α-thalassemia is a type of microcytic hypochromic anemia caused by variants of alpha-globin gene, and is one of the most common monogenic disorders in southern China. The population screening model based on hematologic phenotype has achieved great results in areas with high incidence of thalassemia. However, with the continuous decline of the cost of genetic testing and implementation of screening programs for thalassemia gene carriers, more variants in the alpha-globin gene have been discovered, which also brings great challenges to clinical genetic counseling. From the perspective of alpha-globin genetic analysis, this consensus has discussed the contents of pre- and post-test genetic counseling, with an aim to provide standardized guidance for clinicians.

Objective:To explore the characteristics of SLCO1B1/ SLCO1B3 gene variants among children with Rotor syndrome (RS). Methods:Four children who were admitted to the Department of Hepatology of Hunan Children′s Hospital between January 2019 and January 2022 were selected as the study subjects. Trio-whole exome sequencing was carried out for the four families, and gel electrophoresis was used to verify an insertional variant of long-interspersed element-1 (LINE-1).Results:Genetic testing has identified three variants of the SLCO1B1 gene, including c. 1738C>T (p.R580*), c. 757C>T (p.R253*) and c. 1622A>C (p.Q541P), and two variants of the SLCO1B3 gene, including c. 481+ 22insLINE-1 and c. 1747+ 1G>A among the children. Three of them were found to harbor homozygous variants of the SLCO1B1/ SLCO1B3 genes, and one has harbored compound heterozygous variants. Sanger sequencing confirmed the existence of all variants, and gel electrophoresis has confirmed the existence of the LINE-1 insertional variant of about 6 kb within intron 6 of the SLCO1B3 gene in all children. Conclusion:The pathogenesis of the RS among the four children may be attributed to the variants of the SLCO1B1/ SLCO1B3 genes. The LINE-1 insertion variant of the SLCO1B3 gene may be common among Chinese RS patients.

Objective:To investigate the Chinese anesthesiologist′s proficiency, training experience and needs of flexible bronchoscope-guided awake flexible bronchoscopy intubation (AFBI) using a questionnaire method.Methods:The cluster sampling was used, and self-designed questionnaires that addressed 54 questions in 5 categories were distributed through WeChat and online platforms. The survey took one month, and the answers were automatically recorded by the WeChat server.Results:A total of 1 250 anesthesiologists participated in the survey in 30 provinces of China, 9 of them were not anesthesiologists, and 1 241 (99.28%) questionnaires were validated. In the valid questionnaires, 52.70% (654) of the anesthesiologists were from tertiary hospitals, and 74.78% (928) of the anesthesiologists were attending physicians or above, only 7.57% (94) of the anesthesiologists had sufficient confidence in AFBI. Twenty-five point two two percent (313) of the anesthesiologists preferred fiberoptic intubation as the first tool when dealing with the anticipated difficult airway. Forty-eight point one one percent (597) of the anesthesiologists had implemented AFBI. Among them, 80.74% (482) had experienced unsuccessful AFBI practices. Eight hundred and ninety-four anesthesiologists had received AFBI training, and the most common AFBI training strategy was theoretical lectures. In addition, the degree of satisfaction regarding the theoretical lectures quality, technical training, clinical practice relativity and non-technical skills training was 21.47% (192), 14.32% (128), 12.3% (110) and 17.90% (160), respectively. The degree of satisfaction with all the 4 training elements mentioned above was 7.27% (65).Conclusions:The awareness and practice of Chinese anesthesiologists in terms of clinical application of AFBI to treat difficult airways need to be strengthened at present, and the lack of high-quality AFBI training may be the key.

Spermatogenesis is a continual process that occurs in the testes, in which diploid spermatogonial stem cells (SSCs) differentiate and generate haploid spermatozoa. This highly efficient and intricate process is orchestrated at multiple levels. N⁶-methyladenosine (m⁶A), an epigenetic modification prevalent in mRNAs, is implicated in the transcriptional regulation during spermatogenesis. However, the dynamics of m⁶A modification in non-rodent mammalian species remains unclear. Here, we systematically investigated the profile and role of m⁶A during spermatogenesis in pigs. By analyzing the transcriptomic distribution of m⁶A in spermatogonia, spermatocytes, and round spermatids, we identified a globally conserved m⁶A pattern between porcine and murine genes with spermatogenic function. We found that m⁶A was enriched in a group of genes that specifically encode the metabolic enzymes and regulators. In addition, transcriptomes in porcine male germ cells could be subjected to the m⁶A modification. Our data show that m⁶A plays the regulatory roles during spermatogenesis in pigs, which is similar to that in mice. Illustrations of this point are three genes (SETDB1, FOXO1, and FOXO3) that are crucial to the determination of the fate of SSCs. To the best of our knowledge, this study for the first time uncovers the expression profile and role of m⁶A during spermatogenesis in large animals and provides insights into the intricate transcriptional regulation underlying the lifelong male fertility in non-rodent mammalian species.
Animals ; Male ; Mice ; Cell Differentiation/genetics* ; Mammals/metabolism* ; Methylation ; RNA, Messenger/metabolism* ; Spermatogenesis/genetics* ; Spermatozoa/metabolism* ; Swine/genetics* ; Testis/metabolism* ; Transcriptome ; RNA Methylation/genetics*

Improper control of depth of anesthesia is not only detrimental to the rapid and stable recovery of anesthesia, but also affects the postoperative outcome of patients. Therefore, accurate control of anesthesia depth is an urgent clinical and scientific problem in the field of anesthesiology. At present, different algorithm models derived from electroencephalogram (EEG) signals are used to monitor the depth of anesthesia, but they cannot meet the requirements of anesthesiologists to accurately evaluate the depth of anesthesia. In recent years, the research on the mechanism and modulation of anesthesia-related neural network suggests that it has potential value as a method to monitor depth of anesthesia. Anesthesia-related neural networks mainly include sleep-wake circuit, thalamic-cortical circuit and corticocortical network. A thorough understanding of the neural network involved in the loss of consciousness caused by anesthesia will guide the depth of anesthesia monitoring more accurately and provide possibility for improving the quality of clinical anesthesia resuscitation.

Objective:To investigate the changes and clinical significance of serum matrix metalloproteinase-9 (MMP-9), squamous cell carcinoma antigen (SCC), cytokeratin 19 fragment (CYFRA21-1), carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) in peripheral lung cancer.Methods:Sixty-eight patients with peripheral lung cancer who received treatment in Luqiao Hospital of Taizhou Enze Medical Center (Group) between January 2017 and January 2020 were included in the observation group. Sixty-five patients with benign lung diseases who concurrently received treatment in the same hospital were included in the observation group 1, and another 65 healthy participants who concurrently received physical examination were included in the control group. Serum levels of MMP-9, CYFRA21-1, SCC, NSE and CEA were compared among the three groups. The sensitivity and specificity of using these indicators alone and in combination in the diagnosis of peripheral lung cancer were compared.Results:Serum levels of MMP-9, CYFRA21-1, SCC, NSE and CEA in the observation group (14.98 ± 2.10) ng/mL, (17.13 ± 2.71) ng/mL, (1.98 ± 0.41) μg/mL, (24.13 ± 2.10) ng/mL and (17.10 ± 2.10) ng/mL, respectively, which were significantly higher than those in the observation group 1 [(9.12 ± 1.41) ng/mL, (10.12 ± 1.58) ng/mL, (1.37 ± 0.31) μg/mL, (16.31 ± 1.78) ng/mL, (12.13 ± 1.79) ng/mL] and control group [(5.10 1 ± 0.68) ng/mL, (6.02 ± 0.94) ng/mL, (0.71 ± 0.11) μg/mL, (11.10 ± 1.02) ng/mL, (8.13 ± 1.02) ng/mL] ( F1 = 932.781, F2 = 737.100, F3 = 368.591, F4 = 989.851, F5 = 462.291, all P < 0.05). Serum levels of MMP-9, CYFRA21-1, SCC, NSE and CEA in patients with stage I-II peripheral lung cancer were (11.12 ± 2.10) ng/mL, (9.12 ± 1.85) ng/mL, (1.52 ± 0.21) μg/mL, (18.12 ± 3.02) ng/mL, (7.52 ± 1.02) ng/mL, respectively, which were significantly lower than those in patients with stage III-IV peripheral lung cancer [(15. 89 ± 2.18) ng/mL, (21.56 ± 2.11) ng/mL, (2.04 ± 0.31) μg/mL, (28.15 ± 2.62) ng/mL, (15.12 ± 1.55) ng/mL, t1 = 9.013, t2 = 25.146, t3 = 7.714, t4 = 14.586, t5 = 22.705, all P < 0.05]. The sensitivity (83.33%) and specificity (86.67%) of combined detection of all indicators were significantly higher than those of single detection of MMP-9 (50.00%, 59.68%), CEA (50.00%, 61.29%), CYFRA21-1 (66.67%, 58.06%), SCC (50.00%, 54.84%) or NSE (66.67%, 58.06%) (all P < 0.05). Conclusion:Serum levels of MMP-9, CYFRA21-1, SCC, NSE and CEA in patients with peripheral lung cancer are significantly increased, which has an important value in the diagnosis of peripheral lung cancer. The combined detection of the above indicators can increase the diagnostic accuracy of peripheral lung cancer in the clinic.

Objective:To explore the effects of family-centered conductive education on the muscle strength in children with cerebral palsy and the stress of caregivers.Methods:Totally 92 children with cerebral palsy and 92 their main caregivers admitted into the Affiliated Hospital of Jining Medical University from October 2018 to December 2019 were selected and divided into a control group and a conductive education group according to the random number table, with 46 children with cerebral palsy and their 46 main caregivers in each group. Patients in the control group received routine care, while patients in the conductive education group underwent family-centered conductive education on the basis of routine care. The Chinese version of the Modified Ashworth Scale (MAS) , Caregiver Strain Index (CSI) , and the Chinese version of Family Management Measure (FaMM) were used to evaluate the muscle strength, caregiver pressure, and disease management ability of the two groups before and after intervention. Therefore, there were actually 43 cases in the control group and 42 cases in the conductive education group.Results:After intervention, the MAS scores of the two groups were lower than those at admission, and the score was lower in the conductive education group than in the control group, with statistically significant differences ( P<0.05) ; the CSI score of caregivers in the conductive education group was lower than that in the control group, and the difference was statistically significant ( P< 0.05) , while the FaMM score was higher than that in the control group, with statistically significant difference ( P<0.05) . Conclusions:Family-centered conductive education can effectively reduce the muscle strength of children with cerebral palsy, alleviate the pressure of their caregivers, and improve the caregivers' disease management ability.

Objective To identify risk factors for local recurrence and distant metastasis in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU).Methods We retrospectively reviewed 269 patients with UTUC who had performed RNU from 2003 to 2013 in the Affiliated Hospital of Qingdao University.158 were males and 111 were females,aged range from 37 to 86 years old,left side were 144 cases and right side were 125 cases,157 cases occurred in renal pelvis and 112 cases in ureter,the diameter of tumor ＞ 3 cm were 163 cases,≥ pT3 stage were 143 cases,presence of lymphovascular invasion (LVI) were 35 cases,high grade tumors (G3) were 185 cases,presence of hydronephrosis were 185 cases,multifocal tumors were 28 cases,sessile tumors were 86 cases,neutrophil to lymphocyte ratio(NLR) ≥ 2.0 were 109 cases,estimated glomerular filtration rate (eGFR) ＜ 60ml/(min · 1.73 m2) were 62 cases,plasma fibrinogen ≥3.2 g/L were 129 cases.Univariate and multivariate analyses were performed to identify independent prognostic factors for local recurrence-free survival (IRFS) and distant metastasis-free survival (dMFS).Results The median follow-up was 43.8 months (range 4.4-131.8).30 patients had a local recurrence with a median intermittent period of 19.4 months (range 4.3-71.3).35 patients had a distant metastasis with a median intermittent period of 17.7 months (range 4.1-51.4).In univariate analysis,sessile tumor(P =0.041),tumor multifocality (P =0.027),location in ureter (P =0.001),presence of LVI (P＜0.001),≥pT3 stage(P ＜0.001),eGFR ＜60ml/(min · 1.73 m2) (P =0.009) and plasma fibrinogen ≥ 3.2 g/L (P ＜ 0.001) were associated with lRFS.While high-grade tumor (G3) (P =0.012),sessile tumor (P ＜ 0.001),presence of LVI (P ＜ 0.001),presence of hydronephrosis (P =0.046),and NLR ≥2.0 (P =0.002) were associated with dMFS.Multivariate analysis revealed that location in ureter(HR =4.835,95 ％ CI 1.792-13.044,P =0.002),presence of LVI (HR =5.037,95 ％ CI 2.183-11.230,P ＜ 0.001),≥pT3 stage(HR =2.987,95％ CI 1.078-8.283,P =0.035) and plasma fibrinogen ≥3.20g/L (HR =4.281,95 ％ CI 1.454-12.603,P =0.008) were independent factors for lRFS.Sessile tumor (HR =6.097,95％ CI 2.536-14.660,P ＜ 0.001),presence of LVI (HR =4.191,95％ CI 2.035-8.633,P ＜ 0.001),and NLR ≥2.0 (HR =2.741,95％ CI 1.128-6.657,P =0.026) were independent factors for dMFS.We stratified patients into three risk groups of LR and DM based on the results of the multivariate analysis respectively.The 1-year,3-year,5-year lRFS rates were 99.0％,96.8％,95.0％ in the low-risk group;94.5％,91.2％,87.6％ in the intermediate-risk group;and 77.8％,58.8％,58.8％ in the high-risk group.The differences among groups were significant (P ＜ 0.001).The 1-year,3-year,5-year dMFS rates were 98.4％,97.6％,96.0％ in the low-risk group,88.0％,73.8％,71.8％ in the intermediate-risk group,and 63.7％,42.9％,28.5％ in the high-risk group.The differences among groups were significant as well(P ＜ 0.001).Conclusion Location in ureter,presence of LVI,≥ pT3 stageand plasma fibrinogen ≥3.2 g/L were independent factors for lRFS.Sessile tumor,presence of LVI,and NLR ≥ 2.0 were independent factors for dMFS.The risk stratification models may be useful for identifying the patients with high risk of LR/DM after surgery.

Objective: To investigate the clinical features of children with infectious mononucleosis (IM), to compare the difference of therapeutic effects between general treatment to antiviral therapy for IM. Methods: This prospective study analyzed the clinical data and laboratory test results of 201 cases with IM in our hospital from January 1, 2016 to December 31, 2016. The follow-up period was 6-12 months. The patients were divided into two groups according to the order of admission. The clinical symptoms and laboratory test results of the two groups were observed after hospitalization. Results: Of the total of 201 patients, male to female is 1.72∶1; Age: 8 months to 13 years 6 months (average 4.8±2.8 years), The disease frequently occurred in summer and autumn, accounted for 64.18%.The major clinical manifestations was fever (97.51%), angina (79.10%), enlarged of lymph node(68.66%), eyelid swelling (67.16%), hepatomegaly (53.73%) and splenomegaly (46.77%). There was no statistical difference in duration of fever, improved angina time, lymph nodes(liver, spleen) enlargement recovery time, heterotypic lymphocytes normalization time, lymphocyte function normalization time.There was significant difference in reducing the serum/plasma or total blood EBV-DNA in the short term between antiviral group and general treatment group (P<0.01), but for the long-term reduction of EBV-DNA, there was no significant difference (P>0.05). The low affinity EBV-CA-IgG was converted to high affinity EBV-CA-IgG in 89.41% of patients after 3 months and in 98.68% of patients after 6 months. With the recovery of the disease, the positive rate of EBV-CA-IgM and EBV-EA-IgG decreased. But the positive rate of EBV-NA-IgG increased. Serum/plasma EBV-DNA was completely overcast after 3 months, but after 12 months, the patient’s total blood EBV-DNA positive rate was still 71.11%. Conclusions In general IM patients, there was no significant difference between antiviral therapy and general treatment, so antiviral therapy is not generally recommended. EBV DNA in the whole blood of patients with IM will continue to be positive more than 6-12 months, indicating that to observe changes of IM should not use whole blood samples for EBV DNA testing.

OBJECTIVETo investigate the factors which may influence the imatinib plasma concentration in Chinese patients with gastrointestinal stromal tumor(GIST), and to illuminate the significance of monitoring imatinib plasma concentration in adjuvant therapy for patients with GIST.

METHODSA cross-sectional study with 60 GIST patients who accepted the imatinib therapy after surgery was conducted. They were respectively administrated in 10 domestic hospitals from December 2014 to April 2016, including The First Affiliated Hospital of Nanjing Medical University(n=28), The Affiliated Hospital of Nantong University(n=9), The Affiliated Hospital of Xuzhou Medical College(n=6), Nanjing Drum Tower Hospital(n=5), The Second Affiliated Hospital of Nanjing Medical University (n=2), Jingling Hospital (n=2), The Second People's Hospital of Lianyungang(n=2), Shandong Provincial Hospital(n=2), Jiangsu Province Tumor Hospital(n=2), and The First Affiliated Hospital of Zhejiang University(n=2). Some specific time points for collecting blood sample before and after taking imatinib were determined, then liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used for monitoring imatinib plasma concentration in patients with GIST. Linear regression analysis was used for the correlation analysis of imatinib plasma concentration with dosage, clinicopathologic feature and side effect.

RESULTSPatients who could not tolerate 400 mg imatinib per day(n=3) received 300 mg per day. There was no significant difference in imatinib plasma concentration between patients with 300 mg and those with 400 mg imatinib(n=53)(P=0.527). However, the imatinib plasma concentration in patients with 600 mg imatinib per day (n=4) was significantly higher as compared to those with 400 mg(P=0.000). Linear regression analysis indicated a negative correlation between the imatinib plasma concentration in patients with 400mg imatinib per day for 90 days continuously and body surface area(R=0.074, P=0.035), but no significant correlations of with age, creatinine clearance and serum albumin concentration were observed (all P>0.05). The differences in imatinib plasma concentration were not statistically significant between patients of different gender and those taking proton-pump inhibitor (PPI) or not (both P>0.05). Difference in imatinib plasma concentration between patients with different surgery was significant (P=0.026). Compared to patients who underwent wedge resection, enterectomy and other surgeries, the imatinib plasma concentration of patients with subtotal gastrectomy or total gastrectomy decreased significantly (all P<0.05). After 90 days of taking imatinib continuously, linear regression analysis revealed a negative correlation between imatinib plasma concentration in patients with 400 mg imatinib per day and white blood cell count (R=0.103, P=0.013), and a positive correlation with serum alanine aminotransferase (ALT) concentration (R=0.076, P=0.033).

CONCLUSIONSThe imatinib plasma concentration in patients with larger body surface area, subtotal gastrectomy or total gastrectomy may be lower. For these patients, dosage of imatinib should be considered to increase in order to achieve effective plasma concentration. Excessive imatinib plasma concentration can result in some side effects, such as decrease of white blood cells and liver damage. Therefore, it is significant for receiving optimal clinical therapeutic efficacy to monitor imatinib plasma concentration, adjust imatinib dosage timely and keep imatinib plasma concentration in effective and safe range.

Adult ; Antineoplastic Agents ; administration & dosage ; pharmacokinetics ; Benzamides ; Combined Modality Therapy ; Cross-Sectional Studies ; Female ; Gastrectomy ; Gastrointestinal Stromal Tumors ; drug therapy ; surgery ; Humans ; Imatinib Mesylate ; administration & dosage ; pharmacokinetics ; Male ; Middle Aged ; Piperazines ; Pyrimidines ; Tandem Mass Spectrometry