Despite breakthroughs in immunotherapy for solid tumors, significant variations in treatment efficacy persist. Up to 80% of cancer patients suffer from malnutrition, which leads to: lymphoid atrophy and reduced T-cell reserves; deficiency of substrates required for T-cell activation and expansion; concurrent inflammation hindering T-cell infiltration into tumors; and cachexia accelerating PD-1 antibody clearance. Clinical studies confirm that severe malnutrition significantly impairs immune responses and increases the risk of treatment toxicity. Therefore, implementing standardized nutritional therapy is crucial for optimizing the reserve, activation, expansion, and infiltration capacity of immune cells, thereby providing a sound immune system foundation for immunotherapy. Immunonutrition therapy, by enhancing immunonutrients such as arginine, omega-3 polyunsaturated fatty acids, and nucleotides, reduces the secretion of pro-inflammatory mediators and promotes T-cell activation and proliferation. This enhances anti-tumor immune responses, prolongs survival, and advances cancer treatment towards multimodal combination and precision approaches.

Fibrillin-1(FBN1)is a large-sized, cysteine-rich, calcium-binding extracellular matrix glycoprotein encoded by the FBN1 gene. As a structural component of microfibrils, this protein is widely distributed in the connective tissues of various ocular structures, including the zonules of Zinn, trabecular meshwork, cornea, retina, and its microvessels, providing mechanical support. Studies have shown that mutations in the FBN1 gene, resulting in decreased protein expression, significantly disrupt microfibril assembly and TGF-β-mediated signaling pathways. These pathogenic mechanisms are strongly linked to the development of key ocular disorders, such as lens dislocation, glaucoma, keratoconus, and retinal vascular diseases. This review summarizes and discusses the clinical manifestations and molecular mechanisms of FBN1-related ophthalmic conditions, with the aim of elucidating their pathogenesis and therapeutic strategies while laying molecular foundations for the development of novel targeted therapies.

Objective To summarize the clinical efficacy of modified Morrow surgery in the treatment of hypertrophic obstructive cardiomyopathy. Methods A retrospective analysis was conducted on the clinical data of patients with hypertrophic obstructive cardiomyopathy treated with modified Morrow surgery at Zhongshan Hospital Affiliated to Fudan University from 2020 to 2023. Results A total of 318 patients were enrolled, including 156 males and 162 females, with an average age of (55.6±13.1) years. Preoperative echocardiography showed a mean interventricular septal thickness of (18.1±3.8) mm, peak left ventricular outflow tract pressure difference of (86.4±24.9) mm Hg. The surgery time was (162.3±51.0) min, extracorporeal circulation time was (80.9±31.0) min, and aortic occlusion time was (44.8±20.8) min. After the surgery, transesophageal echocardiography showed that the interventricular septal thickness was (11.0±1.8) mm and left ventricular outflow tract peak pressure difference was (9.4±5.1) mm Hg. The incidence rate of postoperative complete left bundle branch block was 45.3%, Ⅲ° atrioventricular block was 3.8%, and postoperative newly developed atrial fibrillation was 3.1%. The postoperative hospital stay was (6.6±4.9) days, and one perioperative death occurred, with a mortality rate of 0.3%. The follow-up time was (10.3±9.4) months, during which the transthoracic echocardiography revealed a ventricular septal thickness of (12.9±2.9) mm and a peak left ventricular outflow tract pressure difference of (13.9±10.0) mm Hg. Conclusion The modified Morrow procedure for the treatment of hypertrophic obstructive cardiomyopathy is safe and effective, with good results in the short and medium term.

BackgroundInvasive vagus nerve stimulation therapy has been approved for the adjunctive treatment of treatment-resistant depression， which may contribute to the anti-inflammatory properties of vagus nerve stimulation （VNS）， whereas the efficacy of non-invasive transcutaneous cervical vagus nerve stimulation （tcVNS） in treating major depressive disorder （MDD） and its impact on plasma inflammatory factors remain unclear. ObjectiveTo observe the effect of escitaloprom combined with tcVNS on the status of depression， anxiety and sleep quality as well as the plasma levels of interleukin-6 （IL-6） and interleukin-10 （IL-10） in MDD patients， in order to provide references for the recovery and treatment of MDD patients. MethodsFrom August 21， 2019 to April 17， 2024， 45 patients who met the diagnostic criteria for MDD in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） were recruited from the psychosomatic outpatient clinic of the First Affiliated Hospital of Air Force Military Medical University. Subjects were divided into study group （n=23） and control group （n=22） using random number table method. All patients were treated with escitalopram. On this basis， study group added a 30-minute tcVNS therapy once a day for 4 weeks. While control group was given corresponding sham stimulation， and the duration of each stimulation lasted 30 seconds. Before and after 4 weeks of treatment， Hamilton Depression Scale-17 item （HAMD-17） was used to assess depressive symptoms， and HAMD-17 anxiety/somatization subfactor and insomnia subfactor were used to assess patients' anxiety/somatization symptoms and sleep quality. Levels of plasma IL-6 and IL-10 were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsThe generalized estimating equation model yielded a significant time effect for HAMD-17 total score， anxiety/somatization subfactor score and insomnia subfactor score in both groups （Wald χ²=315.226， 495.481， 82.420， P<0.01）. After 4 weeks of treatment， HAMD-17 total score and anxiety/somatization subfactor score of study group were lower than those of control group， with statistically significant differences （Wald χ²=4.967， 32.543， P<0.05 or 0.01）， while no statistically significant difference was found in the insomnia subfactor score between two groups （Wald χ²=0.819， P=0.366）. Significant time effects were reported on plasma IL-6 and IL-10 levels in both groups （Wald χ²=21.792， 5.242， P<0.05 or 0.01）. Compared with baseline data， a reduction in plasma IL-6 levels was detected in both groups （Wald χ²=22.015， 6.803， P<0.01）， and an increase in plasma IL-10 levels was reported in study group （Wald χ²=5.118， P=0.024） after 4 weeks of treatment. ConclusionEscitalopram combined with tcVNS therapy is effective in improving depressive symptoms， anxiety/somatization symptoms and sleep quality in patients with MDD. Additionally， it helps reduce plasma IL-6 levels and increase IL-10 levels. ［Funded by Shaanxi Provincial Key Research and Development Program-General Project （number， 2023-YBSF-185）， www.clinicaltrials.gov number， NCT04037111］

ObjectiveTo observe the clinical efficacy of Tongfu Kuanzhong decoction （TFKZ） in the treatment of constipation-predominant irritable bowel syndrome （IBS-C） with spleen deficiency and Qi stagnation and its effects on anorectal manometry and colonic electrical activity parameters. MethodsSixty-four patients with IBS-C of the spleen deficiency and Qi stagnation type were included as research subjects and were randomized into the observation group （thirty-two cases） and control group （thirty-two cases）. The control group was orally administered mosapride citrate tablets， and the observation group was orally administered TFKZ. Both groups were treated for 4 weeks. The traditional Chinese medicine （TCM） syndrome scores， patient assessment of constipation symptoms （PAC-SYM） score， general anxiety disorder-7 （GAD-7） score， patient health questionnaire-9（PHQ-9）score， anorectal manometry， and colonic electrical activity parameters were observed before and after treatment in the two groups. ResultsThe total points of TCM syndromes were significantly lower in both groups after treatment （P<0.01） and lower in the observation group （P<0.05）. The fecal symptoms， rectal symptoms， abdominal symptoms， and total symptom scores of the patients in both groups were significantly decreased after treatment （P<0.01）， and the rectal symptoms， abdominal symptoms， and total symptom scores of the observation group were lower （P<0.05，P<0.01）. In both groups， the forced anal residual pressure and the initial rectal sensation threshold decreased after treatment （P<0.05，P<0.01）， and forced anal residual pressure in the control group was lower （P<0.01）. After treatment， the GAD-7 and PHQ-9 scores of patients in both groups decreased significantly （P<0.01）， and the GAD-7 score of the observation group was significantly lower （P<0.01）. After treatment， the average wave amplitude at different time points of each lead increased significantly in both groups， compared with that before treatment （P<0.01）. The average wave amplitude of each lead of the ascending colon， descending colon， sigmoid colon， and rectum in the observation group at 5 min before the meal and 10 min after the meal， as well as that of the ascending colon and rectum at 20 min and 30 min after the meal， was higher than that of the control group （P<0.05）. ConclusionTFKZ is effective in the treatment of IBS-C. Its mechanism may be related to the regulation of colonic function by down-regulating the forced anal residual pressure and the initial rectal sensation threshold and up-regulating the amplitude and frequency of intestinal electrical activity in each intestinal segment of the colon.

Background Injury poses a serious threat to human health. As global warming continues to intensify, there is an urgent need to explore the impact of temperature changes on injury deaths. However limited research has focused on this issue. Objective To investigate the relationship between daily mean temperature change (Tm) and injury death, as well as to estimate the associated future death burden in Hunan Province. Methods We employed an individual-level, time-stratified case-crossing design to establish a conditional logistic regression model to analyze the exposure-response relationship between daily mean temperature change and injury death in Hunan Province from 2013 to 2018. Consequently, we conducted subgroup analysis of gender, age group, and injury type. Finally, we estimated the excess burden of injury death attributable to temperature changes under a sustainable development path [low emission scenario (SSP1-2.6)], regional competition path [high emission scenario (SSP3-7.0)], or fossil fuel development path [very high emission scenario (SSP5-8.5)]. Results The study collected 155577 injury deaths in Hunan Province. The results indicated that for each 1 ℃ increment in daily mean temperature, the cumulative excess risk (CER) of injury mortality among Hunan residents increased by 0.71% (95%CI: 0.53%, 0.90%). Notably, the CER for intentional injuries (1.06%, 95%CI: 0.51%, 1.61%) was higher than that for unintentional injuries (0.66%, 95%CI: 0.46%, 0.87%). Warmer temperatures were positively associated with CER of mortality due to drowning, falls, transport injuries, assaults, and suicides, while they were negatively associated with mortality due to poisoning. Compared with 2010–2019, for 2090–2099, the excess mortality rate (EMR) due to ambient temperature increase in Hunan Province under the SSP5-8.5 scenario (14.62/100000, 95%CI: 10.81/100000, 18.40/100000) would be higher than that of the SSP3-7.0 scenario (10.28/100000, 95%CI: 7.58/100000, 12.97/100000) and the SSP1-2.6 scenario (3.35/100000, 95%CI: 2.46/100000, 4.23/100000); the EMR would be around 2.5 times among men (20.64/100000, 95%CI: 14.44/100000, 26.8/100000) than that among women (8.33/100000, 95%CI: 3.98/100000, 12.6/100000). Among unintentional injuries, the leading contributors to EMR would be drowning (4.46/100000), falls (3.96/100000), and transport injuries (2.96/100000). And among intentional injuries, the EMR for suicide (2.08/100000) would be higher than that for assault (0.47/100000). Conclusion Climate warming will increase the total burden of injury-related deaths among residents in Hunan Province, especially in the absence of effective mitigation strategies and measures. It is necessary to strengthen the prevention and control of severe injuries closely related to temperature changes, such as drowning, falls, traffic, and suicides injuries, in order to reduce injury deaths associated with climate change.

Guided by the theory of turbid pathogen disturbing clarity， this paper holds that the pathogenesis of otolith disorders involves the failure of clear yang to ascend and the internal generation of phlegm-turbidity as the initiating factors. The clinical manifestations are characterized by the intermingling of phlegm and fluid， as well as the disturbance between turbid and clear substances， while the root lies in spleen-kidney deficiency and depletion of primordial qi. Treatment strategies are formulated according to the different stages of the disease： in the acute phase， therapy focuses on warming and resolving phlegm-fluid retention， using a modified combination of Linggui Zhugan Decoction （苓桂术甘汤） and Zexie Decoction （泽泻汤）； in the residual phase， the approach shifts to tonifying qi and uplifting clear yang， with a modified combination of Shengxian Decoction （升陷汤） and Shengmai Power （生脉散）； in the consolidation phase， therapy aims to tonify the kidney and replenish essence， employing a modified version of Qiju Dihuang Pill （杞菊地黄丸）.

Objective To explore the efficiency improvement in segmenting neural network with the application of Transformer + U-Net artificial intelligence (AI) and modeling with the application of Python scripts in three-dimensional (3D) printing brachytherapy. Methods A Transformer + U-Net AI neural network model was constructed, and Adam optimizer was used to ensure rapid gradient descent. Computed tomography or magnetic resonance imaging data of patients were standardized and processed as self-made data sets. The training set was used to train AI and the optimal result weight parameters were saved. The test set was used to evaluate the AI ability. Python programming language was used to write an automated script to obtain the output segmentation image and convert it to the STL file for import. The source applicator and needle could be automatically modeled. The time of automatic segmentation and modeling and the time of manual segmentation and modeling were entered by two people, and the difference was verified by paired t-test. Results Dice similarity coefficient (DSC), mean intersection over union (MIOU), and Hausdorff distance (HD95) were used for evaluation. DSC was 0.9341, MIOU was 0.8762, and mean HD95 was 2.516. The mean time of manual segmentation was 1187 s, and the mean time of AI segmentation was 145 s (P < 0.01). The mean time of manual modeling was 321 s, and the mean time of modeling with Python automated scripts was 18 s (P < 0.01). Conclusion The application of Transformer + U-Net automatic segmentation and Python automated scripts can effectively improve work efficiency in the 3D printing brachytherapy for cervical cancer.

OBJECTIVE: To observe the efficacy and safety of eye transcutaneous electrical acupoint stimulation (Eye-TEAS) on preventing the progression of pre-myopic to myopia in children aged 6-12 years. METHODS: A total of 170 pre-myopic children aged 6-12 years were randomly divided into an Eye-TEAS group (85 cases, 3 cases dropped out, 2 cases were eliminated) and a placebo Eye-TEAS group (85 cases, 3 cases dropped out, 2 cases were eliminated). The Eye-TEAS group received Eye-TEAS intervention at bilateral Cuanzhu (BL2), Yuyao (EX-HN4), Sizhukong (TE23), Taiyang (EX-HN5), Sibai (ST2), and Jingming (BL1), with continuous wave at a frequency of 4 Hz and a current of 1-2 mA for 30 min per session. The placebo Eye-TEAS group received sham intervention with the same equipment and procedure, but no electrical stimulation. Both groups received intervention once every other day, at least 3 times a week, for a duration of 20 weeks. After intervention and during the 28-week follow-up period after the intervention completion, the changes in axial length (AL), spherical equivalent refraction (SER), and the incidence of myopia were compared between the two groups. Adherence and safety during the intervention period were also evaluated. RESULTS: Compared before intervention, both groups showed an increase in AL after the intervention and during the follow-up (P<0.01). The AL during follow-up was higher than that after the intervention in the two groups (P<0.01). The Eye-TEAS group exhibited a smaller change in AL than the placebo Eye-TEAS group after the intervention and during follow-up (P<0.01, P<0.05). Compared before intervention, both groups showed a decrease in SER after the intervention and during follow-up (P<0.01). The SER during follow-up was lower than that after the intervention in the two groups (P<0.01). The Eye-TEAS group had a higher SER than the placebo Eye-TEAS group after the intervention (P<0.05). The Eye-TEAS group exhibited a smaller change in SER than the placebo Eye-TEAS group after the intervention and during follow-up (P<0.01). The incidence of myopia in the Eye-TEAS group was lower than that in the placebo group during follow-up (20.0% [14/70] vs 34.7% [25/72], P<0.05). Both groups had good adherence, with no adverse events related to the intervention. CONCLUSION Eye-TEAS can delay the progression of pre-myopic to myopia in children, and has a high safety profile.
Humans ; Child ; Male ; Female ; Acupuncture Points ; Myopia/prevention & control* ; Transcutaneous Electric Nerve Stimulation ; Treatment Outcome ; Disease Progression