ObjectiveTo verify the association between the Ddit3-Trib3-Akt signaling pathway and rat spermatogenesis by constructing an in vitro co-culture system of testis. MethodsTesticular tissue blocks from 20-25-day-old male rats were placed in an in vitro culture system， and the culture medium was replaced every 2 to 3 days. PCR was used to verify the expression of marker genes of various spermatogenic cells. RNA interference technology was employed to verify the correlation between the Ddit3-Trib3-Akt signaling pathway and rat spermatogenesis. ResultsThe co-culture system could be continuously cultured for more than 2.5 months in vitro. RT-PCR showed that specific marker genes of spermatogonia， spermatocyte and spermoblast were expressed. The RNA and protein expression of Trib3 and Akt changed after the knocking down of Ddit3 and Trib3， respectively. It demonstrated the existence of Ddit3-Trib3-Akt signaling pathway in rat spermatogenesis. ConclusionThe culture time of more than 2.5 months indicates that the culture system can temporarily maintain the proliferation and differentiation of stem cells， and simultaneously maintain and stabilize spermatogenesis in a simple system. The successful validation of the Ddit3-Trib3-Akt signaling pathway also confirms that this culture system can be used to study possible molecular mechanisms of spermatogenesis in vitro.

ObjectiveTo explore the potential mechanism of Xiaoqinglong Decoction （小青龙汤， XD） in the treatment of allergic rhinitis. MethodsForty-five rats were randomly assigned to a control group， a model group， a loratadine group， low-， medium- and high-dose XD groups， and low-， medium- and high-dose Mahuang Decoction and Cang'erzi Powder （麻黄汤合苍耳子散， MDCP） groups. Except for the control group， rats were administered with ovalbumin （OVA） and aluminum hydroxide via intraperitoneal injection for 14 days to establish an allergic rhinitis model. After the 14th-day injection， nasal stimulation was continued with 20 μl of 10% OVA solution to maintain the model. Rats in the control group and the model group received 10 ml/（kg·d） of saline， whereas those in the loratadine group were administered with 0.9 mg/（kg·d） of loratadine. The low-， medium- and high-dose XD groups were administered XD at the dose of 2.7， 5.4， and 10.8 g/（kg·d）， respectively. The low-， medium- and high-dose MDCP groups were administered MDCP at the dose of 2.43， 4.86， and 9.72 g/（kg·d）， respectively. All treatments were administered by gavage once daily for 7 consecutive days. One hour after the final gavage， nasal symptom scores were recorded for all group of rats. The next day， serum levels of immunoglobulin E （IgE）， interleukin-4 （IL-4）， and interleukin-13 （IL-13） were measured. HE staining was used to observe the pathological morphology of the nasal mucosal tissue. Quantitative reverse transcription PCR （RT-qPCR） and Western Blot were performed to assess mRNA and protein expression of thymic stromal lymphopoietin （TSLP） and OX40 ligand （OX40L） in the nasal mucosa. ResultsCompared to the control group， total nasal symptom score in the model group significantly increased （P＜0.01）. HE staining revealed disrupted and adhered cilia， thickened basement membranes， and extensive inflammatory cell infiltration in the nasal mucosa. Serum levels of total IgE， IL-4， and IL-13， as well as TSLP and OX40L mRNA and protein expression in the nasal mucosa， were significantly elevated in the model group （P＜0.05 or P＜0.01）. Compared to the model group， the total nasal symptom scores in all drug intervention groups were significantly reduced； the serum total IgE levels in the loratadine group， the low- and medium-dose XD groups， and the low- and high-dose MDCP groups were significantly reduced； and the serum levels of IL-4 and IL-13 in the high-dose XD group and the high-dose MDCP group decreased （P＜0.05 or P＜0.01）. Nasal mucosal structure was improved. Except for the low-dose MDCP group， all other intervention groups showed a significant reduction in TSLP and OX40L mRNA expression in the nasal mucosa （P＜0.01）. All doses of XD and the medium- and high-dose MDCP groups significantly decreased the protein levels of TSLP and OX40L （P＜0.05）. The medium-dose XD group exhibited more improvement of nasal symptom scores and greater suppression of expression of TSLP and OX40L mRNA， and TSLP protein levels compared to the loratadine group （P＜0.05）. ConclusionXD may protect nasal mucosa of rats and alleviate allergic rhinitis by suppressing the TSLP/OX40L pathway， thereby attenuating Th2-mediated immune responses.

ObjectiveTo explore the potential mechanism of Xiaoqinglong Decoction （小青龙汤， XD） in the treatment of allergic rhinitis. MethodsForty-five rats were randomly assigned to a control group， a model group， a loratadine group， low-， medium- and high-dose XD groups， and low-， medium- and high-dose Mahuang Decoction and Cang'erzi Powder （麻黄汤合苍耳子散， MDCP） groups. Except for the control group， rats were administered with ovalbumin （OVA） and aluminum hydroxide via intraperitoneal injection for 14 days to establish an allergic rhinitis model. After the 14th-day injection， nasal stimulation was continued with 20 μl of 10% OVA solution to maintain the model. Rats in the control group and the model group received 10 ml/（kg·d） of saline， whereas those in the loratadine group were administered with 0.9 mg/（kg·d） of loratadine. The low-， medium- and high-dose XD groups were administered XD at the dose of 2.7， 5.4， and 10.8 g/（kg·d）， respectively. The low-， medium- and high-dose MDCP groups were administered MDCP at the dose of 2.43， 4.86， and 9.72 g/（kg·d）， respectively. All treatments were administered by gavage once daily for 7 consecutive days. One hour after the final gavage， nasal symptom scores were recorded for all group of rats. The next day， serum levels of immunoglobulin E （IgE）， interleukin-4 （IL-4）， and interleukin-13 （IL-13） were measured. HE staining was used to observe the pathological morphology of the nasal mucosal tissue. Quantitative reverse transcription PCR （RT-qPCR） and Western Blot were performed to assess mRNA and protein expression of thymic stromal lymphopoietin （TSLP） and OX40 ligand （OX40L） in the nasal mucosa. ResultsCompared to the control group， total nasal symptom score in the model group significantly increased （P＜0.01）. HE staining revealed disrupted and adhered cilia， thickened basement membranes， and extensive inflammatory cell infiltration in the nasal mucosa. Serum levels of total IgE， IL-4， and IL-13， as well as TSLP and OX40L mRNA and protein expression in the nasal mucosa， were significantly elevated in the model group （P＜0.05 or P＜0.01）. Compared to the model group， the total nasal symptom scores in all drug intervention groups were significantly reduced； the serum total IgE levels in the loratadine group， the low- and medium-dose XD groups， and the low- and high-dose MDCP groups were significantly reduced； and the serum levels of IL-4 and IL-13 in the high-dose XD group and the high-dose MDCP group decreased （P＜0.05 or P＜0.01）. Nasal mucosal structure was improved. Except for the low-dose MDCP group， all other intervention groups showed a significant reduction in TSLP and OX40L mRNA expression in the nasal mucosa （P＜0.01）. All doses of XD and the medium- and high-dose MDCP groups significantly decreased the protein levels of TSLP and OX40L （P＜0.05）. The medium-dose XD group exhibited more improvement of nasal symptom scores and greater suppression of expression of TSLP and OX40L mRNA， and TSLP protein levels compared to the loratadine group （P＜0.05）. ConclusionXD may protect nasal mucosa of rats and alleviate allergic rhinitis by suppressing the TSLP/OX40L pathway， thereby attenuating Th2-mediated immune responses.

[摘 要] 目的：探讨乙醛脱氢酶1A1（ALDH1A1）mRNA负载树突状细胞（DC）疫苗体外诱导抗鼻咽癌干细胞免疫反应的能力。方法：体外转录ALDH1A1 mRNA并电转染至人外周血DC，构建ALDH1A1-DC疫苗，转染EGFP mRNA为对照。流式细胞术检测DC表型、淋巴细胞亚群、细胞毒性T 淋巴细胞（CTL）增殖和细胞因子分泌。分选ALDH+和ALDH- C666-1细胞，检测干细胞标志物（CD24、CD133）和干性基因（OCT4、SOX2、Nanog）的表达水平，采用CCK-8法评估ALDH1A1-DC疫苗诱导的特异性免疫杀伤能力。结果：EGFP-DC荧光表达率显著高于未转染DC（P < 0.000 1），ALDH1A1-DC抗原提呈分子HLA-ABC、共刺激分子CD86、CD40和CCR7表达与未转染DC相比显著增强（P = 0.001 3、P = 0.005 9、P = 0.000 4及P = 0.001 9）。与单独淋巴细胞组（T）及空载DC诱导的淋巴细胞组（DC-T）相比，ALDH1A1-DC诱导的CTL比例最高（均P < 0.000 1），分裂指数最高（P = 0.000 2、P = 0.000 3），且CD8+CD69+（P = 0.000 5、P < 0.000 1）和CD8+ IFN-γ+（P = 0.012 6、P = 0.001 9）细胞亚群比例均显著提高。ALDH1A1-DC-T细胞对ALDH+C666-1悬浮细胞球的杀伤效果显著优于ALDH-细胞球（P = 0.001 0），且与其他各组淋巴细胞相比表现出较强的抗ALDH+C666-1悬浮细胞球的免疫效应（P = 0.001 0，P < 0.000 1）。然而，HLA-ABC阻断后其对ALDH+C666-1细胞的特异性杀伤效应显著降低（P < 0.000 1）。结论：mRNA转染DC后可翻译蛋白并促进DC成熟，增强其诱导特异性CTL免疫反应的能力。

Objective: To analyze the mediating effect of social support between family resilience and quality of life among elderly patients with Alzheimer's disease (AD), so as to provide the basis for improving the quality of life among elderly patients with AD. Methods: Elderly patients with AD who aged >60 years admitted to Wenzhou Seventh People's Hospital from August 2017 to June 2021 were selected. Data on demographic information, the severity of AD, and the profile of the primary caregivers were collected through questionnaire surveys. Social support, family resilience, and quality of life were assessed using the Social Support Rating Scale, the Shortened Chinese Version of the Family Resilience Assessment Scale, and the Chinese Version of the Quality of Life in Alzheimer's Disease Scale, respectively. The Process macro program was used to analyze the mediating effect of social support between family resilience and quality of life. Results: A total of 137 elderly patients with AD were surveyed. The mean age of the participants was (69.26±10.93) years. Among them, there were 63 males (45.99%) and 74 females (54.01%). The mean scores for social support, family resilience, and quality of life were (27.93±4.28), (97.34±10.06), and (27.82±7.27) points, respectively. The results of the mediating effect analysis indicated that family resilience could directly and positively affect the quality of life, with an effect value of 0.319 (95%CI: 0.122-0.491). It could also indirectly and positively affect the quality of life through social support, with an effect value of 0.118 (95%CI: 0.030-0.248). The mediating effect accounted for 26.42% of the total effect. Conclusion Social support plays a positive mediating role between family resilience and quality of life among elderly patients with AD.

Objective:To explore the expression of nuclear factor-κB (NF-κB) and β-catenin in skin lesions of condyloma acuminatum, and analyze their relationship with clinical prognosis.Methods:A prospective study was conducted to select 96 patients with condyloma acuminatum admitted to the First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine from December 2020 to June 2023 as the case group. Another 96 normal tissue samples from patients who underwent external genital plastic surgery or circumcision at the same time in the hospital were taken as the control group. All patients in the case group received 5-aminolevulinic acid photodynamic therapy (ALA-PDT) treatment, and the outcome was achieved at 6 months after follow-up. The case group was divided into recurrent subgroups and non- recurrent subgroups based on whether there was a recurrence. The expression of NF-κB and β-catenin in patients with different prognoses between the case group and the control group were compared. The Phi coefficient was used to analyze the correlation between NF-κB, β-catenin, and condyloma acuminatum. COX regression analysis were used to test the relationship between NF-κB, β-catenin and recurrence, and then receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of NF-κB, β-catenin for recurrence in patients with condyloma acuminatum.Results:The positive rates of NF-κB and β-catenin in the lesion tissues of the case group were higher than those in the control group: 55.21%(53/96) vs. 23.96%(23/96), 56.25%(54/96) vs. 36.46%(35/96), and there were statistical differences ( P<0.05). According to the Phi coefficient test, there was a positive correlation between NF-κB and β-catenin positivity and condyloma acuminatum ( r>0, P<0.05). After 6 months of follow-up, 35 of the 96 patients relapsed, with a recurrence rate of 36.46% (35/96). The positive rates of NF-κB and β-catenin in the recurrent subgroup were significantly higher than those in the non-recurrent subgroup: 85.71%(30/35) vs. 37.70%(23/61), 85.71%(30/35) vs. 39.34%(24/61), and there were statistical differences ( P<0.05). COX regression analysis showed that the positive expression of NF-κB and β-catenin was related to the recurrence of patients with condyloma acuminatum after treatment ( HR = 4.017, 3.898, 95% CI 1.516 - 10.646, 1.470 - 10.336, P<0.05). The ROC curve showed that NF-κB, β-catenin, and their combination had moderate predictive value for recurrence in patients with condyloma acuminatum after treatment. The area under the curve (AUC) was 0.740 and 0.732, respectively. Among them, the combined predictive value was the highest, with an AUC of 0.810 ( P<0.05). Conclusions:The positive rates of NF-κB and β-catenin in the skin lesions of patients with condyloma acuminatum are relatively high, and they have certain predictive value for the recurrence of patients after treatment.

Objective:To analyze the effect of joint management of type 2 diabetes mellitus (T2DM) between specialty and community under the model of National Diabetes Prevention and Control Center (DPCC).Methods:A total of 2 527 T2DM patients managed by DPCC Pingshan Center of Shenzhen from January 1, 2022 to December 31, 2024 were retrospectively included. After management, the rate of downturn, reexamination rate, blood pressure compliance rate, metabolic indicators (waist circumference, body mass index, fasting blood glucose, glycosylated hemoglobin, blood lipids) and screening rate of chronic complications of diabetes (atherosclerotic cardiovascular disease, microvascular disease, diabetic peripheral neuropathy) were analyzed. Those included 2022 ( n=564), 2023 ( n=1 477), and 2024 ( n=2 527). Results:The downturn rate in 2022, 2023 and 2024 increased year by year (22.8% vs 67.2% vs 89.9%, P<0.01), and the review rate (41.1% vs 62.2% vs 52.7%, P<0.01), complication screening rate (51.6% vs 85.3% vs 62.2%, P<0.01), blood pressure compliance rate (53.1% vs 78.0% vs 67.2%, P<0.01), body mass index compliance rate (13.2% vs 17.3% vs 28.6%, P<0.01), fasting blood glucose meeting rate (46.4% vs 60.2% vs 68.5%, P<0.01), glycated hemoglobin meeting rate (58.4% vs 63.2% vs 45.6%, P<0.01) were relatively improved. Waist circumference compliance rate (30.6% vs 27.7% vs 21.6%) and blood lipid compliance rate (33.6% vs 35.5% vs 31.9%) were not significantly improved, and the review rate, blood pressure compliance rate and complication screening rate in 2024 were lower than those in 2023 and higher than those in 2022. Conclusions:The combined management of type 2 diabetes under the DPCC model has significant effects on improving the down-conversion rate, rediagnosis rate, blood pressure compliance rate, metabolic index compliance rate and the screening rate of diabetes-related chronic complications in patients with diabetes. At the same time, it was also found that with the progress of hierarchical diagnosis and treatment, the review rate, complication screening rate, blood pressure, waist circumference, blood lipid and glycosylated hemoglobin reached the standard of patients decreased compared with the previous situation, which needs to be further analyzed and improved.

Bispecific antibodies(BsAbs),as an important recent innovation in the field of tumor immunotherapy in recent years,can simultaneously or sequentially target different antigens or two different epitopes of the same antigen.Compared with traditional monoclonal antibodies,they can produce superior therapeutic effects.This article reviews the progress in clinical applications and safety research of BsAbs in cancer therapy,revealing that they(such as blinatumomab,glofitamab,teclistamab,amivantamab,etc.)exhibit significant therapeutic efficacy against hematological malignancies,lung cancer,cervical cancer,melanoma,and other cancers.For cytokine release syndrome(CRS)induced by BsAbs,prophylactic or pre-emptive medication is commonly administered in clinical practice;for neurotoxicity and infections triggered by BsAbs,clinical practice necessitates rigorous monitoring of patients'vital signs and the provision of essential treatments.In addition,different BsAbs exhibit variations in escalation dose,infusion rate,storage duration,and equipment requirements.Therefore,strict adherence to the instructions in the drug package inserts is essential during clinical operations to ensure safety and therapeutic efficacy.In the future,more multicenter trials need to be conducted to validate the efficacy and safety of BsAbs across different tumor types and patient populations,and long-term follow-up data should be accumulated to optimize treatment cycles and dosage regimens.

This study analyzed soil-transmitted nematode infection surveillance data for children 3-9 years of age in Shaanxi Province from 2016 to 2023,to provide a scientific basis for control strategies for soil-transmitted nematode infections in children in the province.Since 2016,according to the requirements of the National Schistosomiasis and Soil-transmitted Nematode Surveillance Program(Trial),several counties and districts in Shaanxi Province were selected as surveillance sites every year.According to geo-graphical position,the surveillance sites were divided into five areas:east,west,south,north and middle,and one administrative vil-lage(community)was selected in each area for monitoring.The eggs of soil-transmitted nematodes(hookworm,Ascaris lumbricoides,Trichuris trichiura,and Enterobius vermicularis)were detected with the Kato-Katz technique in children 3-9 years of age at each sur-veillance site,and the eggs of Enterobius vermicularis were detected again with the cellophane tape anal swab method.The infection rate and intensity for E.vermicularis were calculated.Detection was performed in 12 462 children 3-9 years old at 75 surveillance sites in Shaanxi Province from 2016 to 2023;84 cases of soil-borne nematode infections were detected,and the overall infection rate was 0.67%.The infection rates for Ascaris lumbricoides and E.vermicularis were 0.18%(22/12 462)and 0.50%(62/12 462),respec-tively,and the infection rates for Trichuris trichiura and hookworm were not found.The infection rates of soil-transmitted nematodes in children were 1.28%(16/1 250),0.16%(2/1 252),1.25%(17/1 365),1.20%(18/1 494),0.17%(2/1 169),1.45%(20/1 382),0.00,and 0.36%(9/251),respectively.A linear trend was observed among years(χ2=11.973,P<0.001).The infection rates in the Weifen Basin ecological region,Loess Plateau ecological region,and Qinba Mountains ecological region were 0.51%,1.19%,and 0.72%,respectively,and the differences were statistically significant(χ2=9.726,P=0.008).Significant differences in infection rates were observed among scattered children(1.63%),preschool children(0.66%),and students(0.57%)(χ2=11.189,P=0.004).No significant differences in infection rates were observed by gender,age,and education level.Compared with the infection rates in the entire country and other provinces,the infection rate of soil-transmitted nematodes among children in Shaanxi Province was low,and the main infection species were Ascaris lumbricoides and E.vermicularis.The infection rates greatly varied within Shaanxi Prov-ince,possibly because of differences in economic development levels,children′s living habits,and personal hygiene status across re-gions.In the future,comprehensive control measures should be taken to strengthen the monitoring and control of key areas,popula-tions,and parasite species.

Objective To collect oral exhaled odor spectrum of patients of chronic atrophic gastritis(CAG)with yin deficiency syndrome and detect their gut microbiota;To elucidate the mechanism of odor changes from the perspective of gut microbiota changes;To provide a basic research for the objectification of TCM olfactory diagnosis in CAG.Methods Totally 110 patients with CAG,including 55 patients with CAG yin deficiency syndrome,55 patients with CAG non-yin deficiency syndrome,and 30 healthy individuals were collected.The electronic nose technology was used to collect the oral exhaled odor spectrum of all subjects,and an improved Transformer model was used to identify the breath odor spectrum of CAG yin deficiency syndrome patients and healthy individuals,CAG non-yin deficiency syndrome patients and healthy individuals,CAG yin deficiency syndrome patients and CAG non-yin deficiency syndrome patients.At the same time,16S rRNA high-throughput sequencing method was used to detect the gut microbiota of the subjects'fecal samples,and the correlation analysis between the odor spectrum characteristics of CAG yin deficiency syndrome and gut microbiota was conducted.Results ① Analysis and recognition of odor spectrum characteristic.Amplitude characteristics:The response curves A,C,D,G,H,I and J of the odor spectrum in the CAG yin deficiency syndrome group and the CAG non-yin deficiency syndrome group were all lower in amplitude than those in the healthy group(P<0.01,P<0.05).Slope characteristics:The slopes of response curves A,B,C,D,E,G,H,I and J in the odor spectrum of the CAG yin deficiency syndrome group and the CAG non-yin deficiency syndrome group were lower than those of the healthy group(P<0.01,P<0.05).Pattern recognition:The accuracy of pattern recognition between the CAG yin deficiency syndrome group and the healthy group reached 0.904,with an area under ROC curve(AUC)of 0.91;the accuracy of pattern recognition between the CAG non-yin deficiency syndrome group and the healthy group reached 0.885,AUC=0.89;the accuracy of pattern recognition between the CAG yin deficiency syndrome group and the CAG non-yin deficiency syndrome group reached 0.747,AUC=0.75.② Species composition:At the genus level,compared with the healthy group,the abundance of Actinomyces,Escherichia-Shigella and Tyzzerella in the CAG yin deficiency syndrome group increased(P<0.05),while the abundance of Prevotella,Sutterella and Subdoligranulum decreased(P<0.05);the abundance of[Ruminococcus]_gnavus_group and Escherichia-Shigella in the CAG non-yin deficiency syndrome group increased significantly(P<0.01),while the abundance of Prevotella and Subdoligranulum decreased(P<0.05).Compared with the CAG yin deficiency syndrome group,the non-yin deficiency syndrome group showed significant enrichment of the Dialister(P<0.05).③ Correlation analysis between odor spectrum characteristics and gut microbiota in CAG yin deficiency syndrome:This study identified 17 bacterial genera that showed positive and negative correlations with the amplitude and slope characteristics of the odor spectrum in CAG yin deficiency syndrome,namely Lachnospiraceae_NK4A136_group,Lachnospiraceae_ND3007_group,Faecalibacterium,UCG-002,UCG-005,Coprococcus,CAG-352,Parabacteroides,Actinomyces,Streptococcus,Anaerostipes,Blautia,Dorea,[Eubacterium]_hallii_group,Phascolarctobacterium,Clostridium_sensu_stricto_1,Enterobacter.The above-mentioned bacterial genera could be classified into the following bacterial families:Trichomonas,Clostridia,Porphyromonas,Actinobacteria,Ruminococcus,Streptococcus,Bacteroidetes,Clostridium,Veillonellaceae and Enterobacteriaceae.Conclusion The use of electronic nose technology can accurately identify the oral exhaled odor of patients with CAG yin deficiency syndrome,CAG non-yin deficiency syndrome,and healthy individuals;the odor spectrum characteristics of patients with CAG yin deficiency syndrome are correlated with multiple bacterial genera,and the changes in related metabolites and gases produced by the disruption of their gut microbiota may be one of the biological bases for the changes in oral exhaled odor in CAG yin deficiency syndrome.