Objective: To explore the effects of intergenerational parent-child separation on internalizing and externalizing behavioral problems among rural preschoolers aged 3-6 years, so as to provide empirical evidence for formulating targeted intervention strategies and blocking the intergenerational transmission of parent-child separation. Methods: From March to June, 2024, ten kindergartens were selected from rural areas of Nanling County, Wuhu City, Anhui Province, and 2 279 preschool children aged 3- 6 years, along with their fathers, mothers and primary caregivers, were recruited for survey by cluster convenient sampling method. Children s fathers and mothers reported their own childhood parent-child separation information separately. Information on the children s history of psychological and behavioral problems was reported by the primary caregivers. Information of internalizing and externalizing behavioral problems in preschool children was reported with Strengths and Difficulties Questionnaire (SDQ).The Chi square test was used to compare the differences in the detection rates of psychological and behavioral problems among children with different intergenerational continuity of parent-child separation. Binary Logistic regression model was applied to analyze the association between intergenerational continuity of parent-child separation and internalizing and externalizing behavioral problems in preschool children. Results: The detection rate of internalizing behavioral problems was 27.5% and externalizing behavioral problems was 19.1% among rural preschool children. There were significant differences in internalization behavior, externalization behavior, hyperactivity impulse and peer communication problems among preschool children in different types of parent-child separation groups( χ 2=14.29, 8.80, 17.26, 13.84, all P <0.05). Binary Logistic regression analysis showed that after adjusting for covariates such as children s gender, birth weight, and delivery mode, compared with children without separation, intergenerational continuity of parent-child separation group( OR =1.95), only child separation( OR =1.74) were associated with significant higher risk of conduct problems(both P ＜0.05). Parent-child separation intergenerational continuation groups( OR =1.68), only child separation( OR = 1.47) were associated with significant higher risk of peer problems(both P ＜0.05). Both types of parent-child separation experiences significantly increased the risk of children s prosocial behavior problems，among them, the intergenerational continuation group was 1.99 times that of the control group ( OR =1.99), and the childhood only separation group was 2.09 times that of the control group ( OR =2.09)(both P ＜0.05). Compared with children whose parents and children had no experience of parent-child separation, children in the intergenerational continuation group of parent-child separation had increased risks of both internalizing and externalizing behavior problems ( OR =1.53, 1.65, both P <0.05). Conclusion All types of parent-child separation are associated with internalizing and externalizing behavioral problems among rural children aged 3 to 6 years.

Anti-leucine-rich glioma-inactivated 1 （anti-LGI1） antibody autoimmune encephalitis is a relatively common type of limbic encephalitis，and its etiology remains unclear. It is rare for two individuals with a blood relationship to both suffer from encephalitis with positive anti-LGI1 antibodies. This article reports two sisters who lived in different counties and were diagnosed with anti-LGI1 antibody autoimmune encephalitis successively. The two sisters were diagnosed at an age of 64 and 65 years， respectively. During the course of the disease， both patients had epileptic seizures and slow response， but with different clinical manifestations. They had similar results of cranial magnetic resonance imaging and positive anti-LGI1 antibodies in cerebrospinal fluid and serum. The two patients were treated with glucocorticoid shock therapy and gamma globulin infusion during hospitalization，and both patients had a good prognosis. Recent studies have shown that anti-LGI1 antibody encephalitis is associated with genetic susceptibility.For patients with anti-LGI1 antibody encephalitis， it is necessary to inquire about family history and summarize the features of this type of disease， in order to provide better help for clinical practice.

Objective: The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB). Materials and Methods: This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB. Results: In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%). Conclusion The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

Objective: The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB). Materials and Methods: This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB. Results: In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%). Conclusion The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

Oral squamous cell carcinoma (OSCC) is a malignant tumor that seriously threatens human health. Its typical biological characteristics include strong local invasiveness, high lymph node metastasis rate, and high recurrence rate after treatment. Hepatocyte growth factor (HGF), cellular-mesenchymal to epithelial transition factor (c-Met), and the HGF/c-Met signaling pathway are involved in the regulation of the occurrence and development of OSCC. HGF and c-Met proteins are overexpressed in OSCC, and multiple studies have suggested that they are significantly associated with the malignant characteristics of tumors and poor prognosis. Furthermore, the abnormal activation of the HGF/c-Met signaling pathway (driven by HGF-dependent autocrine/paracrine or non-dependent mechanisms such as MET gene mutations, amplification, fusion, and protein overexpression) can synergistically promote tumor cell invasion, metastasis, and angiogenesis by activating downstream signaling pathways. However, HGF/c-Met can also mediate immune escape by promoting lactate secretion increase, inducing programmed death ligand 1 (PD-L1) expression upregulation, activating and expanding myeloid-derived suppressor cells, and promoting the proliferation of regulatory T cells (Tregs). In addition, the crosstalk between the HGF/c-Met signaling pathway and key pathways such as phosphatidylinositide 3-kinases (PI3K)/protein kinase B (AKT), epidermal growth factor receptor (EGFR), Janus kinase (JAK)/signal transducer and activator of transcription (STAT3), and non-coding RNAs can also promote tumor progression. Currently, three types of targeted drugs have been developed targeting the HGF/c-Met pathway: HGF monoclonal antibody, c-Met monoclonal antibody, and tyrosine kinase inhibitors. Some of these drugs have entered clinical trials. However, the emergence of drug resistance during treatment, especially the bidirectional compensatory activation of alternative signaling pathways such as EGFR, has become a major challenge in clinical practice. This article aims to provide an in-depth analysis of the mechanism of action of the HGF/c-Met pathway in OSCC and its interaction with other pathways, and to review the current research status of existing therapeutic drugs. The aim is to provide an important theoretical basis for developing more effective combined treatment strategies and achieving individualized precise treatment, ultimately improving the clinical prognosis and quality of life of patients.

Objective: To evaluates the association between maternal overweight/obesity during pregnancy and offspring risk of metabolic dysfunction associated steatotic liver disease (MASLD), providing theoretical evidence for early life MASLD prevention. Methods: An online search was conducted across ten databases (CNKI, Wanfang, SinoMed, PubMed, Embase, Web of Science, Cochrane Library, PROSPERO, PQDT Global, ScienceDirect) for research literature on the association between maternal overweight/obesity during pregnancy and the development of MASLD in offspring, with the search period spanning from January 2014 to December 2024. Two researchers independently screened literature, extracted data, and assessed study quality. Statistical analysis was performed using R 4.3.3. Results: Ten studies involving 10 229 participants were included, comprising 4 cohort studies and 6 case control studies. Cohort studies showed that maternal overweight and obesity significantly increased offspring MASLD risk ( RR=1.59, 95%CI=1.06-2.39, P <0.05), with moderate heterogeneity ( I 2=56.9%, P =0.07). Case control studies indicated a positive association between maternal overweight/obesity during pregnancy and offspring risk of MASLD( OR=2.00, 95%CI=1.68-2.39, P < 0.05), with low heterogeneity ( I 2=48.8%, P =0.08). Conclusions Maternal overweight/obesity during pregnancy positively correlates with offspring MASLD risk. Gestational weight management may reduce the risk.

ObjectiveTo investigate the efficacy and underlying mechanisms of Gynostemma pentaphyllum alcohol extract in improving glucose and lipid metabolism disorders in db/db mice through transcriptomics and gut microbiota analysis. MethodsEighteen db/db mice were randomly assigned to the model（DM） group， metformin（MET） group， and G. pentaphyllum alcohol extract（GP） group， with six mice in each group， based on stratification of fasting blood glucose and body weight. An additional six db/m mice were selected as the normal control（NC） group. Mice in the NC and DM groups were administered deionized water （10 mL·kg^-1） daily. The MET group received metformin （0.195 g·kg^-1） by gavage. The GP group was treated with G. pentaphyllum alcohol extract （3.9 g·kg^-1） by gavage for six weeks. Fasting blood glucose was measured every two weeks. After six weeks of intervention， serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， and blood urea nitrogen （BUN） were assessed. Enzyme-linked immunosorbent assay （ELISA） was used to measure insulin （FINS）， adiponectin （ADP）， and tumor necrosis factor-α （TNF-α）. Hematoxylin-eosin （HE） staining was used to observe liver histomorphology， periodic acid-Schiff （PAS） staining was employed to assess hepatic glycogen synthesis， and Oil Red O staining was used to detect hepatic lipid deposition. Liver transcriptomic data were used to identify differentially expressed genes in the liver and conduct enrichment analysis. Real-time PCR was employed to verify the expression levels of adiponectin gene （Adipoq）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， AMP-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor α （PPARα）， glucokinase （GCK）， forkhead box （Fox）O1， FoxO3， phosphoenolpyruvate carboxykinase （PEPCK）， and glucose-6-phosphatase （G6PC）. Metagenomic sequencing was conducted to analyze changes in gut microbiota composition. ResultsCompared with the NC group， the DM group exhibited significantly elevated fasting blood glucose （P<0.01）， serum AST， ALT， TC， TG， LDL-C， and HDL-C （P<0.01）. FINS， homeostatic model assessment for insulin resistance （HOMA-IR）， and the inflammatory cytokine TNF-α were significantly increased （P<0.01）， while ADP was significantly decreased （P<0.05）. Histological analysis confirmed severe hepatic steatosis and excessive lipid accumulation in the DM group， along with markedly reduced glycogen synthesis. Compared with the DM group， the GP group showed significantly decreased fasting blood glucose （P<0.01）， reduced serum TC， LDL-C， and HDL-C levels （P<0.05）， significantly decreased serum TG and AST levels （P<0.01）， significantly reduced FINS， HOMA-IR， and TNF-α levels （P<0.01）， and significantly increased ADP （P<0.01）. Hepatic steatosis and lipid deposition were significantly alleviated， while glycogen synthesis was markedly enhanced. Transcriptomic differential and enrichment analyses suggested that the mechanisms by which G. pentaphyllum alcohol extract improved hepatic glucose and lipid metabolism in db/db mice may involve regulation of the AMPK and FoxO signaling pathways. Real-time PCR results confirmed that expression of PGC-1α， PEPCK， G6PC， FoxO1， and FoxO3 was significantly downregulated following treatment with G. pentaphyllum alcohol extract （P<0.05， P<0.01）， whereas mRNA expression of Adipoq， PPARα， GCK， and AMPK was significantly upregulated （P<0.05， P<0.01）. Metagenomic analysis showed that the relative abundance of Lactobacillus， Alistipes， and Akkermansia species was higher in the GP group than in the DM group. ConclusionG. pentaphyllum alcohol extract may improve glucose and lipid metabolism disorders in db/db mice by regulating the hepatic AMPK/PPARα pathway to suppress lipid deposition and alleviate hepatic steatosis， by inhibiting gluconeogenesis through the AMPK/PGC-1α and FoxO pathways to lower fasting blood glucose， and by increasing the abundance of beneficial gut bacteria such as Lactobacillus， Alistipes， and Akkermansia to restore gut microbiota balance.

ObjectiveTo investigate the efficacy and underlying mechanisms of Gynostemma pentaphyllum alcohol extract in improving glucose and lipid metabolism disorders in db/db mice through transcriptomics and gut microbiota analysis. MethodsEighteen db/db mice were randomly assigned to the model（DM） group， metformin（MET） group， and G. pentaphyllum alcohol extract（GP） group， with six mice in each group， based on stratification of fasting blood glucose and body weight. An additional six db/m mice were selected as the normal control（NC） group. Mice in the NC and DM groups were administered deionized water （10 mL·kg^-1） daily. The MET group received metformin （0.195 g·kg^-1） by gavage. The GP group was treated with G. pentaphyllum alcohol extract （3.9 g·kg^-1） by gavage for six weeks. Fasting blood glucose was measured every two weeks. After six weeks of intervention， serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， and blood urea nitrogen （BUN） were assessed. Enzyme-linked immunosorbent assay （ELISA） was used to measure insulin （FINS）， adiponectin （ADP）， and tumor necrosis factor-α （TNF-α）. Hematoxylin-eosin （HE） staining was used to observe liver histomorphology， periodic acid-Schiff （PAS） staining was employed to assess hepatic glycogen synthesis， and Oil Red O staining was used to detect hepatic lipid deposition. Liver transcriptomic data were used to identify differentially expressed genes in the liver and conduct enrichment analysis. Real-time PCR was employed to verify the expression levels of adiponectin gene （Adipoq）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， AMP-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor α （PPARα）， glucokinase （GCK）， forkhead box （Fox）O1， FoxO3， phosphoenolpyruvate carboxykinase （PEPCK）， and glucose-6-phosphatase （G6PC）. Metagenomic sequencing was conducted to analyze changes in gut microbiota composition. ResultsCompared with the NC group， the DM group exhibited significantly elevated fasting blood glucose （P<0.01）， serum AST， ALT， TC， TG， LDL-C， and HDL-C （P<0.01）. FINS， homeostatic model assessment for insulin resistance （HOMA-IR）， and the inflammatory cytokine TNF-α were significantly increased （P<0.01）， while ADP was significantly decreased （P<0.05）. Histological analysis confirmed severe hepatic steatosis and excessive lipid accumulation in the DM group， along with markedly reduced glycogen synthesis. Compared with the DM group， the GP group showed significantly decreased fasting blood glucose （P<0.01）， reduced serum TC， LDL-C， and HDL-C levels （P<0.05）， significantly decreased serum TG and AST levels （P<0.01）， significantly reduced FINS， HOMA-IR， and TNF-α levels （P<0.01）， and significantly increased ADP （P<0.01）. Hepatic steatosis and lipid deposition were significantly alleviated， while glycogen synthesis was markedly enhanced. Transcriptomic differential and enrichment analyses suggested that the mechanisms by which G. pentaphyllum alcohol extract improved hepatic glucose and lipid metabolism in db/db mice may involve regulation of the AMPK and FoxO signaling pathways. Real-time PCR results confirmed that expression of PGC-1α， PEPCK， G6PC， FoxO1， and FoxO3 was significantly downregulated following treatment with G. pentaphyllum alcohol extract （P<0.05， P<0.01）， whereas mRNA expression of Adipoq， PPARα， GCK， and AMPK was significantly upregulated （P<0.05， P<0.01）. Metagenomic analysis showed that the relative abundance of Lactobacillus， Alistipes， and Akkermansia species was higher in the GP group than in the DM group. ConclusionG. pentaphyllum alcohol extract may improve glucose and lipid metabolism disorders in db/db mice by regulating the hepatic AMPK/PPARα pathway to suppress lipid deposition and alleviate hepatic steatosis， by inhibiting gluconeogenesis through the AMPK/PGC-1α and FoxO pathways to lower fasting blood glucose， and by increasing the abundance of beneficial gut bacteria such as Lactobacillus， Alistipes， and Akkermansia to restore gut microbiota balance.

Objective:To investigate the current status and challenges in legal compliance regarding the collection, utilization, sharing, cross-border transfer, and disposal of human genetic resources (HGR) in international collaboration agreements, and to explore key review points for medical institutions in international cooperation agreements to mitigate legal risks and ensure compliance in HGR-related global collaborations.Methods:We reviewed international collaborative research projects involving Peking University Cancer Hospital that were approved or filed on the National Health Commission (NHC) Administrative Service Platform between July 2019 and April 2025, analyzed the utilization of human genetic resources (HGR) materials and information in these studies, assessd compliance clauses in international agreements related to HGR management, identified gaps, and proposed actionable recommendations.Results:A total of 410 international cooperation projects on human genetic resources were analyzed, of which 302 cooperation agreements signed with sponsors stipulated that research should obtain administrative approval or complete filing for human genetic resources before implementation(73.7%). However, 113 agreements had errors in citing legal provisions or incomplete agreements. A mtotal of 385 studies involved human genetic resource materials, of which 277 agreed on the compliant use of biological samples, but mainly focused on the collection and testing process, with insufficient agreements on the disposal of remaining samples. Some agreements only stipulate that ″compliant collection and use of samples″ is the sole responsibility of medical institutions, ignoring the relevant responsibilities of the sponsor, and the risk allocation is unreasonable. 361 studies involved human genetic resources information, but only 72 explicitly agreed that China′s human genetic resources information should be collected, preserved, used and shared within the approved scope of human genetic resources (less than 20%).Conclusions:The expression of human genetic resources related content in most agreements is not standardized; The management agreement for human genetic resources materials is incomplete and does not cover the entire cycle of sample processing; The responsibilities that the applicant should bear in the cooperation are unclear; The management of human genetic resource information is easily overlooked. It is recommended that medical institutions closely monitor changes in relevant laws, regulations, and management methods, and update the corresponding clauses of the agreement in a timely manner, and improve the situations that should be submitted for administrative approval or filing in the agreement; All parties involved in the cooperation should make compliance commitments for human genetic resources; Clearly stipulate the full cycle management of human genetic resources materials; Pay attention to risk prevention and control in the management of human genetic resources information; Pay attention to the systematic coverage of intellectual property types and the operability of rights implementation in international cooperation.

Objective:To investigate the value of the five-sectional screening method of the central nervous system（CNS）in early detection of fetal CNS abnormalities during the first trimester.Methods:The data of pregnant women who underwent nuchal translucency（NT）screening at the Affiliated Suzhou Hospital of Nanjing Medical University from September 2018 to September 2023 were retrospectively analyzed. And a five-sectional screening method of CNS was performed in all fetuses at the meantime. The five-sectional screening protocol in the first trimester consists of the mid-sagittal plane of the fetal head，trans-ventricular plane，trans-thalamus plane，axial plane of the fetal head at the posterior fossa level，and the sagittal plane of the fetal spine. All fetuses underwent ultrasound screening during the second trimester and the third trimester sequentially after NT screening. All the ultrasound findings were tracked，and all fetuses were followed up until delivery or after induction. Fetuses with CNS abnormalities found or suspected in the first trimester were reviewed by at least one senior physician，and follow-up examinations were routinely performed after 2 weeks to further confirm the diagnosis or find other abnormalities that may be present.Results:A total of 13 679 fetuses were screened，included 11 415 singleton pregnancies and 1 132 twin pregnancies. Among them，there were 289 cases of missed follow-up and unexplained fetal death，included 263 singleton pregnancies and 13 twin pregnancies. A total of 13 390 fetuses were finally included，among which，35 cases developed CNS abnormalities with 34 cases detected by prenatal ultrasound and 1 case of closed spina bifida missed in prenatal diagnosis，and the detection rate of CNS malformation by prenatal ultrasound was 97.14%（34/35）. Of the 35 fetuses with CNS abnormalities，24 were detected by the CNS five-sectional screening method in the first trimester，with a sensitivity of 68.57%，a specificity of 100%，a positive predictive value of 100%，and a negative predictive value of 99.92%. Among them，there were 2 cases of anencephaly，3 cases of exencephaly and 6 cases of encephalocele were all detected in the first trimester. In addition，6 cases of holoprosencephaly，3 cases of severe ventriculomegaly，2 cases of open spina bifida，and 2 cases of Dandy-Walker malformation were detected in the first trimester. In this study，1 case of agenesis of corpus callosum（ACC），1 case of arachnoid cyst，1 case of lissencephaly，1 case of schizencephaly，and 1 case of mega cisterna magna were not detected in early pregnancy.Conclusions:The fetal five-sectional screening method of CNS in the first trimester has high specificity，positive predictive value and negative predictive value for the detection of fetal CNS abnormalities，but the sensitivity is moderate. The five-sectional screening method for CNS in early pregnancy may be an effective method for early detection of fetal CNS abnormalities.