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.

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.

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.

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.
Humans ; Genetic Therapy/methods* ; Pancreatitis/etiology* ; Genetic Predisposition to Disease ; Animals

Objective:To investigate the mechanism of polygonatum and astragalus compound(PA)in inhibiting the progression of lung adenocarcinoma. Methods:CCK-8 assay was used to assess the inhibitory rate of proliferation in A549 and H1299 cells treated with PA at different concentrations and to calculate the half maximal inhibitory concentration(IC50).C57BL/6 mice(KRASG12D/+;TP53flox/flox)were treated with adenovirus carrying Cre enzyme via nasal inhalation to establish a mouse model of primary lung adenocarcinoma.The model mice were fed with PA-containing diet to directly observe the effect of PA on the lung adenocarcinoma tissue.Immunohistochemical staining was used to examine the pathological status of the lung tissue.Bioinformatics analysis indicated that PA affects the progression of lung adenocarcinoma through the apelin-peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC1α)-mitochondrial brown fat uncoupling protein 1(UCP1).Real-time quantitative PCR and Western blotting analysis were used to study the effect of PA on the mRNA and protein expression levels of apelin-PGC1α-UCP1 signaling pathway related genes.An ATP detection kit and flow cytometry were used to evaluate the effect of PA on the ATP and mitochondrial ROS production,respectively,in A549 and H1299 cells.siUCP1 was used to silent the expression of UCP1 while Z160 was used to induce UCP1 overexpression in A549 and H1299 cells,and the changes in ATP and mitochondrial ROS production were examined to further investigate whether PA acts on apelin-PGC1α-UCP1 signaling pathway to affect the progression of lung adenocarcinoma. Results:PA could obviously inhibit the proliferation of A549 and H1299 cells with the IC50 values of 10.66 mg/mL for A549 cells and 9.66 mg/mL for H1299 cells.In the mouse primary lung adenocarcinoma model,PA could effectively inhibit the growth of tumor,downregulate apelin-PGC1α-UCP1 signaling pathway and inhibit the expression of lung adenocarcinoma-promoting gene UCP1.In A549 and H1299 cells,PA could significantly inhibit the expression of apelin,PGC1α and UCP1(P＜0.05),promote the production of ATP(P＜0.000 1)and ROS,restore mitochondrial oxidative phosphorylation,and inhibit aerobic glycolysis(P＜0.01).UCP1 silencing could increase the production of ATP(P＜0.01)and mitochondrial ROS and decrease the expression of key glycolysis enzymes hexokinase 2(HK2)and pyruvate kinase isozyme type M2(PKM2)(P＜0.05).Increasing the expression of UCP1 could reduce the ATP production(P＜0.01)and mitochondrial ROS generation in cells while increase the expression of HK2 and PKM2(P＜0.05).Treating cells with PA and Z160 simultaneously(PA+Z160)could reverse the inhibitory effect of PA on the ATP production and glycolysis of tumor cells(P＜0.05). Conclusion:PA can downregulate the apelin-PGC1α-UCP1 signaling pathway,inhibit mitochondrial uncoupling,restore mitochondrial oxidative phosphorylation,inhibit aerobic glycolysis,reverse the Warburg effect,and thus inhibit lung adenocarcinoma progression.

Objective To analyze the hotspots and developments in the field of language model-assisted artificial intelli-gence(Al)for antibody design and optimization in order to provide reference for research on development of antibodies.Methods By using CiteSpace software,hotspots of research were analyzed based on literature retrieved from the Web of Science,PubMed,and Scopus databases,focusing on three pivotal areas of research related to antibody design and optimization:the construction of pre-trained language models for antibodies,the generation of antibody sequences,and the prediction of three-dimensional structures of antibodies.In addition,this analysis reviewed the major advances in each of the specified research tasks,focusing on the delineation of similarities and differences across studies and dominating challenges in this field.Results From 2019(10 publications)to 2023(89 publications),the scale of and interest in this field kept increasing.Hotspots involved leveraging language models to assist the design or optimization of humanized,high-affinity,and highly specific antibodies.Within each research,methods were characterized by the diversity of model architectures,consistency of training data,and variations in training strategies.Challenges to the field included sparse antigen data,computational power limitations,and insufficient integration of wet and dry lab experiments.Conclusion Research in language model-assisted Al antibody design and optimization is gaining momentum and proves fruitful.However,researchers should be alert to the inadequate attention to antigen-antibody interactions and insufficient integration of experimental and computational validation,conduct more in-depth research and expand applications.

Critical care medicine-related treatment is an interdisciplinary and multi-professional process,often leading to secondary or concomitant mental disorders in clinical practice.Currently,there is no consensus on the pharmacological treatment of related mental illnesses in China.The Chinese Society of Psychosomatic Medicine collaborated with the Critical Care Medicine expert group to form a consensus writing expert group.After a systematic review of relevant literature,summarizing published domestic and foreign literature,and extensive discussions,the consensus was developed.The consensus elaborates on the principles and processes of the standardized use of psychotropic drugs in critical care medicine,as well as the clinical indications,precautions,and specific drug selection of various psychiatric medications,providing feasible suggestions and guidance for the clinical application of psychiatric medications in the intensive care unit.

Objective:To explore the feasibility of functional reconstruction of muscle power in treatment of traumatic muscle defects by transferring part of superficial vastus of lateral thigh.Methods:From March 2020 to March 2023, reconstruction of muscle power with transfer of superficial lateral thigh muscle was performed on 9 patients in the Department of Hand and Foot Microsurgery of Xi'an Fengcheng Hospital. Nine patients were assigned in a study group. A total of 48 patients who previously had the surgery of chimerically grafted superficial vastus of lateral thigh were recruited as the "previous surgery group" and another group of 71 staff volunteers from our hospital were recruited as the "healthy control group". Of the study group, 5 patients had Gustilo type ⅢB injury in forearm (two with defects of flexor muscle group and 3 with extensor muscle group, 2 with the defects in the left and 3 in the right), one had defect of both flexor and extensor muscle groups in dorsal hand, one had defect of right 1st metacarpal with defects of soft tissue and thenar muscle, one had a completely severed right upper arm with a withdrawn musculocutaneous nerve from the biceps brachii and one had Gustilo ⅢC injury in right calf with defects of tibialis anterior, extensor longus and extensor phalangeal muscle. In the emergency surgery, part of the superficial muscles of lateral thigh were taken to reconstruct the muscular power for the defected traumatic muscles. During the surgery, the excessed nerve with a length of 3.0 cm proximally was removed at 3.0 cm from the point where the nerve entered the muscle. In the transfer of superficial chimeric muscle of lateral thigh, a 3.0 cm of sample nerve tissue was taken for HE staining to find out the number of nerve fibers. Musculoskeletal ultrasonography, electromyography and muscle strength test were performed in the postoperative follow-up for observations and evaluations of the effects of surgery. Average length and thickness of muscle were taken from the 48 patients in the "previous surgery group". The measurement was compared with the length of muscle fibers and the number of nerve fibers in the gracilis muscle of the 9 patients in study group. The cross-sectional areas (SCA) at contraction state (C) and resting state (R) of the superficial vastus of lateral thigh were taken from the 71 volunteers in the healthy control group, and the C/R ratio was calculated (CR value). All the 9 patients were included in the postoperative follow up by outpatient visits and via telephone or internet reviews to observe the recovery of muscle strength of the reconstruction of muscle dynamics.Results:In the study group, the number of nerve fibers shown by immunohistochemical HE staining was 1 088±213, with the CR value of graft muscle measured by musculoskeletal ultrasonography at 1.44±0.17. The wound healed smoothly without complication. The average time of postoperative follow-up for the 9 patients was 22.6 (10-38) months. Recovery of muscle strength was found at M5 in 6 patients and M4 in 3 patients. The appearance of the joints was normal. In the previous surgery group, the average muscle thickness of the superficial vastus lateralis muscle was 1.74 cm±0.35 cm and the length of muscle fiber was 8.86 cm±1.59 cm. In the healthy control group, the CR value of the superficial muscle vastus of lateral thigh was found at 1.17±0.12.Conclusion:Reconstruction of muscular power with partial muscle transfer of the superficial vastus of lateral thigh is proposed in this study.

Coronary artery fractional flow reserve (FFR) is a critical physiological indicator for assessment of impaired blood flow caused by coronary artery stenosis. The wire-based invasive measurement of blood flow pressure gradient across stenosis is the gold standard for clinical measurement of FFR. However, it has the risk of vascular injury and requires the use of vasodilators, increasing the time and overall cost of interventional examination. Coronary imaging is playing an important role in clinical diagnosis of stenotic lesions, evaluation of severity of lesions, and planning of therapies. In recent years, the computation of FFR based on the physiological information of blood flow obtained from routinely collected coronary image data has become a research focus in this field. This technique reduces the cost of physiological assessment of coronary lesions and the use of pressure wires. It is beneficial to strengthen the physiological guidance in interventional therapy. In order to better understand this emerging technique, this paper highlights its implementation principle and diagnostic performance, analyzes practical problems and current challenges in clinical applications, and discusses possible future development.
Humans ; Coronary Vessels/diagnostic imaging* ; Fractional Flow Reserve, Myocardial ; Heart ; Constriction, Pathologic ; Coronary Stenosis/diagnostic imaging*

Regional anatomy teaching not only requires students to deal with the basic knowledge of human body including the level, location and adjacent relationship, but also to understand the clinical application of anatomical structure. Based on the four aspects of field anatomy, simulated surgery, clinical application lectures and CBL teaching, this study formulated a suitable assessment method to reconstruct the teaching system of regional anatomy relying on the improvement of the laboratory environment and the teacher team, aiming at cultivating students' clinical practice ability as the core and building a new regional anatomy course to meet the teaching needs of the new era.