Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder primarily caused by pathogenic variants in the TSC1 or TSC2 genes. It is characterized by multisystem hamartomatous lesions and neuropsychiatric manifestations. Here we report a young male patient with TSC involving multiple organs, caused by a heterozygous frameshift mutation in TSC2 (c.2071delC, p.Arg691Alafs^*7). The patient initially presented with classic facial angiofibromas and hypomelanotic macules, and subsequently developed psychiatric and behavioral disturbances with auditory hallucinations. Neuroimaging revealed an intracranial mass lesion, which was confirmed as a subependymal giant cell astrocytoma on postoperative histopathology following surgery performed at an outside institution. After admission, the patient underwent a comprehensive diagnostic workup, and multidisciplinary treatment evaluation revealed extensive multisystem involve-ment, including the nervous system, skin, kidneys, lungs, heart, eyes, pancreas, liver and bones. Combined with relevant literature, this article discusses the molecular mechanisms, clinical phenotypes, and comprehensive management of TSC, in order to provide a reference for the standardized and individualized management of this disease.

ObjectiveTo investigate the current awareness and optimization recommendations on pneumonia with unknown etiology (PUE) surveillance among Shanghai healthcare professionals, and to provide evidence for the improvement of the surveillance system. MethodsIn December 2024, healthcare professional participants from diverse medical and health institutions were randomly selected within each stratum using a stratified cluster sampling method in all 16 districts of Shanghai for questionnaire surveys on their knowledge and suggestions for optimization of the PUE surveillance system. Descriptive statistics analyses, multivariate logistic regressions, and content analyses were used for data analyses. ResultsA total of 385 survey subjects were involved in the study, including 119 professional staffs from disease prevention and control centers and 266 from medical institutions. Those who understood the case definition for PUE correctly accounted for 67.01% (258/385). Multivariate regression model analyses showed that female gender (aOR=2.22, 95%CI: 1.36‒3.66), professionals from disease control institutions (aOR=2.02, 95%CI: 1.12‒3.72), and those who self-assessed as being familiar with the monitoring system (aOR=2.18, 95%CI:1.23‒3.89) had better understanding of the definition. Overall, 89.61% (345/385) of the survey subjects acknowledged the necessity of the surveillance system. Small number of cases meeting the case definition (54.46%, 214/379), insufficient diagnostic awareness (39.84%, 151/379), and lack of incentives for case reporting (29.29%, 111/379) were major problems for the current surveillance system, with variations observed across different types of institutions. Suggested segments for optimizing the surveillance system included monitoring purpose, case definition, form of monitoring and reporting procedure, organization mechanism, and epidemiological investigation and response. ConclusionThe necessity of PUE surveillance is commonly recognized among healthcare workers. However, the existing system falls short in terms of mastery of case definition and overall surveillance adaptability. There is an urgent need for optimization and improvement to enhance the capacity for preventing and controlling emerging and sudden respiratory infectious diseases.

Objective:To investigate intraoperative pathological findings and the interventional effects of "deep cervical lymphaticovenous anastomosis+" (dcLVA+) on deep cervical lymphatic drainage as well as the blood flow of carotid artery and jugular vein in elderly patients with cognitive impairment, and to put forward the thoughts based on the findings from the surgery.Methods:Between May 2024 and December 2024, retrospective analysis of Microsurgery Hospital, Fengcheng Hospital, Xi'an Medical College performed dcLVA+ between the deep cervical lymphatics or lymph nodes and jugular veins in 50 elderly patients with cognitive impairment (19 males and 31 females, aged 55-88 years with 69.94 years in average). Nine patients were found with Clinical Dementia Rating (CDR) score at 1 (mild), 7 with CDR score at 2 (moderate) and 34 with CDR score at 3 (severe). Intraoperative observations based on literature reviews had identified anatomical relationships between the lymphatic sacs containing cervical lymphatic chain and the carotid sheath. The lymph node count, size, distribution, thickness of fat tissue and conditions of lymphatic vessels were documented. Ultrasound was used to compare the blood flow of carotid artery and jugular vein as well as the cross-sectional areas at the planes of hyoid and cricoid cartilage before and after the closure of incisions under anaesthesia in 39 patients. Correlation analyses for Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCa), Activities of Daily Living (ADL) and Agitation behavior score before and 1 week after surgery were performed using Spearman's correlation and Wilcoxon paired tests. P<0.05 was considered statistically significant. Postoperative follow-ups were conducted via the visit of outpatient clinic and WeChat and telephone interviews. Results:In surgery, the cervical lymphatic chain was found running within an almost enclosed sac surrounding the carotid sheath. There were enlarged lymph nodes, increased fat deposition, lymphatic dilation or fibrosis in the sac. The preoperative blood flow in the carotid artery at the planes of hyoid and cricoid cartilage in the 39 patients was recorded at 150.52 ml/min±40.33 ml/min and 358.29 ml/min±129.30 ml/min, while that in the jugular vein was at 172.50 ml/min±63.94 ml/min and 317.00 ml/min±105.21 ml/min, respectively, both were far lower than the normal blood flow. There were statistically significant differences in the blood flow of carotid artery and jugular vein before and after surgery ( P<0.01). It was found that the preoperative blood flow of the internal carotid artery at the plane of hyoid was positively correlated with the preoperative scores of MMSE ( P<0.01), MoCa ( P<0.05) and ADL ( P<0.01). The blood flow of the common carotid artery at the plane of cricoid cartilage was found significantly and positively correlated with the preoperative scores of MMSE ( P<0.05). It was also noted that the blood flow of the internal carotid artery at the plane of hyoid was significantly and positively correlated with the postoperative ADL ( P<0.01) but negatively correlated with the Agitation behavior score ( P<0.05). The blood flow of the common carotid artery at the plane of cricoid cartilage was significantly and positively correlated with the postoperative scores of MMSE and MoCa ( P<0.05). The blood flow of the internal jugular vein at the plane of hyoid was negatively correlated with the Agitation behavior score ( P<0.01). The cross-sectional area of carotid artery at the plane of left hyoid was significantly and positively correlated with the MMSE score ( P<0.05). Statistically significant differences were observed in MMSE, MoCa, ADL and Agitation behavior score before and after surgery ( P<0.01). Conclusion:dcLVA+ shows a certain therapeutic benefit to the elderly patients with cognitive impairment. The intraoperatively observed pathological changes in cervical lymphatic sacs affect deep cervical lymphatic drainage and the blood flow of carotid artery and jugular vein. Further studies are necessary to find out whether the findings from this study would be the specific pathological changes and the morbidity mechanisms among the elderly patients with cognitive impairment.

Purpose To explore the value of tumor intratumoral and peritumoral radiomics models based on dynamic contrast-enhanced MRI in predicting benign and malignant breast tumors.Materials and Methods This retrospective study analyzed clinical data and MRI imaging features from 309 patients with pathologically confirmed solitary breast tumors at the Second Affiliated Hospital of Xiamen Medical College from August 2018 to December 2022.The cohort was randomly divided into training(n=248)and testing(n=61)cohorts in an 8∶2 ratio.Using second-phase dynamic contrast-enhanced MRI images,five distinct peritumoral regions were segmented through 3D-Slicer software:intratumoral region,peritumoral 2 mm region,peritumoral 4 mm region,intratumoral combined with peritumoral 2 mm region and intratumoral combined with peritumoral 4 mm region.Radiomic features were extracted from these regions of interest.Machine learning algorithms integrated with Logistic regression analysis were employed for feature selection,with cross-validation techniques determining the optimal radiomic signature combination.Results Of 309 patients,150 were benign tumors and 159 were malignant tumors.The age,maximum diameter and enhancement type of benign and malignant breast tumors were statistically significant(Z/χ2=-7.695,-5.775,30.248;all P<0.001).For the region of interest of intratumoral combined with peritumoral 4 mm region,the area under curve,sensitivity,specificity,accuracy and F1 scores of the training and validation were 0.893,89.1%,75.0%,82.3%,0.838 and 0.881,74.2%,86.7%,80.3%,0.793,respectively.In the training set,the area under curve of intratumoral combined with peritumoral 4 mm region was significantly higher than that of intratumoral,peritumoral 2 mm,peritumoral 4 mm and intratumoral combined with peritumoral 2 mm regional imaging models(Z=2.506,2.982,3.392,2.157;all P<0.05).The Hosmer-Lemeshow test showed that the calibration curve of the model combined with region of interest of intratumoral combined with peritumoral 4 mm region was highly consistent with the ideal curve(training P=0.381,validation P=0.159).The decision curve indicated that the net benefit of the radiomics model in the region of interest of intratumoral combined with peritumoral 4 mm region was the highest when the risk threshold was between 0 and 1.0.Conclusion The radiomics model has good predictive performance in predicting benign or malignant breast tumors,among them the combined region of interest of intratumoral combined with peritumoral 4 mm region provides the best performance and highest benefit.The technology clinical application will provide a non-invasive predictive method for the differential diagnosis of benign and malignant breast tumors.

Objective:To explore the value of magnetic resonance diffusion kurtosis imaging (DKI) in the assessment of the condition and prognosis of neonatal acute bilirubin encephalopathy (ABE).Methods:A retrospective selection was made of 196 neonates with acute hyperbilirubinemia who were hospitalized in the Second Affiliated Hospital of Shantou University Medical College from June 2021 to September 2023 as the research subjects. According to the presence or absence of brain injury, they were divided into the ABE group ( n=112) and the non-ABE group ( n=84). Based on the neonatal Bilirubine-induced Neurological Dysfunction (BIND) scoring system, children in the ABE group were divided into the mild group ( n=50, score 1-3 points), the moderate group ( n=33, score 4-6 points), and the severe group ( n=29, score 7-9 points). The clinical data and DKI parameters among each group were analyzed. Univariate and multivariate analyses were used to evaluate the influencing factors of prognosis in children with ABE. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of DKI parameters for the prognosis of children with ABE. Results:The birth weight and gestational age in the ABE group were significantly lower than those in the non-ABE group, and the peak value of total bilirubin (TBIL) was significantly higher than that in the non-ABE group (all P<0.05). There was no statistically significant difference in fractional anisotropy (FA) values and mean diffusivity (MD) values among each group of children (all P>0.05). The mean kurtosis (MK) values, axial kurtosis (KA) values, and radial kurtosis (KR) values of children with ABE in the severe group were significantly higher than those in the other groups (all P<0.05). After Spearman correlation analysis, the FA value and MD value of children with ABE were not correlated with the severity of the disease (all P>0.05), while the MK value, KA value and KR value were positively correlated with the severity of the disease (all P<0.05). The patients were followed up for 12 months. Among them, 87 cases had a normal prognosis and 25 cases had a poor prognosis, including 2 cases of cerebral palsy, 5 cases of hearing loss, 4 cases of movement disorders, 12 cases of cerebral palsy combined with hearing loss, and 2 cases of movement disorders combined with hearing loss. The results of univariate analysis showed that there were statistically significant differences in birth weight, peak TBIL, BIND score, MK value, KA value, and KR value between the two groups of children with different prognoses (all P<0.05). The results of Cox multivariate regression analysis showed that birth weight, peak TBIL, BIND score, MK value, KA value, and KR value were independent influencing factors for poor prognosis in children with ABE (all P<0.05). The results of the ROC curve showed that the area under the curve and specificity of the MK value in predicting the poor prognosis of children with ABE were significantly higher than those of the KA and KR values (all P<0.05). Conclusions:The DKI parameters MK value, KA value, and KR value are sensitive indicators reflecting the severity of brain injury and predicting prognosis in children with ABE, among which the MK value has the highest predictive value.

Objective: To investigate the impact of milk and egg supplementation on body composition and bone mineral density of rural primary school students in Yunnan Province, so as to provide a reference for developing targeted nutritional intervention strategies. Methods: In December 2023, a cluster sampling method was adopted to select students from grades one to three in four primary schools each from Jinggu and Shidian countys of Yunnan Province, as the intervention group (662 students). Additionally, two boarding primary schools were selected from each county based on the principle of matching scale and student numbers as the control group (455 students). Starting from April 2023, the intervention group received 200 mL milk and 50 g eggs during the break on school days for 8 months, while the control group maintained their usual diet behavior. Body composition was measured by using bioelectrical impedance analysis, and distal radial bone mineral density was assessed via dual energy X-ray absorptiometry in April and December 2023. The intervention effects were analyzed by using a difference in-differences approach. Results: The final measurements of body fat percentage, skeletal muscle mass and fat free mass of the intervention group and the control group of primary school students were significantly higher than the baseline values, and the net effect of milk and egg intervention on these body composition indicators was not statistically significant ( P >0.05, both before and after adjustment). In contrast, bone mineral density increased significantly by 0.02 g/cm 2 in the intervention group. The net intervention effect on bone mineral density was statistically significant ( β=0.02, 95%CI =0.00-0.04), and remained significant after model adjustment ( β=0.02, 95%CI =0.00-0.04) (both P < 0.05). Subgroup analysis showed statistically significant effects of the intervention among girls ( β=0.02, 95%CI =0.00-0.04), day students ( β=0.04, 95%CI =0.01-0.07), and students with normal nutritional status ( β=0.02, 95%CI =0.00-0.04) (all P <0.05). No significant effect of milk and egg supplementation was observed on body composition indicators (all P <0.05). Conclusions Milk and egg supplementation can improve bone mineral density among rural primary school students in Yunnan Province. It is recommended that rural school aged children should increase intake of milk and eggs to support growth and development.

Pancreatitis is an inflammatory disease influenced by both environmental and genetic factors. It has a high prevalence and mortality rate worldwide, with no radical cure. Breakthroughs have been recently made in genetic research of pancreatitis. Susceptibility genes and pathways have been continuously discovered, which highlighted the roles of genetic factors in hypertriglyceridemic and chronic pancreatitis. Gene therapy may offer radical cure for pancreatitis, though it has remained at the research phase. This article has reviewed the genetic pathogenesis of pancreatitis and current status of gene therapy research, with an aim to provide a reference for attaining definitive cure for the disease.

The liver is one of the essential hubs for maintaining the homeostasis of the organism.Liver aging not only heightens its susceptibility to acute injuries and chronic liver diseases, but also triggers a " chain reaction" of multi-organ aging and dysfunction.With the continuous deepening of the aging population in China, how to prevent, monitor, and evaluate the occurrence, development, and prognosis of liver aging has become an important issue in the field of geriatrics research.Thus, the identification and widespread application of liver aging biomarkers is the key to solving this problem.Therefore, this article reviews the research progress of liver aging-related biomarkers, aiming to provide a basis for the precise prevention and targeted intervention of liver diseases related to aging.

Objective To investigate the therapeutic effects and mechanisms of dexmedetomi-dine and remimazolam on neuropathic pain.Methods A total of 60 SD rats were divided into sham operation group(n=12),spinal nerve ligation(SNL)+NC group(n=12),SNL+DEX group(n=12),SNL+REM group(n=12)and DEX+REM group(n=12).Mechanical withdrawal threshold(MWT)was analyzed in each group.The expression level of pain-related protein c-Fos was detected by Western blot.Autophagy was assessed by immunofluorescence analysis.Enzyme-linked immunosorbent assay(ELISA)was used to measure the expression levels of inflammatory factors[tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1 β),interleukin-6(IL-6)and interleukin-10(IL-10)]of each group.The expression level of oxidative stress factor in each group was ana-lyzed.The expression levels of NFE2L2/NRF2 pathway related proteins were analyzed by Western blot.Results MWT in the SNL+DEX,SNL+REM and DEX+REM groups was significantly high-er than that in the SNL+NC group(P＜0.05).The expression level of c-Fos protein in the SNL+NC group was significantly higher than that in the SNL+DEX,SNL+REM and DEX+REM groups(P＜0.05).The immunofluorescence intensity of LC3 and NeuN in SNL rats was lower than that in sham operation rats,indicating that autophagy of neurons in SNL rats was damaged.The immunofluorescence intensity of LC3 and NeuN in the SNL+DEX group,SNL+REM group and DEX+REM group were significantly higher than those in the SNL+NC group(P＜0.05).The expression levels of TNF-α,IL-1 β and IL-6 in the SNL+DEX group,SNL+REM group and DEX+REM group were signifi-cantly lower than those in the SNL+NC group(P＜0.05).Glutathione(GSH)and catalase(CAT)levels in the SNL+DEX,SNL+REM and DEX+REM groups were significantly higher than those in the SNL+NC group,while malondialdehyde(MDA)levels were significantly lower(P＜0.05).The expression levels of NFE2L2 protein in the SNL+DEX,SNL+REM and DEX+REM groups were significantly lower than that in the SNL+NC group,with the lowest level observed in the DEX+REM group(P＜0.05).Conclusion Dexmedetomidine and remimazolam can re-lieve neuropathic pain in SNL rats by inhibiting the expression of NFE2L2/NRF2 pathway-related proteins and decreasing oxidative stress levels.

Objective:To predict pre-treatment clinical parameters that are associated with poor response and prognosis to ursodeoxycholic acid (UDCA) in patients with primary biliary cholangitis (PBC) and to use second-line treatment drugs in the early stages to delay the progression of the disease so that patients can benefit from early-stage treatment.Methods:Patients diagnosed with PBC at the Second Affiliated Hospital of Kunming Medical University from 2013 to 2022 were collected. Two hundred fifty-seven cases were screened in accordance with the inclusion and exclusion criteria. The response and prognosis conditions one year after treatment were followed up in outpatient and inpatient departments, as well as through telephone calls. Statistical analyses were performed using t-tests, Mann-Whitney U test, χ2 test, Fisher's exact test, and logistic regression analysis according to different data. Results:A total of 257 PBC cases were included, with 223 females (86.80%) and 34 males (13.20%). Univariate and multivariate binary logistic regression analyses showed that baseline high albumin levels [odds ratio ( OR): 0.882, 95% confidence interval ( CI): 0.805～0.967, P=0.008] were a protective factor for PBC patients' response to UDCA treatment after adjusting for different confounding factors, while baseline high alkaline phosphatase ( OR: 1.012, 95% CI: 1.008～1.016, P<0.001) and baseline high neutrophil/lymphocyte ratio (NLR) level ( OR: 1.462, 95% CI:1.079～1.981, P=0.014) were risk factors for a poor response to UDCA. Trend analysis showed that the baseline NLR quantile was positively correlated with the risk of poor response to UDCA ( OR: 5.512, 95% CI: 1.040～29.216, P=0.045) in patients with PBC. Cox proportional hazards regression analysis identified that age [hazard ratio ( HR): 1.050, 95% CI: 1.019～1.082] and NLR value ( HR:1.089, 95% CI:1.021～1.161) were independent influencing risk factors for all-cause mortality in PBC patients ( P<0.05). Conclusion:Baseline high albumin levels are protective factors against a poor biochemical response to UDCA, while baseline high alkaline phosphatase levels and high NLR are risk factors for a poor biochemical response to UDCA in patients with PBC. Additionally, baseline high NLR values are positively correlated with poor biochemical response to UDCA treatment.