OBJECTIVE To study the improvement effect and mechanism of Dendrobium officinale on skin damage in mice with xeroderma. METHODS The mice were randomly divided into control group， model group， and D. officinale group， with 5 mice in each group. Except for the control group （which only underwent shaving treatment）， the mice in all other groups were induced to develop a xeroderma model using an acetone-ether mixture for five consecutive days. The mice in D. officinale group were treated with 200 μL of D. officinale suspension （0.2 mg/mL） two hours after the first modeling each day. Mice in the control group and the model group were applied with an equal volume of pure water； once a day， until the end of the modeling process. After last medication， skin lesions and pathological morphology of the mice were observed. Immunofluorescence was used to detect the expressions of Filaggrin， Loricrin and Ki67 proteins in skin tissue of the mice. The core pathways through which D. officinale improves skin damage in xeroderma were screened using 16S rRNA sequencing combined with gene ontology and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses， and subsequent validation was conducted. RESULTS Compared with the control group， the mice in the model group exhibited obvious scratching behavior， with a large amount of scale on the skin， excessive epidermal keratinization， and thickened stratum spinosum. The skin scale score， epidermal thickness， and the expression levels of Ki67， Filaggrin， and Loricrin proteins in the skin tissue were significantly increased/elevated （ P ＜0.05）. Compared with model group， the mice in the D. officinale group exhibited reduced scratching behavior and scaling， along with a mitigated degree of skin keratinization. The aforementioned quantitative indicators were significantly decreased/reduced （ P ＜0.05）. The results of core pathway screening revealed that the KEGG pathways involving differentially expressed genes included signaling pathways such as interleukin-17 （IL-17） and tumor necrosis factor （TNF）. Further validation experim ents found that after intervention with D. officinale ， mRNA expression of downstream effector molecules CCN1， Hbegf， Tnfrsf12a， and Thbs1 genes in skin tissues were all significantly reduced （ P ＜0.05）. CONCLUSIONS D. officinale can repair skin damage in mice with xeroderma， and its mechanism of action is related to restoring the balance of proliferation and differentiation in keratinocytes and down-regulating the mRNA expressions of CCN1， Hbegf， Tnfrsf12a， and Thbs1.

OBJECTIVE To investigate the application and influencing factors of sodium-dependent glucose transporters 2 inhibitors（SGLT-2i） in patients with heart failure with preserved ejection fraction（HFpEF） in the real world. METHODS Data from 358 patients with HFpEF who were hospitalized at the First Affiliated Hospital of Chongqing Medical University from May 2023 to May 2024 were retrospectively collected. The patients were divided into the SGLT-2i group and the non-SGLT-2i group based on whether they were prescribed SGLT-2i upon discharge. Baseline characteristics， comorbidities， and differences in drug treatment were compared between the two groups. Based on univariate analysis， multivariate Logistic regression analysis was performed to identify independent influencing factors of SGLT-2i use in patients with HFpEF， followed by further stratified analysis. RESULTS Among 358 HFpEF patients， the overall utilization rate of SGLT-2i was 33.5%. Combined with type 2 diabetes [OR＝9.063，95%CI（4.924-16.679） ] ， atrial fibrillation [OR＝3.135，95%CI（1.590-6.178） ] ， coronary artery heart disease [OR＝1.888，95%CI（1.072-3.327） ] and the use of loop diuretics [OR＝3.822， 95%CI （1.588-9.200） ] were all independent influencing factors for the use of SGLT-2i in patients with HFpEF （ P ＜0.05）. The results of the stratified descriptive analysis were consistent with those of the multivariate analysis， showing a higher utilization rate of SGLT-2i among patients with concomitant T2DM，atrial fibrillation， coronary artery heart disease， and those receiving loop diuretics （ P ＜0.05）； whereas the utilization rate of SGLT-2i was comparable across patients with different levels of renal function （ P ＞0.05）. CONCLUSIONS In the real-world clinical practice， the utilization of SGLT-2i in patients with HFpEF remains suboptimal， and treatment coverage still needs to be improved. Their use of SGLT-2i is primarily influenced by the presence of type 2 diabetes， atrial fibrillation， coronary artery heart disease， and the use of loop diuretics.

OBJECTIVE: To assess the carrier frequency of spinal muscular atrophy (SMA) in women of childbearing age in Chongqing and to evaluate prenatal diagnostic outcomes in high-risk couples. METHODS: A total of 17 926 women of childbearing age attending Chongqing Health Center for Women and Children between May 2021 and November 2023 were enrolled, including 3 398 pre-pregnant women and 14 528 pregnant women, all of whom had no clinical phenotype or family history of SMA or related neuromuscular disorders. Real-time quantitative PCR (RT-qPCR) was used to determine the copy number variations in exons 7 and 8 (E7, E8) of the SMN1 gene. High-risk carriers were identified based on the genetic screening results. Multiplex ligation-dependent probe amplification (MLPA) was employed for prenatal diagnosis of fetuses from high-risk couples. This study was approved by the Medical Ethics Committee of Chongqing Health Center for Women and Children (Ethics No.2021-RGI-02). RESULTS: Among the 17 926 women of childbearing age, 298 (1.66%) were identified as heterozygous carriers, including 278 (1.55%) with concurrent deletions of E7 and E8, and 20 (0.11%) with isolated deletions of E7. Seven high-risk couples were identified, six of whom were prenatal couples. Of the two fetuses from these high-risk pregnancies, both exhibited heterozygous deletions of E7 and E8 in the SMN1 gene, while four fetuses showed no abnormalities. CONCLUSION This study provides a comprehensive assessment of the carrier frequency of SMA among women of childbearing age in Chongqing, offering valuable data for the primary and secondary prevention of SMA-related birth defects in the region.
Humans ; Female ; Muscular Atrophy, Spinal/diagnosis* ; Pregnancy ; Prenatal Diagnosis/methods* ; Adult ; Survival of Motor Neuron 1 Protein/genetics* ; Genetic Carrier Screening/methods* ; DNA Copy Number Variations/genetics* ; China ; Genetic Testing ; Heterozygote

OBJECTIVE: To explore the genetic etiology of a Chinese pedigree with recurrent Joubert syndrome with negative results by whole-exome sequencing in the prior proband. METHODS: Chinese pedigree which opted elective abortion at the Women and Children's Hospital Affiliated to Chongqing Medical University in December 2024 was selected as the study subject. Whole-genome sequencing was carried out on fetal tissue after termination of pregnancy. Candidate variants were validated by Sanger sequencing and interpreted, while non-coding variant was analyzed using in silico prediction tools. RNA sequencing and cDNA sequencing were conducted on fetal brain tissue. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.2024YL045-02). RESULTS: Both the fetus and the affected child were found to harbor compound heterozygous variants of the CEP290 gene, namely c.7341dup (p.Leu2448fs*8) (pathogenic, maternally inherited) and c.1523-408G>A (likely pathogenic, paternally inherited). Both in silico analysis and fetal brain RNA sequencing confirmed aberrant RNA splicing caused by the intronic variant. CONCLUSION This case has highlighted the value of combining whole-genome sequencing with RNA functional validation. Above results not only enriched the spectrum of CEP290 gene mutations but also underscored its diagnostic value in resolving complex prenatal cases, providing critical clues for the prenatal diagnosis and recurrence risk assessment in genetic counseling.
Female ; Humans ; Pregnancy ; Abnormalities, Multiple/genetics* ; Antigens, Neoplasm/genetics* ; Cell Cycle Proteins/genetics* ; Cerebellum/abnormalities* ; Cytoskeletal Proteins/genetics* ; Eye Abnormalities/genetics* ; Introns/genetics* ; Kidney Diseases, Cystic/diagnosis* ; Pedigree ; Retina/abnormalities* ; Sequence Analysis, RNA/methods* ; Whole Genome Sequencing/methods* ; Child

Objective:To investigate the methods and skills required for the safe and swift removal of primary or secondary sacral tumors located between the second (inclusive) and fourth sacral vertebrae.Methods:The clinical images, pathology reports, surgical procedures, operation durations, intraoperative bleeding volumes, and postoperative functional follow-up data of 26 patients undergoing sacral tumor resection at the First Affiliated Hospital of Zhengzhou University and Xinjiang Production and Construction Corps Hospital between May 2020 and February 2025 were retrospectively examined. Additionally, the safety measures for sacral tumor resection and techniques for expedited specimen removal were evaluated.Results:According to magnetic resonance imaging (MRI) findings, all 26 patients presented with sacral tumors located between the second (inclusive) and fourth sacral vertebrae. Specifically, 9 patients were diagnosed with primary sacral tumors, pathologically confirmed as chordomas, while 17 patients had secondary sacral tumors. Among the secondary tumor cases, 12 were attributed to recurrent rectal cancer invading the sacrum, and 5 were due to malignant teratomas invading the sacrum. The 26 patients underwent a treatment strategy that began with managing the relationship between the internal iliac artery, vein branches, and the tumor, followed by the resection of the sacrum. During surgery, the bilateral sciatic foramina were accurately positioned, and the presacral fascia was dissected subsequent to the fracture of the sacrum. Among the 26 patients, 9 underwent sacral tumor resection directly through the posterior sacral approach. The average operation time for these patients was (71.1±4.9) minutes, with average blood loss of (186.7±72.8) milliliters. On the other hand, 17 patients underwent sacral tumor resection by transitioning from the supine position to the prone knife position through a combined abdominal and sacral approach. The average operation time for this group was (213.5±19.3) minutes, with average blood loss of (480.0±93.0) milliliters, significantly longer than that of the posterior sacral approach. The follow-up period ranged from 1 to 48 months, with a median of 20 months, ending on March 31, 2025. During this time, 26 patients achieved autonomous defecation with the aid of medication. None of the patients reported any functional movement disorders or pain in their lower limbs. It was observed that two out of the 26 patients developed distant metastasis, while the remaining 24 patients survived without any tumors.Conclusion:By pretreated the relationship between the internal iliac vessels and sacral tumors prior to resecting sacral tumors, utilizing the approach of initially fracturing the sacrum followed by rupturing the presacral fascia, the tumor can be entirely eliminated, resulting in a brief surgical procedure, reduced intraoperative bleeding, and minimal postoperative complications.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Tailored lipid nanoparticles (LNPs)-mediated small interfering RNA (siRNA) nanomedicines show promise in treating liver disease, such as acute liver injury (ALI) and non-alcoholic steatohepatitis (NASH). However, constructing LNPs that address biosafety concerns, ensure efficient delivery, and target specific hepatic subcellular fractions has been challenging. To evade above obstacles, we develop three novel self-degradable "gemini-like" ionizable lipids (SS-MA, SS-DC, SS-MH) by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head. Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release, improving both biosafety and siRNA delivery efficiency. Furthermore, the distance of ester bond and tertiary amino head significantly influences the LNPs' pK _a, thereby affecting endosomal escape, hemolytic efficiency, absorption capacity of ApoE, uptake efficiency of hepatocytes and liver accumulation. We also develop the modified-mannose LNPs (M-LNP) to target liver macrophages specifically. The optimized M-MH_LNP@TNFα exhibits potential in preventing ALI by decreasing tumor necrosis factor α (TNFα) levels in the macrophages, while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol O-acyltransferase 2 (DGAT2) in the hepatocytes. Our findings provide new insights into developing novel highly effective and low-toxic "gemini-like" ionizable lipids for constructing LNPs, potentially achieving more effective treatment for hepatic diseases.