Clinical application of non-invasive prenatal testing for twin pregnancies / 中华医学遗传学杂志

OBJECTIVE@#To evaluate the feasibility of non-invasive prenatal testing (NIPT) for the screening of fetal chromosome aneuploidies in twin pregnancies.@*METHODS@#A total of 2 745 women with twin-pregnancies were subjected for NIPT screening. Chromosomal karyotyping and chromosomal microarray analysis (CMA) were carried out on amniotic fluid samples from those with a high risk for fetal chromosome aneuploidies, and the diagnosis and pregnancy outcome were followed up. The sensitivity, specificity, positive predictive value and false positive rate of the NIPT were calculated.@*RESULTS@#Compared with other chromosomal abnormalities, NIPT had a higher efficacy for trisomy 21 and sex chromosomal aneuploidy (SCA) in twin pregnancies (with sensitivity being 100%, 100%, and specificity being 99.93%, 99.9%, respectively). It is difficult to evaluate the efficacy for trisomies 18 and 13 due to the limited data. For chromosome microdeletions and microduplications spanning 15 ~ 21 Mb, NIPT also had a certain detection rate. Compared with women with natural conception, NIPT had a higher detection rate for those with twin pregnancies by assisted reproduction (P < 0.05).@*CONCLUSION@#It is feasible to use NIPT for the detection of chromosome aneuploidies in women with twin pregnancies.

Immunogenicity, safety and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years / 中华预防医学杂志

Objective: To evaluate the immunogenicity, safety, and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years. Methods: An open-label, multi-center trial was conducted in October 2021. The eligible healthy individuals, aged 18-84 years who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, were recruited from Shangyu district of Shaoxing and Kaihua county of Quzhou, Zhejiang province. All participants were divided into three groups based on the differences in prime-boost intervals: Group A (3-4 months), Group B (5-6 months) and Group C (7-9 months), with 320 persons per group. All participants received the recombinant COVID-19 vaccine (CHO cell). Blood samples were collected before the vaccination and after receiving the booster at 14 days, 30 days, and 180 days for analysis of GMTs, antibody positivity rates, and seroconversion rates. All adverse events were collected within one month and serious adverse events were collected within six months. The incidences of adverse reactions were analyzed after the booster. Results: The age of 960 participants was (52.3±11.5) years old, and 47.4% were males (455). The GMTs of Groups B and C were 65.26 (54.51-78.12) and 60.97 (50.61-73.45) at 14 days after the booster, both higher than Group A's 44.79 (36.94-54.30) (P value<0.05). The GMTs of Groups B and C were 23.95 (20.18-28.42) and 27.98 (23.45-33.39) at 30 days after the booster, both higher than Group A's 15.71 (13.24-18.63) (P value <0.05). At 14 days after the booster, the antibody positivity rates in Groups A, B, and C were 91.69% (276/301), 94.38% (302/320), and 93.95% (295/314), respectively. The seroconversion rates in the three groups were 90.37% (272/301), 93.75% (300/320), and 93.31% (293/314), respectively. There was no significant difference among these rates in the three groups (all P values >0.05). At 30 days after the booster, antibody positivity rates in Groups A, B, and C were 79.60% (238/299), 87.74% (279/318), and 90.48% (285/315), respectively. The seroconversion rates in the three groups were 76.92% (230/299), 85.85% (273/318), and 88.25% (278/315), respectively. There was a significant difference among these rates in the three groups (all P values <0.001). During the sequential booster immunization, the incidence of adverse events in 960 participants was 15.31% (147/960), with rates of about 14.38% (46/320), 17.50% (56/320), and 14.06% (45/320) in Groups A, B, and C, respectively. The incidence of adverse reactions was 8.02% (77/960), with rates of about 7.50% (24/320), 6.88% (22/320), and 9.69% (31/320) in Groups A, B, and C, respectively. No serious adverse events related to the booster were reported. Conclusion: Healthy individuals aged 18-84 years, who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, have good immunogenicity and safety profiles following the sequential booster with the recombinant COVID-19 vaccine (CHO cell).

Immunogenicity, safety and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years / 中华预防医学杂志

Objective: To evaluate the immunogenicity, safety, and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years. Methods: An open-label, multi-center trial was conducted in October 2021. The eligible healthy individuals, aged 18-84 years who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, were recruited from Shangyu district of Shaoxing and Kaihua county of Quzhou, Zhejiang province. All participants were divided into three groups based on the differences in prime-boost intervals: Group A (3-4 months), Group B (5-6 months) and Group C (7-9 months), with 320 persons per group. All participants received the recombinant COVID-19 vaccine (CHO cell). Blood samples were collected before the vaccination and after receiving the booster at 14 days, 30 days, and 180 days for analysis of GMTs, antibody positivity rates, and seroconversion rates. All adverse events were collected within one month and serious adverse events were collected within six months. The incidences of adverse reactions were analyzed after the booster. Results: The age of 960 participants was (52.3±11.5) years old, and 47.4% were males (455). The GMTs of Groups B and C were 65.26 (54.51-78.12) and 60.97 (50.61-73.45) at 14 days after the booster, both higher than Group A's 44.79 (36.94-54.30) (P value<0.05). The GMTs of Groups B and C were 23.95 (20.18-28.42) and 27.98 (23.45-33.39) at 30 days after the booster, both higher than Group A's 15.71 (13.24-18.63) (P value <0.05). At 14 days after the booster, the antibody positivity rates in Groups A, B, and C were 91.69% (276/301), 94.38% (302/320), and 93.95% (295/314), respectively. The seroconversion rates in the three groups were 90.37% (272/301), 93.75% (300/320), and 93.31% (293/314), respectively. There was no significant difference among these rates in the three groups (all P values >0.05). At 30 days after the booster, antibody positivity rates in Groups A, B, and C were 79.60% (238/299), 87.74% (279/318), and 90.48% (285/315), respectively. The seroconversion rates in the three groups were 76.92% (230/299), 85.85% (273/318), and 88.25% (278/315), respectively. There was a significant difference among these rates in the three groups (all P values <0.001). During the sequential booster immunization, the incidence of adverse events in 960 participants was 15.31% (147/960), with rates of about 14.38% (46/320), 17.50% (56/320), and 14.06% (45/320) in Groups A, B, and C, respectively. The incidence of adverse reactions was 8.02% (77/960), with rates of about 7.50% (24/320), 6.88% (22/320), and 9.69% (31/320) in Groups A, B, and C, respectively. No serious adverse events related to the booster were reported. Conclusion: Healthy individuals aged 18-84 years, who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, have good immunogenicity and safety profiles following the sequential booster with the recombinant COVID-19 vaccine (CHO cell).

Research progress on stable gene transfection methods of Plasmodium falciparum / 中国热带医学

@#Abstract: Transfection of Plasmodium falciparum is helpful to study the function of its genes, such as drug resistance. However, transgenic manipulation has been very challenging, mainly due to the high A/T base sequence structure (A+T content of about 82%) and low transfection efficiency of the Plasmodium genome. Electroporation-based transfection of Plasmodium falciparum has been successfully applied in the study of certain genes, and electroporation by preloading is currently the preferred method for introducing foreign DNA into Plasmodium falciparum. The site-directed editing of Plasmodium genes mostly adopts the method of two-plasmid transfection. It is generally believed that successful transfection of Plasmodium requires a large amount of high-purity plasmid DNA and an accurate transfection system. In addition to the evaluation of the current commonly used electrotransfection methods, this paper also introduces a new transfection method, namely lyse-reseal erythrocytes for transfection (LyRET). This paper also review the role of factors such as plasmid DNA concentration, the use of transfection reagents, the setting of transfection parameters, the addition of fresh red blood cells, and the markers of successful transfection in improving the success rate and efficiency of Plasmodium transfection, in the hope of providing a reference for study in this field.

Efficacy of CLAE Chemotherapy Regimen Followed by Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Relapsed/Refractory Acute Leukemia / 中国实验血液学杂志

OBJECTIVE@#To observe the efficacy and safety of CLAE intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with relapsed/refractory acute leukemia (R/R AL).@*METHODS@#CLAE regimen [cladribine 5 mg/(m2·d), d 1-5; cytarabine 1.5 g/(m2·d), d 1-5; etoposide 100 mg/(m2·d), d 3-5] followed by allo-HSCT was used to treat 3 R/R AL patients. The patients received CLAE chemotherapy in relapsed or refractory status and underwent bone marrow puncture to judge myelodysplastic state. After an interval of 3 to 5 days, followed by preconditioning regimen for allo-HSCT [fludarabine 30 mg/(m2·d), d -7 to d -3; busulfan 0.8 mg/kg q6h, d -6 to d -3 or d -5 to d -2. If the bone marrow hyperplasia was not active and the blasts were less than 10%, busulfan should be used for 3 days. If the bone marrow hyperplasia was active and the blasts were more than 10%, busulfan should be used for 4 days]. Cyclosporin A, mycophenolate mofetil and short-term methotrexate were used for graft-versus-host disease (GVHD) prevention. After transplantation, the status of minimal residual disease (MRD) and bone marrow chimerism were regularly monitored in all 3 patients, and demethylation drugs or dasatinib were used to prevent recurrence 3 months after transplantation.@*RESULTS@#2 patients with t(11;19) translocation and relapse/refractory acute myeloid leukemia recurred within 6 months after induction of remission, and received intensive chemotherapy with CLAE regimen followed by haploidentical allo-HSCT and unrelated donor allo-HSCT, respectively. The two patients both relapsed 6 months after transplantation, then achieved complete remission by donor lymphocyte infusion, interferon, interleukin-2 and other methods, and disease-free survival was 2 years after transplantation. The other patient was chronic myelogenous leukemia who developed acute lymphoblastic leukemia during oral administration of tyrosine kinase inhibitor, accompanied by T315I and E255K mutations in ABL1 kinase region and additional chromosomal abnormalities. After morphological remission by induction chemotherapy, central nervous system leukemia was complicated. Intensive chemotherapy with CLAE regimen followed by sibling allo-HSCT was performed in the positive state of MRD. The patient relapsed 3 months after transplantation, and achieved remission after chimeric antigen receptor T-cell (CAR-T) therapy, however, he died 5 months after transplantation because of severe cytokine release syndrome (CRS) and GVHD.@*CONCLUSION@#CLAE regimen followed by allo-HSCT may be an effective salvage treatment option for R/R AL patients to prolong the overall survival.

Advances in traditional Chinese medicine treatment of non-alcoholic fatty liver disease via farnesoid X receptor / 中国中药杂志

Non-alcoholic fatty liver disease(NAFLD) is a chronic metabolic condition with rapidly increasing incidence, becoming a public health issue of worldwide concern. Studies have shown that farnesoid X receptor(FXR)-based modulation of downstream targets can improve liver function and metabolic status in the patients with NAFLD and may be a potential drug target for treating this di-sease. Great progress has been achieved in the development of drugs targeting FXR for the treatment of NAFLD. A number of studies have explored the traditional Chinese medicine and their active ingredients for the treatment of NAFLD via FXR considering the high safety and efficacy and mild side effects. This paper systematically describes the mechanism of traditional Chinese medicines in the treatment of NAFLD via FXR and the downstream targets, aiming to provide precise targets for the drug development and clinical treatment of NAFLD.

Medicinal evolution and modern research progress on Mume Fructus / 中国中药杂志

Prunus mume is an edible and medicinal material, and Mume Fructus is its processed product, which was first recorded in Shennong's Classic of Materia Medica(Shen Nong Ben Cao Jing). It is an effective drug for stopping diarrhea with astringents and promoting fluid production to quiet ascaris. By consulting the ancient herbal works of the past dynasties, modern codes, and other rela-ted literature, this paper sorted out the medicinal evolution of Mume Fructus, examined the ancient efficacy of Mume Fructus and the main indications, and summarized the inclusion of Mume Fructus in national and provincial standards. It is recorded in the ancient herbal works of the past dynasties that Mume Fructus can be processed by various methods such as roasting, stir-frying or micro-frying, stir-frying with charcoal, single steaming, steaming with wine, and steaming after soaking in wine or vinegar, and prepared into pills, powders, and ointments, which are used in the treatment of fatigue, diabetes, malaria, dysentery, ascariasis, and other diseases. Mume Fructus has been included in nine editions of Chinese Pharmacopoeia and 19 provincial and municipal preparation specifications. The processing method of Mume Fructus is determined, namely, clean P. mume should be softened by moistening in water or steaming and pitted. By reviewing the effects of processing on its chemical composition, pharmacological effects, and its modern clinical application, this paper identified the following issues. The ancient application methods of Mume Fructus are diverse but less commonly used in modern times, there is a lack of standardized research on the processing, and the research on the changes caused by the difference in Mume Fructus before and after processing is not deep. Therefore, it is necessary to further investigate the change pattern of its chemical composition before and after processing and its correlation between its medicinal activity to standardize the processing technology and provide a solid basis for the use of Mume Fructus in parts and its quality control.

HbA1c comparison and diagnostic efficacy analysis of multi center different glycosylated hemoglobin detection systems / 中华预防医学杂志

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R2 of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.

HIV self-testing and related factors in men who have sex with men in Shijiazhuang / 中华流行病学杂志

Objective: To understand HIV self-testing and related factors in men who have sex with men (MSM) in Shijiazhuang. Methods: From August to September 2020, convenient sampling was used to recruit MSM in Shijiazhuang. Online questionnaires were used to collect information about their demographic characteristics, sexual behaviors and HIV self-testing. logistic regression model was used to analyze the related factors associated with HIV self-testing. Results: In the 304 MSM respondents, 52.3% (159/304) had HIV self-testing in the past 6 months, and 95.0% (151/159) used fingertip blood HIV detection reagent. Self-purchase was the main way to obtain HIV testing reagents (45.9%, 73/159), followed by supply from MSM social organization (44.7%, 71/159). The reasons for having HIV self-testing were non-specific testing time (67.9%, 108/159) and privacy protection (62.9%,100/159), the reasons for having no HIV self-testing included inability of using (32.4%, 47/145), being unaware of HIV self-testing reagent (24.1%, 35/145), and worry about inaccurate self-testing results (19.3%, 28/145). Multivariate logistic regression analysis showed that being 18-29 years old (aOR=2.68, 95%CI: 1.20-5.94), obtaining free HIV self-testing kits in recent 6 months (aOR=8.61, 95%CI: 4.09-18.11) and making friends through Internet and social software (aOR=2.68, 95%CI: 1.48-4.88) were positive factors for having HIV self-testing. Conclusion: HIV self-testing is a more flexible and convenient way to detect HIV in MSM, and the promotion of HIV self-testing in MSM should be strengthened to further increase the HIV detection rate in this population.

Development and application syndromic surveillance and early warning system in border area in Yunnan Province / 中华流行病学杂志

Objective: To establish a dynamic syndromic surveillance system in the border areas of Yunnan Province based on information technology, evaluate its effectiveness and timeliness in the response to common communicable disease epidemics and improve the communicable disease prevention and control in border areas. Methods: Three border counties were selected for full coverage as study areas, and dynamic surveillance for 14 symptoms and 6 syndromes were conducted in medical institutions, the daily collection of information about students' school absence in primary schools and febrile illness in inbound people at border ports were conducted in these counties from January 2016 to February 2018 to establish an early warning system based on mobile phone and computer platform for a field experimental study. Results: With syndromes of rash, influenza-like illness and the numbers of primary school absence, the most common communicable disease events, such as hand foot and mouth disease, influenza and chickenpox, can be identified 1-5 days in advance by using EARS-3C and Kulldorff time-space scanning models with high sensitivity and specificity. The system is easy to use with strong security and feasibility. All the information and the warning alerts are released in the form of interactive charts and visual maps, which can facilitate the timely response. Conclusions: This system is highly effective and easy to operate in the detection of possible outbreaks of common communicable diseases in border areas in real time, so the timely and effective intervention can be conducted to reduce the risk of local and cross-border communicable disease outbreaks. It has practical application value.

Epidemiological characteristics of pesticide poisoning in Chengdu City from 2012 to 2021 / 中华劳动卫生职业病杂志

Objective: To explore the present situation and epidemiological characteristics of pesticide poisoning in Chengdu City from 2012 to 2021, and to provide scientific evidence for further prevention and control. Methods: In January 2022, the pesticide poisoning report cards of Chengdu City from 2012 to 2021 were collected from the China Disease Control and Prevention Information System. The data of the report card was reorganized and the distribution characteristics of pesticide poisoning such as time, region, gender, age and pesticide types were analyzed. Results: 14326 cases of pesticide poisoning were reported in Chengdu City from 2012 to 2021, 651 deaths, and the fatality rate was 4.54%. The cases of productive pesticide poisoning and unproductive pesticide poisoning were 504 and 13822, respectively. The fatality rates of productive and unproductive pesticide poisoning were 1.39% and 4.66%, which were significant different (χ(2)=11.99, P=0.001). The highest reported cases of pesticide poisoning was in 2013 (1779) and the lowest in 2021 (1047). The number of reported cases showed a downward trend year by year (t=-12.30, P<0.001), and the fatality rates also showed a downward trend year by year (χ(2)(trend)=25.48, P<0.001). The fluctuation range of unproductive pesticide poisoning cases in each month of the year was small, and the productive pesticide poisoning mainly occurred from May to August. The regions with the largest number of reported poisoning cases were Pengzhou (1620), Jianyang (1393), Jintang (1266) and Qionglai (1158). The high incidence of poisoning was among 25-54 years old (50.21%, 7193/14326). The fatality rate in the age group 75-96 years old was the highest (8.98%, 95/1058), and the fatality rates increased gradually with age (χ(2)(trend)=186.03, P<0.001). The pesticides causing poisoning were mainly insecticide (43.86%, 6284/14326) and herbicides (35.75%, 5121/14326). Herbicides paraquat had the highest fatality rate (9.54%, 286/2998) . Conclusion: Pesticide poisoning in Chengdu City is mainly unproductive poisoning. Health education should be carried out for key areas and people, and the control of highly toxic pesticides such as insecticide and herbicides should be strengthened.

Evaluation of the application value of seven tumor-associated autoantibodies in non-small cell lung cancer based on machine learning algorithms / 中华预防医学杂志

Objective: Based on the diagnostic model established and validated by the machine learning algorithm, to investigate the value of seven tumor-associated autoantibodies (TAABs), namely anti-p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGEA1 and CAGE antibodies in the diagnosis of non-small cell lung cancer (NSCLC) and to differentiate between NSCLC and benign lung nodules. Methods: This was a retrospective study of clinical cases. Model building queue: a total of 227 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from November 2018 to June 2021 were collected as the NSCLC group, and 120 cases of benign lung nodules, 122 cases of pneumonia and 120 healthy individuals were selected as the control groups. External validation queue: a total of 100 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from May 2022 to December 2022 were collected as the NSCLC group, and 36 cases of benign lung nodules, 32 cases of pneumonia and 44 healthy individuals were selected as the control groups. In addition, NSCLC was divided into early (stage 0-ⅠB) and mid-to-late (stage ⅡA-ⅢB) subgroups. The levels of 7-TAABs were detected by enzyme immunoassay, and serum concentrations of CEA and CYFRA21-1 were detected by electrochemiluminescence. Four machine learning algorithms, XGBoost, Lasso logistic regression, Naïve Bayes, and Support Vector Machine are used to establish classification models. And the best performance model was chosen based on evaluation metrics and a multi-indicator combination model was established. In addition, an online risk evaluation tool was generated to assist clinical applications. Results: Except for p53, the levels of rest six TAABs, CEA and CYFRA21-1 were significantly higher in the NSCLC group (P<0.05). Serum levels of anti-SOX2 [1.50 (0.60, 10.85) U/ml vs. 0.8 (0.20, 2.10) U/ml, Z=2.630, P<0.05] and MAGEA1 antibodies [0.20 (0.10, 0.43) U/ml vs. 0.10 (0.10, 0.20) U/ml, Z=2.289, P<0.05], CEA [3.13 (2.12, 5.64) ng/ml vs. 2.11 (1.25, 3.09) ng/ml, Z=3.970, P<0.05] and CYFRA21-1 [4.31(2.37, 7.14) ng/ml vs. 2.53(1.92, 3.48) ng/ml, Z=3.959, P<0.05] were significantly higher in patients with mid-to late-stage NSCLC than in early stages. XGBoost model was used to establish a multi-indicator combined detection model (after removing p53). 6-TAABs combined with CYFRA21-1 was the best combination model for the diagnosis of NSCLC and early NSCLC. The optimal diagnostic thresholds were 0.410, 0.701 and 0.744, and the AUC was 0.828, 0.757 and 0.741, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in model building queue, and the AUC was 0.760, 0.710 and 0.660, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in external validation queue. Conclusion: In the diagnosis of NSCLC, 6-TAABs is superior to that of traditional tumor markers CEA and CYFRA21-1, and can compensate for the shortcomings of traditional tumor markers. For the differential diagnosis of NSCLC and benign lung nodule, "6-TAABs+CYFRA21-1" is the most cost-effective combination, and plays an important role in prevention and screening for early lung cancer.

Evaluation of the application value of seven tumor-associated autoantibodies in non-small cell lung cancer based on machine learning algorithms / 中华预防医学杂志

Objective: Based on the diagnostic model established and validated by the machine learning algorithm, to investigate the value of seven tumor-associated autoantibodies (TAABs), namely anti-p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGEA1 and CAGE antibodies in the diagnosis of non-small cell lung cancer (NSCLC) and to differentiate between NSCLC and benign lung nodules. Methods: This was a retrospective study of clinical cases. Model building queue: a total of 227 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from November 2018 to June 2021 were collected as the NSCLC group, and 120 cases of benign lung nodules, 122 cases of pneumonia and 120 healthy individuals were selected as the control groups. External validation queue: a total of 100 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from May 2022 to December 2022 were collected as the NSCLC group, and 36 cases of benign lung nodules, 32 cases of pneumonia and 44 healthy individuals were selected as the control groups. In addition, NSCLC was divided into early (stage 0-ⅠB) and mid-to-late (stage ⅡA-ⅢB) subgroups. The levels of 7-TAABs were detected by enzyme immunoassay, and serum concentrations of CEA and CYFRA21-1 were detected by electrochemiluminescence. Four machine learning algorithms, XGBoost, Lasso logistic regression, Naïve Bayes, and Support Vector Machine are used to establish classification models. And the best performance model was chosen based on evaluation metrics and a multi-indicator combination model was established. In addition, an online risk evaluation tool was generated to assist clinical applications. Results: Except for p53, the levels of rest six TAABs, CEA and CYFRA21-1 were significantly higher in the NSCLC group (P<0.05). Serum levels of anti-SOX2 [1.50 (0.60, 10.85) U/ml vs. 0.8 (0.20, 2.10) U/ml, Z=2.630, P<0.05] and MAGEA1 antibodies [0.20 (0.10, 0.43) U/ml vs. 0.10 (0.10, 0.20) U/ml, Z=2.289, P<0.05], CEA [3.13 (2.12, 5.64) ng/ml vs. 2.11 (1.25, 3.09) ng/ml, Z=3.970, P<0.05] and CYFRA21-1 [4.31(2.37, 7.14) ng/ml vs. 2.53(1.92, 3.48) ng/ml, Z=3.959, P<0.05] were significantly higher in patients with mid-to late-stage NSCLC than in early stages. XGBoost model was used to establish a multi-indicator combined detection model (after removing p53). 6-TAABs combined with CYFRA21-1 was the best combination model for the diagnosis of NSCLC and early NSCLC. The optimal diagnostic thresholds were 0.410, 0.701 and 0.744, and the AUC was 0.828, 0.757 and 0.741, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in model building queue, and the AUC was 0.760, 0.710 and 0.660, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in external validation queue. Conclusion: In the diagnosis of NSCLC, 6-TAABs is superior to that of traditional tumor markers CEA and CYFRA21-1, and can compensate for the shortcomings of traditional tumor markers. For the differential diagnosis of NSCLC and benign lung nodule, "6-TAABs+CYFRA21-1" is the most cost-effective combination, and plays an important role in prevention and screening for early lung cancer.

Relationships between hypertensive disorders in pregnancy and obstructive sleep apnea syndrome / 中华妇产科杂志

Objective: To investigate the impact of obstructive sleep apnea syndrome (OSAS) on pregnancy outcomes, especially the relationship between OSAS and hypertensive disorders in pregnancy (HDP). Methods: A total of 228 pregnant women with high risk of OSAS who underwent sleep monitoring during pregnancy in Peking University People's Hospital from January 2021 to April 2022 were collected by reviewing their medical records for retrospective analysis. According to the diagnosis of OSAS, the pregnant women were divided into OSAS group (105 cases) and non-OSAS group (123 cases). The non-parametric Mann-Whitney U test, χ2 test or Fisher's exact test were used to compare the general data and maternal and fetal outcomes between the two groups, and the occurrence of each type of HDP was further compared. Results: (1) Compared with the non-OSAS group, the median pre-pregnancy body mass index (23.6 vs 27.6 kg/m2) and the proportion of snoring [28.9% (33/114) vs 59.2% (61/103)] in the OSAS group were higher, and the differences were both statistically significant (both P<0.001). (2) The incidence of HDP [67.6% (71/105) vs 39.0% (48/123)] and gestational diabetes mellitus [GDM; 40.0% (42/105) vs 26.8% (33/123)] of pregnant women in the OSAS group were higher than those in the non-OSAS group, and the median delivery week was shorter than that in the non-OSAS group (38.4 vs 39.0 weeks). The differences were all statistically significant (all P<0.05). Between-group differences for the delivery way, postpartum hemorrhage, the rate of intensive care unit admission, preterm birth, small for gestational age infants, neonatal asphyxia, the rate of neonatal intensive care unit admission, newborn birth weight and the proportion of umbilical artery blood pH<7.00 were not statistically significant (all P>0.05). (3) Compared with the non-OSAS group, the incidence of chronic hypertension [11.4% (14/123) vs 22.9% (24/105)] and chronic hypertension with superimposed pre-eclampsia [11.4% (14/123) vs 30.5% (32/105)] were higher in the OSAS group, and the differences were both statistically significant (both P<0.01). Conclusion: OSAS is related to HDP (especially chronic hypertension and chronic hypertension with superimposed pre-eclampsia) and GDM, which could provide a practical basis for the screening, diagnosis and treatment of OSAS in pregnant women at high risk.

Gut microbiota controls the development of chronic pancreatitis: A critical role of short-chain fatty acids-producing Gram-positive bacteria

Chronic pancreatitis (CP) is a progressive and irreversible fibroinflammatory disorder, accompanied by pancreatic exocrine insufficiency and dysregulated gut microbiota. Recently, accumulating evidence has supported a correlation between gut dysbiosis and CP development. However, whether gut microbiota dysbiosis contributes to CP pathogenesis remains unclear. Herein, an experimental CP was induced by repeated high-dose caerulein injections. The broad-spectrum antibiotics (ABX) and ABX targeting Gram-positive (G+) or Gram-negative bacteria (G-) were applied to explore the specific roles of these bacteria. Gut dysbiosis was observed in both mice and in CP patients, which was accompanied by a sharply reduced abundance for short-chain fatty acids (SCFAs)-producers, especially G+ bacteria. Broad-spectrum ABX exacerbated the severity of CP, as evidenced by aggravated pancreatic fibrosis and gut dysbiosis, especially the depletion of SCFAs-producing G+ bacteria. Additionally, depletion of SCFAs-producing G+ bacteria rather than G- bacteria intensified CP progression independent of TLR4, which was attenuated by supplementation with exogenous SCFAs. Finally, SCFAs modulated pancreatic fibrosis through inhibition of macrophage infiltration and M2 phenotype switching. The study supports a critical role for SCFAs-producing G+ bacteria in CP. Therefore, modulation of dietary-derived SCFAs or G+ SCFAs-producing bacteria may be considered a novel interventive approach for the management of CP.

Analysis of pathogenic bacteria distribution and drug resistance characteristics of bloodstream infection in patients with neutrophilic deficiency after chemotherapy in acute leukemia / 中国热带医学

@#Abstract: Objective　To investigate the distribution and drug resistance characteristics of pathogenic bacteria in patients with neutropenic acute leukemia (AL) and bloodstream infections (BSI). Methods　The clinical data of 258 neutropenic acute leukemia patients with bloodstream infections, who admitted to Shengjing Hospital of China Medical University from January 2016 to December 2021, were collected and analyzed for pathogenic bacteria and drug resistance. Results A total of 268 strains of pathogenic bacteria were isolated from 258 patients, including 180 strains of gram-negative bacteria (67.16%), 61 strains of gram-positive bacteria (22.76%), and 27 strains of fungi (10.07%). Gram-negative bacteria were mainly Klebsiella pneumoniae (53/268, 19.78%), Escherichia coli (49/268, 18.28%) and Pseudomonas aeruginosa (41/268, 15.30%). Gram-positive bacteria were mainly coagulase negative Staphylococcus (31/268, 11.57%) and Staphylococcus aureus(17/268, 6.34%). The main fungi were Candida tropicalis (25/268, 9.33%). Escherichia coli (33/268, 12.31%) was the most common pathogen isolated from acute myeloid leukemia (AML), followed by Pseudomonas aeruginosa (25/268, 9.33%), coagulase-negative Staphylococcus (18/268, 6.72%) and Candida tropicalis (18/268, 6.72%). Klebsiella pneumoniae (35/268, 13.06%) was the most common pathogen isolated from acute lymphoblastic leukemia (ALL),followed by Pseudomonas aeruginosa (15/268, 5.60%) and Escherichia coli (14/268, 5.22%). The resistance of Gram-negative bacteria to piperacillin/tazobactam, cefoperazone/sulbactam, imipenem, meropenem, ertapenem, amikacin, cefoxitin, amoxicillin/clavulanic acid was low. Gram-positive bacteria were sensitive to linezolid and vancomycin. Candida was sensitive to flucytosine, amphotericin B and itraconazole. Conclusions　In patients with granulosa after AL chemotherapy combined with BSI, the pathogenic bacteria isolated from AML are diverse, and the pathogenic bacteria isolated from ALL are mainly gram-negative bacteria. Pathogenic bacteria have different degrees of drug resistance to commonly used antibacterial drugs, so it is important to strengthen the monitoring of the distribution of pathogenic bacteria and the change of drug resistance and rational use of antibacterial drugs to minimize the death of patients.

Optimization of β-globin Stable Expression Using the Third Generation Lentiviral Vector for β-thalassemia Therapy / 中国实验血液学杂志

OBJECTIVE@#To provide a research basis for a safe and effective cell therapy for β-thalassemia through optimization of HS4 region of the third generation lentiviral vector for stable expression of β-globin.@*METHODS@#The human β-globin HS4 region in the third generation lentiviral expression vector was optimized to construct the lenti-HBB, and the transcription and translation of β-globin gene were analyzed by RT-PCR and Western blot after the transduction of lenti-HBB in MEL cell line. Furthermore, the erythroid differentiation of CD34+ cells which were transduced lentiviral virus carrying human β-globin from normal human umbilical cord blood cells and peripheral blood cells of patients with β-thalassemia major were confirmed by colony formation assay, cell smear assay and flow cytometry. The safety and effectiveness of the optimized lenti-HBB were verified by NSG mouse in vivo test.@*RESULTS@#The human β-globin was expressed stably in the MEL cells, and CD34+ cells from health umbilical cord blood as well as PBMC from patient with β-thalassemia major transduced with lenti-HBB could be differentiated to mature red blood cells. The β-globin expression and differentiation in CD34+ cells were demonstrated successfully in the NSG mouse for about 35 months after post-transplant.@*CONCLUSION@#Stable β-globin expression through the optimization of HS4 from CD34+ in the third generation lentiviral vector is safe and effective for patients with severe β-thalassemia and other β-globin abnormal diseases.

Prenatal pyrethroid pesticides exposure and neurodevelopment of 2-year-old children: a birth cohort study / 中华预防医学杂志

Objective: To investigate the influence and critical windows of prenatal exposure to pyrethroid pesticides (PYRs) on neurodevelopment of 2-year-old children. Methods: The subjects of this study were derived from the Xuanwei Birth Cohort. A total of 482 pregnant women who participated in the rural district of Xuanwei birth cohort from January 2016 to December 2018 were included. Maternal urinary concentrations of PYRs metabolites during 8-12 gestational weeks, 20-23 gestational weeks and 32-35 gestational weeks were measured with ultra high performance liquid chromatography system coupled with a tandem mass spectrometry detector. Child neurodevelopment was evaluated with the Bayley Scales of Infant and Toddler Development-Third Edition at 2 years of age. Multivariate linear regression models and binary logistic regression models were used to assess the association between PYRs exposure during pregnancy and children's neurodevelopment. Results: A total of 360 mother-child pairs had complete data on maternal urinary PYRs metabolites detection and children's neurodevelopment assessment. The detection rate of any one PYRs metabolites during the first, second and third trimester were 93.6% (337/360), 90.8% (327/360) and 94.2% (339/360), respectively. The neurodevelopmental scores of Cognitive, Language, Motor, Social-Emotional, and Adaptive Behavior of 2-year-old children were (102.3±18.9), (100.2±16.3), (102.0±20.3), (107.8±23.3) and (85.8±18.6) points, respectively. After controlling for confounding factors, 4-fluoro-3-phenoxybenzoic acid (4F3PBA, one of PYRs metabolites) exposure in the first trimester reduced Motor (β=-5.02, 95%CI: -9.08, -0.97) and Adaptive Behavior (β=-4.12, 95%CI:-7.92, -0.32) scores of 2-year-old children, and increased risk of developmental delay of adaptive behavior (OR=2.07, 95%CI:1.13-3.82). Conclusion: PYRs exposure during the first trimester of pregnancy may affect neurodevelopment of 2-year-old children, and the first trimester may be the critical window.

Effects of unsafe sexual behavior and sexual orientation on previous HIV testing and HIV testing willingness among college students in Harbin / 中华流行病学杂志

Objective: To analyze the effects of unsafe sexual behavior and sexual orientation on previous HIV testing and HIV testing willingness among college students in Harbin, to provide a theoretical basis for promoting and promoting HIV testing among them. Methods: A cross-sectional survey design was used to place the automatic vending machine of HIV urine test kit in 9 universities in Harbin from December 2017 to January 2018. The questionnaire star was used to design and recruit college students to carry out an anonymous online survey. The estimated sample size was 6 659. A multivariate logistic regression model was used to analyze the effects of unsafe sexual behavior and sexual orientation on previous HIV testing and HIV testing willingness among college students. WPS 2016 was used to sort out the database, and SPSS 21.0 software was used for statistical analysis. Results: A total of 60 849 valid questionnaires were collected. 19.1% (11 189/58 605) of college students reported having sex. College students who used condoms correctly every time, occasionally or never during sex in the past six months 58.5% (6 206/10 603), 25.2%(2 669/10 603)and 16.3% (1 728/10 603), respectively. Heterosexuality, homosexuality and bisexuality accounted for 94.1% (54 393/57 823), 2.4% (1 369/57 823) and 3.5% (2 061/57 823), respectively. The HIV testing willingness of college students was 73.3% (44 572/60 849). The proportion of previous HIV testing was 10.3% (951/9 241). Results of the multivariate logistic analysis showed that compared with the college students who used condoms correctly whenever they had sex in the past six months, there was no significant difference in the proportion of previous HIV testing among college students who sometimes/occasionally used or never used condoms (OR=0.94,95%CI:0.69-1.29; OR=1.11,95%CI:0.73-1.67), but their willingness to HIV testing was lower (OR=0.79, 95%CI:0.71-0.89; OR=0.48, 95%CI:0.42-0.55); Compared with heterosexual college students, homosexual or bisexual college students have a higher proportion of previous HIV testing (OR=2.62, 95%CI:1.62-4.24; OR=2.04, 95%CI:1.25-3.32), but have lower HIV testing willingness (OR=0.76, 95%CI: 0.62-0.93; OR=0.64, 95%CI: 0.53-0.77). Conclusions: Unsafe sexual behavior existed among college students in Harbin, and college students with weak awareness of HIV prevention also have weak awareness of testing. Behavioral intervention should be strengthened and HIV testing promoted. Compared with heterosexuals, homosexual or bisexual college students had a higher proportion of previous HIV testing, but their willingness to test was lower. The HIV detection mode with better concealment, accuracy, and convenience should be promoted on the college's campus.

Diagnosis of atopic dermatitis: controversies and facts / 中华皮肤科杂志

Atopic dermatitis is a common chronic recurrent atopic constitution-associated inflammatory skin disease mainly characterized by eczematous lesions and itching. Its etiology and pathogenesis are still not very clear, and there are many controversies about its origin, definition, clinical phenotypes and diagnostic criteria. This review analyzes and discusses these controversies in order to provide a meaningful reference for the diagnosis and treatment of atopic dermatitis.