Objective: To investigate the expression changes of cyclin-dependent kinase inhibitor 3(CDKN3) indifferent tumors and its effect on tumor staging, prognosis and immunotherapy. Methods: The expression characteristics of CDKN3 in different cancers using data from TCGA, CCLE, ICGC, and GTEx databases were evaluated. The GEPIA2 platform and Kaplan-Meier analysis were utilized to assess the effect of CDKN3 on tumor pathological staging and survival prognosis. The TIMER platform was employed to explore the influence of CDKN3 on the tumor immune microenvironment and immunotherapy. Its effect on immune checkpoint and key immunotherapeutic predictors using bioinformatics methods was explored. The GeneMANIA tool was used to construct the protein-protein interaction(PPI) network of CDKN3. Kyoto Encyclopedia of Genes and Genomes(KEGG) and Gene Onotology(GO) enrichment analyses were conducted to explore the biological processes and signaling pathways associated with CDKN3. The effect of CDKN3 on HepG2 cell proliferation, invasion, migration, and apoptosis was validated through transfection with CDKN3 siRNA. Results: CDKN3 was found to be widely overexpressed in tumors. High expression of CDKN3 was often associated with advanced pathological staging and poor survival prognosis. CDKN3 expression was negatively correlated with most immune checkpoints and positively correlated with tumor mutation burden(TMB), microsatellite instability(MSI), and mismatch repair(MMR) genes. CDKN3 was associated with cell cycle, cellular senescence, and the p53 signaling pathway. Furthermore, EdU staining, JC-1 staining, Transwell, and Wound Healing assays confirmed that CDKN3 promoted HCC cell proliferation, invasion, and migration while inhibiting apoptosis. Conclusion Abnormal expression of CDKN3 is closely related to tumor staging, prognosis, and immune microenvironment characteristics, making it a potential prognostic marker and immunotherapy adjuvant target in cancer.

Objective To explore the mechanism of 3-methyladenine(3-MA)for alleviating early diabetic renal injury.Methods Mouse models of streptozotocin(STZ)-induced diabetes mellitus were randomized into model group and 3-MA treatment group for daily treatments with normal saline and 10 mg/kg 3-MA by gavage for 6 weeks,respectively.Body weight and fasting blood glucose of the mice were recorded every week.After the treatments,the kidneys of the mice were collected for measurement kidney/body weight ratio,examination of glomerular size with PAS staining,and detection of α-SMA and PCNA expressions using Western blotting and immunohistochemistry.SV40 MES 13 cells cultured in normal glucose(5.6 mmol/L)and high glucose(30 mmol/L)were treated with 24.4 mmol/L mannitol and 5 mmol/L 3-MA for 24 h,respectively,and the changes in cell viability and PCNA expression were examined using CCK8 assay and Western blotting.Bioinformatics analysis of the intersecting gene targets of diabetic kidney disease(DKD)and 3-MA was performed,and the results were verified by Western blotting both in vivo and in vitro.Results In the diabetic mice,treatment with 3-MA produced a short-term hypoglycemic effect,reduced the kidney/body weight ratio and glomerular hypertrophy,and decreased the expressions of α-SMA and PCNA in the renal cortex.In the in vitro study,3-MA significantly lowered the viability and reduced PCNA expression in SV40 MES 13 cells exposed to high glucose.The results of bioinformatic analysis identified AKT1 as the key gene in the therapeutic mechanism of 3-MA for DKD.Western blotting confirmed that 3-MA inhibited the phosphorylation of AKT and S6 in both the renal cortex of diabetic mice and high glucose-treated SV40 MES 13 cells.Conclusion 3-MA suppresses mesangial cell proliferation and alleviates early diabetic renal injury in mice possibly by inhibiting AKT signaling.

Objective:To investigate the efficacy and safety of venetoclax (VEN) combined with hypomethylating agents (HMA) in the treatment of blastic plasmacytoid dendritic cell neoplasms (BPDCN).Methods:A retrospective case series study was conducted. The clinical data of 5 patients with BPDCN treated with VEN combined with azacitidine (AZA) or decitabine (DAC) in the First Affiliated Hospital of Soochow University and Suzhou Hongci Blood Disease Hospital from February 2017 to July 2023 were collected, and the therapeutic effect, adverse reaction and prognosis of all 5 patients were summarized.Results:All 5 BPDCN patients were male with the median onset age [ M ( Q1, Q3)] of 66 years (51 years, 73 years), of which 4 cases were presented with skin lesions and 1 case was presented with lymphadenopathy as the primary symptom. As for the treatment, 3 patients were initially treated with VEN in combination with AZA induction regimen, among which 2 patients achieved complete remission with incomplete blood count recovery (CRi) after 2 cycles of treatment, survived for 26.5 months and 14.6 months, respectively and finally died, and 1 patient achieved partial remission after 1 cycle of treatment and he still survived after 3-month follow-up; 1 patient was initially treated with VEN in combination with DAC induction regimen, and achieved clinical complete remission of non-active disease with residual skin abnormalities after 2 cycles of treatment followed by allogeneic hematologic stem cell transplantation (allo-HSCT) and he was in the state of disease-free survival for 15-month; and another 1 patient experienced a relapse after treatment with acute lymphocytic leukemia-like regimen in combination with allo-HSCT and again achieved CRi after 2 treatment courses of VEN in combination with AZA regimen, and he was in the state of disease-free survival for 30-month follow-up. Treatment-related haematological adverse effects of VEN combined with HMA were mainly neutropenia with fever, reduction of hemoglobin and thrombocytopenia; and non-haematological adverse effects were mainly gastrointestinal reactions such as nausea and vomiting. These adverse events improved with symptomatic supportive therapy, and no treatment-related deaths occurred. Conclusions:BPDCN patients who are unable to tolerate intensive chemotherapy regimens at initial time of diagnosis may attempt induction therapy with VEN+HMA regimen, which has a manageable adverse reaction and may serve as a bridge to allo-HSCT.

Objective To explore the mechanism of 3-methyladenine(3-MA)for alleviating early diabetic renal injury.Methods Mouse models of streptozotocin(STZ)-induced diabetes mellitus were randomized into model group and 3-MA treatment group for daily treatments with normal saline and 10 mg/kg 3-MA by gavage for 6 weeks,respectively.Body weight and fasting blood glucose of the mice were recorded every week.After the treatments,the kidneys of the mice were collected for measurement kidney/body weight ratio,examination of glomerular size with PAS staining,and detection of α-SMA and PCNA expressions using Western blotting and immunohistochemistry.SV40 MES 13 cells cultured in normal glucose(5.6 mmol/L)and high glucose(30 mmol/L)were treated with 24.4 mmol/L mannitol and 5 mmol/L 3-MA for 24 h,respectively,and the changes in cell viability and PCNA expression were examined using CCK8 assay and Western blotting.Bioinformatics analysis of the intersecting gene targets of diabetic kidney disease(DKD)and 3-MA was performed,and the results were verified by Western blotting both in vivo and in vitro.Results In the diabetic mice,treatment with 3-MA produced a short-term hypoglycemic effect,reduced the kidney/body weight ratio and glomerular hypertrophy,and decreased the expressions of α-SMA and PCNA in the renal cortex.In the in vitro study,3-MA significantly lowered the viability and reduced PCNA expression in SV40 MES 13 cells exposed to high glucose.The results of bioinformatic analysis identified AKT1 as the key gene in the therapeutic mechanism of 3-MA for DKD.Western blotting confirmed that 3-MA inhibited the phosphorylation of AKT and S6 in both the renal cortex of diabetic mice and high glucose-treated SV40 MES 13 cells.Conclusion 3-MA suppresses mesangial cell proliferation and alleviates early diabetic renal injury in mice possibly by inhibiting AKT signaling.

BACKGROUND: Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA. METHODS: A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease. RESULTS: The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production. CONCLUSION Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.
Humans ; Aspergillosis, Allergic Bronchopulmonary/complications* ; Aspergillus fumigatus/genetics* ; Asthma/genetics* ; Aspergillus ; Mutation/genetics* ; CARD Signaling Adaptor Proteins/genetics*

Objective:To investigate the effects of 3-methyladenine(3-MA)on extracellular matrix deposition in early diabetic nephropathy(DN)and its mechanism.Methods:A streptozotocin(STZ)-induced type 1 diabetes mouse model was used, and the mice were divided into vehicle control group, diabetes group(STZ group), 3-MA group, and chloroquine(CQ)group, 8 mice in each group. After 6 weeks of intervention, both kidneys were harvested, and the kidney-to-body weight ratio was recorded. Western blotting was performed to detect protein expressions of renal cortex fibronectin, α-smooth muscle actin(α-SMA), LC3, Beclin 1, p62, and vascular endothelial growth factor(VEGF). Immunohistochemistry was used to observe kidney fibronectin staining. Bioinformatics analysis was conducted on shared genes between diabetic nephropathy(DN)gene targets and 3-MA predicted gene targets.Results:Both 3-MA and CQ exhibited certain hypoglycemic effects in diabetic mice. Compared to the STZ group, the kidney-to-body weight ratio decreased in the 3-MA group( P<0.05). Western blotting showed that 3-MA reduced the expression of renal cortex matrix-related proteins fibronectin and α-SMA in diabetic mice( P<0.05 or P<0.01). Immunohistochemistry also revealed that 3-MA reduced fibronectin staining in the kidneys of diabetic mice. Both 3-MA and CQ inhibited the protein expression of renal cortex Beclin 1 in diabetic mice(both P<0.05), while 3-MA increased the expression of renal cortex p62( P<0.05). Bioinformatics analysis indicated a connection between shared genes of DN gene targets and 3-MA predicted gene targets with the VEGF signaling pathway. Western blotting results further showed that 3-MA reduced renal cortex VEGF expression in diabetic mice( P<0.01). Conclusion:3-MA can alleviate extracellular matrix deposition in the kidneys of early DN mice by inhibiting the VEGF signaling pathway.

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

【Objective】 To share the technical key points and experience of transvesical robot-assisted radical prostatectomy (TvRARP). 【Methods】 The clinical data of 13 patients with prostate cancer (PCa) receiving TvRARP during Nov.2021 and May 2022 were collected. The operation time, estimated blood loss, blood transfusion rate, catheter removal time, postoperative length of hospital stay, immediate urinary continence rate, postoperative IIEF-5 score and perioperative complications were evaluated. 【Results】 The operation time was (142±39) min, estimated intraoperative blood loss was (76±40) mL, and no transfusion was needed. The median postoperative IIEF-5 score was 16 (12-22), hospital stay 3 (2-5)days, and catheter removal time 7(5-14)days. Of all 13 patients, 12(92.3%) achieved immediate urinary continence at the removal of catheter. There were no postoperative complications of Clavien Ⅲ and above. Clavien Ⅰ-Ⅱ complications were observed in 4 patients (30.8%). 【Conclusion】 TvRARP is feasible and safe for selected patients with clinically localized PCa, which can ensure promising postoperative urinary continence and preserve erectile functional.

Objective:To explore the surgical method and clinical effect of forearm arterialized venous flap in repair of soft tissue defects of fingers.Methods:A total of 13 cases of finger soft tissue defects with exposure of deep tissue were repaired with forearm arterialized venous flap from January, 2013 to October, 2019. The flap was designed in the forearm, and 2 parallel superficial veins were selected, the diameter of vein was similar to that at recipient site. The long axis of the flap was the same as that of the vein, and the width of the flap was divided into 3 equal parts by the 2 superficial veins. The free flap was cut longitudinally in the middle between 2 vessels under microscope, and a width of about 2 mm of the subcutaneous tissue was removed to the subdermal vascular network. The communicating branch between 2 vessels was ligated, and the subcutaneous tissue between 2 vessels was cut completely. The flap was not inverted, and the cut area was 3.5 cm× 2.5 cm-7.0 cm×4.0 cm. The proximal ends of the 2 vessels in the flap were anastomosed with the arteries and veins of the recipient area.Results:Thirteen flaps survived, and 9 patient entered follow-up for an average of 11(3-23) months. The flaps were soft and had no effect on the joint movement, slightly bloated. The TPD of flaps was 9 - 18 mm, with an average of 13 mm.Conclusion:Forearm arterialized venous flap has the advantages of high survival rate, satisfactory function, finger pulp-type change, superficial location, easy harvest and no sacrifice of main artery. It is an ideal method for repairing finger soft tissue defects.

Objective:To investigate the diagnosis and clinical characteristics of five elderly patients with Chlamydia psittaci-caused severe pneumonia.Methods:Through retrospective analysis, diagnosis and treatment process and clinical characteristics of five elderly inpatients with severe pneumonia caused by Chlamydia psittaci were summarized in the Department of Critical Care Medicine, Quanzhou First Hospital East Street Branch Area, affiliated to Fujian Medical University between January to June 2021.Results:Five patients with severe pneumonia caused by Chlamydia psittaci were aged from 64 to 74 years, with various underlying diseases such as coronary heart disease, chronic heart failure, chronic obstructive pulmonary disease, etc.All patients had an established history of poultry exposure.These cases had high fever, cough, spitting, and dyspnea as the main clinical manifestations.Some of them also had systemic symptoms or weakness of the limbs as the prodromal symptoms.The disease progressed rapidly, with severe respiratory failure, acute kidney injury, and shock appearing soon, accompanied by different degrees of muscle injury, and damage to the heart, liver, blood coagulation, and immune systems at the same time.Laboratory examination showed that levels of inflammatory indicators were increased: at 3, 5, 7 d after admission, the level of C reactive protein was 214.6(153.9-256.3)mg/L, 199.2(115.8-333.8)mg/L, 151.0(11.19-173.7)mg/L, respectively; and interleukin 6 level was 1 241.0(912.1-6822.0)ng/L, 779.1(451.2-7122.0)ng/L, 631.2(7.0-4 321.0)ng/L, respectively.And monitoring results of nutritional index indicated a high metabolic state.The imaging examinations showed that consolidation and ground-glass shadows spreaded to both lungs, may accompany the miliary and nodular shadows, and may also involve pleural which caused pleural effusion.After the clinical use of metagenomic next-generation sequencing(mNGS), mNGS has been confirmed as an important method for the diagnosis of Chlamydia psittaci infection.The disease course and prognosis were related to the severity of the disease, advanced age, underlying diseases, and timely diagnosis and effective treatment.Conclusions:The progression of Chlamydia psittaci pneumonia to severe disease may be related to advanced age, more basic diseases such as chronic cardiopulmonary disease, smoking, and timely diagnosis and treatment.Generally, laboratory and imaging examinations have no diagnostic specificity, but mNGS is of great significance for early diagnosis, transition to target treatment and improvement of prognosis.