Objective: To investigate the influencing factors for kinesiophobia among elderly patients with chronic obstructive pulmonary disease (COPD), so as to provide the reference for alleviating kinesiophobia among COPD patients. Methods: From December 2023 to July 2024, COPD patients aged 60 years and above who sought medical treatment at a tertiary grade-a hospital in Guiyang City were selected. Demographic information was collected through questionnaire surveys. Kinesiophobia, exercise self-efficacy, social support, type D personality and coping styles were assessed using the Chinese version of Tampa Scale for Kinesiophobia, the Chinese version of the Self-Efficacy for Exercise Scale, Social Support Rating Scale, Type D Personality Scale and Chinese version of the Medical Coping Modes Questionnaire, respectively. Factors affecting kinesiophobia among elderly patients with COPD were analyzed using a multiple linear regression model. Results: A total of 300 COPD patients were surveyed, including 238 males (79.33%) and 62 females (20.67%). The majority of patients had a disease duration of less than 5 years, with 130 cases (43.33%). The average kinesiophobia score was (48.01±7.74) points. The average exercise self-efficacy score was (3.39±1.01) points. The average social support score was (34.42±6.76) points. There were 280 patients (93.33%) with type D personality. The average scores of the confrontation, avoidance, and resignation dimensions of coping styles were (17.42±5.00), (13.76±1.91), and (11.81±2.95) points, respectively. Multiple linear regression analysis showed that age (70-<80 years, β'=0.124; ≥80 years, β'=0.205), educational level (primary school and below, β'=0.228; junior high school, β'=0.182), household monthly income per capita (<3 000 yuan, β'=0.234; 3 000~<5 000 yuan, β'=0.165), social support (β'=0.294), type D personality (β'= 0.170), and coping styles (confrontation dimension, β'=-0.140; avoidance dimension, β'=0.154; resignation dimension, β'=0.175) statistically associated with kinesiophobia among elderly patients with COPD. Conclusion Kinesiophobia among elderly patients with COPD is associated with age, educational level, household monthly income per capita, social support, type D personality and coping styles.

OBJECTIVE: To investigate the effectiveness of tibial transverse transport (TTT) in treating Wagner grade 3-4 type 2 diabetic foot ulcers and analyze dynamic changes in immunoglobulin levels. METHODS: The clinical data of 68 patients with Wagner grade 3-4 type 2 diabetic foot ulcers treated with TTT between May 2022 and September 2023 was retrospectively analyzed. The cohort included 49 males and 19 females, aged 44-91 years (mean, 67.3 years), with 40 Wagner grade 3 and 28 grade 4 ulcers. The duration of type 2 diabetes ranged from 5 to 23 years, with an average of 10 years. The number of wound healing cases, healing time, amputation cases, death cases, and complications were observed and recorded. Serum samples were collected at 6 key time points [1 day before TTT and 3 days, 7 days (the first day of upward transverse transfer), 14 days (the first day of downward transverse transfer), 21 days (the first day after the end of transfer), 36 days (the first day after the removal of the transfer device)], and the serum immunoglobulin levels were detected by flow cytometry including immunoglobulin G (IgG), IgA, IgM, IgE, complement C3 (C3), C4, immunoglobulin light chain κ (KAP), immunoglobulin light chain λ (LAM). RESULTS: All the 68 patients were followed up 6 months. Postoperative pin tract infection occurred in 3 cases and incision infection in 2 cases. Amputation occurred in 5 patients (7.4%) at 59-103 days after operation, and 8 patients (11.8%) died at 49-77 days after operation; the wounds of the remaining 55 patients (80.9%) healed in 48-135 days, with an average of 80 days. There was no recurrence of ulcer, peri-osteotomy fracture, or local skin necrosis during follow-up. The serum immunoglobulin levels of 55 patients with wound healing showed that the levels of IgG and IgM decreased significantly on the 3rd and 7th day after operation compared with those before operation ( P<0.05), and gradually returned to the levels before operation after 14 days, and reached the peak on the 36th day. IgA levels continued to decrease with time, and there were significant differences at all time points when compared with those before operation ( P<0.05). The level of IgE significantly decreased at 21 days after operation compared with that before operation ( P<0.05), while it was higher at other time points than that before operation, but the difference was not significant ( P>0.05). The level of C3 showed a clear treatment-related increase, which was significantly higher on the 7th, 14th, and 21st days after operation than that before operation ( P<0.05), and the peak appeared on the 14th day. The change trend of C4 level was basically synchronous with that of C3, but the amplitude was smaller, and the difference was significant at 7 and 14 days after operation compared with that before operation ( P<0.05). There was no significant difference in KAP/LAM between different time points before and after operation ( P>0.05). CONCLUSION TTT can accelerate wound healing, effectively treat diabetic foot ulcer, and reduce amputation rate, and has definite effectiveness. The potential mechanisms of TTT in the treatment of diabetic foot ulcers include the dynamic regulation of IgG, IgA, IgM, and IgE levels to balance the process of inflammation and repair, and the periodic increase of C3 and C4 levels may promote tissue cleaning, angiogenesis, and anti-infection defense.
Humans ; Male ; Female ; Middle Aged ; Aged ; Diabetic Foot/immunology* ; Wound Healing ; Adult ; Retrospective Studies ; Aged, 80 and over ; Treatment Outcome ; Tibia/transplantation* ; Diabetes Mellitus, Type 2/complications* ; Amputation, Surgical ; Immunoglobulins/blood* ; Immunoglobulin G/blood*

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

Objective:To analyze the proportion of patients with acute primary angle-closure glaucoma (PACG) after the outbreak of coronavirus disease 2019 (COVID-19) in patients undergoing glaucoma surgery and the factors influencing morbidity.Methods:A cross-sectional study was performed.The cluster sampling method was used to collect 141 glaucoma patients hospitalized for glaucoma surgery after the outbreak of COVID-19 in Xuzhou First People's Hospital from December 16, 2022, to January 16, 2023, and 231 glaucoma patients hospitalized for surgery in the same 1-month period from 2019 to 2020, 2020 to 2021, 2021 to 2022 through the hospital information system.Ninety-two eyes of 92 patients with acute PACG after the outbreak were selected as a study group, and 21 eyes of 21 patients with acute PACG hospitalized during the same 1-month period from 2021 to 2022 were selected as a control group.The proportion of patients with different types of glaucoma during the observation period was analyzed.The proportion of patients with acute PACG and the clinical characteristics of acute PACG were analyzed, including age, sex, visual acuity, intraocular pressure (IOP), and anterior chamber angle status.Epidemiological data such as the use of anti-cold medications, and changes in living habits and moods (including daily water intake and anxiety) of patients after COVID-19 infection were obtained by telephone follow-up.Anxiety levels of patients in the study group were assessed using the Hospital Depression and Anxiety Scale (HADS).The triggering factors of acute PACG attack after the COVID-19 outbreak were analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Xuzhou First People's Hospital (No.xyyll[2023]114).Written informed consent was obtained from each subject.Results:The proportion of acute PACG patients in Xuzhou First People's Hospital within one month after the outbreak in 2022 to 2023 increased significantly compared with the same period in 2021 to 2022, 2020 to 2021 and 2019 to 2020, and the differences were statistically significant ( χ2=31.066, 33.331, 20.804; all at P<0.001).There was no statistical significance in the distribution of the number of eyes with different grades of visual acuity, IOP, the number of eyes with IOP ≥30 mmHg (1 mmHg=0.133 kPa), and the distribution of the number of eyes with different anterior chamber angles between the two groups (all at P>0.05).Patients in the control group had no history of COVID-19 infection or use of cold medicines at disease onset.During disease onset, all 92 (100%) patients in the study group had positive COVID-19 nucleic acid test results, of which 57 (61.96%) patients had a history of oral anti-cold medication use.During the same period, 49 (100%) hospitalized patients with other types of glaucoma had positive COVID-19 nucleic acid test results, of which 20 (40.82%) patients had a history of oral cold medication.There was a statistically significant difference in the proportion of patients taking oral cold drugs between acute PACG and other types of glaucoma in the study group ( χ2=5.764, P=0.016).During the outbreak of COVID-19, the study group reported that the daily water intake had increased to varying degrees than before.In the study group, 76 patients had anxiety, accounting for 82.6%.Multiple linear regression analysis showed that IOP=19.052+ 0.009×daily water intake+ 0.858×HADS score ( R2=0.780), and the standardized coefficients of daily water intake and HADS score were 0.542 and 0.452, respectively.Daily water intake had a greater effect on IOP than HADS score. Conclusions:The proportion of acute PACG patients among hospitalized surgical glaucoma patients increased significantly after the COVID-19 outbreak, which is related to risk factors such as oral anti-cold medications containing vasoconstrictors or antihistamines, increased daily water intake, anxiety and other lifestyle, and mood changes.

AIM:To investigate the activation of Cl-channels by sodium taurocholate(NaTC)in mouse pan-creatic acinar cells.METHODS:The single isolated pancreatic acinar cells from FVB/N mice were prepared using colla-genase digestion method.Whole-cell patch clamp technique was performed to record the currents.Intracellular adenosine triphosphate(ATP)dependence of the channels was examined via eliminating ATP from the pipette solution.Anion per-meability of the channels was investigated with ion-exchange method.The pharmacological characteristics of the channels was confirmed by two Cl-channel blockers.The volume sensitivity of the channels was detected using 47%hypertonic bathing solution.Extracellular Ca2+dependence of activating the channels was examined through eliminating Ca2+from the bathing solution.Intracellular reactive oxygen species(ROS)level was detected by an oxidation-sensitive fluorescent probe,2',7'-dichlorofluorescin diacetate.The experiment was repeated 6 times in each group.RESULTS:Extracellular application of 5 mmol/L sodium taurocholate induced a Cl-current,exhibiting the properties of outward-rectification,a se-lectivity sequence of I->Br-≥Cl->gluconate-and intracellularATP dependence(P<0.01).The currents were inhibited by chloride channel blocker 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid disodium salt hydrate(DIDS)and tamoxifen and by 47%hypertonicity stimulation(P<0.01).When ROS production was scavenged by N-acetyl-L-cysteine,the sodi-um taurocholate-induced Cl-currents were unaffected.The effect of sodium taurocholate on ROS production did not alter with the treatment with DIDS.Sodium taurocholate failed to induce Cl-currents when Ca2+was absent in extracellular bath-ing solution(P>0.05).CONCLUSION:Sodium taurocholate activates Cl-channels in mouse pancreatic acinar cells,which is dependent on extracellular Ca2+but not ROS pathway.

Kirsten rat sarcoma viral oncogene homolog(KRAS)gene is one of the most commonly mutated oncogenes.It has been found that KRAS inhibitors have the potential therapeutic effect on cancer patients with this gene mutation.In this study,machine learning was applied to develop a QSAR(quantitative structure-activity relationship)model for KRAS small molecule inhibitors.A total of 1857data points of IC50 and SMILES(simplified molecular input line entry system)for KRAS inhibitors were collected from three databases:ChEMBL,BindingDB,and PubChem.And nine different classifiers were constructed using three different feature screening methods combined with three machine learning models,namely,random forest,support vector machine,and extreme gradient boosting machine.The results showed that the SVM model combined with mutual information feature selection exhibited the best performance:AUCtest=0.912,ACCtest=0.859,F1test=0.890.Moreover,it also demonstrated good predictive performance on the external validation set(AUCExt=0.944,RecallExt=0.856,FPRExt=0.111).This study provides a new technical route for KRAS inhibitor screening in natural product databases using artificial intelligence methods.

Eye tracking technique is an examination method to record eye movements and gaze position over time and task,common eye movement parameters include sweep,smooth pursuit,gaze,and visual search.Neurodegenerative diseases such as Alzheimer disease,AD,fronto temporal dementia(FTD),dementia with Lewy bodies(DLB),Parkinson disease,PD,multi-system atrophy(MSA),progressive supranuclear palsy(PSP),motor neuron disease(MND)and corticobasal degeneration(CBD),etc.,have different degrees and manifestations of abnormalities in the above eye movement parameters.For example,there are different degrees of prolonged sweep latency and increased sweep error rate among different diseases.Eye movement tracking technology is of great value in the early identification,diagnosis and auxiliary differential diagnosis of cognitive dysfunction in various neurodegenerative diseases,and is a new method that is non-invasive,convenient,objective and accurate.

To retrieve, evaluate, and integrate evidence related to the operational procedures of ambulatory blood pressure monitoring (ABPM) in adults, aiming to enhance the accuracy and effectiveness of ambulatory blood pressure monitoring.

The orphan nuclear receptor Nur77 is emerging as an attractive target for cancer therapy, and activating Nur77's non-genotypic anticancer function has demonstrated strong therapeutic potential. However, few Nur77 site B ligands have been identified as excellent anticancer compounds. There are no co-crystal structures of effective anticancer agents at Nur77 site B, which greatly limits the development of novel Nur77 site B ligands. Moreover, the lack of pharmaceutical ligands restricts Nur77's therapeutic proof of concept. Herein, we developed a first-in-class Nur77 site B ligand (NB1) that significantly inhibited cancer cells by mediating the Nur77/Bcl-2-related apoptotic effect at mitochondria. The X-ray crystallography suggests that NB1 is bound to the Nur77 site B with a distinct binding mode. Importantly, NB1 showed favorable pharmacokinetic profiles and safety, as evidenced by its good oral bioavailability in rats and lack of mortality, bodyweight loss, and pathological damage at the 512.0 mg/kg dose in mice. Furthermore, oral administration of NB1 demonstrated remarkable in vivo anticancer efficacy in an MDA-MB-231 xenograft model. Together, our work discovers NB1 as a new generation Nur77 ligand that activates the Nur77/Bcl-2 apoptotic pathway with a safe and effective cancer therapeutic potency.

【Objective】 To analyze the causes of a case of hemolytic disease of the fetus and newborn (HDFN),and investigate the genetic background of maternal Rh deletion D--formation. 【Methods】 Blood samples of maternal and fetus were collected, and ABO blood typing, Rh blood typing, antibody screening and identification test were performed to explore the blood group serological characteristics of Rh deletion type D--, and Rh gene sequence was performed on parturient. 【Results】 The maternal blood group was identified to be O type, D--, and the anti-Hr0 antibody against Rh high-frequency antigen was suspected to be caused by multiple pregnancies which passes through the placental barrier and enable fetus to obtain anti Hr0 antibody, leading to HDFN, with genetic testing result as RH RHCE* Ce/RHCE* Ce. 【Conclusion】 In-depth research on the formation mechanism of Rh D-- in parturient should be conducted to provide clinical value for HDFN blood exchange treatment and blood transfusion in special blood group population.