ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

Background The moderation role of environmental factors in the spread of hand-foot-and-mouth disease (HFMD) has attracted much attention, but the existing conclusions are inconsistent. For example, some scholars believe that high temperature, high humidity, and high concentrations of fine particulate matter (PM_2.5) and nitrogen dioxide (NO₂) increase the risk of HFMD, but other scholars have reached the opposite conclusion, or believe that there is no significant relationship. Objective Based on distributed lag nonlinear model (DLNM), to investigate the relationship between the incidence of HFMD and meteorological and air pollutant variables in Lianyungang City, and to provide scientific basis for early warning. Methods Daily data of meteorological factors and air pollutants in Lianyungang City from 2021 to 2024 were retrieved. Meteorological factors included average daily temperature, average wind speed, average air pressure, and relative humidity. Air pollutant indicators included PM_2.5, inhalable particulate matter (PM₁₀), carbon monoxide (CO), sulfur dioxide (SO₂), NO₂, and ozone (O₃). Spearman correlation analysis was used to analyze their correlations with HFMD, and the R package (version 4.3.1) dlnm was used to construct a DLNM model. Results During the study period, a total of 10503 cases were reported, with a male to female ratio of 1.47∶1 and the highest proportion of scattered children (49.97%). The Spearman correlation analysis results showed that daily average temperature (r=0.40), relative humidity (r=0.17) and O₃ (r=0.14) were positively correlated with the incidence of HFMD (all Ps<0.01), while average air pressure (r=−0.34), PM_2.5 (r=−0.24), PM₁₀ (r=−0.24), CO (r=−0.22), and NO₂ (r=−0.06) were negatively correlated with it (all Ps<0.05). There was no statistical relationship of SO₂ and average wind speed with the incidence of HFMD (both Ps>0.05). The cumulative risk effect was greatest when the daily average temperature was 28.50 ℃ (CRR=4.63, 95%CI: 2.68, 8.01). The average wind speed below 0.50 m·s⁻¹ and in the range of 2.50-3.50 m·s⁻¹ showed an acute risk effect, and low pressure (below 1016.00 hPa) could immediately increase the risk of the disease. The cumulative risk effect was greatest when the relative humidity was 100% (CRR=3.16, 95%CI: 1.77, 5.65). The greatest cumulative protective effects of PM_2.5 and PM₁₀ were present at concentrations of 158.00 μg·m⁻³ (CRR=0.12, 95%CI: 0.01, 0.99) and 561.50 μg·m⁻³ (CRR=0.01, 95%CI: 0.01, 0.99) respectively. The protective effect of CO was the strongest at the highest concentration (67.00 μg·m⁻³) (RR=0.67, 95%CI: 0.34, 0.64). The cumulative protective effects of SO₂ and NO₂ were both most significant at the concentration of 0.50 μg·m⁻³. Low concentrations of O₃ (below 48.00 μg·m⁻³) showed a risk effect, and the single-day protective effect was significant when the concentration was 141.00 μg·m⁻³. Conclusion There is a nonlinear and hysteretic relationship between environmental factors and the incidence of HFMD. A rational and efficient early warning and prevention and control system can be constructed accordingly.

Children， as a special group， frequently experience of off-label drug use worldwide. Common reasons for off-label drug use in children include the lack of data on pediatric patients during the clinical trial stage of drug development， delayed updates to drug instructions， and the non-standard professional behavior of some doctors. Off-label drug use in children is a double-edged sword. It could save lives and provide a way to explore additional functions of drugs， while it may also lead to the phenomenon of hyper-indication abuse， increasing the risk of adverse drug events. Regulating off-label drug use in children can safeguard the best treatment rights and interests of children. It is recommended to encourage pharmaceutical enterprises to conduct research and development of pediatric new drugs， simplify the approval process for drug instructions amendments， accumulate evidence-based medical evidence for off-label drug use in children， standardize the process of off-label drug use in children in medical institutions， continuously improve the standardized diagnosis and treatment capabilities of pediatricians， and actively cooperate with the families of pediatric patients in diagnosis and treatment， so as to comprehensively safeguard the rights and interests of both doctors and patients.

Objective To explore the clinical significance of miR-423-5p in ischemic stroke and its effects on SH-SY5Y cell apoptosis along with the underlying mechanisms.Methods Plasma samples were collected from three stroke-prone patients who subsequently developed acute ischemic stroke(AIS)within 24 hours.High-throughput sequencing was used to identify miR-423-5p as a key target.Venous blood samples were collected from 46 AIS pa-tients within 24 hours of onset and from 46 matched control cases.RT-qPCR was performed to measure the plasma expression of miR-423-5p in both groups.The diagnostic value of miR-423-5p for AIS was evaluated using receiver operating characteristic(ROC)curve.After overexpression and knockdown of miR-423-5p in SH-SY5Y cells,flow cytometry was performed to detect apoptosis in each group to analyze the potential relationship between miR-423-5p and SH-SY5Y cell apoptosis.Western blot was used to measure changes in the expression level of the ap-optotic protein cleaved caspase-3 and the anti-apoptotic proteins Bcl-2 and Bcl-xL.Results The expression of miR-423-5p in 3 AIS patients showed significant difference before and after onset.Plasma miR-423-5p expression was significantly elevated in AIS patients versus controls(P＜0.001).ROC analysis indicated its strong diagnostic potential for AIS.Overexpression of miR-423-5p increased the apoptosis rate and cleaved caspase-3 ex-pression of SH-SY5Y cells after OGD/R,and decreased the expression of Bcl-2 and Bcl-xL,while knocking down miR-423-5p had the opposite effect.Conclusions The expression of miR-423-5p is upregulated in the plasma of patients with ischemic stroke compared to healthy controls.Furthermore,miR-423-5p promotes OGD/R-induced apoptosis in SH-SY5Y cells by increasing the level of cleaved caspase-3 and suppressing the expression of Bcl-2 and Bcl-xL.

Objective To investigate the effectiveness and safety of electroconvulsive therapy(ECT)in reducing suicidal ideation and depressive symptoms of major depressive disorder patients,as well as its effect on cognitive function.Methods A total of 160 adolescent patients with major depressive disorder were recruited for this study.The ECT group(n=81)received conventional antidepressant medication combined with 8 sessions of electroconvulsive therapy,and the control group(n=79)received conventional antidepressant medication only.Depressive symptoms,suicidal ideation,and cognitive functioning were assessed using 17-item Hamilton rating scale for depression(HAMD-17)and self-rating idea of suicide scale(SIOSS),at baseline(before ECT),after ECT,and at 2 and 6 weeks after treatment.The Montreal cognitive assessment(MoCA)was used to evaluate the cognitive function of the patients,and the patients were followed up for side effects such as dizziness and nausea.Results Generalized estimating equation(GEE)analysis of HAMD-17 and SIOSS scores showed significant group×time interaction effects(P<0.01).Both groups exhibited a reduction in HAMD-17 scores before and after treatment(scores at four time points:ECT group 24.59±4.56 vs.13.25±4.32 vs.6.20±1.95 vs.3.62±2.04,control group 23.48±3.66 vs.15.42±3.11 vs.10.10±2.05 vs.4.68±2.01;P<0.01).The mean difference in HAMD-17 scores before and after treatment was-9.62±3.13 in the ECT group,and was-8.16±1.71 in the control group.Additionally,suicidal ideation reduced in both groups after treatment(SIOSS scores at four time points:ECT group 18.57±2.85 vs.10.93±3.52 vs.8.02±2.79 vs.3.70±1.96,control group 18.97±3.03 vs.15.51±2.98 vs.11.11±2.18 vs.6.44±1.78;P<0.01).For cognitive function scores,there was no interaction between group and time(P=0.21),the difference in the change in MoCA scores at different follow-up time points was significant(P<0.01),and the difference in the change in MoCA scores between the two groups was not significant(P=0.05),and the cognitive functions of the two groups could be restored to the baseline level at 6 weeks after treatment.No severe side effects were reported in either group of patients during the study.Conclusions Our findings confirm that ECT is effective and safe for improving suicidal ideation and depressive symptoms in adolescents with major depressive disorder.The impairment of cognitive function by ECT in adolescent patients with major depressive disorder is reversible.

Chimeric antigen receptor T (CAR-T) lymphocytes are at the forefront of adoptive immunotherapy research, and this technology has significantly advanced the prospects of tumor immunotherapy. CAR-T therapy has demonstrated remarkable efficacy in haematological tumours of lymphoid origin and provided therapeutic possibility for solid tumours. Currently, CAR-T cell preparation predominantly involves transfection of T cells with viral vectors. However, the production of viral vectors is time-consuming, expensive, and the vectors have low loading capacity, along with insertion instability. Consequently, there is a pressing need to develop more convenient and precise non-viral gene delivery methods. This paper reviews the most promising non-viral gene delivery technologies, including CRISPR/Cas9 gene editing, transposon systems such as Sleeping Beauty (SB) and PiggyBac (PB), and mRNA, and anticipates the future development of non-viral vector-based CAR-T therapies.
Humans ; Immunotherapy, Adoptive/methods* ; Receptors, Chimeric Antigen/immunology* ; Animals ; Gene Transfer Techniques ; Genetic Vectors/genetics* ; Gene Editing ; CRISPR-Cas Systems/genetics* ; DNA Transposable Elements/genetics* ; T-Lymphocytes/immunology* ; Neoplasms/immunology*

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Objective:To explore the efficacy and safety of one-hole split endoscope (OSE) minimally invasive surgery for the treatment of single-segment thoracic ossification of the ligamentum flavum (TOLF).Methods:This retrospective non-randomized controlled study included 41 patients with single-segment TOLF who underwent surgery at Qilu Hospital of Shandong University between July 2019 and July 2023. Patients were divided into two groups: the OSE group (19 cases) treated with one-hole split endoscope minimally invasive surgery and the open group (22 cases) treated with traditional laminectomy and pedicle screw fixation. There were no significant differences between the two groups on gender, age, disease duration, affected segment, presence or absence of dural ossification, and residual cross-sectional vertebral canal area on CT ( P>0.05). Additionally, perioperative surgical time, estimated blood loss (EBL), incision length, hospital stay duration, hospitalization costs and follow-up duration were compared. The Japanese Orthopaedic Association (JOA) score and Oswestry Disability Index (ODI) were compared preoperatively and at the last follow-up. Complications were also recorded. Results:All patients successfully completed the surgery with no significant differences at the last follow-up ( P>0.05). Compared with the open group, the OSE group had a significantly shorter operative time (133.1±16.8 vs. 160.5±22.6 min), lower EBL (91.2±15.0 vs. 192.5±43.8 ml), shorter incision length (2.6±0.5 vs. 7.9±1.9 cm), reduced hospital stay (3.9±0.8 vs. 5.6±0.8 days), and lower hospitalization costs (34,874.9±4,568.6 vs. 53,162.3±9,815.6 yuan) (all P<0.05). AAt the final follow-up, JOA scores (8.5±0.8 vs. 8.6±1.2) and ODI values (16.7%±2.1% vs. 17.7%±4.4%) showed no significant differences between the OSE and open groups ( P>0.05). During the perioperative period and follow-up, complications occurred in 2 patients in the OSE group (1 cerebrospinal fluid leak, 1 poor wound healing) and in 8 patients in the open group (5 cerebrospinal fluid leaks, 1 neurological deterioration, 2 poor wound healing). Conclusion:OSE minimally invasive surgery is an effective treatment for single-segment thoracic ossification of the ligamentum flavum. Compared with open surgery, it provides advantages such as minimal invasiveness and fewer complications.

Objective:To evaluate the efficacy and safety of treatments in phase Ⅰ oncology clinical trials in patients with advanced non-small-cell lung cancer(NSCLC).Methods:We retrospectively analyzed the clinical data of 65 patients with advanced NSCLC who received phase Ⅰ antitumor trial drugs at the Clinical Trial Research Center of The First Affiliated Hospital of Bengbu Medical University from January 2020 to December 2023.The efficacy and occurrence of serious adverse events(SAEs)were analyzed.Results:The objective response rate(ORR)and disease control rate(DCR)were 9.2%and 61.4%,respectively,whereas the median progression-free survival(PFS)and overall survival(OS)were 2.9 and 15.1 months,respectively.Previously receiving second-line or more lines of treatment and SAE occurrence were independent risk factors for a shorter PFS(P<0.05).A history of smoking and previous second-line or more lines of treatment were inde-pendent risk factors for a shorter OS(P<0.05).The SAE incidence was 15.4%,and no treatment-related deaths occurred.Conclusions:Treat-ments in phase Ⅰ oncology clinical trials are beneficial for patients with advanced NSCLC.Patients with a higher number of previous treat-ment lines and those who experienced SAEs during the trial had a shorter PFS,whereas patients with no smoking history and fewer previous treatment lines had a longer overall survival.The overall safety of the treatments was acceptable.

Objective To evaluate the efficacy and safety of polyethylene glycol electrolyte powder(PEG)combined with linaclotide(Lin)for bowel preparation in elderly constipated patients before colonoscopy.Methods In this prospective,randomized controlled trial,90 elderly patients with constipation undergoing colonoscopy were recruited at our hospital from June 2022 to December 2023.Participants were randomly assigned to three groups(n=30 each):PEG-3L alone,PEG-3L+Lin,and PEG-2L+Lin.Primary outcome was Boston Bowel Preparation Scale(BBPS)score and secondary outcomes included adverse event rates,colonoscopy completion rate,withdrawal time,and polyp detection rate.Statistical analysis was performed using independent t-tests and chi-square tests.Results The PEG-3L+Lin group achieved significantly higher BBPS scores than both PEG-3L alone and PEG-2L+Lin groups did(both P<0.001).The PEG-2L+Lin group also outperformed the PEG-3L alone group in cleansing efficacy(90.0%vs.76.7%,P=0.008).The PEG-2L+Lin group demonstrated the best tolerability and lowest adverse event rate,the PEG-3L group had the longest withdrawal time(P<0.05),but the three groups showed no significant difference in polyp detection rates.Conclusion PEG combined with linaclotide significantly improves bowel cleansing in elderly constipated patients.PEG-2L+Lin regimen provides optimal balance between efficacy,safety,and tolerability,making it a preferable choice for this population.