Casein kinase 2-interacting protein-1 (CKIP-1) is a multifunctional scaffold protein with a pleckstrin homology domain. Its dynamic subcellular localization enables dual roles in tumor progression, “promoting” or “suppressing” malignancy by regulating immune metabolism and signaling networks within the tumor immune microenvironment (TIME). This review synthesizes current knowledge on CKIP-1’s structural characteristics and TIME regulatory mechanisms. We highlight that CKIP-1 inhibits macrophage M2 polarization, antagonizes Smurf1-mediated oncoprotein ubiquitination, and modulates key pathways, including TGF-β and PI3K/AKT. Targeting CKIP-1 enhances the efficacy of immune checkpoint inhibitors and CAR-T therapy, but clinical translation faces challenges, such as unclear tissue-specific mechanisms and combination toxicity. This review aims to synthesize the regulatory functions of CKIP-1 in the tumor immune microenvironment, thereby offering a theoretical basis for precision immunotherapy targeting CKIP-1 and further analyzing its dynamic mechanisms to advance clinical applications.

Degenerative cervical myelopathy(DCM)is a group of diseases caused by cervical spine degeneration that compresses the spinal cord.It is a major cause of spinal cord dysfunction in adults,and its incidence is increasing globally.In the late stage,DCM could lead to paralysis due to spinal cord injury,which makes rapid,effective,and accurate medical diagnosis clinically significant.Deep learning(DL)technology can assist physicians in the rapid and accurate diagnosis of DCM by analyzing and processing a large amount of imaging data to extract features of the affected regions.In recent years,DL algorithm models have been leveraged for DCM-related research,which has become a focal point of intelligent medical development.In this review,domestic and international literature is surveyed,and the research progress and application of DL technology in the auxiliary diagnosis and prognosis evaluation of DCM are systematically summarized,aiming to provide a reference for intelligent diagnosis in clinical practice.

Objective:To explore the level of triglyceride-glucose (TyG) index and its effect and clinical value in predicting breast cancer.Methods:A retrospective case-control study was conducted. A total of 700 patients with breast tumors who underwent surgical treatment in the Inner Mongolia Autonomous Region People's Hospital from July 2021 to June 2024 were selected, and finally 625 patients were included, including 388 patients with benign breast tumors and 237 patients with breast cancer, and all lesions were determined to be benign or malignant by pathology after surgery. Triglyceride and blood glucose data were collected to calculate the TyG index. The correlation between TyG index and occurrence of breast cancer was analyzed by univariate and multivariate binary logistic regression models. With postoperative pathological diagnosis as the gold standard, the receiver operating characteristic (ROC) curve was used to evaluate the efficacy of TyG index in distinguishing breast cancer from benign breast tumors.Results:The age of patients in the breast cancer group and the benign breast tumor group was (57±12) years old and (42±12) years old, respectively. There were statistically significant differences in the distributions of patients between the two groups in terms of nationality, marital status, height, body mass, body mass index (BMI), cholesterol, low-density lipoprotein cholesterol, triglyceride, blood glucose levels, and color ultrasound Breast Imaging Report and Data System (BI-RADS) classification (all P < 0.05), and there was no statistically significant difference in the level of high-density lipoprotein cholesterol between the two groups ( P > 0.05); the TyG index in the breast cancer group was higher than that in the benign breast tumor group (8.6±0.6 vs. 8.4±0.6), and the difference was statistically significant ( P <0.001). Logistic regression analysis showed that in the model with only the TyG index as a variable, the risk of breast cancer increased with the increase of TyG index [ OR = 1.97, 95% CI: 1.48-2.63, P < 0.001, Hosmer-Lemeshow (HL) test P = 0.077]; in the model with 6 variables including TyG index, nationality, marriage, height, body mass and BMI, the risk of breast cancer increased with the increase of TyG index ( OR = 1.47, 95% CI: 1.08-2.00, P = 0.015, HL test P = 0.832); however, after adding age and BI-RADS classification variables, although the TyG index was still an independent influencing factor for the occurrence of breast cancer ( OR = 0.58, 95% CI: 0.35-0.96, P = 0.033, HL test P = 0.165), the rise of TyG index was an independent protective factor for the occurrence of breast cancer; in the two variable models including TyG index and BI-RADS classification, the TyG index was not an independent influencing factor for the occurrence of breast cancer ( OR = 1.10, 95% CI: 0.72-1.70, P = 0.659), suggesting that the TyG index may not be able to assist in the diagnosis of breast cancer by ultrasound. ROC curve analysis showed that the area under the curve to distinguish breast cancer and benign breast tumor according to the TyG index was 0.623, the optimal critical value of the TyG index was 8.51, the corresponding sensitivity was 59.5%, and the specificity was 62.4%. Conclusions:The TyG index of breast cancer patients is higher than that of benign breast tumor patients. Breast tumor patients with elevated TyG index have an increased risk of breast cancer, which may be a potential non-invasive biomarker of breast cancer.

Objective To investigate the role of the ubiquitin specific protease 22(USP22)/lysine specific demethylase 3A(KDM3A)pathway in improving ischemia-reperfusion injury of hypoxic cardiomyocytes in sevoflurane postconditioning(SPC).Methods H9c2 rat cardiomyocytes were divided into control group,hypoxia/reoxygenation(H/R)group,H/R+sevoflurane(Sevo)group,H/R+Sevo+si-NC group,H/R+Sevo+si-USP22 group and H/R+Sevo+si-KDM3A group.Real time fluorescence quantitative PCR(qRT-PCR)and Western blotting were used to detect the mRNA and protein expression of USP22 and KDM3A,cell activity was detected by cell counting kit-8,apoptosis rate was detected by flow cytometry,and ELISA was used to detect the levels of creatine kinase MB(CK-MB)and cardiac troponin I(cTn I),while the assay kit was used to detect the levels of lactate dehydrogenase(LDH).Immunoprecipitation assay was used to detect the interaction between USP22 and KDM3A proteins,as well as KDM3A ubiquitination.Results Compared with the control group,the mRNA and protein expression of USP22 in H/R group cells decreased(t=49.574,14.852),cell activity decreased(t=46.597),cell apoptosis rate,CK-MB,cTn I and LDH levels increased(t=17.722,21.346,22.863,9.722),KDM3A protein expression decreased(t=15.879),and ubiquitination level increased,the differences were statistically significant(all P<0.01).Compared with the H/R group,the mRNA and protein expression of USP22 in H9c2 cells in the H/R+Sevo group increased(t=24.648,17.644),cell activity increased(t=44.703),apoptosis rate,CK-MB,cTn I and LDH levels decreased(t=13.736,18.018,17.012,13.856),KDM3A protein expression increased(t=12.970),ubiquitination level decreased,and the differences were statistically significant(all P<0.01).Compared with the H/R+Sevo+si-NC group,the cell viability of the H/R+Sevo+si-USP22 group was decreased(t=20.785),the apoptosis rate,CK-MB,cTn I and LDH levels were increased(t=6.821,6.862,6.442,3.781),the KDM3A protein expression was decreased(t=4.648),and the ubiquitination level was increased,and the differences were statistically significant(all P<0.05).USP22 was enriched in the promoter of KDM3A,and there was a direct regulatory relationship between USP22 and KDM3A.Compared with the H/R+Sevo+si-NC group,the cell viability was decreased(t=16.501),the apoptosis rate and the levels of CK-MB,cTn I and LDH were increased in the H/R+Sevo+si-KDM3A group(t=8.954,10.533 6.801,8.004),and the differences were statistically significant(all P<0.01).Conclusion SPC attenuates H/R-induced H9c2 cardiomyocyte injury,and the mechanism may be related to the up-regulation of USP22 stabilizing KDM3A protein levels.

Recently, male reproductive health has attracted extensive attention, with the adverse effects of circadian disruption on male fertility gradually gaining recognition. However, the mechanism by which circadian disruption leads to damage to male reproductive system remains unclear. In this review, we first summarized the dual regulatory roles of circadian clock genes on the male reproductive system: (1) circadian regulation of testosterone synthesis via the hypothalamic-pituitary-testicular (HPT) and hypothalamic-pituitary-adrenal (HPA) axes; (2) non-circadian regulation of spermatogenesis. Next, we further listed the possible mechanisms by which circadian disruption impairs male fertility, including interference with the oscillatory function of the reproductive system, i.e., synchronization of the HPT axis, crosstalk between the HPT axis and the HPA axis, as well as direct damage to germ cells by disturbing the non-oscillatory function of the reproductive system. Future research using spatiotemporal omics, epigenomic assays, and neural circuit mapping in studying the male reproductive system may provide new clues to systematically unravel the mechanisms by which circadian disruption affects male reproductive system through circadian clock genes.
Male ; Humans ; Animals ; Circadian Clocks/physiology* ; Hypothalamo-Hypophyseal System/physiology* ; Circadian Rhythm/genetics* ; Spermatogenesis/physiology* ; Pituitary-Adrenal System/physiology* ; Testis/physiology* ; Testosterone/biosynthesis* ; CLOCK Proteins ; Infertility, Male/physiopathology*

This study aimed to investigate the effect of saltwater stir-fried Plantaginis Semen(SPS) on renal fibrosis in rats and decipher the underlying mechanism. Thirty-six Sprague-Dawley rats were randomly assigned into control, model, losartan potassium, and low-, medium-, and high-dose(15, 30, and 60 g·kg~(-1), respectively) SPS groups. Rats in other groups except the control group were subjected to unilateral ureteral obstruction(UUO) to induce renal fibrosis, and the modeling and gavage lasted for 14 days. After 14 consecutive days of treatment, the levels of serum creatinine(Scr) and blood urea nitrogen(BUN) in rats of each group were determined by an automatic biochemical analyzer. Hematoxylin-eosin(HE) and Masson staining were used to evaluate pathological changes in the renal tissue. Western blot and immunofluorescence assay were conducted to determine the protein levels of fibronectin(FN), collagen Ⅰ, vimentin, and α-smooth muscle actin(α-SMA) in the renal tissue. The mRNA levels of epithelial-mesenchymal transition(EMT)-associated transcription factors including twist family bHLH transcription factor 1(TWIST1), snail family transcriptional repressor 1(SNAI1), and zinc finger E-box binding homeobox 1(ZEB1), as well as inflammatory cytokines such as interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α), were determined by RT-qPCR. Human renal proximal tubular epithelial(HK2) cells exposed to transforming growth factor-β(TGF-β) for the modeling of renal fibrosis were used to investigate the inhibitory effect of SPS on EMT. Network pharmacology and Western blot were employed to explore the molecular mechanism of SPS in alleviating renal fibrosis. The results showed that SPS significantly reduced Scr and BUN levels and alleviated renal injury and collagen deposition in UUO rats. Moreover, SPS notably down-regulated the protein levels of FN, collagen Ⅰ, vimentin, and α-SMA as well as the mRNA levels of SNAI1, ZEB1, TWIST1, IL-1β, IL-6, and TNF-α in the kidneys of UUO rats and TGF-β-treated HK-2 cells. In addition, compared with Plantaginis Semen without stir-frying with saltwater, SPS showed increased content of specific compounds, which were mainly enriched in the mitogen-activated protein kinase(MAPK) signaling pathway. SPS significantly inhibited the phosphorylation of extracellular signal-regulated kinase(ERK) and p38 MAPK in the kidneys of UUO rats and TGF-β-treated HK2 cells. In conclusion, SPS can alleviate renal fibrosis by attenuating EMT through inhibition of the MAPK signaling pathway.
Animals ; Epithelial-Mesenchymal Transition/drug effects* ; Rats, Sprague-Dawley ; Male ; Rats ; Fibrosis/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Kidney Diseases/pathology* ; Kidney Tubules/pathology* ; Humans

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by impaired motility of cilia and flagella. Mutations in cilia- and flagella-associated protein 300 ( CFAP300 ) are associated with human PCD and male infertility; however, the underlying pathogenic mechanisms remain poorly understood. In a consanguineous Chinese family, we identified a homozygous CFAP300 loss-of-function variant (c.304delC) in a proband presenting with classical PCD symptoms and severe sperm abnormalities, including dynein arm deficiency and acrosomal malformation, as confirmed by transmission electron microscopy (TEM). Histological analysis revealed multiple morphological abnormalities of the sperm flagella in CFAP300 -mutant individual, whereas immunofluorescence demonstrated markedly reduced CFAP300 expression in the spermatozoa of the proband. Furthermore, tandem mass tag (TMT)-based quantitative proteomics showed that the CFAP300 mutation reduced key spermatogenesis proteins (e.g., sperm flagellar 2 [SPEF2], solute carrier family 25 member 31 [SLC25A31], and A-kinase anchoring protein 3 [AKAP3]) and mitochondrial ATP synthesis factors (e.g., SLC25A31, cation channel sperm-associated 3 [CATSPER3]). It also triggered abnormal increases in autophagy-related proteins and signaling mediator phosphorylation. These molecular alterations are likely to contribute to progressive deterioration of sperm ultrastructure and function. Notably, successful pregnancy was achieved via intracytoplasmic sperm injection (ICSI) using the proband's sperm. Overall, this study expands the known CFAP300 mutational spectrum and offers novel mechanistic insights into its role in spermatogenesis.
Humans ; Male ; Infertility, Male/pathology* ; Acrosome/pathology* ; Sperm Tail/pathology* ; Pedigree ; Spermatozoa ; Adult ; Loss of Function Mutation ; Ciliary Motility Disorders/genetics* ; Spermatogenesis/genetics* ; Female

OBJECTIVE: To evaluate the effect and safety of Chinese medicine (CM) Fuzheng Huazhuo Decoction (FHD) in treating patients with coronavirus disease 2019 (COVID-19) who persistently tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This retrospective cohort study was conducted at Shanghai New International Expo Center shelter hospital in China between April 1 and May 30, 2022. Patients diagnosed as COVID-19 with persistently positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test results for ⩾8 days after diagnosis were enrolled. Patients in the control group received conventional Western medicine (WM) treatment, while those in the FHD group received conventional WM plus FHD for at least 3 days. The primary outcome was viral clearance time. Secondary outcomes included negative conversion rate within 14 days, length of hospital stay, cycle threshold (Ct) values of the open reading frame 1ab (ORF1ab) and nucleocapsid protein (N) genes, and incidence of new-onset symptoms during hospitalization. Adverse events (AEs) that occurred during the study period were recorded. RESULTS: A total of 1,765 eligible patients were enrolled in this study (546 in the FHD group and 1,219 in the control group). Compared with the control group, patients receiving FHD treatment showed shorter viral clearance time for nucleic acids [hazard ratio (HR): 1.500, 95% confidence interval (CI): 1.353-1.664, P<0.001] and hospital stays (HR: 1.371, 95% CI: 1.238-1.519, P<0.001), and a higher negative conversion rate within 14 days (96.2% vs. 82.6%, P<0.001). The incidence of new-onset symptoms was 59.5% in the FHD group, similar to 57.8% in the control group (P>0.05). The Ct values of ORF1ab and N genes increased more rapidly over time in the FHD group than those in the control group post-randomization (ORF1ab gene: β =0.436±0.053, P<0.001; N gene: β =0.415 ±0.053, P<0.001). The incidence of AEs in the FHD group was lower than that in the control group (24.2% vs. 35.4%, P<0.001). No serious AEs were observed. CONCLUSION FHD was effective and safe for patients with persistently positive SARS-CoV-2 PCR tests. (Registration No. ChiCTR2200063956).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Retrospective Studies ; Male ; Female ; Middle Aged ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects* ; COVID-19/virology* ; Adult ; Aged ; Treatment Outcome

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a major health concern in northwest China; however, the impact of particulate matter (PM) exposure during sand-dust storms (SDS) remains poorly understood. Therefore, this study aimed to investigate the association between PM exposure on SDS days and COPD hospitalization risk in arid regions. METHODS: Data on daily COPD hospitalizations were collected from 323 hospitals from 2018 to 2022, along with the corresponding air pollutant and meteorological data for each city in Gansu Province. Employing a space-time-stratified case-crossover design and conditional Poisson regression, we analyzed 265,379 COPD hospitalizations. RESULTS: PM exposure during SDS days significantly increased COPD hospitalization risk [relative risk ( RR) for PM _2.5, lag 3:1.028, 95% confidence interval ( CI): 1.021-1.034], particularly among men and the elderly, and during the cold season. The burden of PM exposure on COPD hospitalization was substantially high in Northwest China, especially in the arid and semi-arid regions. CONCLUSION Our findings revealed a positive correlation between PM exposure during SDS episodes and elevated hospitalization rates for COPD in arid and semi-arid zones in China. This highlights the urgency of developing region-specific public health strategies to address adverse respiratory outcomes associated with SDS-related air quality deterioration.
Humans ; China/epidemiology* ; Pulmonary Disease, Chronic Obstructive/chemically induced* ; Particulate Matter/analysis* ; Hospitalization/statistics & numerical data* ; Male ; Female ; Middle Aged ; Aged ; Air Pollutants/analysis* ; Environmental Exposure/adverse effects* ; Spatio-Temporal Analysis ; Adult ; Sand ; Air Pollution

Objective:To analyze the therapeutic efficacy and long-term outcomes of wire-assisted dynamic traction with corrective device for congenital nipple inversion.Methods:A retrospective study was conducted on 22 female patients (42 nipples) with congenital nipple inversion treated at the Department of Plastic Surgery, Peking Union Medical College Hospital from January to December 2017. The patients′ age was 18-54 (27.6±1.9) years. All patients underwent wire-assisted dynamic traction correction. Postoperative indicators including numerical rating scale (NRS) pain scores, nipple skin microcirculatory disorders, and traction duration were recorded. Follow-up assessments via telephone interviews were completed by September 20, 2022; mean follow-up time was (63.68±3.73) months. Evaluating questions included nipple retraction, fertility status and breastfeeding outcomes.Results:Pain in the operative area was non-radiating, and the pain level decreased over time. Mean NRS were (5.4±1.5) scores on surgery day, decreasing to (4.4±1.2) scores at postoperative day 1 and (3.3±1.7) scores at day 2. Microcirculatory assessments revealed Grade 0-I (intact skin) in 78.6% (33/42), Grade II (skin ulceration) in 14.3% (6/42), and Grade III (partial necrosis) in 7.1% (3/42) of the nipples, with no Grade IV necrosis observed. Successful device placement was achieved in all cases (42/42), with traction duration ranging 6-15 (9.6±0.6) months. Follow-up data from 12 patients (23 nipples) showed mild retraction in 3 nipples. Three patients subsequently delivered infants and successfully achieved breastfeeding.Conclusion:The wire-assisted dynamic traction method with corrective device demonstrates satisfactory therapeutic outcomes for congenital nipple inversion patients with favorable long-term maintenance and breastfeeding compatibility.