods avoid the risk of "Killer Turn". Postoperative functional evaluation adopts multi-dimensional indicators: subjective evaluation relies on scales such as Lysholm and International Knee Documentation Committee (IKDC); objective evaluation assesses stability through Telos stress test and posterior drawer test; imaging evaluation takes MRI as the core; psychological evaluation is assisted by the Tampa scale of kinesiophobia-11 (TSK-11). However, there are obvious shortcomings, such as the lack of PCL-specific evaluation tools. CONCLUSION Enhanced recovery after PCL reconstruction requires the integration of precise surgery, individualized rehabilitation, and comprehensive subjective and objective evaluation. In the future, biomaterials and digital technologies should be integrated to optimize the full-cycle management of PCL reconstruction, thereby improving functional recovery and the effect of return to sports.
Humans ; Posterior Cruciate Ligament Reconstruction/rehabilitation* ; Posterior Cruciate Ligament/injuries* ; Recovery of Function ; Knee Joint/physiopathology* ; Knee Injuries/rehabilitation* ; Return to Sport ; Enhanced Recovery After Surgery ; Tendons/transplantation* ; Arthroscopy

Objective:To evaluate the impact of donor characteristics on the prognosis of myelodysplastic syndrome (MDS) patients undergoing haplo-identical transplantation (HIDT) .Methods:A retrospective analysis of 203 MDS patients who received HIDT was conducted to evaluate how donor factors influenced transplant outcomes.Results:In MDS patients undergoing haploidentical transplantation, donors over 50 years were associated with higher EBV reactivation (2-year cumulative incidence 42.9% vs 22.0% for <50 years old; P=0.010). Female donors were linked to increased severe chronic GVHD compared with male donors (2-year incidence 11.9% vs 4.0% ; P=0.017). Additionally, 2-year overall survival (OS) was slightly lower with female donors than male donors (56.6% vs 69.7% ), but the difference was not statistically significant ( P=0.073). Donor-recipient blood type did not affect post-transplant OS or cumulative relapse rates. Donor-recipient kinship analysis revealed that child donors, compared to haploidentical sibling or parent donors, had lower rates of grade Ⅱ–Ⅳ acute GVHD (27.2% vs 45.7% vs 53.5%, P=0.007) and 2-year EBV reactivation (13.9% vs 29.3% vs 38.9%, P=0.001). For donors under 20 years, donor gender did not significantly affect 2-year OS ( P=0.913), relapse-free survival ( P=0.716), or 100-day incidence of grade Ⅱ–Ⅳ acute GVHD ( P=0.359) . Conclusion:For MDS patients undergoing HIDT, donors over 50 should be avoided. Male and child donors are preferred, while donor gender does not significantly affect outcomes if the donor is under 20 years old.

BACKGROUND:Digital three-dimensional reconstruction technology is gradually applied to orthopedic diseases with the advantages of visualization,accuracy and non-invasiveness,but there is less evidence-based support for its use in artificial hip hemiarthroplasty for intertrochanteric fractures of the femur in the elderly. OBJECTIVE:To investigate the application value and economic effects of digital three-dimensional reconstruction techniques in artificial hip hemiarthroplasty of intertrochanteric fractures of the femur in the elderly. METHODS:One hundred and thirty elderly patients with intertrochanteric femur fractures admitted to Zunyi First People's Hospital from January 2019 to December 2022 were selected and randomly divided into a control group(n=65)and an observation group(n=65).Artificial hip hemiarthroplasty was performed in both groups.The control group adopted the film template measurement method for manual preoperative planning while the observation group adopted a digital three-dimensional reconstruction technique.Preoperative planning and intraoperative actual application of prosthesis compliance rate,fibrinogen,D-dimer,bilateral femoral eccentric distance difference,bilateral lower limb length difference,Harris hip function score,visual analog scale score,excellent and good rate of hip function,complications,and hospitalization cost were observed in both groups. RESULTS AND CONCLUSION:(1)The proportion of acetabular side and femoral side prosthesis in grade 0(fully compliant)was higher in the observation group than that in the control group(P<0.05).(2)Fibrinogen and D-dimer levels in the observation group were lower than those in the control group 3 days after surgery(P<0.05).(3)The difference in bilateral femoral eccentric distance and the difference in bilateral lower limb length in the observation group were smaller than those in the control group immediately after surgery(P<0.05).The differences in Harris and visual analog scale scores were not significantly different between the two groups preoperatively,6 and 12 months postoperatively(P>0.05).There was no significant difference in excellent and good rate of hip function between the two groups 12 months postoperatively(P>0.05).(4)There was no significant difference in the complication rate between the two groups(P>0.05).The hospitalization cost of the observation group was higher than that of the control group(P<0.05).(5)It is indicated that digital three-dimensional reconstruction technology applied in artificial hip hemiarthroplasty of intertrochanteric femoral fracture in the elderly can not only accurately determine the prosthesis type before surgery,but also accurately reconstruct the bilateral lower limbs offline,but its hospitalization cost is high.

Objective To investigate the application value of the quantitative parameters of collateral circulation based on computed tomography perfusion(CTP)in evaluating the clinical prognosis of patients with acute ischemic stroke(AIS).Methods A total of 126 patients with AIS caused by middle cerebral artery occlusion were enrolled,collateral circulation were reconstructed and scored via multiphase computed tomography angiography(mCTA)based on CTP.The hypoperfusion intensity ratio(HIR)and collateral vessel density(CVD)were calculated.All patients were divided into good prognosis group(72 cases)and poor prognosis group(54 cases)based on 90 d modified Rankin scale(mRS)scores.Differences in cardiovascular risk factors,National Institutes of Health Stroke Scale(NIHSS)scores,Albert stroke program early CT(ASPECT)scores,Tmax＞10 s volume,Tmax＞6 s volume,core infarct area volume,and final infarct volume between the two groups were compared.Binary logistic regression was employed to identify independent predictors of the clinical prognosis,and the DeLong test was used to compare the efficacy of different predictors in predicting clinical prognosis.Results The good prognosis group had significantly higher ASPECT scores,mCTA scores,and CVD,but significantly lower HIR,Tmax＞10 s volume,and baseline NIHSS scores compared to the poor prognosis group(P＜0.05).Binary logistic regression analysis showed that ASPECT scores[odds ratio(OR)=0.780],mCTA scores(OR=0.669),CVD(OR=0.595),and HIR(OR=28.968)were independent predictors of clinical prognosis(P＜0.05).DeLong test found no significant difference in area under the curve(AUC)values between mCTA scores,CVD and HIR in predicting the clinical prognosis of AIS patients(P＞0.05).Conclusion Quantitative parameters such as CVD and HIR related to collateral circulation have a strong diagnostic efficacy in predicting the 90 d clinical prognosis in patients with AIS.

Objective To investigate how maternal MTR gene polymorphisms and their interactions with periconceptional folic acid supplementation are associated with the incidence of ventricular septal defects(VSD)in offspring.Methods A case-control study was conducted,recruiting 426 mothers of infants with VSD under one year old and 740 mothers of age-matched healthy infants.A questionnaire survey collected data on maternal exposures,and blood samples were analyzed for genetic polymorphisms.Multivariable logistic regression analysis and inverse probability of treatment weighting were used to analyze the associations between genetic loci and VSD.Crossover analysis and logistic regression were utilized to examine the additive and multiplicative interactions between the loci and folic acid intake.Results The CT and TT genotypes of the maternal MTR gene at rs6668344 increased the susceptibility of offspring to VSD(P<0.05).The GC and CC genotypes at rs3768139,AG and GG at rs1050993,AT and TT at rs4659743,GG at rs3768142,and GT and TT at rs3820571 were associated with a decreased risk of VSD(P<0.05).The variations at rs6668344 demonstrated an antagonistic multiplicative interaction with folic acid supplementation in relation to VSD(P<0.05).Conclusions Maternal MTR gene polymorphisms significantly correlate with the incidence of VSD in offspring.Mothers with variations at rs6668344 can decrease the susceptibility to VSD in their offspring by supplementing with folic acid during the periconceptional period,suggesting the importance of periconceptional folic acid supplementation in genetically at-risk populations to prevent VSD in offspring.