Objective To identify long non-coding RNA (lncRNA) associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and investigate their mechanisms. Methods Peripheral blood samples were collected from RA-ILD patients (n＝3), RA patients without lung involvement (n＝3), and healthy controls (n＝3). Next-generation sequencing was performed to screen differentially expressed lncRNA. A human fibrotic lung cell model was established by inducing the MRC-5 cell line with transforming growth factor-β (TGF-β). Following siRNA-mediated knockdown of target genes, changes in inflammatory and oxidative stress-related genes were analyzed via real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blotting and dual-luciferase reporter (DLR) assays were used to validate protein expression, ubiquitination levels, and nuclear translocation of oxidative stress regulators, and antioxidant response element (ARE) transcriptional activity. Rescue experiments were conducted to confirm the role of target lncRNA in oxidative stress and inflammation in fibrotic lung cells. Results High-throughput sequencing revealed significant downregulation of LINC00638 in RA-ILD patients. Knockdown of LINC00638 markedly reduced transcriptional levels of interleukin (IL)-4, nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and superoxide dismutase 2 (SOD2), while increasing IL-6, IL-1β, interferon-γ (IFN-γ), and reactive oxygen species (ROS) levels. Furthermore, LINC00638 knockdown decreased Nrf2 protein expression, increased its ubiquitination, reduced nuclear translocation, and suppressed ARE transcriptional activity. In MRC-5 cells, LINC00638 knockdown combined with N-acetylcysteine treatment restored Nrf2 and HO-1 levels while reducing IL-6 expression. Conclusions LINC00638 suppresses inflammatory responses in RA-ILD by activating the Nrf2/ARE antioxidant signaling pathway, suggesting its potential as a therapeutic target for diagnosis and treatment.

Peptide-drug conjugates (PDCs) have emerged as a promising modality in precision oncology, enabling targeted delivery of cytotoxic payloads while minimizing off-target toxicity. The integration of covalent warheads, such as those based on sulfur(VI) fluoride exchange (SuFEx) chemistry, enhances drug-target residence time and tumor accumulation. However, existing screening methods for covalent peptide (CP) libraries require post-translational warhead conjugation, limiting throughput. Here, we present an integrated mRNA display platform that incorporates covalent warheads during ribosomal synthesis, enabling efficient screening of ultra-diverse covalent macrocyclic peptide libraries (>10¹³ variants). This approach, using site-specific incorporation of N-chloroacetyl-d-phenylalanine and fluorosulfate-l-tyrosine, accelerated the discovery of irreversibly binding (K _i = 3.58 μmol/L) Nectin-4-targeting peptide CP-N1-N₃ via proximity-triggered SuFEx. The peptide was further conjugated to cytotoxic payloads, yielding the covalent PDC CP-N1-MMAE with potent cytotoxicity (IC₅₀ ≈ 43 nmol/L) against MDA-MB-468 cells. This platform establishes a new paradigm for precision covalent drug discovery.

The thalamic reticular nucleus (TRN) plays a crucial role in regulating sensory encoding, even at the earliest stages of visual processing, as evidenced by numerous studies. Orientation selectivity, a vital neural response, is essential for detecting objects through edge perception. Here, we demonstrate that somatostatin (SOM)-expressing and parvalbumin (PV)-expressing neurons in the TRN project to the dorsal lateral geniculate nucleus and modulate orientation selectivity and the capacity for visual information processing in the primary visual cortex (V1). These findings show that SOM-positive and PV-positive neurons in the TRN are powerful modulators of visual information encoding in V1, revealing a novel role for this thalamic nucleus in influencing visual processing.
Animals ; Somatostatin/metabolism* ; Parvalbumins/metabolism* ; Neurons/physiology* ; Thalamic Nuclei/physiology* ; Visual Pathways/physiology* ; Mice ; Mice, Inbred C57BL ; Visual Perception/physiology* ; Male ; Mice, Transgenic ; Visual Cortex/physiology* ; Primary Visual Cortex/cytology*

Objective To observe the effects of Shengxue Tongbian Granules on colonic myoelectricity and Ca2+/CaM/MLCK signaling pathway in rats with slow transit constipation(STC)of blood deficiency and intestinal dryness syndrome;To explore its mechanism for the treatment of STC.Methods The STC model of blood deficiency and intestinal dryness syndrome was established by intragastric administration of loperamide combined with tail bloodletting.The rats were divided into control group,model group,mosapride citrate group and Shengxue Tongbian Granules group,with 8 rats in each group.The administration group was given corresponding drugs by gavage for 14 days.The general condition of rats before and after treatment was observed,the fecal water content was detected,the slow wave frequency,amplitude,and coefficient of variation of colonic electromyography were detected using a biological function experimental system,and intestinal propulsion rate was detected.HE staining was used to observe the pathological changes of colon tissue,the concentration of Ca2+ in colonic smooth muscle cells was detected by colorimetry,the expression of Cx43,calmodulin(CaM),myosin light chain kinase(MLCK)and p-MLC20 in smooth muscle tissue were detected by Western blot.Results Compared with the control group,the body mass,fecal water content and intestinal propulsion rate of rats in the model group decreased(P<0.01),the slow wave frequency of colonic electromyography slowed down,the coefficient of variation of frequency increased(P<0.01),and the amplitude and coefficient of variation of slow wave increased(P<0.01);colonic mucosal structure was damaged,with visible inflammatory changes and significant erosion,and the concentration of Ca2+ and the expressions of Cx43,CaM,MLCK,p-MLC20 proteins in colonic smooth muscle cells were significantly decreased(P<0.01).Compared with the model group,the body mass,fecal water content and intestinal propulsion rate of the rats in the mosapride citrate group and the Shengxue Tongbian Granules group significantly increased(P<0.05,P<0.01),the slow wave frequency of colonic electromyography increased and the coefficient of variation of frequency decreased(P<0.01),and the slow wave amplitude and amplitude variation coefficient decreased(P<0.05,P<0.01);the colonic mucosal structure was relatively intact,the erosion situation was improved,and the Ca2+ concentration,Cx43,CaM,MLCK and p-MLC20 protein expressions in colonic smooth muscle cells significantly increased(P<0.01).Conclusion Shengxue Tongbian Granules can improve defecation symptoms and promote colonic motility in STC rats with blood deficiency and intestinal dryness syndrome,which may be related to regulating colonic myoelectric rhythm and activating Ca2+/CaM/MLCK signaling pathway.

Objective To observe the effect of buccal needle therapy on perioperative analgesia in patients undergoing laparoscopic radical colon cancer surgery.Methods Sixty patients underwent dective laparoscopic radical of colon cancer surgery were selected,32 males and 28 females,aged 45-74 years,BMI 18.5-25.0 kg/m2 and ASA physical status Ⅱ or Ⅲ.The patients were divided into two groups using the randomized numerical table method:buccal needle group and control group,30 patients in each group.Before the induction of anesthesia,the buccal needle group was given buccal needle therapy once,and buc-cal needle therapy was performed once a day at 9 a.m.in the postoperative period,leaving the needle in place for 30 minutes each time,for 3 consecutive days of treatment,and the control group was not treated with buccal needle therapy.The amount of intraoperative propofol,remifentanil,sufentanil used in the 48 hours postoperative period and recorded.VAS pain scores were recorded at 1 hour,4,24,and 48 hours postoperatively.Venous blood was collected at the time of admission to the hand room and at 1 day,2,and 3 days postoperatively,respectively,and the concentrations of plasma C-reactive protein(CRP),interleu-kin-6(IL-6),and tumor necrosis factor-alpha(TNF-α)were measured.The occurrence of adverse reactions within 48 hours after operation was recorded.Results Compared with the control group,intraop-erative propofol,remifentanil,the amount of sufentanil used and the number of analgesic pump presses with-in 48 hours after operation in the buccal needle group were significantly reduced in the buccal needle group(P＜0.05),VAS pain scores were significantly lower at 1 hour,4,24,and 48 hours postoperatively(P＜0.05),CRP,IL-6,and TNF-α concentrations were significantly lower at 1 day,2,and 3 days postopera-tively(P＜0.05),and nausea and vomiting,incidence of laryngospasm and laryngeal discomfort were sig-nificantly reduced(P＜0.05).Conclusion The perioperative use of buccal needle therapy in patients un-dergoing laparoscopic radical colon cancer surgery can effectively reduce pain,inhibit inflammatory respon-ses,and decrease the incidence of postoperative adverse reactions.

Objective:To study the clinicopathological features of Sjogren′s syndrome (SS) with liver injury and to improve the understanding of this disease.Methods:Forty-nine patients with SS complicated with liver injury were collected from Beijing Ditan Hospital, Capital Medical University from October 2008 to January 2022. All patients underwent ultrasound-guided liver biopsy, and all specimens were stained with HE. The histopathologic characteristics were observed and the pathologic indexes were graded. Immunohistochemical stains for CK7, CK19, CD38, MUM1 and CD10 were performed by EnVision method; and special histochemical stains for reticulin, Masson′s trichrome, Rhodanine, Prussian blue, periodic acid Schiff (PAS) and D-PAS stains were conducted .Results:The age of patients ranged from 31 to 66 years, including 3 males and 46 females. SS combined with drug-induced liver injury was the most common (22 cases, 44.9%), followed by autoimmune liver disease (13 cases, 26.5%, including primary biliary cholangitis in eight cases, autoimmune hepatitis in 3 cases, and PBC-AIH overlap syndrome in 2 cases), non-alcoholic fatty liver disease (NAFLD, 9 cases, 18.4%) and other lesions (5 cases, 10.2%; including 3 cases of nonspecific liver inflammation, 1 case of liver amyloidosis, and 1 case of porto-sinusoidal vascular disease). Among them, 28 cases (57.1%) were associated with obvious interlobular bile duct injury, mainly in SS combined with PBC group and drug-induced liver injury group. Twenty-three cases (46.9%) were associated with hepatocyte steatosis of varying degrees. In SS with autoimmune liver disease group, ISHAK score, degree of fibrosis bile duct injury, bile duct remodeling, lymphocyte infiltration of portal area, and plasma cell infiltration, MUM1 and CD38 expression; serum ALP and GGT, IgM; elevated globulin; positive AMA, proportion of AMA-M2 positive and IgM positive were all significantly higher than those in other groups(all P<0.05). Serum ALT, direct bilirubin and SSA positive ratio in SS combined with drug liver group were significantly higher than those in other groups(all P<0.05). The serum total cholesterol level in SS combined with PBC group ( P=0.006) and NALFD group ( P=0.011) were significantly higher than those in other groups ( P<0.05). Conclusions:The pathologic manifestations of SS patients with liver injury are varied. The inflammatory lesions of SS patients with autoimmune liver disease are the most serious, and the inflammatory lesions of SS patients with non-alcoholic fatty liver disease and non-specific inflammation are mild. Comprehensive analysis of liver histopathologic changes and laboratory findings is helpful for the diagnosis of SS complicated with different types of liver injury.

Objective:To investigate the clinicopathological characteristics of rashes in monkeypox patients through a series of skin biopsies, and examine their pathological features and the most effective tests.Methods:Patients with monkeypox virus infection admitted to Beijing Ditan Hospital from June to August 2023 were identified. Among them, 24 patients underwent skin biopsies for clinical pathological study that were included in this study. Clinical information, rash pictures, and nucleic acid test results were analyzed using histopathology, immunohistochemistry, RNAscope ? hybridization and electron microscopy. Results:All 24 patients were male, including 14 patients with concurrent human immunodeficiency virus infection. Their average age was (32.3±5.4) years. The nucleic acid test confirmed monkeypox virus infection. The clinical feature of monkeypox rashes was solitary rather than clustered distribution, with rashes occurring in similar phase, distinguishing it from herpesvirus. The rashes in these patients were mostly scattered, with an average of (13.0±11.8) rashes, and most commonly present in the perineum, face, limbs, and trunk. The three main pathological features of these rashes were ballooning degeneration of the epidermal spinous cell layer, the characteristic intra-cytoplasmic Guarnieri′s bodies and significant infiltration of inflammatory cells in whole dermal layer. Immunohistochemistry, RNAscope ? hybridization, and electron microscopy can all effectively detect the monkeypox virus. Electron microscopy showed viral replication in various types of skin cells. Conclusions:The study describes the pathological features of monkeypox virus rashes. Pathological examination of skin biopsy samples is helpful to diagnose these rashes. The study suggests that the monkeypox virus has a unique epitheliotropic affinity and can infect various types of cells in the skin.

Objective:To examine the burden and trends of acute viral hepatitis in Guangdong Province from 1990 to 2019, and provide reference evidences for hepatitis prevention and control in the province.Methods:Data on acute viral hepatitis (hepatitis A, B, C, and E) in Guangdong from 1990 to 2019 were extracted from the Global Burden of Disease Study 2019 database. The incidence, prevalence, mortality, and disability-adjusted life years (DALY) data were analyzed by age and gender, and the estimated annual percentage change (EAPC) was calculated to describe the changing trends in disease burden.Results:From 1999 to 2019, the standardized incidence, prevalence, mortality, and DALY of acute viral hepatitis in Guangdong were higher than the national averages. In 2019, 51.43% (2 245 087/4 365 221) of acute viral hepatitis cases in Guangdong Province were mainly attributed to hepatitis B, and 77.18% (106/138) of deaths were due to acute hepatitis B. In different age groups, except for acute hepatitis B, which was more common in adults, the incidence rates of other types of viral hepatitis such as hepatitis A, B, and E showed an overall decreasing trend with age. The mortality rates of different types of acute viral hepatitis, except for the <5 age group, increased with age. The overall incidence and mortality rates of acute viral hepatitis were higher in men than in women.Conclusions:The overall burden of acute viral hepatitis in Guangdong declined in 2019, but remained higher than the national level. Further efforts are needed to strengthen hepatitis prevention and screening in different population in Guangdong Province, especially in children and the elderly.

Objective This study aims to analyze the proteomic characteristics of peripheral blood in patients with lung cancer coexistent with pulmonary tuberculosis(LC-PTB),identify the differential proteins compared with lung cancer(LC)patients,and conduct functional analysis on these proteins.Methods The study included 8 LC-PTB patients and 10 LC patients.The LC patients were newly diagnosed and confirmed by pathology and did not receive any anti-tumor treatment before,while the PTB patients were Mycobacterium tuberculosis positive at the time of sampling.Liquid chromatography-tandem mass spectrometry(LC-MS/MS)was applied to perform proteomic mass spectrometry to assess the differential proteins,and then functional analysis was conducted via bioinformatics.Results A total of 5,185 proteins were detected between two groups.Through differential expression screening,190 proteins(58 upregulated and 132 downregulated)were identified to be differentially expressed.Subcellular localization analysis revealed that the differential proteins were mainly concentrated in the cytoplasm,nucleus,and extracellular matrix.KEGG pathway and GO analysis showed the roles of differential proteins in biological processes including immune response,metabolism,and secretion regulation.Protein interaction network analysis highlighted the importance of SORT1,SAR1B,RPS6KB1,VWF,SHC1,SRPRB,CTSD,TARDBP,RPLP0,PSMA2,RPS6,XPO1,PRKACB,and HLA-DRB1 in LC-PTB.Additionally,the expression changes in proteins like ADA2,MAP3K1,and GLS2 might be closely associated with the development of LC-PTB.Conclusions The proteomic profile comprehensively described the proteomic characteristics of LC-PTB and identified numerous differentially expressed proteins,which could provide further clues for research on biological mechanism of LC-PTB.

Objective To develop and evaluate the equivalence of the Mandarin test material for tracking of noise tolerance(TNT)test.Methods Six different speech materials were developed(themes including daily life,entertainment,family,festivals,outdoors,and school).Four-minute TNT tests were measured in 21 normal hear-ing subjects using six different test materials.For each session,the tolerable noise level(TNL)and TNT scores were acquired and calculated for 3 time windows(31～240 s,31～120 s,151～240 s).Results Statistic analysis showed significant differences in the TNL(F=43.611,P＜0.05)among the normal hearing listeners.There were statistically significant differences in standardize z-scored TNT scores of the six different materials in the three time windows(P＜0.05).Post-hoc comparisons revealed that all significant differences involved the family and daily life themes.Conclusion Entertainment,festival,outdoors and school themed test materials can serve as the materials of Mandarin tracking of noise tolerance test and can be appied in research and clinical testing.