OBJECTIVE To investigate the effect and mechanism of modified Lichong decoction （MLCD） on the apoptosis of transplanted tumor cells in nude mice. METHODS Human gastric cancer AGS cells were cultured， and a nude mice transplanted tumor model was established. The nude mice were divided into the model group and MLCD low-， medium- and high-dose groups （150， 300， 600 mg/kg）. They were given distilled water or the corresponding drug solution by gavage once daily for four consecutive weeks. The size of transplanted tumors in nude mice was measured every six days， and the tumor volume was calculated. After the medication， the nude mice were sacrificed， and the transplanted tumor tissues were isolated. The contents of lactate dehydrogenase （LDH） and reactive oxygen species （ROS） in the transplanted tumor tissues were detected， and the changes in mitochondrial membrane potential were assessed. The pathological morphological changes were observed. The enzymatic activities of caspase-3， caspase-8， and caspase-9， as well as protein expressions of Fas and FasL and mRNA expressions of caspase-3， caspase-8， caspase-9， Fas and FasL in the transplanted tumor tissues， were detected. RESULTS Compared with the model group， the volume of transplanted tumors in nude mice from all MLCD dose groups was reduced to varying degrees. The contents of LDH and ROS， as well as the enzymatic activities of caspase-3， caspase-8 and caspase-9， were significantly increased/enhanced. The mitochondrial membrane potential was significantly decreased. The protein expressions of Fas and FasL， and the mRNA expressions of caspase-3， caspase-8， caspase-9， Fas and FasL were significantly up-regulated. Most of these differences were statistically significant （ P ＜0.05 or P ＜0.01）. Pathological results showed that with increasing doses of MLCD， the cellular density in the transplanted tumor tissues gradually decreased， and typical morphological features of apoptosis， such as loosening and increasing fragmentation， became more prominent. CONCLUSIONS MLCD can induce apoptosis in transplanted tumor cells of nude mice， and its mechanism may be related to the activation of the Fas/FasL pathway and the caspase apoptotic pathway.

The ability to localize sound sources rapidly allows human beings to efficiently understand the surrounding environment. Previous studies have suggested that there is an auditory "where" pathway in the cortex for processing sound locations. The neural activation in regions along this pathway encodes sound locations by opponent hemifield coding, in which each unilateral region is activated by sounds coming from the contralateral hemifield. However, it is still unclear how these regions interact with each other to form a unified representation of the auditory space. In the present study, we investigated whether functional connectivity in the auditory "where" pathway encoded sound locations during passive listening. Participants underwent functional magnetic resonance imaging while passively listening to sounds from five distinct horizontal locations (-90°, -45°, 0°, 45°, 90°). We were able to decode sound locations from the functional connectivity patterns of the "where" pathway. Furthermore, we found that such neural representation of sound locations was primarily based on the coding of sound lateralization angles to the frontal midline. In addition, whole-brain analysis indicated that functional connectivity between occipital regions and the primary auditory cortex also encoded sound locations by lateralization angles. Overall, our results reveal a lateralization-angle-based representation of sound locations encoded by functional connectivity patterns, which could add on the activation-based opponent hemifield coding to provide a more precise representation of the auditory space.
Humans ; Sound Localization/physiology* ; Male ; Female ; Magnetic Resonance Imaging ; Young Adult ; Functional Laterality/physiology* ; Adult ; Brain Mapping ; Auditory Cortex/physiology* ; Acoustic Stimulation ; Auditory Pathways/physiology* ; Brain/physiology*

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Objective:To investigate the protective effect of Dendrobium officinale polysaccharides(DOP)on intestinal mucosal barrier damage,and to elucidate the possible mechanism.Methods:Ten female C57BL/6 mice,aged 5 months,were selected as young group;twenty femal C57BL/6 mice,aged 15 months,were randomly divided into aged group and DOP treatment group(200 mg·kg-1,DOP group),with 10 mice in each group.The mice in DOP group were administrated with DOP by gavage.The body mass,food intakes and hanging time of the mice in various groups were detected.HE staining was used to observe the pathomorphology of intestinal and spleen tissues of the mice in various groups.Immunohistochemical staining was used to detect the expressions of intestinal atresin 1(ZO-1)and Mucin 2(MUC2)in intestinal tissue of the mice in various groups.The intestinal baterial metabolite medium(IBMM)were prepared to intervene the Caenorhabditis elegans(C.elegans),and the C.elegans were randomly divided into Young-IBMM group,Aged-IBMM group,and DOP-IBMM group.Immuno-fluorescence method was used to analyze the intestinal lipofuscin accumulation levels on the 1st day and the 12th day of the C.elegans in various groups.Brilliant blue staining was used to assess the intestinal leakage on the 1st day and the 12th day of C.elegans in various groups.The Caco-2 cells were randomly divided into Young-IBMM,Aged-IBMM and DOP-IBMM groups,and Western blotting method was used to detect the expression levels of ZO-1,Occludin,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),phosphorylated myosin light chain(p-MLC),myosin light chain kinase(MLCK)proteins in the Caco-2 cells in various groups.Results:Compared with young group,the body mass of the mice in aged group was increased(P＜0.05),the amount of food intake was decreased(P＜0.05),and the hanging time was decreased(P＜0.05);compared with aged group,the body mass of the mice in DOP group was significantly decreased(P＜0.01),the amount of food intake was increased(P＜0.05),and the hanging time was significantly extended(P＜0.01).The HE staining results showed that compared with young group,the thickness of intestinal mucosa of the mice in aged group became thinner,the goblet cells were reduced,the intestinal villi were disordered with different lengths,a large amount of hemosiderin was found on the surface of the spleen,the cell components in the red medullary were reduced,and the lymphatic sheath and lymphatic nodes around the intra-white pulp artery remained or almost disappeared;compared with aged group,the thickness of the intestinal mucosa of the mice in DOP group was increased,the goblet cells were increased,the length of the intestinal villi was consistent and neatly arranged,the overall function of the red pulp of the spleen was improved,and the components of the white pulp were increased.The immunohistochemical staining results showed that compared with young group,the expression levels of ZO-1 and MUC2 proteins in intestinal tissue of the mice in aged group were significantly decreased(P＜0.05 or P＜0.001);compared with aged group,the expression levels of ZO-1 and MUC2 proteins in the intestinal tissue of the mice in DOP group were significantly increased(P＜0.05 or P＜0.001).The immuno-fluorescence analysis showed that compared with Young-IBMM group,the intestinal lipofuscin accumulation level of C.elegans in Aged-IBMM group was significantly increased(P＜0.001);compared with Aged-IBMM group,the intestinal lipofuscin accumulation level of C.elegans in DOP-IBMM group was significantly reduced(P＜0.001).The brilliant blue staining showed that compared with Young-IBMM group,the bright blue dye leaked into the whole body of C.elegans from intestinal tissue in Aged-IBMM group,and the intestinal structure became blurred and was difficulted to be observed;compared with Aged-IBMM group,the leakage of bright blue dye of C.elegans in DOP-IBMM was reduced.The Western blotting results showed that compared with Young-IBMM group,the expression levels of TNF-α,IL-6,p-MLC,and MLCK proteins in the Caco-2 cells in Aged-IBMM group were significantly increased(P＜0.01 or P＜0.001),and the expression levels of ZO-1 and Occludin proteins were significantly decreased(P＜0.05 or P＜0.01);compared with Aged-IBMM,the expression levels of TNF-α,IL-6,p-MLC and MLCK proteins in the Caco-2 cells in DOP-IBMM group were significantly decreased(P＜0.01),and the expression levels of ZO-1 and Occludin proteins were significantly increased(P＜0.05 or P＜0.01).Conclusion:DOP has an ameliorating effect on intestinal mucosal barrier damage in the aged mice,and its mechanism may be related to the improvement of intestinal barrier damage by regulating intestinal bacterial metabolites,inhibiting the p-MLC/MLCK signal pathway,restoring the expression of tight junction complexes,and reducing the level of intestinal inflammation.

Objective:To evaluate the effect of robot-assisted laparoscopic technology via abdominal approach for patients with primary retroperitoneal tumors.Methods:A retrospective cohort analysis was conducted for the clinical data of 71 patients who underwent robot-assisted laparoscopic resection of primary retroperitoneal tumor via abdominal approach at the Department of Urology of Sir Run Run Shaw Hospital,Zhejiang University School of Medicine from January 2015 to December 2023. There were 35 male and 36 female patients. The age ( M(IQR)) was 56(21) years (range: 21 to 83 years). The median tumor diameter was 46 (31) mm (range: 15 to 134 mm). Postoperative pathology revealed 58 benign and 13 malignant cases. Patients were divided into non-adherent group ( n=47) and adherent group ( n=24) based on whether the tumor was adhered to major organs or vessels. Perioperative and postoperative situation were compared between the two groups. Data comparisons were conducted using independent samples t-test for normally distributed continuous variables, Mann-Whitney U tests for non-normally distributed data, χ2 test or Fisher′s exact test for categorical variables. Kaplan-Meier survival analysis was employed to estimate 3-year recurrence or metastasis rate and 3-year mortality rate. Results:Operative time was 120(60) minutes (range: 45 to 440 minutes), intraoperative blood loss was 50 (80) ml (range: 10 to 2 000 ml). The median change of intraoperative mean arterial pressure was 40 (19) mmHg(1 mmHg=0.133 kPa)(range: 10 to 112 mmHg). Intraoperative blood transfusion was required in 7 cases, whereas 64 cases did not necessitate transfusion. The change in hemoglobin levels before and after surgery was (17.9±13.6) g/L (range:-16 to 53 g/L), and the median change in serum creatinine levels was 2.0 (14.5) μmol/L (range:-71.0 to 100.4 μmol/L). Postoperative fasting duration was 2.0 (1.5) days (range: 1 to 6 days), and the median hospital stay was 10.0 (7.5) days (range: 4 to 24 days). No perioperative mortality occurred in any of the patients. The non-adherent group had shorter operation time, less estimated blood loss, lower blood transfusion rate, smaller delta value of hemoglobin before and after surgery, larger delta value of creatinine before and after surgery, fewer postoperative complications, shorter postoperative fasting time, and shorter length of hospital stay than the adherent group(all P<0.05), while there was no significant difference in mean arterial pressure fluctuation between the two groups ( P>0.05). Follow-up data were available for 69 patients, with a median follow-up duration of 39 (43) months (range: 4 to 88 months). Among these patients, 40 completed the 3-year follow-up. The 3-year recurrence or metastasis rate was 10.14%, and the 3-year mortality rate was 2.90%. Conclusions:Robot-assisted laparoscopic technology via abdominal approach for resection of primary retroperitoneal tumors is safe and feasible. It can also achieve secure surgical outcome for primary retroperitoneal tumors adherent to surrounding organs or vessels, albeit with increased surgical complexity and slower postoperative recovery compared to non-adherent cases.

Objective:To evaluate the cost-effectiveness of Artificial Intelligence(AI)-assisted physician image interpretation in the screening of early-stage lung cancer(stage Ⅰ)from the perspective of the healthcare system,so as to provide evidence for screening strategy optimization.Methods:Based on community populations,a decision tree model was constructed to simulate the cost-effectiveness of two screening strategies:Al-assisted physician image interpretation and independent physician image interpretation,and the Incremental Cost-Effectiveness Ratio(ICER)was calculated.Results:In the basic analysis,the per capita costs of the AI-assisted group and the physician group were 1 483 yuan and 1 489 yuan,respectively,and the effectiveness was 17.02 Quality-Adjusted Life Years(QALYs)and 16.99 QALYs,respectively.Compared with the physician group,the AI-assisted group saved 6 yuan per case and obtained an additional 0.03 QALY per case.The ICER was negative,indicating that the AI-assisted group had an absolute advantage.Threshold analysis showed that when the inspection cost of Al-assisted physician image interpretation increased to 428 yuan per case,the average cost per case was the same between these two groups,and the ICER was 0.When the inspection cost of Al-assisted physician image interpretation was above 428 yuan,the ICER was positive,still demonstrating economic efficiency.Conclusion:AI-assisted image interpretation is cost-effective in the screening of early-stage lung cancer and can facilitate the"early detection,early diagnosis,and early treatment"of lung cancer based on improving the efficiency and accuracy of screening,so as to provide scientific support for health system resource optimization.

Summarized the nursing experience of a patient with concurrent Nectriahaematococca infection after allogeneic hematopoietic stem cell transplantation. The nursing points included: implementing infection prevention and control measures to prevent the recurrence of severe infections. Provide goal oriented care measures to control skin infection symptoms. Provide preventive nursing interventions for fungal keratitis to prevent potential infections from occurring. Strengthen medication management and be vigilant against adverse drug reactions.Implementing multiple forms of psychological care to enhance confidence in disease treatment. After active treatment and meticulous care, the patient infection was controlled and successfully discharged on the 59th day after transplantation.

Objective:To investigate the effect of Yiqi Shengqing Formula on neuronal damage in ischemic stroke(IS)rats by regulating brain-derived neurotrophic factor(BDNF)-extracellular regulated protein kinase(ERK)-cyclic adenosine monophosphate-responsive element binding protein(CREB)signal pathway.Methods:IS rat model was prepared by modified thread suppository method,and randomly divided into model group,low dose Yiqi Shengqing Formula(3 g/kg)group,high dose Yiqi Shengqing Formula(6 g/kg)group,high dose Yiqi Shengqing Formula(6 g/kg)+empty load group,high dose Yiqi Shengqing Formula(6 g/kg)+BDNF knockdown group,with 10 rats in each group,another 10 healthy rats were set as sham operation group.After intervention with Yiqi Shengqing Formula and plasmid,neural function of rats in each group was scored with Longa scoring method;Morris water maze test was used to detect cognitive impairment of rats in each group;Nissl staining was used to detect the number of neurons in ischemic peripheral brain tissue and hippocampus of rats in each group;synaptic morphology of ischemic peripheral brain tissue was detected by silver staining;levels of TNF-α and IL-8 in brain tissue and serum of rats in each group were measured by ELISA;expressions of BDNF-ERK-CREB signal pathway related proteins in rat brain were detected by Western blot.Results:Compared with sham operation group,synaptic morphology of ischemic peripheral brain tissue in model group was severely damaged,retention time in target quad-rant,times of crossing platform,the number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were decreased significantly(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were increased significantly(P<0.05).Compared with model group,synaptic morphological damage of ischemic peripheral brain tissue in rats in low dose Yiqi Shengqing Formula group and high dose Yiqi Shengqing Formula group was alleviated,retention time in target quadrant,times of crossing platform,the number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were increased(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were decreased(P<0.05).Compared with low dose Yiqi Shengqing Formula group,damage of synaptic morphology in ischemic peripheral brain tissue of rats in high dose Yiqi Shengqing Formula group was further alleviated,retention time in target quadrant,times of crossing platform,the number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were further increased(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were further reduced(P<0.05).Compared with high dose Yiqi Shengqing Formula group,synaptic morphological damage of ischemic peripheral brain tissue in high dose Yiqi Shengqing Formula+BDNF knockdown group was aggravated,retention time in target quadrant,times of crossing the platform,number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were decreased(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were increased(P<0.05);there was no significant changes in each index of rats in high dose Yiqi Shengqing Formula+empty load group(P>0.05).Conclusion:Yiqi Shengqing Formula can inhibit the neuroinflammation of IS rats by activating BDNF-ERK-CREB signal,thereby reducing the damage of its neurons and improving its neural function.

Objectives:To investigate the physical growth status of pediatric patients with transfusion-dependent thalassemia (TDT) and analyze the effects of treatment-related and socioeconomic factors on physical growth.Methods:Based on the specialized thalassemia database from gene therapy clinical research at the Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, we collected data on height and weight development, family economic status, and medical records of 338 pediatric patients with TDT from October 2023 to May 2024. The length/height-for-age and body mass index (BMI) -for-age were classified based on the Growth Standard for Children under 7 Years of Age, Standard for Height Level Classification among Children and Adolescents Aged 7-18 Years, and Dietary Guidelines for Chinese Residents. Logistic regression analysis was conducted to assess the effects of family economic status and disease-related treatment on length/height-for-age and BMI-for-age.Results:Among the 338 patients, 118 were children and 220 were adolescents (192 males and 146 females), with a median age of 12 years (range: 0.8-18) and a median diagnosis duration of 10.3 years (range: 0.5-17.9). Subtypes included α-thalassemia [21 cases (6.2%) ], β-thalassemia [288 cases (85.2%) ], and combined αβ-thalassemia[29 cases (8.6%) ]. The monthly household income of patients was concentrated in 3 000-5 000 yuan (39.9%) and 5 001-10 000 yuan (34.9%), whereas 67.2% of the families had monthly medical expenses of <3 000 yuan. Of the patients, 75.5% received their first transfusion before 1 year of age. The proportions of children and adolescents with pretransfusion hemoglobin (HGB) of ≤70 g/L were 4.2% and 6.4%, respectively. Adolescents demonstrated significantly higher rates of transfusion frequency of <4 weeks/session, monthly red blood cell infusion of >2 U, serum ferritin (SF) of ≥5 000 μg/L, iron chelation therapy, and splenectomy compared with children (all P<0.05). Of the 338 patients, 26.0%, 22.8%, and 8.9% demonstrated stunted growth, underweight, and concurrent stunted growth with underweight, respectively. No significant difference was observed in the stunted growth rates between children (22.9%) and adolescents (27.7%) ( P=0.402). However, the underweight rate in adolescents (26.8%) was significantly higher than that in children (15.3%) ( P=0.023). The multivariate analysis determined the following risk factors for stunted growth: monthly household income of <10 000 yuan (5 001-10 000 yuan: OR=5.49, 95% CI: 1.48-35.76; 3 000-5 000 yuan: OR=6.87, 95% CI: 1.88-44.60; <3 000 yuan: OR=9.29, 95% CI: 2.20-64.77), pretransfusion HGB of ≤70 g/L ( OR=3.25, 95% CI: 1.07-10.18), and SF of ≥5 000 μg/L ( OR = 3.04, 95% CI: 1.20-7.70). Longer diagnostic duration was associated with underweight ( OR=1.10, 95% CI: 1.01-1.20) . Conclusions:Children and adolescents with TDT with pretransfusion SF of ≥5 000 μg/L, HGB of ≤70 g/L, low monthly household income, or longer diagnosis duration were significantly more likely to experience delayed physical growth.

Objective:To investigate the combined therapeutic role of the AKT inhibitor MK2206 and Ruxolitinib in treating Myeloproliferative Neoplasms (MPN) driven by a calreticulin (CALR) gene mutation.Methods:① Murine bone marrow c-kit + cells were isolated by sacrificing mice and harvesting bone marrow from the femur, tibia, and ilium for subsequent c-kit + cell sorting. ② A CALR transplantation mouse model was established. GFP-tagged retroviral vectors containing either the CALR gene mutation or the migR1 control were constructed, packaged in Platinum-E cells, and used to transduce murine bone marrow c-kit + cells. These transduced cells were then transplanted into lethally irradiated female recipient mice via tail vein injection. ③ Following successful engraftment, the mice were randomly assigned to four treatment groups for intragastric administration. Complete blood counts were monitored periodically, and the spleen size and weight of transplanted mice were measured. ④ Flow cytometry was used to quantify the proportions of GFP + tumor cells, megakaryocytic lineage cells, and hematopoietic stem cells in both splenic and bone marrow tissues. Histopathological examination was performed to evaluate the degree of tumor cell infiltration in these organs. Results:① Following gavage treatment, peripheral blood platelet (PLT) and white blood cell counts were significantly lower in the combined AKT inhibitor MK2206 and Ruxolitinib group compared to the MK2206, Ruxolitinib, and control groups ( P<0.05). ② In comparison with the MK2206 and Ruxolitinib monotherapy groups, the combination therapy group exhibited a significant reduction in spleen weight and a marked improvement in splenomegaly at 30 weeks post-transplantation ( P<0.05). ③ After four weeks of continuous treatment, combined administration resulted in a significant decrease in the proportion of megakaryocytic lineage cells and GFP + tumor cells in the bone marrow and spleen ( P<0.05). Additionally, the proportion of hematopoietic stem cells in the bone marrow was also significantly reduced ( P<0.05). ④ Histopathological analysis (H&E staining) of bone marrow and spleen tissues confirmed that the combined regimen decreased both tumor cell infiltration and the proportion of abnormal megakaryocytes in these organs. Conclusion:The combination of AKT inhibitor MK2206 and Ruxolitinib is effective at significantly ameliorating disease symptoms and reducing tumor infiltration in vivo in mice with a myeloproliferative tumor transplantation driven by a CALR gene mutation.