Bone marrow suppression is one of the common adverse reactions to radiotherapy and chemotherapy. Anticancer treatments such as radiotherapy and chemotherapy first directly damage the patient′s peripheral blood cells, impairing qi and blood; further, they damage the actively proliferating cell populations in the bone marrow, impairing yin and blood; and then they interfere with hematopoietic stem cells, impairing essence and blood. This process is rapid and intense, consistent with the characteristics of " acute deficiency syndrome" , marked by sudden onset, rapid changes, critical condition, complexity and variability, multiple complications, and poor prognosis. Given this, its diagnosis and treatment should differ from those of general deficiency syndromes. This paper advocates the principles and ideas of diagnosis and treatment such as " preventing first and treating early to prevent changes; supplementing for deficiency and strengthening vital qi to eliminate pathogenic factor; urgent rescue for critical conditions, no time to lose; and comprehensive supplementing throughout the process, with severe cases requiring singular action" . This approach is intended to provide theoretical reference and practical guidance for bone marrow suppression after radiotherapy and chemotherapy.

The interaction between m⁶A-methylated RNA and chromatin modification remains largely unknown. We found that targeted inhibition of bromodomain-containing protein 4 (BRD4) by siRNA or its inhibitor (JQ1) significantly decreases mRNA m⁶A levels and suppresses the malignancy of breast cancer (BC) cells via increased expression of demethylase AlkB homolog 5 (ALKBH5). Mechanistically, inhibition of BRD4 increases the mRNA stability of ALKBH5 via enhanced binding between its 3' untranslated regions (3'UTRs) with RNA-binding protein RALY. Further, BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21 (TRIM21) and ALKBH5, resulting in the ubiquitination and degradation of ALKBH5 protein. JQ1-increased ALKBH5 then demethylates mRNA of extra spindle pole bodies like 1 (ESPL1) and reduces binding between ESPL1 mRNA and m⁶A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3), leading to decay of ESPL1 mRNA. Animal and clinical studies confirm a critical role of BRD4/ALKBH5/ESPL1 pathway in BC progression. Further, our study sheds light on the crosstalks between histone modification and RNA methylation.

Acute pancreatitis (AP) is a life-threatening gastrointestinal disorder for which no effective pharmacological treatments are currently available. One of the pharmacological targets that merits further research is the neurokinin 1 receptor (NK1R), which is found on pancreatic acinar cells and responds to the neuropeptide substance P (SP) that participates in AP. Although a few studies have stated the involvement of SP/NK1R in neurogenic inflammation in AP development, the regulatory mechanism remains unclear. In this study, we found that following activation of NK1R by SP, β-arrestin1, a scaffold protein of NK1R, down-regulated transcription of Adss, Adsl, and Ampd in the purine nucleotide cycle, thereby inhibiting mitochondrial function through fumarate depletion. Interestingly, we identified magnolol as a new and natural NK1R inhibitor with a non-nitrogenous biphenyl core structure. It exhibited a beneficial effect on AP by restoring purine nucleotide cycle metabolic enzymes and fumarate levels. Our study not only provides new therapeutic strategies, leading compounds, and drug translation possibilities for AP, but also provides important clues for the study of downstream mechanisms driven by SP in other diseases.

Objective:To reassess the prognostic value of minimal residual disease (MRD) and IKZF1 gene deletions in adults with B-cell acute lymphoblastic leukemia (B-ALL) who received pediatric-specific chemotherapy regimens during the Nanfang Hospital PDT-ALL-2016 trial.Methods:We retrospectively analyzed the prognosis of 149 adult patients with B-ALL who were admitted to Nanfang Hospital from January 2016 to September 2020. Prognostic factors were identified using Cox regression models.Results:The complete remission rate was 93.2% in 149 patients, with a 5-year overall survival (OS) rate of (54.3±5.0) % and a cumulative incidence of relapse (CIR) of (47.5±5.2) %. The Cox regression analysis revealed that MRD positivity at day 45 (MRD 3) after induction therapy was independently associated with relapse risk ( HR=2.535, 95% CI 1.122-5.728, P=0.025). Deletion of IKZF1 gene was independently associated with mortality risk ( HR=1.869, 95% CI 1.034-3.379, P=0.039). Based on MRD 3 and IKZF1 gene status, we categorized adult patients with B-ALL into the low-risk (MRD 3-negative and IKZF1 gene deletion-negative) and high-risk (MRD 3-positive and/or IKZF1 gene wild type) groups. The 5-year OS and CIR rates were (45.5±6.0) % vs (69.4±8.6) % ( P<0.001) and (61.6±8.3) % vs (25.5±6.5) % ( P<0.001), respectively, in the high-risk and low-risk groups, respectively. The multivariate analysis showed that the high-risk group was an independent risk factor for OS ( HR=3.937, 95% CI 1.975-7.850, P<0.001) and CIR ( HR=4.037, 95% CI 2.095-7.778, P<0.001) . Conclusion:The combined use of MRD and IKZF1 gene in prognostic stratification can improve clinical outcome prediction in adult patients with B-ALL, helping to guide their treatment.

Background: Insulin resistance (IR) is the key pathological basis of many metabolic disorders. Lack of asialoglycoprotein receptor 1 (ASGR1) decreased the serum lipid levels and reduced the risk of coronary artery disease. However, whether ASGR1 also participates in the regulatory network of insulin sensitivity and glucose metabolism remains unknown. Methods: The constructed ASGR1 knockout mice and ASGR1-/- HepG2 cell lines were used to establish the animal model of metabolic syndrome and the IR cell model by high-fat diet (HFD) or drug induction, respectively. Then we evaluated the glucose metabolism and insulin signaling in vivo and in vitro. Results: ASGR1 deficiency ameliorated systemic IR in mice fed with HFD, evidenced by improved insulin intolerance, serum insulin, and homeostasis model assessment of IR index, mainly contributed from increased insulin signaling in the liver, but not in muscle or adipose tissues. Meanwhile, the insulin signal transduction was significantly enhanced in ASGR1-/- HepG2 cells. By transcriptome analyses and comparison, those differentially expressed genes between ASGR1 null and wild type were enriched in the insulin signal pathway, particularly in phosphoinositide 3-kinase-AKT signaling. Notably, ASGR1 deficiency significantly reduced hepatic gluconeogenesis and glycogenolysis. Conclusion The ASGR1 deficiency was consequentially linked with improved hepatic insulin sensitivity under metabolic stress, hepatic IR was the core factor of systemic IR, and overcoming hepatic IR significantly relieved the systemic IR. It suggests that ASGR1 is a potential intervention target for improving systemic IR in metabolic disorders.

The rise in global life expectancy has led to an increase in the older population, presenting significant challenges in managing infectious diseases. Aging affects the innate and adaptive immune systems, resulting in chronic low-grade inflammation (inflammaging) and immune function decline (immunosenescence). These changes would impair defense mechanisms, increase susceptibility to infections and reduce vaccine efficacy in older adults. Cellular senescence exacerbates these issues by releasing pro-inflammatory factors, further perpetuating chronic inflammation. Moreover, comorbidities, such as cardiovascular disease and diabetes, which are common in older adults, amplify immune dysfunction, while immunosuppressive medications further complicate responses to infections. This review explores the molecular and cellular mechanisms driving inflammaging and immunosenescence, focusing on genomic instability, telomere attrition, and mitochondrial dysfunction. Additionally, we discussed how aging-associated immune alterations influence responses to bacterial, viral, and parasitic infections and evaluated emerging antiaging strategies, aimed at mitigating these effects to improve health outcomes in the aging population.
Humans ; Aging/physiology* ; Communicable Diseases/immunology* ; Immunosenescence/physiology* ; Inflammation/immunology* ; Genomic Instability

As the main weapon of cellular immunity,CD4+ T cells play a vital role in controlling and eliminating infections,and are an important barrier for the body to resist infections.Respiratory tract infectious diseases caused by influenza virus infection have extremely high infectivity,morbidity and mortality.The infection mechanism is relatively complicated and has not been fully ex-plained.The exuberant immune response induced by the body after influenza virus infection is described as a"cytokine storm"which is related to pro-inflammatory cytokines and tissue damage,which may eventually lead to acute lung injury.Therefore,this article sum-marizes the current research progress,focusing on the mechanism of CD4+T cells in the cytokine storm induced by influenza virus in-fection and the impact of acute lung injury,providing relevant ideas and theoretical guidance for follow-up research,with a view to the disease caused by influenza virus bring new and effective methods of diagnosis and treatment.

Objective:To analyze the incidence of recent complications in patients with osteoarthritis of the knee (OA) after medial opening wedge high tibial osteotomy(MOWHTO) and its influence on clinical effect.Methods:The clinical data of 131 patients with knee OA who received MOWHTO at Department of Sports Medicine and Arthroscopy,Tianjin Hospital from April 2017 to September 2018 were analyzed retrospectively. There were 75 males and 56 females, aged (62.8±5.1) years (range:48 to 70 years). Complications and clinical outcomes of patients were recorded and the proximal medial angle of tibia (MPTA), the International Knee Documentation Committee Subjective Knee Form (IKDC), the Western Ontario and McMaster Universities(WOMAC) Osteoarthritis Index and Knee Injury and Osteoarthritis Outcome score(KOOS) were collected before and 1 year after operation and compared between complication group and non-complication group. Data were analyzed by paired-samples t test, independent samples t test and χ 2 test. Results:The follow-up time was (18.5±3.4) months (range:13 to 22 months). Complications occurred in 22 patients(16.8%), including 8 cases(6.1%) of hematoma, 5 cases(3.8%) of neurosensory abnormality, 4 cases(3.1%) of intramuscular venous thrombosis, 2 cases(1.5%) of deep venous thrombosis, 3 cases(2.3%) of loss of correction angle, 3 cases(2.3%) of superficial infection, 2 cases(1.5%) of deep infection, 2 cases(1.5%) of delayed union of fracture, 1 case(0.8%) of postoperative stiffness, 1 case (0.8%) of hinge point cortex fracture. There were no significant difference in MPTA ((86.5±2.0)° vs. (86.7±2.1)°, t=-0.41, P=0.68) , IKDC ((86.4±4.8) vs.(85.5±6.9), t=0.74, P=0.50) , WOMAC ((87.7±6.5) vs. (86.1±5.8), t=1.16, P=0.25). There were no significant difference in knee scores except for the KOOS pain score ((79.4±4.4) vs. (87.2±5.9), t=-5.90, P<0.01) and sports and recreation score ((83.2±3.0) vs. (88.0±4.7), t=-6.14, P<0.01) . Conclusion:Short-term complications of MOWHTO can be managed appropriately through early diagnosis and individualized treatment and have no significant negative effect on knee function recovery of patients.

Objective:To analyze the incidence of recent complications in patients with osteoarthritis of the knee (OA) after medial opening wedge high tibial osteotomy(MOWHTO) and its influence on clinical effect.Methods:The clinical data of 131 patients with knee OA who received MOWHTO at Department of Sports Medicine and Arthroscopy,Tianjin Hospital from April 2017 to September 2018 were analyzed retrospectively. There were 75 males and 56 females, aged (62.8±5.1) years (range:48 to 70 years). Complications and clinical outcomes of patients were recorded and the proximal medial angle of tibia (MPTA), the International Knee Documentation Committee Subjective Knee Form (IKDC), the Western Ontario and McMaster Universities(WOMAC) Osteoarthritis Index and Knee Injury and Osteoarthritis Outcome score(KOOS) were collected before and 1 year after operation and compared between complication group and non-complication group. Data were analyzed by paired-samples t test, independent samples t test and χ 2 test. Results:The follow-up time was (18.5±3.4) months (range:13 to 22 months). Complications occurred in 22 patients(16.8%), including 8 cases(6.1%) of hematoma, 5 cases(3.8%) of neurosensory abnormality, 4 cases(3.1%) of intramuscular venous thrombosis, 2 cases(1.5%) of deep venous thrombosis, 3 cases(2.3%) of loss of correction angle, 3 cases(2.3%) of superficial infection, 2 cases(1.5%) of deep infection, 2 cases(1.5%) of delayed union of fracture, 1 case(0.8%) of postoperative stiffness, 1 case (0.8%) of hinge point cortex fracture. There were no significant difference in MPTA ((86.5±2.0)° vs. (86.7±2.1)°, t=-0.41, P=0.68) , IKDC ((86.4±4.8) vs.(85.5±6.9), t=0.74, P=0.50) , WOMAC ((87.7±6.5) vs. (86.1±5.8), t=1.16, P=0.25). There were no significant difference in knee scores except for the KOOS pain score ((79.4±4.4) vs. (87.2±5.9), t=-5.90, P<0.01) and sports and recreation score ((83.2±3.0) vs. (88.0±4.7), t=-6.14, P<0.01) . Conclusion:Short-term complications of MOWHTO can be managed appropriately through early diagnosis and individualized treatment and have no significant negative effect on knee function recovery of patients.

Objective To investigate the feasibility of non-operative management (NOM) by comparing the therapeutic effects between NOM and total mesorectal excision (TME) for rectal cancer patients with clinical complete response (cCR) after neo-adjuvant chemoradiotherapy.Methods A total of 135 patients with stage Ⅱ/Ⅲ rectal cancer who obtained cCR after neo-adjuvant chemoradiotherapy in Sun Yat-sen University Cancer Center from 2006 to 2016 were recruited and assigned into the NOM (n =43) and standard operative management (SOM) groups (n=92).The local recurrence rate,accumulative local control (LC) rate after salvage therapy,disease-free survival (DFS),overall survival (OS) and sphincter preservation rate were statistically compared between two groups.Kaplan-Meier analysis and log-rank test were utilized to calculate the LC,OS and DFS.Chi-square test was performed to calculate the sphincter preservation rate.Results The mean follow-up duration was 39 months (range:10-127 months).Of 135 patients,the local recurrence rate and distant metastasis rate were 3.7％ and 11.1％,and the 3-year DFS and OS were 90.5％ and 97.0％.In the NOM and SOM groups,the 3-year DFS were 87％ and 93％,and the 5-year DFS were 73％ and 87％(P=0.089).The 3-year OS were 98％ and 99％,and the 5-year OS were 98％ and 97％ (P=0.578).In the NOM group,the local recurrence rate was 12％ (n =5),80％ of patients received salvage treatment and the accumulative LC rate was calculated as 98％.In the SOM group,the local recurrence rate was 0,which was significantly lower than that in the NOM group (P=0.O10).In the NOM group,the sphincter preservation rate was 93％,significantly higher compared with 70％ in the SOM group (P=0.030).Conclusions It is feasible for rectal cancer patients with cCR to receive NOM following neo-adjuvant chemoradiotherapy.Partial locally recurrent patients can be healed by timely salvage therapy,thereby averting TME and relevant complications and enhancing the quality of life of rectal cancer patients.