This case report presents a 16-year-old male patient with deficiency of adenosine deaminase 2(DADA2). The patient had a history of Raynaud′s phenomenon with digital ulcers since childhood. As the disease progressed, the patient developed retinal vasculitis, intracranial hemorrhage, skin necrosis, severe malnutrition, refractory hypertension, and gastrointestinal bleeding. Genetic testing revealed compound heterozygous mutations in the ADA2 gene (paternal c.1072G > A pathogenic mutation + maternal c.1065C > A variant of unknown clinical significance). ADA2 enzyme activity was significantly reduced (0.1 U/L). A multidisciplinary treatment team developed an individualized plan to address key issues, including nutritional support, blood pressure control, rehabilitation, pain management, and balancing anticoagulation/bleeding risks. After systematic intervention, the patient′s condition showed partial improvement. This case reveals clinical challenges such as anticoagulation decisions and nutritional support of DADA2. It also emphasizes the importance of early molecular diagnosis, tumor necrosis factor-α inhibitor targeted therapy, and multidisciplinary collaboration in management, underlining the core value of precision medicine in rare disease management.

Objective To study the brain functional connectivity(FC)changes in patients with normal tension glau-coma(NTG)and healthy volunteers using FC technique of resting-state functional magnetic resonance imaging(rs-fMRI)based on V1 region seed point(ROI),so as to explore the pathogenesis and early diagnosis of NTG.Methods Fourteen NTG patients(NTG group)who met the inclusion criteria and 14 healthy controls(HCs group)were enrolled.The clinical data of all subjects were collected,and rs-fMRI was performed in both groups.The magnetic resonance data was pre-pro-cessed by software,and bilateral A1 regions were taken as the ROI to analyze their correction with the whole brain voxel time series and obtain the FC value between the ROI and the whole brain by comparison of FC values in resting state be-tween the groups.Pearson correlation analysis was used to explore the relationship between FC value in the brain regions with significant differences with the ROI and clinical variables in the NTG group.Results Compared with the subjects in the HCs group,there were no statistically significant differences in age,gender,body weight,cup-disc ratio and 24 h mean intraocular pressure of patients in the NTG group(all P＞0.05),and there were statistically significant differences in the best corrected visual acuity(BCVA)of both eyes and peripapillary retinal nerve fiber layer thickness(RNFLT)(all P＜0.05).The Pearson correlation analysis showed that FC value of the brain regions with abnormal FC to V1 region were cor-related with RNFLT in the NTG group(P＜0.05).ROI1-left superior frontal gyrus,ROI1-right superior frontal gyrus,ROI2-left cingulate gyrus and ROI2-right middle frontal gyrus were significantly positively correlated with RNFLT(all P＜0.05).Compared with the HCs group,the brain regions with reduced FC to the right ROI in the NTG group were the left superior frontal gyrus and right superior frontal gyrus;the brain regions with reduced FC to the left ROI were the left cingulate gyrus and right middle frontal gyrus.Conclusion Compared to healthy individuals,NTG patients have significant changes in the functional connections between certain specific brain regions and V1 region,including bilateral superior frontal gyrus,left cingulate gyrus,and middle frontal gyrus.The changes in brain functional activity may be caused by visual dysfunction caused by NTG,leading to functional impairment of the visual and cognitive emotion processing brain regions,which may be one of the potential neuropathological mechanisms in NTG patients.

Objective To explore the changes in macular microcirculation status and visual function in patients with normal tension glaucoma(NTG)using the optical coherence tomography angiography(OCTA)and microperimeter MP-3 and analyze the correlation between the two.Methods In this cross-sectional observational study,17 NTG patients(30 eyes)were collected as the NTG group and then divided into mild,moderate and severe NTG subgroups according to the severity of the disease.During the same period,13 healthy subjects(23 eyes)with the same age and gender distribution were selected as the control group.OCTA was used to obtain linear density(LD)and perfusion density(PD)of superficial retinal vessels in the macular area.The microperimeter MP-3 was used to measure retinal sensitivity(RS)within 10° and fixation rate at 2° and 4° of the macular area.The OCTA parameters and microperimeter MP-3 parameters were compared among all groups,and the correlation between OCTA parameters and microperimeter MP-3 parameters in NTG patients was analyzed.Results There were no significant differences in LD and PD between the control group and the mild NTG sub-group in the central and nasal sides of the macula;the LD and PD in the remaining regions and overall average LD and PD showed a gradual downward trend in the control group and the mild,moderate and severe NTG subgroups.Compared with the control group,the RS of the mild NTG subgroup was lower in the inferior and temporal regions of the macular area.The RS of each region and overall average RS in the macular area decreased with the aggravation of the NTG.In the NTG group,LD and PD were significantly positively correlated with RS in each region and overall average RS in the macular area(all P＜0.05).In the NTG group,LD and PD were positively correlated with P2 in some regions of the macular area.Con-clusion Compared with the control group,the macular microcirculation status and visual function of NTG patients signif-icantly decreased with the progression of the disease;there is a significant correlation between macular LD and RS in NTG patients.

The close relationship between gastric cancer (GC) and type 2 diabetes mellitus (T2DM) has garnered significant attention. On one hand, T2DM may play a role in the development and progression of GC, correlating with poor patient outcomes. On the other hand, after radical surgery for GC, T2DM can be effectively managed, potentially improving tumor prognosis. In recent years, bariatric and metabolic surgery (BMS) has revolutionized T2DM treatment for obese and overweight patients. Comparative analyses reveal similarities between surgical approaches for gastric cancer and BMS, leading to the emergence of the onco-metabolic surgery (OMS) concept, which suggests that radical tumor resection and T2DM remission in GC patients can be potentially achieved through a single procedure. However, there are notable differences between OMS and BMS, including target populations, surgical details, and perioperative management. Therefore, optimizing the application of the OMS concept in GC patients holds significant clinical importance. This article provides a review to facilitate the better implementation of this concept in practice.

The close relationship between gastric cancer (GC) and type 2 diabetes mellitus (T2DM) has garnered significant attention. On one hand, T2DM may play a role in the development and progression of GC, correlating with poor patient outcomes. On the other hand, after radical surgery for GC, T2DM can be effectively managed, potentially improving tumor prognosis. In recent years, bariatric and metabolic surgery (BMS) has revolutionized T2DM treatment for obese and overweight patients. Comparative analyses reveal similarities between surgical approaches for gastric cancer and BMS, leading to the emergence of the onco-metabolic surgery (OMS) concept, which suggests that radical tumor resection and T2DM remission in GC patients can be potentially achieved through a single procedure. However, there are notable differences between OMS and BMS, including target populations, surgical details, and perioperative management. Therefore, optimizing the application of the OMS concept in GC patients holds significant clinical importance. This article provides a review to facilitate the better implementation of this concept in practice.

Gastric cancer with hemorrhage and cerebral infarction is a serious complica-tion with poor prognosis in clinic. Although the incidence rate is extremely low, the fatality and disability rates are very high. In addition, the opposition in treatment between the two complica-tions increases the difficulty of clinical diagnosis and treatment. The authors report the diagnosis and treatment of a gastric cancer patient with hemorrhage and new cerebral infarction, in order to to provide reference for related treatments.

Objective To analyze the characteristics of work-related musculoskeletal disorders (WMSDs) among sonographers in Guangdong Province, and to explore the disease pattern of the cases. Methods A total of 512 sonographers from 31 hospitals in Guangdong Province were selected as the research subjects using stratified cluster sampling method. The prevalence of WMSDs in the past year was investigated using the Musculoskeletal Disorders Questionnaire, and the characteristics of WMSDs were analyzed. Latent class analysis was used to identify the disease pattern of WMSDs. Results The overall prevalence of WMSDs was 94.3%. The top five affected body parts were right shoulder, neck, right hand/wrist, lower back and right forearm/elbow, with the prevalence of 80.3%, 75.4%, 61.1%, 55.5% and 45.3%, respectively. The prevalence of WMSDs was higher on the right side for the shoulder, hand/wrist, forearm/elbow, hip/leg and knee compared with the left side (80.3% vs 31.3%, 61.1% vs 13.9%, 45.3% vs 10.0%, 17.4% vs 8.6%, 13.1% vs 8.4%, all P<0.05). The prevalence of WMSDs increased with work years, as well the prevalence of WMSDs in the top five affected body parts among the sonographers (all P<0.05). However, there were no statistical differences in prevalence of WMSDs between general hospitals and maternal and child health hospitals, tertiary hospitals and non-tertiary hospitals, Pearl River Delta hospitals and non-Pearl River Delta hospitals; there was also no statistical difference between different genders and age groups of the sonographers (all P>0.05). The best-fit latent disease pattern for sonographers WMSDs comprised three categories： symptom of neck-right shoulder, symptom of neck-lower back-right shoulder-right elbow-right hand/wrist, and symptom of multi-parts above the knees, with the latent probabilities of 0.438, 0.427 and 0.135, respectively. Conclusion The prevalence of WMSDs in sonographers is extremely high, with a dose-effect relationship with work years. The most common affected parts are neck, lower back and right shoulder, right hand/wrist, and right forearm/elbow. The prevalence of WMSDs in the right side of limb was higher than that in the left. WMSDs primarily occur in multiple parts simultaneously. The most common symptoms occur in the neck-right shoulder and neck-lower back-right shoulder-right elbow-right hand/wrist.

Ischemic-type biliary lesion (ITBL) refers to biliary tract injury caused by insufficient blood supply of hepatic artery, which is one of the main factors affecting the long-term survival and quality of life of liver transplant recipients. The incidence of ITBL is associated with cold and warm ischemia, acute and chronic rejection, cytomegalovirus infection and the bile effect, etc. The occurrence of ITBL is a complicated process involving with multiple factors and steps. The therapeutic option of ITBL is extremely limited. A large proportion of ITBL patients should undergo repeated liver transplantation. ITBL has become one of the most critical factors preventing further advancement of liver transplantation. Hence, it is of significance to strengthen prevention and explore more effective modalities. Recent studies have found that toxic injury of bile salts plays a central role in ITBL. Active regulation of bile components, regulation of bile acid-related receptor expression and blockage or activation of bile acid-related signaling pathways probably have potentials in the prevention and treatment of ITBL. In this article, the cytotoxicity of bile salts and the mechanism of bicarbonate umbrella in the incidence and progression of ITBL after liver transplantation were reviewed, aiming to provide reference for the diagnosis and treatment of ITBL.

The causes for male sexual orientation are complicated, which have not yet been clarified. Recent years have witnessed fruitful progress in the field of biology, while the impact of environment has received little attention. Adverse childhood experiences (ACEs), identified as a special environment in the early stage of development, can affect the individual phenotype by DNA methylation. Given the relationships among male sexual orientation, ACEs, and DNA methylation, as well as based on the existing theory, this article proposes the model "ACEs-DNA methylation-male sexual orientation"from the perspective of environment and epigenetics, aiming to provide a theoretical basis for future research.
Adverse Childhood Experiences ; Child ; DNA Methylation ; Female ; Humans ; Male ; Sexual Behavior

Objective:To solve the problems in intensity-modulated radiation therapy (IMRT) planning, such as large labor cost and high dependence on the experience of physicists and great inconsistency in the quality of plan, and to discuss an unsupervised automatic treatment planning procedure of IMRT.Methods:The eclipse scripting application programming interface (ESAPI) within the Eclipse treatment planning system (TPS) 15.6 and optimization parameters tree search algorithm (OPTSA) were used to emulate and realize the whole planning process. Interacted with the TPS through ESAPI, relevant dosimetric parameters were input and output. The OPTSA evaluated the plan qualities based on dosimetric parameters of the targets and organs at risk (OARs) and iteratively adjusted the optimization objective parameters to achieve a progressively improving IMRT plan. In order to verify the effectiveness of the automatic planning, twenty historical rectum cancer cases were selected from the clinical database, and the dose distribution and specific dosimetric parameters were compared between the plans generated by the OPTSA and the manual plans under the same constraints.Results:All the auto plans have met clinical requirements. Furthermore, 90% and 10% of the auto plans were deemed as clinically improved and equally compared with the manual plans, respectively. The average CI for the PTV was 0.88 and 0.80 for the auto and manual plans respectively. Compared with the manual plans, the mean doses of all the OARs in the auto plans were reduced by 11% in average. The average elapsed time of automatic planning and manual planning was (28.15±3.61) and (36.7±4.6) min, respectively.Conclusions:The plans created by the proposed algorithm have been shown to be at least as good as the manual plans. In addition, this method can shorten the labor time in plan designing while ensuring the plan quality and consistency of the plan.