Objective To analyze the status of persistent human papillomavirus (HPV) infection and the distribution of viral subtypes in the Zhengzhou region. Methods Clinical data of 55239 patients who underwent HPV-DNA genotyping tests from 2018 to 2024 were collected. On the basis of HPV follow-up results, patients were divided into three groups: 849 cases of infection with the same HPV type, 255 cases of persistent infection with different HPV types, and 857 cases of transient HPV infection. Results Among the 9232 initially-screened patients who were positive with HPV, the high-risk HPV (HR-HPV) positive rate was 84.6% (7813/9232), and predominant subtypes were HPV-16 (20.8%), HPV-52 (17.2%), and HPV-53 (9.6%). The low-risk HPV (LR-HPV) positive rate was 15.4% (1419/9232), mainly HPV-81 (28.1%) and HPV-42 (27.0%). Among the 1961 follow-up cases, the rates of persistent and non-persistent infections with the same HPV type were 35.7% (701/1961) and 7.5% (148/1961), respectively. The rates of persistent and non-persistent infections with different HPV types were 10.9% (214/1961) and 2.1% (41/1961), respectively. Meanwhile, 43.7% (857/1961) tested negative upon follow-up. Among the 701 cases of persistent infection with the same HPV type, HR-HPV accounted for 85.7% (601/701), and LR-HPV accounted for 14.3% (100/701). Among the 214 cases of persistent infection with different HPV types, 89.7% (192/214) were high-risk transitions, and 10.3% (22/214) were low-risk transitions. Regardless of HPV types, HR-HPV was more likely to cause persistent infection than LR-HPV. In addition, over 60% of HR-HPV persistent infections resolved within 18 months, 30% developed into persistent infections, and only 15% of patients had persistent infections that last more than 24 months. Conclusion Persistent HPV infections are predominantly high-risk types. Most patients clear the infection within 18 months, approximately 30% develop persistent infections, and about 15% of patients have persistent infections that last more than 24 months. However, the HR-HPV persistent infection rates across different age groups slightly differ.

Objective To investigate the effects of icariin on high glucose-induced autophagy and apoptosis of podocytes,and the regulating effects on mammalian target of rapamycin(mTOR)/serine-threonine kinase(Akt)/cyclic adenosine monophosphate response element binding protein(CREB)pathway.Methods The mouse podocytes MPC5 were taken and divided into five groups:normal control group(5.5 mmol·L-1 glucose),high glucose group(30 mmol·L-1 glucose),icariin group(30 mmol·L-1glucose+5 μmol·L-1icariin),GDC-0349 group(30 mmol·L-1glucose+50 μmol·L-1 GDC-0349),icariin+GDC-0349 group(30 mmol·L-1 glucose+5 μmol·L-1 icariin+50 μmol·L-1 GDC-0349).Cultured for 48 hours,the tetramethylazozolium salt method was used to detect the viability of MPC5 cells;acridine orange staining was used to observe the autophagy of MPC5 cells;apoptosis of MPC5 cells was detected by flow cytometry;Western blotting was used to detect the expression of autophagy[microtubule associated protein one light chain 3(LC3)II,LC3Ⅰ,autophagy-related protein(Beclin-1)],apoptosis[Bcl-2 related X protein(Bax),B cell lymphoma-2(Bcl-2)]and mTOR/Akt/CREB pathway-related proteins of MPC5 cells.Results Compared with the normal control group,the cell viability,expression levels of Bcl-2,phosphorylated mTOR(p-mTOR)/mTOR,phosphorylated Akt(p-Akt)/Akt,phosphorylated CREB(p-CREB)/CREB protein of MPC5 cells in the high glucose group were significantly decreased(P＜0.05),the autophagy ability was enhanced,the autophagosome showed orange fluorescence,and the apoptosis rate,LC3Ⅱ/LC3Ⅰ,Beclin-1,Bax protein expression levels were significantly increased(P＜0.05).Compared with the high glucose group,the cell viability,LC3Ⅱ/LC3Ⅰ,Beclin-1,Bcl-2,p-mTOR/mTOR,p-Akt/Akt,p-CREB/CREB protein expression levels of MPC5 cells in icariin group were significantly increased,the autophagy ability was further enhanced,the number of autophagosomes was increased,the autophagosomes showed brick red fluorescence(P＜0.05),the apoptosis rate and Bax protein expression level were significantly decreased(P＜0.05),and the cell viability,LC3Ⅱ/LC3Ⅰ,Beclin-1,Bcl-2,p-mTOR/mTOR,p-Akt/Akt and p-CREB/CREB proteins expression levels of MPC5 cells in GDC-0349 group were significantly decreased,the autophagy ability was weakened,the number of autophagosomes was reduced,the autophagosomes showed orange fluorescence(P＜0.05),and the apoptosis rate and Bax protein expression level were significantly increased(P＜0.05);icariin+GDC-0349 could reverse the effect of icariin on high glucose induced MPC5 cells(P＜0.05).Conclusion Icariin promotes elevated glucose-induced podocyte autophagy and inhibits apoptosis by activating the mTOR/Akt/CREB pathway.

Objective:To carry out genetic analysis on two families with carriers of small terminal translocations using karyotyping analysis and genomic copy number variation sequencing (CNV-seq).Methods:Two couples undergoing prenatal diagnosis at the Tianjin Central Hospital of Obstetrics and Gynecology respectively on April 12, 2020 and December 17, 2021 were selected as the study subjects. With informed consent, amniotic fluid and peripheral blood samples were collected and subjected to conventional karyotyping and CNV-seq analysis for the detection of chromosomal microdeletion/duplications.Results:Both couples had given births to children with chromosomal aberrations previously, and both fetuses were found to have abnormal karyotypes. CNV-seq showed that they had harbored microdeletion/duplications, and their mothers had both carried balanced translocations involving terminal fragments of chromosomes.Conclusion:For fetuses with small chromosomal segmental abnormalities, their parental origin should be traced, and the diagnosis should be confirmed with combined genetic techniques.

[This corrects the article DOI: 10.1016/j.apsb.2021.07.006.].

Objective:To investigate the influencing of inferior mediastinum and esophageal hiatus lymph node metastasis by submucosal different venous divisions of esophagogastric junction (EGJ) invaded in Siewert type Ⅱ adenocarcinoma of esophagogastric junction (AEG).Methods:The retrospective case-control study was conducted. The clinicopathological data of 547 patients with Siewert type Ⅱ AEG who were admitted to Shanxi Cancer Hospital from January 2018 to December 2021 were collected. There were 461 males and 86 females, aged 61 (range, 33?75)years. Observa-tion indicators: (1) lymph node metastasis rate in different groups; (2) influencing factors of inferior mediastinum lymph node metastasis in Siewert type Ⅱ AEG; (3) influencing factors of esophageal hiatus lymph node metastasis in Siewert type Ⅱ AEG. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and com-parison between groups was conducted using the Mann-Whitney U test. Count data were described as percentages or absolute numbers, and comparison between groups was conducted using the chi-square test. The univariate analysis was conducted using the corresponding statistical methods based on data type. The Logistic regression model was used for multivariate analysis. Results:(1) Lymph node metastasis rate in different groups. The lymph node metastasis rate in No. 1, 2, 3, 4sa, 4sb, 7, 8a, 9, 11,20, 108, 110 of the 547 patients was 17.37%(95/547), 6.76%(37/547), 46.44%(254/547), 1.65%(9/547), 1.10%(6/547), 23.22%(127/547), 4.39%(24/547), 3.11%(17/547), 3.47%(19/547), 3.66%(20/547), 0.55%(3/547), 4.20%(23/547), respectively. Of the 547 patients, there were 456 cases with proximal of AEG invading submucosal palisade venous of EGJ including 4 cases with inferior mediastinum lymph node metastasis and no case with media mediastinum or up media-stinum lymph node metastasis. There were 91 cases with proximal of AEG invading submucosal perforator venous of EGJ including 18 cases with inferior mediastinum lymph node metastasis, 3 cases with media mediastinum lymph node metastasis and no case with up mediastinum lymph node metastasis. (2) Influencing factors of inferior mediastinum lymph node metastasis in Siewert type Ⅱ AEG. Results of multivariate analysis showed that age, tumor invading submucosal perforator venous of EGJ and histological classification were independent influencing factors for inferior media-stinum lymph node metastasis of Siewert type Ⅱ AEG ( odds ratio=0.93, 23.33, 0.31, 95% confidence interval as 0.87?0.99, 4.18?130.28, 0.12?0.78, P<0.05). (3) Influencing factors of esophageal hiatus lymph node metastasis in Siewert type Ⅱ AEG. Tumor invading submucosal perforator venous of EGJ was an independent influencing factor for esophageal hiatus lymph node metastasis of Siewert type Ⅱ AEG ( odds ratio=14.95, 95% confidence interval as 2.46?90.76, P<0.05). Conclusion:Age, tumor invading submucosal perforator venous of EGJ and histological classification are independent influencing factors for inferior mediastinum lymph node metastasis of Siewert type Ⅱ AEG, and tumor invading submucosal perforator venous of EGJ is an independent influencing factor for esophageal hiatus lymph node metastasis.

Objective:To compare the efficacy of the Preterm Infant Oral Feeding Readiness Assessment Scale (PIOFRA) and Preterm Infant Oral Feeding Ability Readiness Assessment Scale (POFARA) in predicting the outcome of first oral feeding in preterm infants.Methods:This study was a cross-sectional study. From February 2021 to February 2022, 276 premature infants treated in the Neonatal Intensive Care Unit of the Second Affiliated Hospital of Air Force Medical University of People's Liberation Army and the Second Affiliated Hospital of Shaanxi University of Chinese Medicine were selected by convenience sampling method. According to the outcome of the first oral feeding, the premature infants were divided into a successful first oral feeding group ( n=227) and a failed first oral feeding group ( n=49). PIOFRA and POFARA were used to evaluate premature infants. The area under the receiver operating characteristic curve ( AUC), sensitivity, specificity, Youden index and other indicators were used to compare the predictive efficacy of the two scales for the first oral feeding outcome of premature infants. Results:The success rate of first oral feeding for premature infants was 82.25% (227/276). The PIOFRA and POFARA scores of the successful first oral feeding group were higher than those of the failed first oral feeding group ( P<0.01). The AUC of PIOFRA was 0.830. When the total score of PIOFRA was 27.00, the sensitivity was 78.40%, the specificity was 75.50%, and the Youden index was 0.539 ( P<0.01), and its prediction efficiency was the highest. The AUC of POFARA was 0.928. When the total score of POFARA was 33.00, the sensitivity was 79.70%, the specificity was 95.90%, and the Youden index was 0.757 ( P<0.01), and its prediction efficiency was the highest. The AUC, sensitivity, specificity and Youden index of POFARA were higher than those of PIOFRA. Conclusions:The predictive efficacy of POFARA is higher than that of PIOFRA. It is recommended to use POFARA for the evaluation and prediction of the outcome of first oral feeding in premature infants.

Clinical application of doxorubicin (DOX) is heavily hindered by DOX cardiotoxicity. Several theories were postulated for DOX cardiotoxicity including DNA damage and DNA damage response (DDR), although the mechanism(s) involved remains to be elucidated. This study evaluated the potential role of TBC domain family member 15 (TBC1D15) in DOX cardiotoxicity. Tamoxifen-induced cardiac-specific Tbc1d15 knockout (Tbc1d15^CKO) or Tbc1d15 knockin (Tbc1d15^CKI) male mice were challenged with a single dose of DOX prior to cardiac assessment 1 week or 4 weeks following DOX challenge. Adenoviruses encoding TBC1D15 or containing shRNA targeting Tbc1d15 were used for Tbc1d15 overexpression or knockdown in isolated primary mouse cardiomyocytes. Our results revealed that DOX evoked upregulation of TBC1D15 with compromised myocardial function and overt mortality, the effects of which were ameliorated and accentuated by Tbc1d15 deletion and Tbc1d15 overexpression, respectively. DOX overtly evoked apoptotic cell death, the effect of which was alleviated and exacerbated by Tbc1d15 knockout and overexpression, respectively. Meanwhile, DOX provoked mitochondrial membrane potential collapse, oxidative stress and DNA damage, the effects of which were mitigated and exacerbated by Tbc1d15 knockdown and overexpression, respectively. Further scrutiny revealed that TBC1D15 fostered cytosolic accumulation of the cardinal DDR element DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Liquid chromatography-tandem mass spectrometry and co-immunoprecipitation denoted an interaction between TBC1D15 and DNA-PKcs at the segment 594-624 of TBC1D15. Moreover, overexpression of TBC1D15 mutant (∆594-624, deletion of segment 594-624) failed to elicit accentuation of DOX-induced cytosolic retention of DNA-PKcs, DNA damage and cardiomyocyte apoptosis by TBC1D15 wild type. However, Tbc1d15 deletion ameliorated DOX-induced cardiomyocyte contractile anomalies, apoptosis, mitochondrial anomalies, DNA damage and cytosolic DNA-PKcs accumulation, which were canceled off by DNA-PKcs inhibition or ATM activation. Taken together, our findings denoted a pivotal role for TBC1D15 in DOX-induced DNA damage, mitochondrial injury, and apoptosis possibly through binding with DNA-PKcs and thus gate-keeping its cytosolic retention, a route to accentuation of cardiac contractile dysfunction in DOX-induced cardiotoxicity.

OBJECTIVE To interpret Teacher Training Syllabus for Clinical Pharmacist Training Program （2023 edition） （hereinafter referred as to the “new syllabus”）， and to provide reference and guidance for promoting the implementation of the new syllabus and realizing the quality-improving goal of the reform of the clinical pharmacist teacher training program initiated by China Hospital Association. METHODS From the perspective of the management and based on the position of the designer， the new syllabus was interpreted from four aspects： the background of its compilation and release， the process of its compilation and its characteristics， the key improvements of the program and the points for attention about its subsequent implementation. RESULTS & CONCLUSIONS The development and release of the new syllabus provide a “construction blueprint” for the reform of the clinical pharmacist teacher training program of the China Hospital Association. The whole process of compiling the new syllabus is characterized by four basic features： theory-led， goal-oriented， research-based， and synergistic. Compared with the previous syllabus， in addition to the adjustment of the text structure，the new syllabus presents more complete and clearer competence requirements for clinical teaching competence in terms of training objectives； in terms of training content， it further structures the group of task items， pays attention to the 育。E-mail：zhenjiancun@163.com sequential planning and time arrangement of items， and puts forward both quantitative and qualitative refinement requirements for each specific training task；in terms of training methods， it emphasizes the interaction of lecturing， demonstrating and guiding， and the progression of observation， operation and reflection， with the intention of guiding teacher trainees to “learn how to teach by teaching”. In the subsequent implementation of the new syllabus， it is necessary for the teacher training bases to attach great importance to the guarantee of training conditions and process quality management， and to organize the teacher training team to do a good job in the two training programs of “clinical pharmacist training” and “clinical pharmacist teacher training”. Based on further improving the connection between the two training programs， the teacher training team should continue to explore the scientific model of clinical pharmacist teacher training oriented by clinical teaching competence.

【Objective】 To establish RH gene mRNA sequencing method based on nanopores sequencing and to explore the RHD and RHCE mRNA transcripts in D positive and D^el individuals. 【Methods】 From March 2021 to May 2022, 5 RhD positive samples and 5 D^el samples screened out by hospitals in Chengdu were sent to our laboratory for futher examination. The erythrocytes and buff coat were isolated, then DNA and RNA were extracted.All 10 samples were genotyped by PCR-SSP. After the mRNA was reversely transcribed into cDNA, the full-length mRNA of RHD and RHCE genes were simultaneously amplified by a pair of primers. Sanger sequencing and third-generation sequencing technology based on Nanopore were used to sequence the amplified products, and the types and expressions of different splices of RHD and RHCE gene mRNA transcripts were analyzed. 【Results】 The method established in this study can simultaneously amplify the full length transcripts of RHD and RHCE. Ten different RHD gene mRNA transcripts and nine RHCE gene mRNA transcripts were detected in 10 samples. RHD full-length transcript (RHD-201) can be detected in RhD D^el type, but the expression amount was significantly lower than that in RhD positive samples. The expression amount of transcript RHD-207 (Del789) in D^el samples was significantly higher than that in RhD positive samples. The transcript RHD-208 (Del8910+ 213) was only detected in RhD D^el type individuals, and no significant difference was found between other RHD transcripts and all RHCE transcripts in the two phenotypes. 【Conclusion】 In this study, an analytical method for sequencing full-length transcript isomers of RHD and RHCE mRNA via the third generation was successfully established, and complex alternative splicing patterns were found in RHD and RHCE genes, providing a new method for the study of alternative splicing of blood group gene variants mRNA.

Background Air pollutants PM_2.5 and its adsorbed metal elements are important factors affecting public health. Objective To explore the distribution characteristics and sources of metal elements in atmospheric PM_2.5 in Lanzhou from 2019 to 2020, and to assess the health risks of metal elements to different groups of residents through inhalation. Methods From January 2019 to December 2020 in two districts of Lanzhou City (Chengguan District and Xigu District), regular PM_2.5 and metal elements [antimony (Sb), aluminum (Al), arsenic (As), beryllium (Be), cadmium (Cd), chromium (Cr), mercury (Hg), lead (Pb), manganese (Mn), nickel (Ni), selenium (Se), and thallium (Tl)] were regularly monitored, and their concentrations were described by the median (M) and 25^th and 75^th percentiles (P₂₅, P₇₅) as not following a normal distribution (because the detection rates of the five elements Be, Cr, Hg, Ni, and Se were less than 70%, the five elements were not included in subsequent analysis), and then compared with the secondary concentration limits in the Ambient Air Quality Standards (GB 3095-2012). The differences between the medians of the two groups were compared by the Mann-Whitney U rank sum test, and the differences among the medians of multiple groups were compared by the Kruskal-Wallis H rank sum test; the enrichment factor (EF) method and principal component analysis were used to evaluate the pollution degree of the metals and their sources; the health risks of five non-carcinogenic metals (Sb, Al, Pb, Mn, and Tl) and two carcinogenic metals (As and Cd) in PM_2.5 were evaluated by hazard index (HI) and hazard quotient (HQ) using the incremental lifetime cancer risk (LCR) model and the non-carcinogenic risk assessment model, respectively. Results The PM_2.5 concentrations [M (P₂₅, P₇₅)] in Lanzhou City were 38.50 (26.00, 65.00) and 41.00 (29.00, 63.10) μg·m⁻³ in 2019 and 2020, respectively, and the difference was not statistically significant (Z=−0.989, P > 0.05). The average levels of the metal elements from high to low were: Al > Pb > Mn > As > Cd > Sb > Tl, and the annual average concentration of each metal element in 2019 was higher than that in 2020 (P<0.05). The M ( P₂₅, P₇₅) of PM_2.5 concentrations in Chengguan and Xigu districts were 52.98 (17.00, 61.00) and 55.40 (17.00, 67.00) μg·m⁻³, respectively, with no statistically significant differences (P<0.05); the concentrations of Sb and Al in Chengguan District were lower than those in Xigu District (P<0.05), and the concentrations of other metal elements were not different between the two areas (P>0.05). There were seasonal differences in the concentrations of PM_2.5 and seven metal elements in Lanzhou City (except P_Al=0.007, the other P_s < 0.001). The results of the enrichment factor method showed that the EF values of the six metals (Sb, Al, As, Cd, Pb and Tl) were all greater than 1. Among them, except As, the EF values of other metal elements were all greater than 10, and the EF values of Al and Cd were both greater than 100. The results of principal component analysis showed that the variance contributions of the three principal components were 45.61%, 24.22%, and 14.42%, and the cumulative contribution reached 84.25%. The principal component 1 included Pb, As, Cd, and Sb, the principal component 2 included Al and Mn, and the principal component 3 contained Tl. The non-carcinogenic risks of the five metals were, in descending order, Al > Mn > Pb > Tl > Sb, among which the HQ values of the remaining four metals were less than 1 for adults and children, except the HQ value of Al for adults, which was greater than 1. The ILC values of carcinogenic metal As for adult males, adult females, and children were 2.68×10⁻⁵, 2.51×10⁻⁵, and 1.45×10⁻⁵, respectively; the ILC values of carcinogenic metal Cd for adult males, adult females, and children were 1.53×10⁻⁶, 1.43×10⁻⁶, and 8.26×10⁻⁷, respectively. Conclusion There is pollution of atmospheric PM_2.5 and its adsorbed metal elements in Lanzhou. As and Cd elements may pose potential carcinogenic risks to the residents.