OBJECTIVE To explore the mechanism of the active ingredient compatibility（quercetin， quercitrin and kaempferol at a mass ratio of 2∶9∶3）of Dimocarpus longan Lour. leaves（abbreviated as CDL） on ameliorating glucose and lipid metabolism disorders in type 2 diabetes mellitus （T2DM） rats. METHODS SD rats were randomly divided into blank control group， model group， metformin hydrochloride group （100 mg/kg）， and CDL high-， medium- and low-dose groups （280， 140， 75 mg/kg）， with 10 rats in each group. Rats in the blank control group were fed with standard chow， while rats in the other groups were given high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin to establish the T2DM rat model. After successful modeling， rats in each administration group were given corresponding drug solution， and rats in the blank control group and model group were intragastrically administered with equal volume of pure water， once a day， for consecutive 4 weeks. Fasting blood glucose （FBG） was detected at fixed time every week. The curves of oral glucose tolerance test （OGTT） and intraperitoneal insulin tolerance test （IPITT） were plotted， and the area under curve （AUC） was calculated. The pancreatic islet function indexes [fasting insulin （FINS）， homeostasis model assessment of insulin resistance （HOMA-IR）， insulin sensitivity index （ISI）]，blood lipid indexes [total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）] and hepatic glycogen content were determined. The pathological morphological changes of liver and pancreatic tissues were observed. The protein and mRNA expression levels of molecules related to phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway in liver tissues were detected. RESULTS Compared with the blank control group， the FBG， AUC of IPITT curve， AUC of OGTT curve， HOMA-IR， the levels of FINS， TC， TG and LDL-C， as well as the protein and mRNA expression of phosphatase and tensin homolog， forkhead box protein O1 and glycogen synthase kinase-3β in liver tissues were significantly increased in the model group （ P ＜0.05）. ISI， the levels of HDL-C and hepatic glycogen content， along with the protein and mRNA expression of PI3K， insulin receptor substrate-1， Akt and protein expression of phosphorylated Akt in liver tissues were markedly decreased （ P ＜0.05）. In model group rats， the arrangement of hepatocytes was irregular， the overall structure of pancreatic lobules was disordered， and a large number of inflammatory cell infiltration was observed. Compared with the model group， most of the above quantitative indexes were significantly reversed in the CDL high-dose group （ P ＜0.05）， and the pathological lesions of liver and pancreas were obviously alleviated. CONCLUSIONS CDL can regulate glucose and lipid metabolism disorders， elevate insulin sensitivity and relieve insulin resistance in T2DM rats. Its mechanism may be related to the activation of the PI3K/Akt signaling pathway.

OBJECTIVE To explore the mechanism of the active ingredient compatibility（quercetin， quercitrin and kaempferol at a mass ratio of 2∶9∶3）of Dimocarpus longan Lour. leaves（abbreviated as CDL） on ameliorating glucose and lipid metabolism disorders in type 2 diabetes mellitus （T2DM） rats. METHODS SD rats were randomly divided into blank control group， model group， metformin hydrochloride group （100 mg/kg）， and CDL high-， medium- and low-dose groups （280， 140， 75 mg/kg）， with 10 rats in each group. Rats in the blank control group were fed with standard chow， while rats in the other groups were given high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin to establish the T2DM rat model. After successful modeling， rats in each administration group were given corresponding drug solution， and rats in the blank control group and model group were intragastrically administered with equal volume of pure water， once a day， for consecutive 4 weeks. Fasting blood glucose （FBG） was detected at fixed time every week. The curves of oral glucose tolerance test （OGTT） and intraperitoneal insulin tolerance test （IPITT） were plotted， and the area under curve （AUC） was calculated. The pancreatic islet function indexes [fasting insulin （FINS）， homeostasis model assessment of insulin resistance （HOMA-IR）， insulin sensitivity index （ISI）]，blood lipid indexes [total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）] and hepatic glycogen content were determined. The pathological morphological changes of liver and pancreatic tissues were observed. The protein and mRNA expression levels of molecules related to phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway in liver tissues were detected. RESULTS Compared with the blank control group， the FBG， AUC of IPITT curve， AUC of OGTT curve， HOMA-IR， the levels of FINS， TC， TG and LDL-C， as well as the protein and mRNA expression of phosphatase and tensin homolog， forkhead box protein O1 and glycogen synthase kinase-3β in liver tissues were significantly increased in the model group （ P ＜0.05）. ISI， the levels of HDL-C and hepatic glycogen content， along with the protein and mRNA expression of PI3K， insulin receptor substrate-1， Akt and protein expression of phosphorylated Akt in liver tissues were markedly decreased （ P ＜0.05）. In model group rats， the arrangement of hepatocytes was irregular， the overall structure of pancreatic lobules was disordered， and a large number of inflammatory cell infiltration was observed. Compared with the model group， most of the above quantitative indexes were significantly reversed in the CDL high-dose group （ P ＜0.05）， and the pathological lesions of liver and pancreas were obviously alleviated. CONCLUSIONS CDL can regulate glucose and lipid metabolism disorders， elevate insulin sensitivity and relieve insulin resistance in T2DM rats. Its mechanism may be related to the activation of the PI3K/Akt signaling pathway.

OBJECTIVE To systematically evaluate the methodological quality of the postoperative chemotherapy guidelines/ consensuses for ovarian epithelial tumor. METHODS A search was conducted across databases including PubMed， Embase， Web of Science， CBM， VIP， Chinese Medical Journal Data， Wanfang Data， and CNKI， as well as the official websites of GIN， NICE， Medlive， AHRQ， CSCO， ASCO， and NCCN. The search period was from the establishment of the databases/websites to March 10， 2025. The quality of the included guidelines/consensus was evaluated by using the AGREE-Ⅱ tool. RESULTS A total of 16 guidelines/consensuses were included. The domain scores of AGREE-Ⅱ evaluation were as follows： scope and purpose of 85.07%， participants of 47.92%， rigor of development of 57.49%， clarity of presentation of 88.02%， applicability of 8.20%， and independence of 53.39%. Among them， 14 were recommended at grade B and 2 were recommended at grade C. The subgroup analysis by different countries/regions and different types of studies showed that the scores for participants， rigor of development， and independence of the guidelines/consensuses in China were significantly lower than foreign countries （P＜0.05）； the scores for participants and rigor of development of the guidelines were significantly higher than consensuses （P＜0.05）. The guideline/ consensus recommendation results indicated that grade B guidelines/consensus recommend platinum-based combination chemotherapy as the preferred adjuvant chemotherapy regimen for stage Ⅰ high-grade serous carcinoma patients；platinum-based combination chemotherapy±bevacizumab was recommended as the preferred adjuvant chemotherapy regimen for stage Ⅱ-Ⅳ high- grade serous carcinoma patients and for platinum-sensitive recurrent high-grade serous carcinoma patients； non-platinum single- agent chemotherapy±bevacizumab was recommended as the preferred chemotherapy regimen for platinum-resistant recurrent high- grade serous carcinoma patients. CONCLUSIONS The overall quality of postoperative chemotherapy guidelines/consensuses for ovarian epithelial tumor is not high. The methodological quality of guidelines/consensuses in China is still lagging behind that of foreign countries. The recommendations differ from those in foreign countries. It is recommended to improve the aspects of participants， rigor of development， and independence， to recommend treatment plans based on the different stages of ovarian cancer， and develop guidelines/consensuses that align with China’s national conditions.

OBJECTIVE: To explore the clinical characteristics and genetic basis of two Chinese pedigrees affected with Joubert syndrome. METHODS: Clinical data of the two pedigrees was collected. Genomic DNA was extracted from peripheral blood samples and subjected to high-throughput sequencing. Candidate variants were verified by Sanger sequencing. Prenatal diagnosis was carried out for a high-risk fetus from pedigree 2. RESULTS: The proband of pedigree 1 was a fetus at 23⁺⁵ weeks gestation, for which both ultrasound and MRI showed "cerebellar vermis malformation" and "molar tooth sign". No apparent abnormality was noted in the fetus after elected abortion. The fetus was found to harbor c.812+3G>T and c.1828G>C compound heterozygous variants of the INPP5E gene, which have been associated with Joubert syndrome type 1. The proband from pedigree 2 had growth retardation, mental deficiency, peculiar facial features, low muscle tone and postaxial polydactyly of right foot. MRI also revealed "cerebellar dysplasia" and "molar tooth sign". The proband was found to harbor c.485C>G and c.1878+1G>A compound heterozygous variants of the ARMC9 gene, which have been associated with Joubert syndrome type 30. Prenatal diagnosis found that the fetus only carried the c.485C>G variant. A healthy infant was born, and no anomalies was found during the follow-up. CONCLUSION The compound heterozygous variants of the INPP5E and ARMC9 genes probably underlay the disease in the two pedigrees. Above finding has expanded the spectrum of pathogenic variants underlying Joubert syndrome and provided a basis for genetic counseling and prenatal diagnosis.
Female ; Humans ; Pregnancy ; Pedigree ; Cerebellum/abnormalities* ; Abnormalities, Multiple/diagnosis* ; Eye Abnormalities/diagnosis* ; Kidney Diseases, Cystic/diagnosis* ; Phosphoric Monoester Hydrolases/genetics* ; Retina/abnormalities* ; East Asian People ; Mutation

This paper reviews the status quo and influencing factors of family life quality of the elderly with dementia, mainly from effect of the elderly with dementia on the family at home and abroad, the predictive factors affecting family quality of life and social support system, so as to provide theoretical basis for improving family quality of life of the elderly with dementia in the future.

Objective:To analyze the efficacy and safety of radioactive 125I seed implantation in the treatment of unresectable early-stage non-small cell lung cancer (NSCLC), in order to provide data for clinical practice and relevant research. Methods:A retrospective study was conducted on the data of 39 patients with early-stage NSCLC who received CT-guided radioactive 125I seed implantation from Dec 2010 to Dec 2018 in multiple hospitals.The seed implantation process consisted of preoperative planning and design, CT-guided puncture, seed implantation, and postoperative evaluation and dose verification.The efficacy and complications of the treatment were analyzed.The clinical efficacy was evaluated by adopting the Response Evaluation Criteria in Solid Tumors (RECIST) (v1.1) and the adverse reactions were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Results:All the patients were 70 years old on average (51-85). The median lesion diameter was 2.7 cm (1.1-6.0 cm), the median seed activity was 0.7 mCi (0.6-0.8 mCi), while the median follow-up duration was 29 months (3-97 months). Meanwhile, the 1-, 3-, and 5-year overall local control rates were 89.5%, 79%, and 79%, respectively, and the 1-, 3-, and 5-year overall survival rates were 100%, 74.8%, and 49.9%, respectively.Local recurrence and distant metastasis were the main causes of failure, accounting for 17.9% (7 cases) each.The incidence of pneumothorax was 56.4% (22 cases), among which nine cases (23.1%) required invasive closed thoracic drainage.Only 1 case of grade-2 radiation pneumonia (2.6%) was observed, with no other adverse reactions such as dermatoses, esophagitis, or myelitis being discovered.As indicated by univariate analysis, the patients with KPS scores of 80-90, pathological type of adenocarcinoma, T stage of T 1-2, and D90>180 Gy exhibited better local control ( χ2=6.202, P<0.05). Meanwhile, high D90 was also associated with a higher survival rate ( χ2=6.907, P<0.05). Conclusions:Radioactive 125I seed implantation is a safe and effective treatment for unresectable early-stage NSCLC.In cases where external beam radiotherapy is not available, radioactive 125I seed implantation can be considered as one of the treatment options.Pneumothorax is the most common complication of radioactive 125I seed implantation, and adenocarcinoma (pathological type) and higher values of D90 are predictors of better local control.

OBJECTIVETo carry out genetic analysis on a child with developmental delay and multiple malformation.

METHODSThe karotypes of the child and her parents were analyzed with routine chromosomal G-banding. Their genomic DNA was analyzed with array comparative genomic hybridization (aCGH).

RESULTSThe karyotype of the proband was determined as 46,XX,del(6)(q22),inv(6)(p21.1q21), while no karyotypic abnormality was detected in her parents. aCGH has identified in the child a de novo 800 kb deletion encompassing the RUNX2 gene at 6p21.1 and a de novo 11.79 Mb deletion at 6q21-q22.31.

CONCLUSIONBoth of the de novo deletions are pathogenic. Deletion of the RUNX2 gene probably underlies the cleidocranial dysplasia in the patient, while the 6q21-q22.31 deletion may result in malformation of the brain.

Child, Preschool ; Chromosome Banding ; Chromosome Deletion ; Chromosomes, Human, Pair 6 ; Cleidocranial Dysplasia ; genetics ; Comparative Genomic Hybridization ; Core Binding Factor Alpha 1 Subunit ; genetics ; Female ; Genetic Testing ; Humans ; Karyotyping

Objective To evaluate the prognostic value of human antibacterial peptide LL-37 in elderly patients with sepsis. Methods Elderly sepsis patients over 65-year-old satisfied the diagnostic criteria for sepsis and septic shock admitted to intensive care unit of East Hospital of Tongji University from January 2016 to December 2017 were enrolled (elderly sepsis group). Aged community-acquired pneumonia (CAP) patients hospitalized during the same period were enrolled as a control group for pneumonia, and the aged health check-ups served as a healthy control group during the same period. The peripheral blood LL-37 levels of all patients on the 1st, 3rd, 7th day of admission and the results on the day of physical examination in the healthy control group and on the day of admission in aged CAP group were recorded. C-reactive protein (CRP), arterial blood lactate (Lac), procalcitonin (PCT) were monitored, and acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) and sequential organ failure assessment (SOFA) scores were calculated based on the worst values within 24 hours. The correlation between LL-37 and various indicators was analyzed by Spearman method. According to the 28-day clinical outcome, the elderly patients with sepsis were divided into survival group and non-survival group. The differences in all parameters between the two groups were compared. The statistically significant indicators were analyzed by receiver operating characteristic (ROC) curve, and the predictive value of each indicator for prognosis was evaluated. Results ① A total of 113 elderly patients with sepsis were enrolled in the final analysis, including 67 patients in sepsis group and 46 patients in septic shock group. Thirty-two patients were enrolled as healthy controls and 31 elderly patients with CAP as elderly pneumonia group. The PCT, CRP, Lac, APACHEⅡ and SOFA scores of the patients in the three groups were higher than those of the healthy control group, and they were gradually increased with the severity of infection. There was no significant difference in gender or age among the groups. Compared with the healthy control group, the other three groups had higher LL-37 level after admission, the LL-37 levels in the sepsis group and the septic shock group were decreased with the prolongation of the hospitalization time, and they were lower than the pneumonia group at 7 days after admission [LL-37 (μg/L): 1 403.9±501.9, 1 517.1±676.4 vs. 1 608.4±816.2, both P > 0.05]. It was shown by correlation analysis that the LL-37 level in peripheral blood of elderly patients with sepsis was significantly negatively correlated with APACHEⅡ score (r = -0.329, P = 0.007) and SOFA score (r = -0.344, P = 0.005), but no significant correlation with Lac was found (r = -0.128, P = 0.311). ② The 28-day survival analysis revealed that of the 113 elderly patients with sepsis, 54 (47.8%) survived at 28 days and 59 (52.2%) died. There was no significant difference in gender, age, PCT or CRP levels at 1 day after admission between the two groups. The 1-day Lac, APACHEⅡ and SOFA scores of the patients in the non-survival group were significantly higher than those in the survival group, they were gradually increased with the prolongation of the hospitalization time, and they were significantly higher than those in the survival group at 7 days after admission [Lac (mmol/L): 2.4 (1.4, 4.4) vs. 1.0 (0.8, 1.7), APACHEⅡ score: 21.77±5.85 vs. 13.74±4.99, SOFA score: 9.62±4.78 vs. 3.18±2.71, all P < 0.01]. With the prolongation of admission, there was no significant change in LL-37 level of peripheral blood in the survival group. The LL-37 level in the non-survival group showed a downward tendency, and it was significantly lower than that in the survival group at 7 days after admission (μg/L: 1 277.8±642.6 vs. 1 620.6±461.6, P < 0.05). It was shown by ROC curve analysis that the LL-37 in peripheral blood, Lac, APACHEⅡ score and SOFA score at 7-day of admission of elderly patients with sepsis had predictive value for prognosis, and LL-37 had the best predicted effect for 28-day death, the area under the ROC curve (AUC) of LL-37 was 0.670, 95% confidence interval (95%CI) = 0.513-0.757, when the optimal cut-off value was 1 283.0 μg/L, the sensitivity was 75.7%, and the specificity was 61.5%. Conclusions The expression of LL-37 increased in the early course of the disease in elderly patients with sepsis. However, as the disease progressed and worsened, the level of LL-37 had a decline tendency and was associated with death. The dynamic monitoring of LL-37 combined with APACHEⅡ and SOFA scores had clinical guidance value in predicting the prognosis of sepsis in the elderly.

OBJECTIVETo analyze the molecular mechanism and prognosis of a child with aortic stenosis and thumb aplasia.

METHODSThe karotypes of the child and his parents were analyzed with routine G-banding. Their genomic DNA was also analyzed with array comparative genomic hybridization(aCGH) for chromosomal duplications/deletions.

RESULTSNo karyotypic abnormality was detected at cytogenetic level for the child and his parents. aCGH identified a de novo 5.86 Mb deletion at 2q22.3-q23.3 in the child.

CONCLUSIONThe child was diagnosed with 2q23.1 microdeletion syndrome. MBD5 may be the key gene for the 2q23.1 microdeletion syndrome.

Objective To probe into the optimal concentration of Wnt-11 to induce the differentiation of bone marrow mesenchymal stem cells (BMMSCs)into cardiomyocyte-like cells in vitro.Methods BMMSCs were isolated from the bone marrow of SD rats using whole bone marrow culture method.After cultured for 48 h, BMMSCs of the second generation were utilized for directed induction.Based on the final concentration of Wnt-11 , BMMSCs were divided up into Group A (100 ng/mL),Group B (200 ng/mL),Group C (400 ng/mL)and Group D (blank control).After 72-hour induction,the cells were cultured in complete medium for 4 weeks while cells in Group D were cultured only in the complete medium.The morphological changes were observed under the phase contrast microscope.Surface antigen expression of BMMSCs was identified by flow cytometry.When cells were cultured for 4 weeks,the expressions of Desmin,Connexin43 and cTnI were detected by immunocytochemistry. Meanwhile, the ultrastructural changes were observed using transmission electron microscope. The mRNA expressions of cardiac transcription factors GATA-4,Nkx2.5 andα-MHC in BMMSCs were detected by RT-qPCR at 1,2 and 4 weeks after induction.Results Primary BMMSCs formed cell colonies at 2 weeks;the cells were mainly fusiform or star-shape,and a few irregularly-shaped ones were also visible.The passaged cells were larger than those of primary culture.After induction,the cells exhibited long shuttle-shape and were aligned in parallel. Flow cytometery displayed that the positive rate of the surface antigens of BMMSCs CD29,CD45,and CD90 was 97.9%,0.4% and 99.5%,respectively.When BMMSCs-induced via Wnt-11 were cultured for 4 weeks,Desmin, cTnI and Connexin43 were all positively expressed in induction groups.Whereas in the blank control group they were slightly positive or negative;the positive rate in Group B was the highest (P<0 .05 ).Transmission electron microscopy exhibited that organelles such as rough endoplasmic reticulum,mitochondria,as well as some ribosomes were visible in the cytoplasm of these cells in each induction group.In addition,myofilaments were arranged in parallel in the cytoplasm.The cells in induction groups could express GATA-4 and Nkx2 .5 in the first week,and then the expression of them decreased in the second week,but then increased in the fourth week;gene expression in induction Group B was significantly higher than in the other two induction groups (P<0 .05 ).The expression of GATA-4 and Nkx2 .5 in Group D was 1 ,α-MHC was not expressed in the four groups during the culture period. Conclusion Wnt-11 can induce the differentiation of BMMSCs into cardiomyocyte-like cells in vitro,and the optimal concentration of Wnt-11 is 200 ng/mL.