Objective:To observe the efficacy and safety of combined lienal polypeptide injection therapy in the treatment of Mycoplasma pneumoniae pneumonia（MPP）in children aged 3 to 14 years old in multiple clinical centers.Methods:A randomized，controlled，multi-center clinical study design was adopted.A total of 240 hospitalized children aged 3 to 14 years old with MPP from 7 hospitals from September 1，2023 to January 31，2024 were included.According to the severity of pneumonia，they were divided into the mild MPP group with 80 cases and the severe MPP/refractory MPP（SMPP/RMPP）group with 160 cases，and then randomly divided into the control group and the experimental group at a ratio of 1 ∶1，using the random number table method.After screening，subjects entered a treatment period of 5 to 7 days.The control group was treated with azithromycin，while the experimental group was treated with azithromycin plus lienal polypeptide injection .The recovery of lung CT，length of hospital stay，duration of fever，cough score，whether mild cases developed into severe or refractory cases，duration of hormone use，use of intravenous immunoglobulin（IVIG），bronchoscopy treatment，and immune function were observed between the two groups to evaluate the efficacy of lienal polypeptide injection.Adverse events after medication，vital signs，blood routine，urine routine，liver function，myocardial enzymes，renal function，and electrocardiogram were observed to evaluate the safety. Results:A total of 231 subjects have completed the trial in the 7 hospitals，including 118 cases in the experimental group and 113 cases in the control group.Main observation index：the rate of lung CT aggravation in the experimental group was lower than that in the control group（2.6% vs 15.3%， P<0.01），and the difference was statistically significant.Secondary indexes：there were no statistically significant differences in the length of hospital stay，duration of fever，cough score，duration of hormone use，whether IVIG treatment was used，the number of bronchoscopy treatment cases，and immunoglobulin between the two groups（all P>0.05）.However，the rate of cases of plastic bronchitis（PB）found under bronchoscopy in the experimental group was lower than that in the control group（0 vs 18.8%， P=0.03），and the difference was statistically significant.Among the mild MPP（72 cases），there were no statistically significant differences in the length of hospital stay，duration of fever，cough score，duration of hormone use，whether IVIG treatment was used，the number of bronchoscopy treatment cases，and the improvement rate of lung CT between the two groups（all P>0.05）.However，compared with the control group，the rate of cases developing into SMPP/RMPP in the experimental group was less（24.3% vs 48.6%， P=0.03），and the difference in IgG before and after treatment was small［0.53（-0.04，1.18）g/L vs 1.33（0.48，2.25）g/L， P=0.01］.Among the SMPP/RMPP cases（159 cases），the rate of cases of PB found under bronchoscopy in the experimental group was less than that in the control group（0 vs 20%， P=0.04），and the rate of cases with aggravated lung CT in the experimental group was less than that in the control group（1.3% vs 19.5%， P<0.01），and the improvement rate of lung CT in the experimental group was higher than that in the control group（88.8% vs 75.3%， P=0.03），with statistically significant differences.There were no statistically significant differences in the length of hospital stay，duration of fever，cough score，duration of hormone use，whether IVIG treatment was used，the number of bronchoscopy treatment cases，and immunoglobulin between the two groups（all P>0.05）.Two cases in the experimental group developed rashes，which improved after the drug was discontinued.There were no serious adverse reactions such as abnormal vital signs like dyspnea and cyanosis due to the use of lienal polypeptide injection.There were no obvious changes in blood routine，liver function，myocardial enzymes，renal function，electrocardiogram，and urine routine values before and after medication compared with the baseline. Conclusion:The combined use of lienal polypeptide injection in the treatment of MPP in children can reduce the probability of the transformation from mild cases to SMPP/RMPP，reduce the rate of aggravation of the image findings，promote the absorption of lung inflammation，reduce the rate of PB found under bronchoscopy，and has good safety.

Objective:To investigate the relationship between social interaction and emotional experience in older adults,and the moderating effects of social interaction objects and personality traits on their relationship.M-ethod:Totally 208 elderly individuals were selected and assessed with a self-designed demographic information questionnaire and the NEO Personality Inventory(NEOPI).The Rochester Interaction Record(RIR)was used to record 14 days of social activity,and the Positive-Negative Affect Scale(PANAS)was used to evaluate emotions after each interaction.Using Mplus Multilevel Model(MLM)for model construction.Results:Through model con-struction,it was found that the interaction between openness and communication quality was statistically significant(β=0.45,P＜0.05).When the dependent variable was positive emotion,the higher the openness of elderly people,the stronger the connection between communication quality and positive emotion.When interacting with non-family members,the interaction between openness and social quality was statistically significant(β=0.52,P＜0.05).The higher the openness of older adults,the stronger the connection between social quality and positive emotions.Conclusion:It suggests that older adults with moderate or higher levels of openness have a stronger con-nection between social interaction quality and positive emotions when interacting with non-family members.That is,the higher the quality of interaction,the more positive emotions could be promoted,but negative emotions could not be reduced.

Cochlear implantation is the most effective method to restore hearing in patients with severe and profound hearing impairment.There are individual differences in rehabilitation after cochlear implantation.In order to better understand the underlying factors of rehabilitation,machine learning has been gradually applied to the reha-bilitation prediction of cochlear implant patients.Since related literature is still in its infancy,many problems still remain unresolved,such as insufficient sample size and lack of diversification of data features.We suggest that fu-ture research may expand the sample size,optimize machine learning models,and fully explore the predictive factors affecting the rehabilitation of cochlear implantation,and make machine learning a better tool in the area of cochlear implantation.

Objective:To investigate potential factors associated with nephrocalcinosis in children with X-linked hypophosphatemic rickets (XLH).Methods:A case-control study was conducted involving XLH children who were regularly followed up at Children′s Hospital of Nanjing Medical University, from January 2016 to January 2024.Patients diagnosed with nephrocalcinosis were assigned to the case group, and those without nephrocalcinosis served as controls.A retrospective analysis was performed to examine the correlation between nephrocalcinosis and laboratory parameters, as well as the diagnostic value of relevant factors.Multivariable Logistic regression was used to identify factors associated with nephrocalcinosis in children with XLH.Receiver operating characteristic (ROC) curves were plotted for the significant factors, and the areas under the curve (AUC) were compared using Delong′s test to evaluate differences in predictive performance.Results:Univariate analysis revealed significant differences between the case and control groups in serum calcium, urinary calcium, urinary calcium/creatinine ratio, urinary phosphorus, and renal tubular maximum reabsorption rate of phosphate/glomerular filtration rate (TmPi/GFR) (all P<0.05).However, multivariate logistic regression analysis identified only urinary calcium ( B=0.489, P=0.001) and TmPi/GFR ( B=-0.886, P=0.007) as independent predictors, while the urinary calcium/creatinine ratio was not statistically significant.The sensitivity, specificity, optimal cutoff value, and AUC for urinary calcium in predicting nephrocalcinosis were 0.842, 0.833, 0.614 mmol/L, and 0.851 ( P<0.01), respectively.For TmPi/GFR, the corresponding values were 0.900, 0.877, 0.573 mmol/L, and 0.875 ( P<0.01).The Delong test showed no significant difference in AUC between the combined indicator and TmPi/GFR ( Z=-1.555, P=0.120) or urinary calcium alone ( Z=-1.598, P=0.110). Conclusions:Urinary calcium and TmPi/GFR are significantly associated with nephrocalcinosis in children with XLH and demonstrate good predictive performance for early detection.The combination of these two indicators does not outperform either individual marker in diagnostic accuracy.

The pharmaceutical industry faces challenges in quality digitization for complex multi-stage processes, especially in small-sample systems. Here, an intelligent quality prediction and diagnostic (IQPD) framework was developed and applied to Tong Ren Tang's Niuhuang Qingxin Pills, utilizing four years of data collected from four production units, covering the entire process from raw materials to finished products. In this framework, a novel path-enhanced double ensemble quality prediction model (PeDGAT) is proposed, which combines a graph attention network and path information to encode inter-unit long-range and sequential dependencies. Additionally, the double ensemble strategy enhances model stability in small samples. Compared to global traditional models, PeDGAT achieves state-of-the-art results, with an average improvement of 13.18% and 87.67% in prediction accuracy and stability on three indicators. Additionally, a more in-depth diagnostic model leveraging grey correlation analysis and expert knowledge reduces reliance on large samples, offering a panoramic view of attribute relationships across units and improving process transparency. Finally, the IQPD framework integrates into a Human-Cyber-Physical system, enabling faster decision-making and real-time quality adjustments for Tong Ren Tang's Niuhuang Qingxin Pills, a product with annual sales exceeding 100 million CNY. This facilitates the transition from experience-driven to data-driven manufacturing.

OBJECTIVES: To investigate the effects of quercetin on cuproptosis and L-type calcium currents in the myocardium of diabetic rats. METHODS: Forty SD rats were randomized into control group and diabetic model groups. The rat models of diabetes mellitus (DM) induced by high-fat and high-sugar diet combined with streptozotocin (STZ) injection were further divided into DM model group, quercetin treatment group, and empagliflozin treatment group (n=10). Blood glucose and body weight were measured every other week, and cardiac function of the rats was evaluated using echocardiography. HE staining, Sirius red staining, and wheat germ agglutinin (WGA) analysis were used to observe the changes in myocardial histomorphology, and serum copper levels and myocardial FDX1 expression were detected. In cultured rat cardiomyocyte H9c2 cells with high-glucose exposure, the effects of quercetin and elesclomol, alone or in combination, on intracellular CK-MB and LDH levels and FDX1 expression were assessed, and the changes in L-type calcium currents were analyzed using patch-clamp technique. RESULTS: The diabetic rats exhibited elevated blood glucose, reduced body weight, impaired left ventricular function, increased serum copper levels and myocardial FDX1 expression, decreased L-type calcium currents, and prolonged action potential duration. Quercetin and empagliflozin treatment significantly lowered blood glucose, improved body weight, and restored cardiac function of the diabetic rats, and compared with empagliflozin, quercetin more effectively reduced serum copper levels, downregulated FDX1 expression, and enhanced myocardial L-type calcium currents in diabetic rats. In H9c2 cells, high glucose exposure significantly increased myocardial expressions of FDX1, CK-MB and LDH, which were effectively lowered by quercetin treatment; Elesclomol further elevated FDX1, CK-MB and LDH levels in the exposed cells, and these changes were not significantly affected by the application of quercetin. CONCLUSIONS Quercetin ameliorates myocardial injury in diabetic rats possibly by suppressing myocardial cuproptosis signaling and restoring L-type calcium channel activity.
Animals ; Quercetin/pharmacology* ; Calcium Channels, L-Type/metabolism* ; Diabetes Mellitus, Experimental/metabolism* ; Rats, Sprague-Dawley ; Rats ; Myocytes, Cardiac/drug effects* ; Myocardium/pathology* ; Male

The central amygdala (CeA) is a crucial modulator of emotional, behavioral, and autonomic functions, including cardiovascular responses. Despite its importance, the specific circuit by which the CeA modulates blood pressure remains insufficiently explored. Our investigations demonstrate that photostimulation of GABAergic neurons in the centromedial amygdala (CeM^GABA), as opposed to those in the centrolateral amygdala (CeL), produces a depressor response in both anesthetized and freely-moving mice. In addition, activation of CeM^GABA axonal terminals projecting to the nucleus tractus solitarius (NTS) significantly reduces blood pressure. These CeM^GABA neurons form synaptic connections with NTS neurons, allowing for the modulation of cardiovascular responses by influencing the caudal or rostral ventrolateral medulla. Furthermore, CeM^GABA neurons targeting the NTS receive dense inputs from the CeL. Consequently, stimulation of CeM^GABA neurons elicits hypotension through the CeM-NTS circuit, offering deeper insights into the cardiovascular responses associated with emotions and behaviors.
Animals ; GABAergic Neurons/physiology* ; Male ; Central Amygdaloid Nucleus/physiopathology* ; Hypotension/physiopathology* ; Mice ; Blood Pressure/physiology* ; Mice, Inbred C57BL ; Solitary Nucleus/physiology* ; Photic Stimulation ; Neural Pathways/physiology*

Neutralizing antibodies have been designed to specifically target and bind to the receptor binding domain (RBD) of spike (S) protein to block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus from attaching to angiotensin converting enzyme 2 (ACE2). This study reports a distinctive nanobody, designated as VHH21, that directly catalyzes the S-trimer into an irreversible transition state through postfusion conformational changes. Derived from camels immunized with multiple antigens, a set of nanobodies with high affinity for the S1 protein displays abilities to neutralize pseudovirion infections with a broad resistance to variants of concern of SARS-CoV-2, including SARS-CoV and BatRaTG13. Importantly, a super-resolution screening and analysis platform based on visual fluorescence probes was designed and applied to monitor single proteins and protein subunits. A spontaneously occurring dimeric form of VHH21 was obtained to rapidly destroy the S-trimer. Structural analysis via cryogenic electron microscopy revealed that VHH21 targets specific conserved epitopes on the S protein, distinct from the ACE2 binding site on the RBD, which destabilizes the fusion process. This research highlights the potential of VHH21 as an abzyme-like nanobody (nanoabzyme) possessing broad-spectrum binding capabilities and highly effective anti-viral properties and offers a promising strategy for combating coronavirus outbreaks.
Single-Domain Antibodies/immunology* ; Spike Glycoprotein, Coronavirus/metabolism* ; SARS-CoV-2/immunology* ; Animals ; Humans ; Antibodies, Neutralizing/immunology* ; Camelus ; COVID-19/immunology* ; Antibodies, Viral/immunology* ; Angiotensin-Converting Enzyme 2

Objective:To explore the cognitive characteristics, influencing factors, and treatment needs regarding biologic agents among patients with psoriasis.Methods:A cross-sectional study was conducted. Patients with psoriasis attending the Department of Dermatology, Xijing Hospital, Air Force Medical University were selected from October to December 2022, and from June to December 2023. A self-designed electronic questionnaire was used for investigation, covering demographic characteristics, psoriasis history (disease types, disease duration, previous treatments, etc.), biologics knowledge (sources of awareness, core cognitive dimensions), and treatment needs.Results:The valid questionnaire response rate reached 93.2% (439/471). The ages of enrolled patients were 35.95 ± 12.57 years, and the disease duration was 7.90 ± 3.26 years. Psoriasis vulgaris was the predominant type (363 cases, 82.69%). The overall awareness rate of biologics slightly increased from 68.62% (105/153) in 2022 to 72.38% (207/286) in 2023 ( P > 0.05). Primary information sources included new media (WeChat/internet) platforms (168 cases, 53.84%) and peer-to-peer sharing (115 cases, 36.86%), while physician counseling merely accounted for 9.29% (29 cases) ( P < 0.001). Insufficient knowledge of biologics was manifested primarily as poor awareness of comorbidities (47.60%, 209/439) and treatment monitoring protocols (22.32%, 98/439). Core concerns regarding biologic therapy included safety (73.34%, 322/439), economic burden (65.14%, 286/439), and long-term efficacy (63.55%, 279/439) ; 60.13% (264/439) of the patients expected rapid improvement of skin symptoms. As for treatment modalities, 90.20% (396/439) of the patients preferred regimens with extended dosing intervals. Conclusions:The patients with psoriasis demonstrated an imbalance in their cognitive structure regarding biologic agents. Their treatment needs exhibited multidimensional characteristics, emphasizing not only rapid clearance of skin lesions but also greater importance of treatment safety and cost-effectiveness.

Objective:To investigate the different clinical characteristics and prognosis of patients with diabetic nephropathy (DN) accompanied by IgA deposition diagnosed by renal biopsy.Methods:The study was a retrospective cohort study. Clinical and pathological data of patients diagnosed with DN through renal biopsy in Beijing Anzhen Hospital affiliated to Capital Medical University from January 1, 2010 to March 31, 2023 were retrospectively collected. The clinical and pathological characteristics and prognosis of DN patients with IgA deposition and DN control group patients without IgA deposition were compared. Immunofluorescence staining was used to detect the intensity of galactose-deficient IgA1 (Gd-IgA1) staining in renal tissue of DN patients with DN IgA deposition, and grouping was performed according to whether the staining intensity was≥2+. Enzyme linked immunosorbent assay was used to detect the serum level of Gd-IgA1 in patients. A 50% decrease in estimated glomerular filtration rate (eGFR) from baseline or progression to end-stage renal disease within 5 years was defined as a renal endpoint event, and Kaplan-Meier survival analysis and Log-rank test were used to compare the difference in cumulative incidence of renal endpoint events between two groups of patients.Results:A total of 101 DN patients were enrolled in this study, including 68 males (67.3%) and 33 females (32.7%), with age of (52.2±10.3) years and a median follow-up time of 13.5(4.8, 26.3) months. There were 44 patients with IgA deposition (43.6%) and 57 patients without IgA deposition (56.4%). Compared with DN control group, Kaplan-Meier analysis showed that DN patients with IgA deposition had a higher cumulative incidence of renal endpoint within 5 years ( χ2=6.473, P=0.011). The proportion of positive glomerular Gd-IgA1 (KM55) staining in the DN patients with IgA deposition was 54.5% (24/44), and immunofluorescence examination showed consistent distribution of Gd-IgA1 and IgA in the glomerular mesangial and capillary regions. The serum level of Gd-IgA1 in the glomerular Gd-IgA1 positive patients was significantly higher than that in those negative patients [(6 296.4± 1 535.4) μg/L vs. (4 057.4±1 082.0) μg/L, t=-3.037, P=0.010]. In DN patients with IgA deposition, the age of the subgroup with endpoint events was younger [(42.8±6.9) years vs. (53.3±9.4) years, t=-3.440, P=0.002], the duration of proteinuria was shorter [6.0(1.0, 22.0) months vs. 12.0(10.0, 36.0) months, Z=-2.150, P=0.032], and the proportion of patients with glomerular Gd-IgA1 staining intensity ≥2+ was higher [Fisher'exact test, 30.8%(4/13) vs. 0(0/20), P=0.017]. Kaplan-Meier survival analysis showed that patients with glomerular Gd-IgA1 staining intensity≥2+ had a significantly higher cumulative incidence of renal endpoint events ( χ2=4.846, P=0.028). Conclusion:DN patients with glomerular IgA deposition and Gd-IgA1 positivity may be associated with worse prognosis.