Objective:To enhance the understanding of clinical doctors on the concurrence of Sj?gren′s syndrome (SS) and myasthenia gravis (MG), provide reference forclinical diagnosis and treatment.Methods:The medical record of SS、MG patient Taian Central hospital in october 2021 was reviewed and a retrospective analysis was conducted. Based on the key words, the main databases domestic and abroad from Jan 1973 to April 2024. The cases reported in the literature were searched out and merged with our case and analyzed by SPSS 27.0. The measurement data of normal distribution were expressed by mean standard deviation ± s, and the measurement data of abnormal distribution were expressed by M( Q1, Q3). Counting data were expressed as examples and percentages (%) . Results:Twenty-one patients with SS complicated with MG were reviewed. Among them, 19(90.5%) patients were female. The average age was (47.6 ± 3.1) years, and the median time from onset to diagnosis was 24 (11, 78) months. There were 11 patients (52.4%) with myasthenia gravis as the initial presentation. The main clinical manifestations of patients with myasthenia muscle fatigue (80.9%, 17/21), gravis include fatigue ptosis (71.4%, 15/21), diplopia, blurred vision (57.1%, 12/21), dysphagia (33.3%, 7/21), joint pain (33.3%, 7/21), odysarthria, and unclear speech (23.8%, 5/21), hair loss (14.3%, 3/21), and swelling of the excocrine glands(9.5%, 2/21). Eighteen patients (85.7%, 18/21) showed positive anti acetylcholine receptor antibodies. Sixteen patients (76.2%) were positive for ANA, and 14 patients (66.8%) were positive for anti SSA or (and) anti SSB antibodies. Four patients (19.0%) also had other autoimmune diseases (Hashimoto′s thyroiditis, rheumatoid arthritis, optic neuritis). In terms of treatment, cholinesterase inhibitors were the most common treatment measure, applied to 18 patients (85.7%), followed by glucocorticoid therapy, and applied to 14 patients (66.8%). In addition, 7 patients (33.3%) received immunosuppressive agents therapy, 5 patients (23.8%) underwent thymectomy, 2 patients (9.5%) received intravenous human immunoglobulin injection, and 1 patient (4.8%) underwent plasma exchange. All patients showed improvement after treatment.Conclusion:SS and MG are both autoimmune diseases, and their coexistence is rare. Clinicans should be aware of this rare association. Early diagnosis is crucial for the treatment and prognosis of patients,and requiresa comprehensive assessment of clinical symptoms, laboratory tests, and auto-antibody test results.

The monkeypox pandemic has caused two public health emergencies of international concern from 2022 to 2025,causing great impact on the global health system. Early diagnosis and treatment of the monkeypox virus depend on quick, sensitive, and accurate detection methods. The clustered regular interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system, characterized by its unique target gene sequence recognition, and cis-and trans-cleavage activity, has been regarded as the next-generation nucleic acid detection tool in the field of pathogen diagnosis. CRISPR/Cas has been used for detecting monkeypox virus in combination with different amplification and result readout approaches. Although it still faces many challenges, the CRISPR/Cas system is expected to achieve diversified development and provide strong technical support for rapid, accurate, and affordable detection approaches for infectious diseases.

Objective To prepare a variety of quality control(QC)materials for SARS-CoV-2 variants as an addition to the conven-tional SARS-CoV-2 nucleic acid QC products for the laboratory detection of mutant strains by optimizing the preparation and purification process of MS2 phage virus-like particle(VLP)technique,and evaluate their performances.Methods The typical mutation sequence fragments or full length S genes were designed and synthesized according to the genomic information of SARS-CoV-2 variants.Then,they were inserted into the downstream of maturase gene,coat protein and the pac-site of MS2 phage to construct a series of recombi-nant expression vectors.After induced by the prokaryotic expression system,the VLP products were purified through the polyethylenei-mine precipitation,ultrafiltration,nuclease digestion,and gel filtration chromatography.The obtained VLP were validated by the nucle-ic acid electrophoresis,protein electrophoresis,protein concentration determination,and fluorescence PCR,and their performances such as nucleic acid residue and stability were also evaluated.Results A total of 10 kinds of VLP containing the targeted sequences of the gene to be tested were prepared.The length of the foreign sequence wrapped in them ranged from 297 bp to 3 822 bp,which could be combined into a variety of QC materials for the mutation detection of different SARS-CoV-2 variants.The prepared VLP QC materials could not be effectively amplified without nucleic acid extraction or reverse transcription steps during the routine nucleic acid detection.The simulated QC samples remained stable after repeated freeze-thaw cycles.They could be stored stably for 2 months at 25 ℃ and 4 weeks at 37 ℃.Conclusion The established preparation and combined purification process of VLP QC materials can encapsulate vari-ous exogenous nucleic acid sequences with different lengths into the viral coat protein to form VLP,with high production efficiency.The VLP QC products prepared by the above process have stable performance and almost no residual exogenous nucleic acid,which can ef-fectively meet clinical requirements and ensure the quality of laboratory testing.

Interleukin- (IL) 23 drives pathogenic differentiation of Th17 cells via the JAK2-STAT3 signaling pathway, upregulates IL-17A/IL-22 expression, and disrupts intestinal barrier integrity, thereby playing a pivotal role in the pathogenesis of Crohn's disease (CD). IL-23p19 inhibitors—exemplified by risankizumab, mirikizumab, and guselkumab—precisely block this pathway. Key phase 3 trials have demonstrated their efficacy in CD, showing significant clinical benefits in patients refractory to conventional therapies or biologics, with no new safety signals identified. The ultimate treatment goal for CD is deep healing (mucosal-transmural-biochemical composite remission) as defined by STRIDE II. However, current evidence exhibits critical limitations: absence of head-to-head drug comparisons, insufficient data on biologic-experienced subpopulations, and heterogeneous follow-up durations leading to uncertainties in long-term safety. Future studies require standardized head-to-head trials with enhanced subgroup analyses to optimize precision therapeutics.

Objective To prepare a variety of quality control(QC)materials for SARS-CoV-2 variants as an addition to the conven-tional SARS-CoV-2 nucleic acid QC products for the laboratory detection of mutant strains by optimizing the preparation and purification process of MS2 phage virus-like particle(VLP)technique,and evaluate their performances.Methods The typical mutation sequence fragments or full length S genes were designed and synthesized according to the genomic information of SARS-CoV-2 variants.Then,they were inserted into the downstream of maturase gene,coat protein and the pac-site of MS2 phage to construct a series of recombi-nant expression vectors.After induced by the prokaryotic expression system,the VLP products were purified through the polyethylenei-mine precipitation,ultrafiltration,nuclease digestion,and gel filtration chromatography.The obtained VLP were validated by the nucle-ic acid electrophoresis,protein electrophoresis,protein concentration determination,and fluorescence PCR,and their performances such as nucleic acid residue and stability were also evaluated.Results A total of 10 kinds of VLP containing the targeted sequences of the gene to be tested were prepared.The length of the foreign sequence wrapped in them ranged from 297 bp to 3 822 bp,which could be combined into a variety of QC materials for the mutation detection of different SARS-CoV-2 variants.The prepared VLP QC materials could not be effectively amplified without nucleic acid extraction or reverse transcription steps during the routine nucleic acid detection.The simulated QC samples remained stable after repeated freeze-thaw cycles.They could be stored stably for 2 months at 25 ℃ and 4 weeks at 37 ℃.Conclusion The established preparation and combined purification process of VLP QC materials can encapsulate vari-ous exogenous nucleic acid sequences with different lengths into the viral coat protein to form VLP,with high production efficiency.The VLP QC products prepared by the above process have stable performance and almost no residual exogenous nucleic acid,which can ef-fectively meet clinical requirements and ensure the quality of laboratory testing.

Interleukin- (IL) 23 drives pathogenic differentiation of Th17 cells via the JAK2-STAT3 signaling pathway, upregulates IL-17A/IL-22 expression, and disrupts intestinal barrier integrity, thereby playing a pivotal role in the pathogenesis of Crohn's disease (CD). IL-23p19 inhibitors—exemplified by risankizumab, mirikizumab, and guselkumab—precisely block this pathway. Key phase 3 trials have demonstrated their efficacy in CD, showing significant clinical benefits in patients refractory to conventional therapies or biologics, with no new safety signals identified. The ultimate treatment goal for CD is deep healing (mucosal-transmural-biochemical composite remission) as defined by STRIDE II. However, current evidence exhibits critical limitations: absence of head-to-head drug comparisons, insufficient data on biologic-experienced subpopulations, and heterogeneous follow-up durations leading to uncertainties in long-term safety. Future studies require standardized head-to-head trials with enhanced subgroup analyses to optimize precision therapeutics.

The monkeypox pandemic has caused two public health emergencies of international concern from 2022 to 2025,causing great impact on the global health system. Early diagnosis and treatment of the monkeypox virus depend on quick, sensitive, and accurate detection methods. The clustered regular interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system, characterized by its unique target gene sequence recognition, and cis-and trans-cleavage activity, has been regarded as the next-generation nucleic acid detection tool in the field of pathogen diagnosis. CRISPR/Cas has been used for detecting monkeypox virus in combination with different amplification and result readout approaches. Although it still faces many challenges, the CRISPR/Cas system is expected to achieve diversified development and provide strong technical support for rapid, accurate, and affordable detection approaches for infectious diseases.

Objective:To enhance the understanding of clinical doctors on the concurrence of Sj?gren′s syndrome (SS) and myasthenia gravis (MG), provide reference forclinical diagnosis and treatment.Methods:The medical record of SS、MG patient Taian Central hospital in october 2021 was reviewed and a retrospective analysis was conducted. Based on the key words, the main databases domestic and abroad from Jan 1973 to April 2024. The cases reported in the literature were searched out and merged with our case and analyzed by SPSS 27.0. The measurement data of normal distribution were expressed by mean standard deviation ± s, and the measurement data of abnormal distribution were expressed by M( Q1, Q3). Counting data were expressed as examples and percentages (%) . Results:Twenty-one patients with SS complicated with MG were reviewed. Among them, 19(90.5%) patients were female. The average age was (47.6 ± 3.1) years, and the median time from onset to diagnosis was 24 (11, 78) months. There were 11 patients (52.4%) with myasthenia gravis as the initial presentation. The main clinical manifestations of patients with myasthenia muscle fatigue (80.9%, 17/21), gravis include fatigue ptosis (71.4%, 15/21), diplopia, blurred vision (57.1%, 12/21), dysphagia (33.3%, 7/21), joint pain (33.3%, 7/21), odysarthria, and unclear speech (23.8%, 5/21), hair loss (14.3%, 3/21), and swelling of the excocrine glands(9.5%, 2/21). Eighteen patients (85.7%, 18/21) showed positive anti acetylcholine receptor antibodies. Sixteen patients (76.2%) were positive for ANA, and 14 patients (66.8%) were positive for anti SSA or (and) anti SSB antibodies. Four patients (19.0%) also had other autoimmune diseases (Hashimoto′s thyroiditis, rheumatoid arthritis, optic neuritis). In terms of treatment, cholinesterase inhibitors were the most common treatment measure, applied to 18 patients (85.7%), followed by glucocorticoid therapy, and applied to 14 patients (66.8%). In addition, 7 patients (33.3%) received immunosuppressive agents therapy, 5 patients (23.8%) underwent thymectomy, 2 patients (9.5%) received intravenous human immunoglobulin injection, and 1 patient (4.8%) underwent plasma exchange. All patients showed improvement after treatment.Conclusion:SS and MG are both autoimmune diseases, and their coexistence is rare. Clinicans should be aware of this rare association. Early diagnosis is crucial for the treatment and prognosis of patients,and requiresa comprehensive assessment of clinical symptoms, laboratory tests, and auto-antibody test results.

OBJECTIVE To analyze the clinicopathological features of laryngeal squamous carcinoma tumors and their correlation with prognosis in order to improve the understanding and diagnosis of laryngeal squamous cell carcinoma.METHODS The clinical and pathological data(including gender,age,stage,differentiation,immunohistochemistry,etc.)of 179 patients with laryngeal squamous cell carcinoma[171 males,8 females,aged 30-84(61.53±8.02)years]who were treated in Department of Otolaryngology Head and Neck Surgery,The First and Second Clinical Medical Schools of Ningxia Medical University from January 2015 to December 2022 were retrospectively studied,and the effects of various factors on prognosis were analyzed.RESULTS Among the 179 patients with laryngeal squamous cell carcinoma,the male-to-female ratio was 21.4:1,and the incidence was high in the age group of 60-79 years old(58.7%),and the youngest age of onset was 30 years old.The main clinical manifestations were hoarseness 138 cases(77.1%),sore throat 16 cases(8.9%)and pharyngeal foreign body sensation 13 cases(7.3%).Glottic type was more common in the primary site 135 cases(75.4%),and 31 cases were accompanied by cervical lymph node metastasis(17.3%).The degree of differentiation was more common in the moderately differentiated type 80 cases(44.7%).The positive rates of immunohistochemistry markers p16,EGFR(epidermal growth factor receptor),PD-1/PD-L1 and VEGF(vascular endothelial growth factor)were 20.3%,96.4%,36.4%and 77.3%,respectively.Univariate Kaplan-Meier survival analysis showed that the site of disease,lymph node metastasis,and tumor stage were significantly correlated with disease recurrence.Multivariate Cox regression analysis showed that the clinical stage of the tumor was an independent risk factor for the prognosis of the disease(HR=3.715,95%CI:1.519-9.088,P=0.04).CONCLUSION The stage of laryngeal squamous cell carcinoma,the site of the disease,and the metastasis of the lymph nodes are the main factors affecting the prognosis.The high positive expression rate of immunohistochemistry markers EGFR and VEGF is worth paying attention to Targeted therapy for patients with positive PD-1/PD-L1 testing is a promising research direction.

Spermatogenesis is a continual process that occurs in the testes, in which diploid spermatogonial stem cells (SSCs) differentiate and generate haploid spermatozoa. This highly efficient and intricate process is orchestrated at multiple levels. N⁶-methyladenosine (m⁶A), an epigenetic modification prevalent in mRNAs, is implicated in the transcriptional regulation during spermatogenesis. However, the dynamics of m⁶A modification in non-rodent mammalian species remains unclear. Here, we systematically investigated the profile and role of m⁶A during spermatogenesis in pigs. By analyzing the transcriptomic distribution of m⁶A in spermatogonia, spermatocytes, and round spermatids, we identified a globally conserved m⁶A pattern between porcine and murine genes with spermatogenic function. We found that m⁶A was enriched in a group of genes that specifically encode the metabolic enzymes and regulators. In addition, transcriptomes in porcine male germ cells could be subjected to the m⁶A modification. Our data show that m⁶A plays the regulatory roles during spermatogenesis in pigs, which is similar to that in mice. Illustrations of this point are three genes (SETDB1, FOXO1, and FOXO3) that are crucial to the determination of the fate of SSCs. To the best of our knowledge, this study for the first time uncovers the expression profile and role of m⁶A during spermatogenesis in large animals and provides insights into the intricate transcriptional regulation underlying the lifelong male fertility in non-rodent mammalian species.
Animals ; Male ; Mice ; Cell Differentiation/genetics* ; Mammals/metabolism* ; Methylation ; RNA, Messenger/metabolism* ; Spermatogenesis/genetics* ; Spermatozoa/metabolism* ; Swine/genetics* ; Testis/metabolism* ; Transcriptome ; RNA Methylation/genetics*