Background The pathogenesis of silicosis has not been fully elucidated, and microRNAs (miRNA) may be involved in the occurrence and development of silicosis. Objective To investigate the effect of miR-204-3p inhibitor on the epithelial-mesenchymal transition (EMT) process and silicosis fibrosis in silicon dioxide dust-induced alveolar epithelial cells. Methods A co-culture model of macrophages and epithelial cells was established using a Transwell chamber. NR8383 macrophages were seeded into the upper chamber of the Transwell, and RLE-6TN cells were seeded into the lower chamber. After 24 h of culture, the medium in the lower chamber was discarded, washed three times with phosphate-buffered saline (PBS), and replaced with serum-free medium. The cells were divided into four groups: control group, silicosis group, miRNA NC group, and miR-204-3p inhibitor group. The lower chamber was transfected with miRNA NC for the miRNA NC group or the miR-204-3p inhibitor for the miR-204-3p inhibitor group. The lower chambers of the remaining two groups were added by equal amounts of serum-free medium. After 24 h, except for the control group that received an equal volume of serum-free medium, the upper chambers of the remaining three groups were treated with 800 μg·mL⁻¹ silicon dioxide dust. Morphological changes in each group were observed under a microscope. The mRNA and protein expression levels of EMT-related factors, including α-smooth muscle actin (α-SMA), Vimentin, N-Cadherin, and E-Cadherin, were detected by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot. The mRNA and protein expression levels of fibrosis-related factors, including Collagen I, Collagen III, and Fibronectin, were also assessed by RT-qPCR and Western blot. The fluorescence expression intensities of α-SMA, N-Cadherin, and E-Cadherin were evaluated by immunofluorescence. Results The morphological observation revealed that RLE-6TN cells in the control group exhibited a regular oval shape. After treatment with silicon dioxide, the cells predominantly displayed a long spindle shape. Following the intervention with the miR-204-3p inhibitor, the number of long spindle-shaped cells increased, and the intercellular gaps widened. The RT-qPCR results showed that, compared with the control group, the silicosis group exhibited significantly higher relative mRNA expression levels of EMT-related markers (α-SMA, Vimentin, and N-Cadherin) (P<0.05), while the relative mRNA expression level of E-Cadherin was significantly reduced (P<0.05); the relative mRNA expression levels of fibrosis-related markers (Collagen I, Collagen III, and Fibronectin) were also significantly elevated (P<0.05). Compared with the miRNA NC group, the miR-204-3p inhibitor group showed significantly increased relative mRNA expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), decreased E-Cadherin mPNA expression (P<0.05), and elevated mPNA expression of Collagen I, Collagen III, and Fibronectin (P<0.05). The Western blot analysis indicated that, compared with the control group, the silicosis group had significantly higher protein expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), lower E-Cadherin protein expression (P<0.05), and increased protein expression of Collagen I, Collagen III, and Fibronectin (P<0.05). Compared with the miRNA NC group, the miR-204-3p inhibitor group exhibited significantly elevated protein expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), reduced E-Cadherin expression (P<0.05), and increased protein expression of Collagen I, Collagen III, and Fibronectin (P<0.05). The immunofluorescence analysis demonstrated that, compared with the control group, the silicosis group showed enhanced fluorescence intensities of α-SMA and N-Cadherin and reduced fluorescence intensity of E-Cadherin. Compared with the miRNA NC group, the miR-204-3p inhibitor group exhibited increased fluorescence intensities of α-SMA and N-Cadherin and decreased fluorescence intensity of E-Cadherin. Conclusion The miR-204-3p inhibitor may exacerbate the EMT process and silicosis fibrosis in silicon dioxide-induced RLE-6TN cells. miR-204-3p plays a negative regulatory role in silicosis fibrosis.

OBJECTIVE: To observe the clinical efficacy of 3D printing spinal external fixator combined with McKenzie therapy for patients with lumbar dics herniation (LDH). METHODS: Sixty patients with LDH between January 2022 and January 2023 were enrolled. Among them, 30 patients were given McKinsey training. According to different treatment methods, all patients were divided into McKenzie group and McKenzie + 3D printing group, 30 patients in each group. The McKenzie group provided McKenzie therapy. The McKenzie + 3D printing group were treated with 3D printing spinal external fixation brace on the basis of McKenzie therapy. Patients in both groups were between 25 and 60 years of age and had their first illness. In the McKenzie group, there were 19 males and 11 females, with an average age of (48.57±5.86) years old, and the disease duration was (7.03 ±2.39) months. The McKenzie + 3D printing group, there were 21 males and 9 females, with an average age of (48.80±5.92) years old, and the disease duration was(7.30±2.56) months. Pain was evaluated using the visual analogue scale (VAS), and lumbar spine function was assessed using the Oswestry disability index (ODI) and the Japanese Orthopaedic Association (JOA) score. VAS, ODI and JOA scores were compared between two groups before treatment and at 1, 3, 6, 9 and 12 months after treatment. RESULTS: All patients were followed up for 12 months. The VAS for the McKenzie combined with 3D printing group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were(6.533±0.860), (5.133±1.008), (3.933±0.868), (2.900±0.759), (2.067±0.640), (1.433±0.504), respectively. In the McKenzie group, the corresponding scores were (6.467±0.860), (5.067±1.048), (4.600±0.968), (3.533±1.008), (2.567±0.728), (1.967±0.809), respectively. The ODI of the McKenzie group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were (41.033±6.810)%, (37.933±6.209)%, (35.467±6.962)%, (27.567±10.081)%, (20.800±7.531)%, (13.533±5.158)%, respectively. For the McKenzie combined with 3D printing group, the corresponding ODI were(38.033±5.605)%, (33.000±6.192)%, (28.767±7.045)%, (22.200±5.517)%, (17.700±4.836)%, (11.900±2.771)%, respectively. The JOA scores of the McKenzie combined with 3D printing group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were(8.900±2.074), (13.133±2.330), (15.700±3.583), (20.400±3.480), (22.267±3.084), (24.833±2.640), respectively. In the McKenzie group, the corresponding scores were(9.200±2.091), (12.267±2.406), (15.333±3.198), (18.467±2.240), (20.133±2.751), (22.467±2.849), respectively. Before the initiation of treatment, no statistically significant differences were observed in the VAS, ODI, and JOA scores between two groups (P>0.05). At 3, 6, 9, and 12 months post-treatment, the VAS in the McKenzie combined with 3D printing group was significantly lower than that in the McKenzie group, and the difference was statistically significant (P<0.05). The comparison of ODI between two groups at 1, 3, 6, 9, and 12 months post-treatment revealed statistically significant differences (P<0.05). At 6, 9, and 12 months post-treatment, the JOA score in the McKenzie combined with 3D printing group was significantly higher than that in the McKenzie-only group, and the difference was statistically significant (P<0.05). CONCLUSION The combination of 3D printed functional spinal external fixation brace with McKenzie therapy can significantly improve and maintain lumbar function in patients with LDH.
Humans ; Male ; Female ; Middle Aged ; Printing, Three-Dimensional ; Intervertebral Disc Displacement/surgery* ; External Fixators ; Lumbar Vertebrae/surgery* ; Adult ; Braces ; Treatment Outcome

Insulin-like growth factor 2 (IGF2) is a critical endocrine mediator implicated in male reproductive physiology. To investigate the correlation between IGF2 protein levels and various aspects of male infertility, specifically focusing on sperm quality, inflammation, and DNA damage, a cohort of 320 male participants was recruited from the Women's Hospital, Zhejiang University School of Medicine (Hangzhou, China) between 1 st January 2024 and 1 st March 2024. The relationship between IGF2 protein concentrations and sperm parameters was assessed, and Spearman correlation and linear regression analysis were employed to evaluate the independent associations between IGF2 protein levels and risk factors for infertility. Enzyme-linked immunosorbent assay (ELISA) was used to measure IGF2 protein levels in seminal plasma, alongside markers of inflammation (tumor necrosis factor-alpha [TNF-α] and interleukin-1β [IL-1β]). The relationship between seminal plasma IGF2 protein levels and DNA damage marker phosphorylated histone H2AX (γ-H2AX) was also explored. Our findings reveal that IGF2 protein expression decreased notably in patients with asthenospermia and teratospermia. Correlation analysis revealed nuanced associations between IGF2 protein levels and specific sperm parameters, and low IGF2 protein concentrations correlated with increased inflammation and DNA damage in sperm. The observed correlations between IGF2 protein levels and specific sperm parameters, along with its connection to inflammation and DNA damage, underscore the importance of IGF2 in the broader context of male reproductive health. These findings lay the groundwork for future research and potential therapeutic interventions targeting IGF2-related pathways to enhance male fertility.
Humans ; Male ; Insulin-Like Growth Factor II/metabolism* ; Infertility, Male/genetics* ; DNA Damage ; Adult ; Inflammation/metabolism* ; Spermatozoa/metabolism* ; Semen Analysis ; Semen/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Histones/metabolism* ; Interleukin-1beta/metabolism*

OBJECTIVE: To explore and evaluate the efficacy and safety of a modified thiotepa-based conditioning regimen combined with autologous hematopoietic stem cell transplantation (ASCT) for the treatment of primary central nervous system lymphoma (PCNSL). METHODS: In a retrospective, single center, single arm study, we collected data of 28 patients with PCNSL who underwent high-dose chemotherapy followed by autologous stem cell transplantation (HDC-ASCT) at our center from March 2021 to December 2024. The clinical characteristics of the patients, the conditioning regimen details, treatment-related toxicities and adverse reactions, post-transplant disease remission status, and survival outcomes were analyzed. RESULTS: A total of 28 patients were included. Among them, 19 patients received ASCT as first-line consolidation therapy in complete response (CR) or partial response (PR) status, and 9 patients with relapsed/refractory disease underwent salvage ASCT. The median time to neutrophil engraftment was 9 days (range: 5-11 days), and the median time to platelet engraftment was 10 days (range: 6-13 days). All patients achieved CR at the initial efficacy evaluation post-ASCT. The main complications during the transplantation period were febrile neutropenia (26 cases) and grade 3 diarrhea (9 cases). No transplantation-related mortality occurred. Post-ASCT, 19 patients received maintenance therapy, which was demonstrated to be safe and effective. Three patients relapse, and one patient died. The median progression-free survival (PFS) and overall survival (OS) of patients were not reached. The estimated 1-year and 2-year cumulative PFS rates were 88.4% and 66.3%, respectively, while the 1-year and 2-year OS rates were both 94.1%. CONCLUSION The modified thiotepa-based conditioning regimen combined with ASCT is safe and effective for the treatment of PCNSL.
Humans ; Thiotepa/therapeutic use* ; Retrospective Studies ; Transplantation, Autologous ; Transplantation Conditioning/methods* ; Central Nervous System Neoplasms/therapy* ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Middle Aged ; Adult ; Lymphoma/therapy* ; Treatment Outcome ; Aged

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

In this article,the mechanism of Shanxian Granule in inhibiting liver cancer,lung cancer,sarcoma,melanoma and other tumors was reviewed,with a view to providing a theoretical basis for the clinical research of Shanxian Granules in the treatment of malignant tumors.Shanxian Granule are the pure Chinese medicine preparation for counteracting malignant tumor developed by the Oncology Research Team of Shaanxi University of Chinese Medicine on the basis of the theory of traditional Chinese medicine syndrome differentiation and treatment combined with decades of clinical experience as well as the achievements of modern pharmacological research.Shanxian Granule are mainly composed of Crataegi Fructus,Agrimoniae Herba,Panacis Quinquefolii Radix,Curcumae Rhizoma,Testudinis Carapax et Plastrum,Trionycis Carapax,Corydalis Rhizoma,and Polyporus,and have the actions of benefiting qi and nourishing yin,supporting healthy-qi and cultivating the essence,activating blood and removing stasis,and eliminating swelling and counteracting cancer.The compatibility of Shanxian Granule embodies the principle of supporting healthy-qi but avoiding maintaining pathogens,and eliminating pathogens but avoiding injuring healthy-qi.The granules can effectively inhibit the growth and metastasis of liver cancer,lung cancer,sarcoma,melanoma and other tumors both in vivo and in vitro,alleviate the clinical symptoms of tumor patients,and improve their prognosis.The anti-tumor mechanism of Shanxian Granules is related to the enhancement of body immune function,inhibition of tumor cell proliferation,enhancement of tumor cell apoptosis,inhibition of tumor cell invasion and metastasis as well as the tumor angiogenesis.

Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

The aim of this study was to investigate the prevalence of spotted fever group rickettsia(SFGR)in wild rodents collected from Fengshan County in the Guangxi Zhuang Autonomous Region,and to determine their species.Wild rodents were captured in cages in Fengshan County,Hechi City,Guangxi Zhuang Autonomous Region.The rodents were identified according to morphological characteristics,and the findings were confirmed through molecular biology methods.Subsequently,spleen samples were collected,and DNA was extracted.The outer membrane protein A(ompA)gene was amplified with semi-nested PCR to determine the species of SFGR in captured wild rodents.After sequencing of the PCR products,homology and phylogenetic analyses of ompA gene sequences were performed.A total of 105 wild rodents belonging to seven species were captured.FGR was detected in six rodent species(Bandicota indica,Leopoldamys edwardsi,Mus caroli,Mus Pahari,Rat-tus andamanensis,and Rattus losea,but not Berylmys bower si),and the total positivity rate was 23.8％.Three Rickettsia species,Candidatus Rickettsia jingxinensis,Rickettsia raoultii,and Rickettsia sibirica,were identified from analysis of the ompA gene sequence.This study revealed the presence of three species of SFGR infecting wild rodents from Fengshan County,Guangxi Zhuang Autonomous Region,thus suggesting that Fengshan County is a natural focus of tick-borne spotted fever.This study highlights the need to strengthen monitoring and prevention measures for rickettsiosis.