JMJD1C (Jumonji Domain Containing 1C), a member of the lysine demethylase 3 (KDM3) family, is universally required for the survival of several types of acute myeloid leukemia (AML) cells with different genetic mutations, representing a therapeutic opportunity with broad application. Yet how JMJD1C regulates the leukemic programs of various AML cells is largely unexplored. Here we show that JMJD1C interacts with the master hematopoietic transcription factor RUNX1, which thereby recruits JMJD1C to the genome to facilitate a RUNX1-driven transcriptional program that supports leukemic cell survival. The underlying mechanism hinges on the long N-terminal disordered region of JMJD1C, which harbors two inseparable abilities: condensate formation and direct interaction with RUNX1. This dual capability of JMJD1C may influence enhancer-promoter contacts crucial for the expression of key leukemic genes regulated by RUNX1. Our findings demonstrate a previously unappreciated role for the non-catalytic function of JMJD1C in transcriptional regulation, underlying a mechanism shared by different types of leukemias.
Core Binding Factor Alpha 2 Subunit/genetics* ; Humans ; Leukemia, Myeloid, Acute/pathology* ; Jumonji Domain-Containing Histone Demethylases/chemistry* ; Gene Expression Regulation, Leukemic ; Oxidoreductases, N-Demethylating/genetics* ; Cell Line, Tumor

Proteolysis-targeting chimeras (PROTACs) have shown considerable therapeutic potential across diverse fields such as cancer, inflammation, and neurodegenerative diseases, with numerous candidates already progressing into clinical trials. More recently, their application in antiviral therapy has been rapidly gaining momentum. This review systematically outlines the mechanistic foundations and design principles of PROTACs, highlights recent advances targeting coronaviruses (including SARS-CoV-2), hepatitis C virus, human immunodeficiency virus, and influenza viruses, and critically assesses key challenges—particularly the limited diversity of E3 ligase ligands, suboptimal oral bioavailability, and the lack of integrated platforms for druggability evaluation. Looking ahead, innovations in ligand discovery, pathway modulation, delivery technologies, and conditionally activated PROTAC designs are anticipated to overcome these barriers, ushering in a new era of precise and effective antiviral therapeutics.

Objective:To retrospectively analyze the clinical characteristics of 193 Chinese patients with McCune-Albright syndrome (MAS).Methods:By using keywords " McCune-Albright syndrome", " Albright syndrome", or " fibrous dysplasia " as the search terms, 193 cases of MAS reported in China from January 1990 to November 2022 from the Wanfang data, CNKI, VIP, PubMed, and Embase databases were obtained, and their clinical data was retrospectively analyzed. Intergroup comparisons were carried out by using t test, Mann-Whitney U test, and χ2 test. Results:The 193 MAS patients had included 42 males and 151 females, with the median first-visit age of females being younger than males. The typical triad group had accounted for 46.1% of patients, and the middle first-visit and diagnosis age was younger than the atypical group. The primary reason for first-visit in males of MAS was fibrous dysplasia (FD), whilst that in females of MAS was peripheral precocious puberty (PPP). FD has occurred in 84.5% of the patients, with an average age of onset age being 6.1 years old, and 90% was ≤ 16 years of age. Endocrine hyperfunction was found in 79.3% of the patients, with a higher proportion in females compared with males ( P<0.05). Pituitary involvement was seen in 21.8% of the patients, and the incidence of craniofacial FD and cranial nerve compression was significantly higher in those with elevated growth hormone (GH) than without ( P<0.05). Café-au-Lait Spots were noted in 86.5% of the patients, and 28.3% (28/99) had located on the different side of FD. Conclusion:Most MAS patients had atypical manifestations and multi-systemic involvement. It is more common and occurs earlier in females. The most common reasons for initial diagnosis in male and female patients were FD and PPP, respectively. Patients with elevated GH should be examined for cranial nerve compression.

Objective:To compare the clinical outcomes of anterolateral femoral interregional flap with turbocharge technique and traditional anterolateral femoral flap in repair of large limb wounds.Methods:Clinical data of 38 patients with large limb surface wound(11 cm×39 cm-16 cm×65 cm)admitted to the Sir Run Run Shaw Hospital,Zhejiang University School of Medicine from May 2018 to May 2022 were retrospectively analyzed.Eighteen patients were treated by anterolateral thigh perforator flap combined with superficial circumflex iliac artery flap(ALTP-SCIAP)with turbocharge technique(interregional flap group);while 20 patients were treated with unilateral or bilateral anterolateral femoral flaps,combined with skin grafting if necessary(traditional anterolateral femoral flap group).The survival of skin flap,repair of donor area,complications and patient satisfaction were compared between the two groups.Results:In interregional flap group,18 flaps were harvested and transplanted,the flap width,length and the viable area were(9.9±2.0)cm,(44.2±3.5)cm and(343.2±79.9)cm2,respectively.In traditional anterolateral femoral flap group,29 flaps were harvested and transplanted,the flap width,length and the viable area were(11.0±2.8)cm,(21.7±3.2)cm and(186.4±49.2)cm2,respectively.There were significant differences in the flap length and the viable area between the two groups(t=22.365 and 8.345,both P<0.05).In the interregional flap group,the donor site of flap was closed by direct suture in 11 flaps,by skin retractor assisted suture in 6 flaps,and by skin grafting in one flap.In traditional anterolateral femoral flap group,the donor site of flap was closed by direct suture in 12 flaps,by skin retractor assisted suture in 11 flaps,and by skin grafting in 6 flaps.The skin graft rates of the two groups were 5.6%(1/18)and 20.7%(6/29),respectively(χ2=2.007,P>0.05).The interregional flap group had lower postoperative complications rate(5.6%vs.35.0%,χ2=4.942,P<0.05)and higher patient satisfaction rate(94.4%vs.70.0%,χ2=4.448,P<0.05)than traditional anterolateral femoral flap group.Conclusion:Compared with the traditional anterolateral femoral flap,the anterolateral femoral interregional flap with turbocharge technique has a larger flap area,most of the donor areas of the flap can be sutured directly without skin grafting and with less complications and a higher patient satisfaction rate.

Objective The diagnostic efficacy of the two gene methylation indexes was verified by lung biopsy or postoperative disease examination results.Methods A prospective study was conducted to collect 99 patients diagnosed with pulmonary nodules and masses in the Third People's Hospital of Yunnan Province from March 2019 to March 2020.After bronchoscopy and BALF samples were collected,regular follow-up,lung puncture biopsy and post-operative disease examination were performed.Results Ninety-nine patients with pulmonary nodules and masses were divided into lung cancer group(n = 50)and benign lung disease group(n = 49)after pathological diagnosis.The age of patients in the lung cancer group was(62.64±9.71)years,and that of the benign lung disease group was(60.48±13.69)years,and there was a statistical difference between the two groups(P = 0.032).In the diagnosis of lung cancer,the sensitivity and specificity of SHOX2 and RASSF1A genes alone were found to be 72%and 58%,respectively,and 92.3%and 95.9%,respectively.The combined test of the two genes showed a higher sensitivity in the diagnosis of lung cancer,0.84,compared to 0.102 in the benign disease group(P<0.001).ROC curve analysis showed that the sensitivity of the two genes could be increased to 84%when methylation was combined.Conclusion The methylation test of SHOX2 and RASS1A gene in alveolar lavage fluid has a good value in the diagnosis of lung cancer patients with pulmonary nodules and masses and SHOX2 combined with RASSF1A can be an important supplementary tool for early diagnosis of lung cancer when imaging and histological diagnosis are unclear.

Objective To construct and validate a clinical prediction model for delayed extubation undergoing non-emergency major surgery based on the random forest algorithm.Methods Clinical data of 7 528 patients undergoing non-emergency major surgery under general anesthesia from January 2018 to De-cember 2022 were retrospectively collected.The patients were divided into two groups according to whether extubation was performed within 2 hours after surgery:non-delayed extubation group(≤2 hours)and de-layed extubation group(＞2 hours).All the patients were randomly divided into a training set and a valida-tion set in a ratio of 7 ∶ 3.The predictive factors for delayed extubation after surgery were screened through LASSO regression and Logistic regression.The random forest model was established and verified by random forest algorithm.Results There were 123 patients(1.6%)experienced delayed extubation after surgery.ASA physical status,department,intraoperative use of flurbiprofen ester,dexmedetomidine,glucocorticoid,hypocalcemia,severe anemia,intraoperative blood transfusion,and airway spasm were identified as inde-pendent predictive factors for delayed extubation.The area under curve(AUC)value of the random forest prediction model in the validation set was0.751(95%CI0.742-0.778),and the sensitivity was98.1%,and the specificity was 41.9%.Conclusion The predictive model of delayed extubation undergoing non-e-mergency major surgery based on random forest algorithm has a good predictive value,which may be helpful to prevent delayed extubation undergoing non-emergency major surgery.

AIM:To investigate the role of ClC-3 chloride channel in the promotion of radio sensitization of na-sopharyngeal carcinoma CNE-2Z cells by dihydroartemisinin(DHA).METHODS:MTT was used to detect the inhibito-ry effect of DHA on the viability of CNE-2Z cells and normal nasopharyngeal epithelial NP69-SV40T cells,the radio sensi-tization effect of DHA on CNE-2Z cells was detected by cloning assay,the expression of ClC-3 protein was detected by Western blot,the expression of ClC-3 protein was down-regulated by siRNA technology,and the chlorine current of cells was recorded by whole cell patch-clamp technology.RESULTS:(1)Compared with NP69-SV40T cells,DHA selective-ly inhibited the proliferation of CNE-2Z cells,with IC10 values of(13.020±4.831)μmol/L and(5.244±1.050)μmol/L,respectively(P＜0.01).(2)The results of clonal formation experiments showed that DHA had a radio sensitizing effect on CNE-2Z cells,with a radio sensitization ratio of 1.9.(3)DHA could activate the chlorine channel of CNE-2Z cells and produce an outward chlorine current,but had no effect on the chlorine channel of NP69-SV40T cells.(4)DHA promoted the expression of ClC-3 chloric channel protein in CNE-2Z cells(P＜0.01).(5)Chlorine channel blocker NPPB could in-hibit the radio sensitizing effect of DHA on CNE-2Z cells by 1.84 times,and also inhibited the chlorine current activated by DHA.(6)the down-regulation of CNE-2Z ClC-3 protein could inhibit the radio sensitization effect of DHA on CNE-2Z cells by 4.19 times,and the activation of chlorine current by DHA on CNE-2Z cells was no longer produced.CONCLU-SION:DHA has a radio sensitizing effect on nasopharyngeal carcinoma CNE-2Z cells,which is likely to be related to the activation of ClC-3 chloride channel.

Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.

BACKGROUND:Premature birth is a major global health problem associated with high mortality and morbidity.White matter injury is the most common brain injury in preterm infants.Salvia miltiorrhiza is a traditional herbal plant that is commonly used to treat cardiovascular and cerebrovascular diseases in Asian countries. OBJECTIVE:To investigate the therapeutic effect of Salvia miltiorrhiza on white matter injury in preterm infants. METHODS:Eighteen neonatal male Sprague-Dawley rats at 3-day gestational age were selected and randomized into normal group,white matter injury group,and Salvia miltiorrhiza group.Animal models of preterm white matter injury were established by permanent ligation of the right common carotid artery in the latter two groups.Rats in the Salvia miltiorrhiza group were given intraperitoneal injection of Salvia miltiorrhiza(5 mg/kg·d)for 7 consecutive days.Normal group and white matter injury group were given the same volume of PBS for intervention.On the 14th day after modeling,the rats were sacrificed.Brains were pathologically observed by hematoxylin-eosin staining under microscope,and the expression levels of myelin basic protein and CC1 in brain tissue were visualized using immunofluorescence.Furthermore,liquid chromatography-tandem mass spectrometry was used to analyze possible pathways for the action of Salvia miltiorrhiza. RESULTS AND CONCLUSION:In the white matter injury group,the structure of the corpus callosum was irregular and the cells appeared swollen and necrotic.In addition,induction of white matter injury resulted in significantly reduced myelin formation,with irregular and loosely arranged nerve fibers and significantly decreased myelin sheaths.Interestingly,white matter injury rats treated with Salvia miltiorrhiza had reduced cellular swelling,reduced lesions,and increased myelin sheaths.The expression of myelin basic protein was closely related to myelin formation,and CC1 was a marker of myelin oligodendrocytes.Salvia miltiorrhiza significantly up-regulated the expressions of myelin basic protein and CC1 in white matter injury rats(P＜0.000 1),indicating that Salvia miltiorrhiza alleviated white matter injury.Liquid chromatography-tandem mass spectrometry analysis showed that the therapeutic effect of Salvia miltiorrhiza in the rat model of white matter injury was closely related to the regulation of complement and coagulation cascades.To conclude,Salvia miltiorrhiza may be a potential therapeutic agent for treating preterm white matter injury.

Objective:To investigate the expression of nuclear matrix protein 4 (NMP4) in hepatocellular carcinoma (HCC), and its relationship with clinicopathological features and survival prognosis of patients.Methods:The clinical data of 100 HCC patients who were treated with radical resection of liver cancer in the Department of Hepatobiliary Surgery of the Third Affiliated Hospital of Wenzhou Medical University from July 1, 2014 to July 1, 2019 were retrospectively analyzed. There were 63 males and 37 females, aged (58.5±10.4) years old. Immunohistochemical method was used to detect the expression of NMP4 protein in HCC cancer tissue and the corresponding adjacent normal tissue. According to the expression of NMP4 in HCC tissues, 100 patients were divided into two groups: the NMP4-positive expression group ( n=62) and the NMP4-negative expression group ( n=32). Univariate analysis was performed on the relationship between NMP4 expression and clinical pathological features as well as overall survival of HCC patients. Cox multivariate analysis was performed on the factors influencing postoperative prognosis of HCC patients. Results:Immunohistochemistry results showed that NMP4 was primarily expressed in the nucleus, the positive expression rate of NMP4 in HCC tissues was higher than that in adjacent non-cancerous tissues [62.0% (62/100) vs. 8.0%(8/100)], and the difference was statistically significant ( χ2=2.12, P=0.003). Univariate analysis revealed that the overall survival of HCC patients was correlated with the degree of tumor differentiation, tumor length, BCLC stage, number of tumor foci, vascular tumor thrombus and expression of NMP4 (all P<0.05). Cox multivariate analysis revealed that low differentiation, high BCLC stage (stage C), number of tumor foci (≥3), and positive expression of NMP4 were independent risk factors affecting postoperative survival and recurrence-free survival of HCC patients. The median overall survival and median recurrence-free survival of HCC patients in the NMP4-positive expression group were 22.3 months and 11.5 months, respectively. In contrast, that in the NMP4-negative expression group were 40.6 months and 19.4 months, respectively. The cumulative survival rate and recurrence-free survival rate of HCC patients in the NMP4-positive expression group were lower than those in the NMP4-negative expression group, and the differences were statistically significant (both P<0.05). Conclusion:Positive NMP4 expression was closely correlated with malignant biological progression and poor prognosis of HCC patients.