Lung cancer is the leading type of cancer death, and most patients with lung cancer are diagnosed at an advanced stage and have a very poor prognosis. Although low-dose computed tomography (LDCT) has entered the clinic as a screening tool for lung cancer, its false-positive rate is more than 90%. As one of the epigenetic modifications of research hotspots, DNA methylation plays a key role in a variety of diseases, including cancer.Hypermethylation of tumor suppressor genes and hypomethylation of proto-oncogenes are important events in tumorigenesis and development. Therefore, DNA methylation analysis can provide some useful information for the early screening, diagnosis, treatment and prognosis of lung cancer. Although invasive methods such as tissue biopsy remain the gold standard for tumor diagnosis and monitoring, they also have limitations such as inconvenience in sampling. In recent years, there has been a rapid development of liquid biopsy, which can detect primary or metastatic malignancies and reflect the heterogeneity of tumors. In addition, the blood sample can be collected in a minimally invasive or non-invasive format and is well tolerated in older and frail patients. This article explores some of the emerging technologies for DNA methylation analysis and provides an overview of the application of DNA methylation in the diagnosis and treatment of lung cancer.

Purpose To investigate the clinicopathological features and prognosis of alpha-fetoprotein-producing colorectal carcinoma(AFPCRC).Methods 42 cases of AFPCRC from 2 012 colorectal carcinomas of preoperative serum AFP detected and surgically resected were identified.The clinicopathological data of AFPCRC and other 42 cases of conventional colorectal carcinoma exactly matched for age,gender,stage were also col-lected.Immunohistochemical EnVision method was performed to detect the expression of HER2,MMR,p53,AFP,Glypican3,and SALL4.Cases presenting HER2 2+were further analyzed by fluorescence in situ hybridization.Elastic staining was per-formed in cases with ambiguous extramural venous invasion.The clinicopathlogical features and prognosis between two groups were compared.Cases with AFPCRC were divided into high-AFP group and low-AFP group.The clinicopathological features and prognosis of the two groups were compared.Results AF-PCRC accounted for 2.1％(42/2 012)of colorectal carcinoma in the same period.The frequency of extramural vascular inva-sion and moderate/high grade of tumor budding of AFPCRC was 35.7％and 61.9％,while that of control group was 14.3％and 40.5％respectively.The 5-year survival rate of AFPCRC and control group was 66.8％and 85.1％respectively.The differ-ence of aforementioned clinicopathological features between 2 groups was significant(P＜0.05).The proportion of tumor in rectum in the high-AFP group was significantly higher than that in the low-AFP group(61.9％vs 23.8％,P＜0.05).Conclu-sion AFPCRC is a rare subset of colorectal carcinoma,which has a propensity for extramural vessel invasion,moderate-or high-grade of tumor budding and poor prognosis.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To assess the effectiveness and feasibility of carrier detection for Spinal muscular atrophy (SMA) by using digital PCR assay.Methods:Peripheral blood samples were collected from 214 pregnant women who were routinely screened for SMA carriers, of which 204 were randomly selected samples and 10 were samples with known copy numbers of SMN1 exons 7 and 8. Samples with known copy numbers of SMN1 exons 7 and 8 were randomly mixed into the experiment to validate the performance of the digital PCR assay. The copy numbers of SMN1 exons 7 and 8 and SMN2 exons 7 and 8 in peripheral blood samples were detected by digital PCR assay. The results of SMN1 exons 7 and 8 were compared with those of the quantitative PCR method to assess the reliability and clinical performance of the digital PCR assay. Results:Among the 204 random samples, digital PCR has detected five samples with simultaneous heterozygous deletion of SMN1 exons 7 and 8, three samples with heterozygous deletion of SMN1 exon 8 only, and 196 samples with no deletion of SMN1 exons 7 and 8. Ten samples with known SMN1 exons 7 and 8 copy numbers were detected with the expected values. The digital PCR test results were fully consistent with that of the quantitative PCR. Conclusion:The results of digital PCR for the detection of copy number variation of SMN1 exons 7 and 8 were consistent with qPCR. Digital PCR assay was able to clearly distinguish the copy number of the target genes, therefore can be used for SMA carrier screening. Moreover, it can also detect copy number of SMN2 exons 7 and 8, which can provide more information for genetic counseling.

Prepubertal-type testicular neuroendocrine tumor is a rare neoplasm of low malignant potential, which is classified as germ cell tumors unrelated to germ cell neoplasia in situ, and needs to be differentiated from metastatic neuroendocrine tumor, postpubertal-type testicular neuroendocrine tumor, and testicular seminoma. The clinicopathological and molecular features of a case of prepubertal-type testicular neuroendocrine tumor were reported. The tumour cells were uniform in size and arranged in nested and insular pattern. The tumor was positive for CgA and Syn, and the Ki-67 index was less than 2% by immunostaining. Next-generation sequencing identified no variants of pathogenicity, potential pathogenicity or uncertain significance. The patient was followed without evidence of recurrence and metastasis 56 months after surgery.

Purpose: We aimed to identify effectiveness-associated indicators and evaluate the optimal tumor reduction rate (TRR) after two cycles of neoadjuvant chemotherapy (NAC) in patients with invasive breast cancer. Methods: This retrospective case-control study included patients who underwent at least four cycles of NAC at the Department of Breast Surgery between February 2013 and February 2020. A regression nomogram model for predicting pathological responses was constructed based on potential indicators. Results: A total of 784 patients were included, of whom 170 (21.68%) reported pathological complete response (pCR) after NAC and 614 (78.32%) had residual invasive tumors. The clinical T stage, clinical N stage, molecular subtype, and TRR were identified as independent predictors of pCR. Patients with a TRR > 35% were more likely to achieve pCR (odds ratio, 5.396; 95% confidence interval [CI], 3.299–8.825). The receiver operating characteristic (ROC) curve was plotted using the probability value, and the area under the ROC curve was 0.892 (95% CI, 0.863–0.922). Conclusion TRR > 35% is predictive of pCR after two cycles of NAC, and an early evaluation model using a nomogram based on five indicators, age, clinical T stage, clinical N stage, molecular subtype, and TRR, is applicable in patients with invasive breast cancer.

Hepatic cholesterol accumulation is an important contributor to hypercholesterolemia, which results in atherosclerosis and cardiovascular disease (CVD). ATP-citrate lyase (ACLY) is a key lipogenic enzyme that converts cytosolic citrate derived from tricarboxylic acid cycle (TCA cycle) to acetyl-CoA in the cytoplasm. Therefore, ACLY represents a link between mitochondria oxidative phosphorylation and cytosolic de novo lipogenesis. In this study, we developed the small molecule 326E with an enedioic acid structural moiety as a novel ACLY inhibitor, and its CoA-conjugated form 326E-CoA inhibited ACLY activity with an IC₅₀ = 5.31 ± 1.2 μmol/L in vitro. 326E treatment reduced de novo lipogenesis, and increased cholesterol efflux in vitro and in vivo. 326E was rapidly absorbed after oral administration, exhibited a higher blood exposure than that of the approved ACLY inhibitor bempedoic acid (BA) used for hypercholesterolemia. Chronic 326E treatment in hamsters and rhesus monkeys resulted in remarkable improvement of hyperlipidemia. Once daily oral administration of 326E for 24 weeks prevented the occurrence of atherosclerosis in ApoE^-/- mice to a greater extent than that of BA treatment. Taken together, our data suggest that inhibition of ACLY by 326E represents a promising strategy for the treatment of hypercholesterolemia.

OBJECTIVE: To explore the effectiveness of the percutaneous parallel screw fixation via the posterolateral "safe zone" for Hawkins type Ⅰ-Ⅲ talar neck fractures. METHODS: A retrospective analysis was conducted on the clinical data from 35 patients who met the selection criteria of talar neck fractures between January 2019 and June 2021. According to the surgical method, they were divided into a study group (14 cases, using percutaneous posterolateral "safe zone" parallel screw fixation) and a control group (21 cases, using traditional open reduction and anterior cross screw internal fixation). There was no significant difference in gender, age, affected side, Hawkins classification, and time from injury to operation between the two groups ( P>0.05). The operation time, bone healing time, complications, and Hawkins sign were recorded, and the improvement of pain and ankle-foot function were evaluated by visual analogue scale (VAS) score and American Orthopaedic Foot and Ankle Society (AOFAS) ankle and hindfoot score at last follow-up. The overall quality of life was assessed by the short form of 12-item health survey (SF-12), which was divided into physical and psychological scores; and the satisfaction of patients was evaluated by the 5-point Likert scale. RESULTS: The operation time in the study group was significantly shorter than that in the control group ( P<0.05). All patients werefollowed up 13-35 months, with an average of 20.6 months; there was no significant difference in the follow-up time between the two groups ( P>0.05). The time of bone healing in the study group was shorter than that in the control group, and the positive rate of Hawkins sign (83.33%) was higher than that in the control group (33.33%), and the differences were significant ( P<0.05). In the control group, there were 2 cases of incision delayed healing, 7 cases of avascular necrosis of bone, 3 cases of joint degeneration, 1 case of bone nonunion, and 3 cases of internal fixation irritation; while in the study group, there were only 2 cases of joint degeneration, and there was a significant difference in the incidence of complications between the two groups ( P<0.05). At last follow-up, there was no significant difference in VAS score between the two groups ( P>0.05), but the SF-12 physical and psychological scores, AOFAS ankle and hindfoot scores, and patients' satisfaction in the study group were significantly better than those in the control group ( P<0.05). CONCLUSION The treatment of Hawkins type Ⅰ-Ⅲ talar neck fractures with percutaneous parallel screw fixation via the posterolateral "safe zone" can achieve better effectiveness than traditional open surgery, with the advantages of less trauma, fewer complications, faster recovery, and higher patient satisfaction.
Humans ; Retrospective Studies ; Quality of Life ; Fractures, Bone/surgery* ; Fracture Fixation, Internal/methods* ; Bone Screws ; Joint Dislocations ; Treatment Outcome

OBJECTIVES: To investigate genotype-phenotype characteristics and long-term prognosis of neonatal carbamoyl phosphate synthetase 1 (CPS1) deficiency among children through newborn screening in Zhejiang province. METHODS: The clinical and follow-up data of children with CPS1 deficiency detected through neonatal screening and confirmed by tandem mass spectrometry and genetic testing in Zhejiang Province Newborn Disease Screening Center from September 2013 to August 2023 were retrospectively analyzed. RESULTS: A total of 4 056 755 newborns were screened and 6 cases of CPS1 deficiency were diagnosed through phenotypic and genetic testing. Ten different variations of CPS1 genewere identified in genetic testing, including 2 known pathogenic variations (c.2359C>T and c.1549+1G>T) and 8 unreported variations (c.3405-1G>T, c.2372C>T, c.1436C>T, c.2228T>C, c.2441G>A, c.3031G>A, c.3075T>C and c.390-403del). All patients had decreased citrulline levels (2.72-6.21 μmol/L), and varying degrees of elevated blood ammonia. The patients received restricted natural protein intake (special formula), arginine and supportive therapy after diagnosis, and were followed-up for a period ranging from 9 months to 10 years. Three patients experienced hyperammonemia, and one patient each had attention deficit hyperactivity disorder, transient facial twitching and increased muscle tone. One patient died, while the other five surviving patients had normal scores of the Ages & Stages Questionnaires (ASQ) and Griffiths Development Scales up to the present time; 4 cases had combined height or weight lag and one case was normal in height and weight. CONCLUSIONS Low citrulline levels and hyperammonemia are common in CPS1 deficiency patients in Zhejiang. Most gene variants identified were specific to individual families, and no hotspot mutations were found. Early diagnosis through newborn screening and following standardized treatment can significantly improve the prognosis of the patients.
Child ; Humans ; Infant, Newborn ; Carbamoyl-Phosphate Synthase I Deficiency Disease/therapy* ; Neonatal Screening ; Follow-Up Studies ; Hyperammonemia ; Citrulline/genetics* ; Retrospective Studies ; Mutation

An 11-day-old female neonate was admitted for cough with mouth foaming and feeding difficulties. The laboratory results indicated hyperlactatemia, elevated markers of myocardial injury and inflammation, and high levels of acylcarnitine octanoylcarnitine and decanoylcarnitine in tandem mass spectrometry. Ultrasonography and MRI suggested cardiac insufficiency and hypertrophic cardiomyopathy. Whole exome sequencing showed that both the proband and her elderly sister had a compound heterozygous variant of c.1492dup (p.T498Nfs*13) and c.1376T>C (p.F459S) in the ATAD3A gene, inherited from their father and mother, respectively. The diagnosis of Harel-Yoon syndrome was confirmed. The proband and her sister were born with clinical manifestations of metabolic acidosis, hyperlactatemia, feeding difficulties, elevated markers of myocardial injury as well as cardiac insufficiency, and both died in early infancy.
Humans ; Infant, Newborn ; Female ; Aged ; Mutation ; Hyperlactatemia ; ATPases Associated with Diverse Cellular Activities/chemistry* ; Membrane Proteins/genetics* ; Mitochondrial Proteins/genetics*