Objective: To explore the correlation between the composition of bone marrow lymphocyte subsets and the clinical attributes observed in de novo AML patients, as well as their influence on prognosis. Methods: A detailed study was carried out on a cohort of 191 de novo acute myeloid leukemia patients who were admitted to our medical center between October 2022 and September 2024. In addition, a group of 24 patients with iron deficiency anemia individuals was carefully chosen as the control cohort. The proportions of lymphocyte subsets within the bone marrow of de novo AML patients were analyzed. Furthermore, an in-depth analysis was performed to investigate the association between the expression levels of these subsets in de novo AML patients and their clinical attributes, as well as their prognostic implications. Results: The proportion of CD19 and CD56 lymphocytes within the bone marrow of de novo AML patients significantly diminished compared to the control cohort (8.5% vs 13.2% P<0.05, and 15.5% vs 18.0%, P<0.05). Conversely, no significant discrepancies were observed in the CD3 , CD3 CD4 , and CD3 CD8 lymphocyte percentages between the AML patients and control group (71.7% vs 72.1%, 32.5% vs 33.7% and 32.8% vs 35.7%, P>0.05). When analyzing the relationships between lymphocyte subsets within the bone marrow of de novo patients and their respective clinical characteristics, patients aged 60 years and above exhibited diminished percentages of CD3 CD8 lymphocytes in the bone marrow compared to their younger counterparts (31.6% vs 34.1%, P<0.05), while the CD56 lymphocyte subsets demonstrated an increased prevalence (17.2% vs 14.4%, P<0.05). Furthermore, patients with leukocytosis (WBC≥100×10 /L) presented lower levels of CD3 and CD3 CD4 lymphocytes in the bone marrow compared with those without it (65.3% vs 72.9% P<0.05, and 28.9% vs 33.2%, P<0.05), respectively. The AML1-ETO fusion gene-positive cohort exhibited a higher prevalence of CD3 CD8 lymphocytes in the bone marrow than in the negative group (38.2% vs 32.3%, P<0.05), whereas the FLT3-ITD mutation-positive group presented a decreased prevalence of CD56 lymphocytes compared with the negative group (12.4% vs 16.8%, P<0.05). In addition, the NPM1 mutation-positive group demonstrated lower levels of CD3 CD8 lymphocytes in the bone marrow than in the negative group (29.1% vs 33.3%, P<0.05). Variables such as tumor protein p53(TP53) mutation positive, the absence of hematopoietic stem cell transplantation, and CD3 CD4 lymphocyte proportions below 25% were identified as independent adverse prognostic indicators for AML patients (P<0.05). Conclusion: The pathogenesis of AML is closely associated with an imbalance in bone marrow lymphocyte subsets. The FLT3-ITD mutation potentially contributes to the dysregulation of CD56 lymphocyte subset expression. The AML1-ETO fusion gene and NPM1 mutation are implicated in the abnormal expression of CD3 CD8 lymphocytes within the bone marrow. Moreover, the percentage of CD3 CD4 lymphocytes in the bone marrow serves as a prognostic factor for de novo AML patients.

Objective: To explore the correlation between the composition of bone marrow lymphocyte subsets and the clinical attributes observed in de novo AML patients, as well as their influence on prognosis. Methods: A detailed study was carried out on a cohort of 191 de novo acute myeloid leukemia patients who were admitted to our medical center between October 2022 and September 2024. In addition, a group of 24 patients with iron deficiency anemia individuals was carefully chosen as the control cohort. The proportions of lymphocyte subsets within the bone marrow of de novo AML patients were analyzed. Furthermore, an in-depth analysis was performed to investigate the association between the expression levels of these subsets in de novo AML patients and their clinical attributes, as well as their prognostic implications. Results: The proportion of CD19 and CD56 lymphocytes within the bone marrow of de novo AML patients significantly diminished compared to the control cohort (8.5% vs 13.2% P<0.05, and 15.5% vs 18.0%, P<0.05). Conversely, no significant discrepancies were observed in the CD3 , CD3 CD4 , and CD3 CD8 lymphocyte percentages between the AML patients and control group (71.7% vs 72.1%, 32.5% vs 33.7% and 32.8% vs 35.7%, P>0.05). When analyzing the relationships between lymphocyte subsets within the bone marrow of de novo patients and their respective clinical characteristics, patients aged 60 years and above exhibited diminished percentages of CD3 CD8 lymphocytes in the bone marrow compared to their younger counterparts (31.6% vs 34.1%, P<0.05), while the CD56 lymphocyte subsets demonstrated an increased prevalence (17.2% vs 14.4%, P<0.05). Furthermore, patients with leukocytosis (WBC≥100×10 /L) presented lower levels of CD3 and CD3 CD4 lymphocytes in the bone marrow compared with those without it (65.3% vs 72.9% P<0.05, and 28.9% vs 33.2%, P<0.05), respectively. The AML1-ETO fusion gene-positive cohort exhibited a higher prevalence of CD3 CD8 lymphocytes in the bone marrow than in the negative group (38.2% vs 32.3%, P<0.05), whereas the FLT3-ITD mutation-positive group presented a decreased prevalence of CD56 lymphocytes compared with the negative group (12.4% vs 16.8%, P<0.05). In addition, the NPM1 mutation-positive group demonstrated lower levels of CD3 CD8 lymphocytes in the bone marrow than in the negative group (29.1% vs 33.3%, P<0.05). Variables such as tumor protein p53(TP53) mutation positive, the absence of hematopoietic stem cell transplantation, and CD3 CD4 lymphocyte proportions below 25% were identified as independent adverse prognostic indicators for AML patients (P<0.05). Conclusion: The pathogenesis of AML is closely associated with an imbalance in bone marrow lymphocyte subsets. The FLT3-ITD mutation potentially contributes to the dysregulation of CD56 lymphocyte subset expression. The AML1-ETO fusion gene and NPM1 mutation are implicated in the abnormal expression of CD3 CD8 lymphocytes within the bone marrow. Moreover, the percentage of CD3 CD4 lymphocytes in the bone marrow serves as a prognostic factor for de novo AML patients.

Objective:To observe the clinical outcomes of continued pregnancy in pregnant women with cesarean scar pregnancy (CSP).Methods:A retrospective analysis was performed on the pregnancy outcomes of 55 pregnant women who were diagnosed with CSP at the Second Affiliated Hospital of Army Medical University during the first trimester of pregnancy from August 1st, 2018 to October 31st, 2021 and strongly requested to continue the pregnancy.Results:Of the 55 pregnant women, 15 terminated the pregnancy in the first trimester, 1 underwent hysterotomy at 23 weeks of gestation due to cervical dilation, and 39 (71%, 39/55) continued pregnancy to the third trimester achieving live births via cesarean section. The gestational age of the 39 pregnant women delivered by cesarean section was 35 +6 weeks (range: 28 +5-39 +2 weeks), of whom 7 cases at 28 +5-33 +6 weeks, 20 cases at 34-36 +6 weeks, and 12 cases at 37-39 +2 weeks. The results of pathological examination were normal placenta in 3 cases (8%, 3/39), placenta creta in 4 cases (10%, 4/39), placenta increta in 9 cases (23%, 9/39) and placenta percreta in 23 cases (59%, 23/39). Among the 36 pregnant women who were pathologically confirmed as placenta accreta spectrum disorders (PAS) after surgery, the last prenatal ultrasonography showed placenta previa in 27 cases (75%, 27/36) and not observed placenta previa in 9 cases. The median intraoperative blood loss, autologous blood transfusion, and allogeneic suspended red blood cell infusion of 39 pregnant women during cesarean section were 1 000 ml (300-3 500 ml), 300 ml (0-2 000 ml) and 400 ml (0-2 400 ml), respectively. The uterine preservation rate was 100% (39/39), and only 1 case received cystostomy due to intracystic hemorrhage. The birth weight of the newborn was 2 580 g (1 350-3 800 g), and 1 case of mild asphyxia. Conclusions:Pregnant women with CSP who continue pregnancy under close monitoring after adequate ultrasound evaluation and doctor-patient communication could achieve better maternal and infant outcomes, but pregnant women with CSP are highly likely to continue pregnancy and develop into PAS. Effective hemostasis means and multidisciplinary team cooperation are needed in perinatal period for ensuring maternal and fetal safety.

Objective:To compare the prognoses of salvage liver transplantation fulfilling the Criteria of Milan, University of California San Francisco(UCSF)and Hangzhou.Methods:Clinical data were retrospectively reviewed for 256 patients with recurrent hepatocellular carcinoma(HCC)undergoing donation after citizen death(DCD)liver transplantation(LT)from January 2015 to October 2019.They were divided into two groups of primary(PLT, n=175)and salvage(SLT, n=81). General profiles, tumor pathological characteristics and postoperative complications of two groups were compared by T-test, rank-sum or χ2 test.Kaplan-Meier method and Log rank test were employed for comparing overall survival rate(OS)and recurrence-free survival rate(RFS)between two groups.In SLT group, 31 cases fulfilled Milan criteria, 45 cases UCSF criteria and 69 cases Hangzhou criteria.OS/RFS of three groups were compared.According to there was downstaging or bridging treatment pre-LT, SLT group was divided into downstaging group(n=32)and non-downstaging group(n=49). OS/RFS of two groups were compared.According to the Rescit1.1 criteria, downstaging group were divided into remission group(n=14)and non-remission group(n=18)and OS/RFS of two groups were compared. Results:The operative durations of PLT and SLT groups were(439.5±74.9)and(475.1±83.4)min respectively.There was significant inter-group difference( P<0.05); However, no significant inter-group difference existed in amount of intraoperative bleeding, blood transfusion, postoperative hospital stay or incidence of postoperative complications(all P>0.05). No significant difference existed in OS/RFS between PLT and SLT groups( P>0.05). No significant difference existed in OS at 1/3/5 years post-SLT among Milan, UCSF and Hangzhou criteria groups(all P>0.05); However, RFS in Milan criteria group at 1/3/5 years post-SLT were 93.5%, 81.7% and 81.7% respectively.They were significantly higher than 68.9%, 59.7% and 59.7% in UCSF criteria group and 78.3%, 58.8% and 55.5% in Hangzhou criteria group(all P<0.05). For patients on downstaging therapy, OS in the Remission group at 1, 3 and 5 years post-SLT were 100%, 73% and 73% respectively, which was significantly higher than 83.3%, 49.4% and 0 in non-Remission group( P=0.042). RFS in the Remission group at 1, 3 and 5 years post-SLT were 100%, 62.5% and 46.9% respectively, which was significantly higher than 52.9%, 0 and 0 in no-Remission group( P=0.001). Conclusions:The survival outcome of SLT recipients is similar to that of PLT recipients.The overall survival of SLT recipients shows no significant difference between Milan, UCSF and Hangzhou criteria.However, SLT recipients fulfilling Milan criteria have the longest recurrence-free time.The prognosis of patients with remission after preoperative descending treatment is superior to that of patients without remission.

Cabozantinib, mainly targeting cMet and vascular endothelial growth factor receptor 2, is the second-line treatment for patients with advanced hepatocellular carcinoma (HCC). However, the lower response rate and resistance limit its enduring clinical benefit. In this study, we found that cMet-low HCC cells showed primary resistance to cMet inhibitors, and the combination of cabozantinib and mammalian target of rapamycin (mTOR) inhibitor, rapamycin, exhibited a synergistic inhibitory effect on the in vitro cell proliferation and in vivo tumor growth of these cells. Mechanically, the combination of rapamycin with cabozantinib resulted in the remarkable inhibition of AKT, extracellular signal-regulated protein kinases, mTOR, and common downstream signal molecules of receptor tyrosine kinases; decreased cyclin D1 expression; and induced cell cycle arrest. Meanwhile, rapamycin enhanced the inhibitory effects of cabozantinib on the migration and tubule formation of human umbilical vascular endothelial cells and human growth factor-induced invasion of cMet inhibitor-resistant HCC cells under hypoxia condition. These effects were further validated in xenograft models. In conclusion, our findings uncover a potential combination therapy of cabozantinib and rapamycin to combat cabozantinib-resistant HCC.
Anilides/pharmacology* ; Animals ; Carcinoma, Hepatocellular/drug therapy* ; Cell Line, Tumor ; Cell Proliferation ; Endothelial Cells/metabolism* ; Humans ; Liver Neoplasms/drug therapy* ; Pyridines/pharmacology* ; Sirolimus/pharmacology* ; Xenograft Model Antitumor Assays

【Objective】 To assess three severe acute respiratorysyndrome coronavirus 2 (SARS-CoV-2) enzyme linked immunosorbent assays (ELISA) and one pseudotype lentivirus-based neutralization test (ppNAT) in detecting the convalescent plasma antibody levles from COVID-19. 【Methods】 30 COVID-19 convalescent plasma samples were screened for antibodies against SARS-CoV-2 using three kinds of SARS-CoV-2 ELISA reagents and one ppNAT test in Shenzhen. The controls consisted of plasma samples from 32 healthy blood donors in February 2019. The diagnostic efficacy analysis of various SARS-CoV-2 ELISA reagents was performed using real-time fluorescent Polymerase Chain Reaction (RT-PCR). We also analyzed correlation between different immunological reagents and the age, gender, hospitalization, and severity of illness. 【Results】 The positive yielding rate of ppNAT and three kinds of IgG ELISA was higher than that of IgM ELISA. The positive yielding rates of three kinds of IgG ELISA were 100%(30/30), 93.33%(28/30), and 96.67%(29/30) respectively, while the yielding rates in control group were all 0. The positive yielding rate of three IgM ELISAs were 93.33%(28/30), 70%(21/30)and 46.67% (14/30). All the cases from negative control group were negative for IgG and IgM. Pearson correlation coefficient was calculated; there was a strong correlation between ELISA reagent 2 IgG and ELISA reagent 3 IgG (r=0.765, P<0.01). The correlation between ppNAT, ELISA reagent 3 IgG and the age of recovered patients was 0.422 and 0.385, respectively (P<0.05), while no significant correlation was found between the duration of hospitalization, severity of illness, gender and antibody signal/cutoff (S/CO) (P>0.05). 【Conclusion】 In the convalescent plasma with nucleic acid confirmed covid-19, the yielding rates of different IgM antibodies varied greatly. Antibody levels were influenced by age to some extent.

Research has shown mutations in the voltage-gated sodium channel gene SCN2A to be associated with developmental delays and infantile seizures in patients with early-onset epileptic encephalopathies (EOEEs). Here, we report the case of an infant with a de novo SCN2A mutation with EOEE who had medically refractory seizures that improved with a ketogenic diet (KD) implemented at an age less than 2 months. On the day of his birth, the infant presented with a pattern of convulsions with dozens of episodes per day. An initial video electroencephalogram revealed poor reactivity of background activity, with multiple partial episodes starting from the right temporal region, and abnormal electrical activity in the right hemisphere. The seizures previously were not controlled with successive therapy with phenobarbital, topiramate, and levetiracetam. Genetic testing revealed the presence of a mutation in the SCN2A gene (c.4425C>G, p.Asn1475Lys). The infant’s seizures decreased significantly with a combination of KD and medication. The present case exemplifies the potential for personalized genomics in identifying the etiology of an illness. Furthermore, the KD appears to feasible in infants younger than 2 months and might elicit good responses to EOEE associated with SCN2A mutation.

Objective:To investigate the imaging anatomical features of donor liver blood vessels in laparoscopic left lateral donor liver acquisition and their clinical significance.Methods:The retrospective and descriptive study was conducted. The clinical data of 39 living donor liver transplantation (LDLT) donors who were admitted to Huashan Hospital Affiliated to Fudan University between October 2016 and December 2018 were collected. There were 10 males and 29 females, aged (31±7)years. The clinical data of 39 LDLT recipients were collected. There were 26 males and 13 females, aged 8 months (range, 4-68 months). Abdominal enhanced computed tomography and three-dimensional vascular reconstruction were performed on donors to evaluate the anatomical characteristics of hepatic vessels. All the donors underwent laparoscopic left lateral donor liver acquisition. Observation indicators: (1) three-dimensional vascular reconstruction of preoperative imaging; (2) surgical conditions; (3) follow-up. Follow-up was performed using outpatient examination to detect complications of recipients after LDLT up to October 2019. Measurement data with normal distribution were expressed as Mean± SD, and comparison between groups was analyzed by the t test. Measurement data with skewed distribution were represented as M (range). Count data were expressed as absolute numbers or percentages. Results:(1) Three-dimensional vascular reconstruction of preoperative imaging: the anatomical characteristics of hepatic artery and hepatic vein revealed by three-dimensional vascular reconstruction of preoperative imaging of 39 donors included ① middle hepatic artery was present in 11 donors, among which 5 started from the right hepatic artery, 3 from the confluence of the right and left hepatic artery, and 3 from the left hepatic artery. Two donors had anatomical variation in the left hepatic artery which was presentation of left accessory hepatic artery originated from the left gastric artery. The other 26 donors had no middle hepatic artery or anatomical variation in the left hepatic artery. ② The left hepatic vein and the middle hepatic vein of 9 donors were respectively drained into the inferior vena cava. Seven donors had the left upper branch of the left hepatic vein, and 23 donors had a joint trunk of the left hepatic vein and the middle hepatic vein which drained into the inferior vena cava. (2) Surgical conditions: ① all the 39 donors successfully underwent laparoscopic left lateral donor liver acquisition. The operation time and volume of intraoperative blood loss were (160±32)minutes and (142±74)mL. ② Of 11 donors with middle hepatic artery, left hepatic artery was the dominant artery in 8 donors and was used for hepatic artery anastomosis and reconstruction in liver transplantation, middle hepatic artery started from left hepatic artery in 3 donors and the joint trunk of left and middle hepatic artery was used for hepatic artery anastomosis and reconstruction in liver transplantation. Of 2 donors with anatomical variation in the left hepatic artery, one had left accessory hepatic artery as the dominant artery and the other had left hepatic artery as the dominant artery. Left accessory hepatic artery and left hepatic artery were respectively used for hepatic artery anastomosis and reconstruction in liver transplantation. The other 26 donors had left hepatic artery for hepatic artery anastomosis and reconstruction in liver transplantation. ③ Among the 39 donors, 11 received intraoperative left hepatic vein preferred approach and 28 received intraoperative non-left hepatic vein preferred approach. The operation time and volume of intraoperative blood loss of donors with left hepatic vein preferred approach were (147±22)minutes and (110±44)mL, respectively, versus (169±33)minutes and (154±81)mL of donors with non-left hepatic vein preferred approach, showing significant differences in the above indicators between the two groups ( t=4.19, 2.81, P<0.05). (3) Follow-up: 39 donors were followed up for 10 months. During the follow-up, there was no hepatic artery anastomotic bleeding, stenosis, ischemic bile duct injury and biliary stenosis caused by poor hepatic arterial blood supply, or any complications related to hepatic venous outflow tract stenosis. Conclusions:Three-dimensional vascular reconstruction before laparoscopic left lateral donor liver acquisition can reveal the anatomical variation of middle hepatic artery and left hepatic artery, which can guide the selection of surgical approach. The left hepatic vein preferred approach is recommended for the qualified donor in the laparoscopic left lateral donor liver acquisition, which can shorten the operation time and reduce the volume of intraoperative blood loss.

Since the outbreak of Corona Virus Disease 2019 (COVID-19) in December 2019, the number of new confirmed cases in Wuhan has been increasing, and medical resources are in short supply. Under this grim situation, makeshift hospitals have been used to treat patients with mild symptoms and achieved the largest capacity. Under the model of concentrated admission in makeshift hospitals with limited medical resources, the frontline surgeons adopt strict disease observation and treatment strategies, actively carry out psychological counseling for patients, and organize multidisci-plinary teams to deal with chronic and emergency surgical diseases of patients with COVID-19. Combined with their own clinical practices, the authors summarize a series of clinical experiences for the treatment of patients with COVID-19.

OBJECTIVE: To explore the clinical features of a Chinese pedigree affected with skeletal muscle sodium channelopathies due to variation of SCN4A gene. METHODS: Potential variation of the 24 exons of the SCN4A gene was screened using PCR and Sanger sequencing. RESULTS: Four family members were affected with the disease in an autosomal dominant inheritance pattern. Three patients had normekalemic periodic paralysis, while 1 showed paramyotonia congenita. Genetic analysis detected a missense variation c.2078T>C (p.Ile693Thr) in exon 13 of the SCN4A gene in the proband and other 3 affected relatives. CONCLUSION Normokalemic periodic paralysis and paramyotonia congenita can occur in different family members with skeletal muscle sodium channelopathies due to c.2078T>C(p.Ile693Thr) variation of SCN4A gene.
Channelopathies ; genetics ; Humans ; Muscle, Skeletal ; physiopathology ; Mutation ; NAV1.4 Voltage-Gated Sodium Channel ; genetics ; Pedigree