ObjectiveTo compare the contents and relative molecular weight distributions of proteins and polypeptides in Naoxuekang dropping pills， Huoxue Tongmai capsules and Maixuekang capsules of Hirudo single medicinal preparations， to evaluate the in vitro anticoagulant， antiplatelet and fibrinolytic activities of the three preparations， and to investigate the effects of temperature， pH and digestive enzymes on the anticoagulant activities of the three preparations. MethodsThe contents of soluble proteins and polypeptides in the three preparations were determined by bicinchoninic acid assay（BCA） and Bradford method， and the relative molecular weight distributions of the three preparations were determined by electrophoresis combined with gel chromatography. The antithrombin activity of the three preparations was evaluated by fibrinogen-thrombin time（Fibg-TT） method， and their anticoagulant activities were further assessed by the elongations of activated partial thromboplastin time（APTT）， prothrombin time（PT） and thrombin time（TT）. The antiplatelet aggregation activities of the three preparations were measured by turbidimetry and the fibrinolytic activities were measured by fibrin plate method. Relative TT was used as index to investigate the effects of temperature， pH and digestive enzyme buffer on anticoagulant activities of the three preparations. ResultsAt the lowest single dosage， the contents of proteins and polypeptides were in the order of Maixuekang capsules>Huoxue Tongmai capsules>Naoxuekang dropping pills. Both Huoxue Tongmai capsules and Maixuekang capsules had 11 electrophoretic bands between 4.0 kDa and 90 kDa， the bands of Maixuekang capsules were more clear in the range of >25 kDa， and there was 1 obvious band at 14 kDa for the two capsules. Huoxue Tongmai capsules had one specific band at 9.0 kDa and Maixuekang capsules had one specific band at 48.0 kDa. Naoxuekang dropping pills only had 2 electrophoretic bands at 6.5 kDa and 8.5 kDa， primarily containing peptides below 2 kDa， most of which were oligopeptides. The anticoagulant activity concentrations of the three preparations exhibited a certain dose-dependent effect. At the lowest single dosage， The anticoagulant activity concentrations were ranked as Naoxuekang dropping pills>Huoxue Tongmai capsules>Maixuekang capsules. The prolongation effect of the three preparations on coagulation time was dose-dependent. At the same concentration， the prolongation effect of Naoxuekang dropping pills and Huoxue Tongmai capsules was APTT prolongation rate>TT prolongation rate>PT prolongation rate， whereas for Maixuekang capsules， the sequence was TT prolongation rate>APTT prolongation rate>PT lengthening rate. At the single minimum dosage， the order of APTT prolongation rate was Maixuekang capsules>Huoxue Tongmai capsules≈Naoxuekang dropping pills， the order of PT prolongation rate was Naoxuekang dropping pills≈Maixuekang capsules>Huoxue Tongmai capsules， and the order of TT prolongation rate was Maixuekang capsules>Huoxue Tongmai capsules>Naoxuekang dropping pills. The three preparations showed dose-dependent effects on platelet aggregation induced by adenosine diphosphate（ADP） and arachidonic acid（AA）， and the effect induced by ADP was stronger than that induced by AA. The anti-platelet aggregation effect of Naoxuekang dropping pills was significantly stronger than that of Maixuekang capsules（P<0.01）， whereas Huoxue Tongmai capsules had the effect of promoting platelet aggregation. None of the three preparations had the ability to dissolve fibrin. The anticoagulant activity of Naoxuekang dropping pills was least affected by heating， while the activities of the two capsules decreased significantly within 5 min above 80 ℃， and continued to decrease within 2 h. Compared with pure water， the anticoagulant activities of the three preparations could be increased by 1-3 times under strong acidity（pH 1-3）. In the pepsin buffer， the anticoagulant activity of Naoxuekang dropping pills could be increased by 1-3 times， while the anticoagulant activities of Huoxue Tongmai capsules and Maxuekang capsules were significantly decreased， the lowest levels were about 60% and 20%， respectively. In trypsin buffer， the anticoagulant activities of Naoxuekang dropping pills， Huoxue Tongmai capsules and Maixuekang capsules decreased significantly， and the lowest levels decreased to about 41%， 41% and 35%， respectively. ConclusionThe contents of proteins and polypeptides and relative molecular weights of the preparations derived from lyophilized fresh Hirudo powder， dried Hirudo powder and reflux extract of Hirudo decrease sequentially， and the anticoagulant activity decrease gradually， but the anticoagulant pathway is different. And the anti-platelet aggregation activity of the reflux extract is significantly enhanced. The heat resistance and gastrointestinal stability of the three preparations increase successively， and the first two are suitable for enteric-soluble preparations， while the latter is suitable for routine oral administration. The above results can provide data reference for the rationality of different preparation methods， active substances， pharmacodynamics and mechanism of Hirudo preparations.

  Objective  To analyze the current status of the development of adaptation guidelines in China, as well as their methodological quality and the reporting quality, in order to provide reference for the development of adaptation guidelines.  Methods  We searched and collected adaptation guidelines led by Chinese researchers or institutions from 2015 to 2023 from four electronic databases, China National Knowledge Infrastructure, WanFang Data Knowledge Service Platform, SinoMed and PubMed, extracted the basic information of the adapted guidelines, and assessed their methodological quality and reporting quality using the Appraisal of Guidelines for REsearch and Evaluation (AGREE) Ⅱ and RIGHT-Ad@pt tools.  Results  A total of 14 adaptation guidelines were included, mainly focusing on nursing (42.9%, 6/14), with the most frequently used adaptation method of ADAPTE (71.4%, 10/14), and with reference to pre-existing guidelines mainly from the United States, the United Kingdom, and international organizations. Assessment by the AGREE Ⅱ tool showed that the average methodological quality score of the adapted guidelines was 36.6%. The scores were relatively high in the domains of clarity of expression and rigor of formulation (44.4% and 54.9%), and lowest in the domain of applicability (15.3%). The results of the RIGHT-Ad@pt tool showed that the reporting quality of the adaptation guidelines was relatively good, with the highest reporting rate of 91.2% and the lowest of 35.3%, and the reporting rates of seven articles were higher than 70%.  Conclusions  Adaptation guidelines in China are still in their infancy, with a relatively small number and mainly focusing on the nursing field. The most commonly used adaptation method is the ADAPTE method. The methodological quality and reporting quality of adaptation guidelines need to be further improved, and more research should be conducted on the specific conditions and timing of adaptation guidelines development.

Objective:The drug-resistant genes carried by carbapenem-resistant Klebsiella pneumoniae(CRKP)limit clinical treatment options,and its virulence genes severely affect patient prognosis.This study aims to investigate the distribution of virulence genes,capsular serotypes,and molecular epidemiological characteristics of CRKP in ICU,to understand the characteristics of CRKP infections in ICU,and to provide a scientific basis for effective monitoring and control of CRKP infections in ICU. Methods:A total of 40 non-duplicate strains of CRKP isolated from the ICU of Guangdong Provincial People's Hospital between January 2021 and December 2022 were collected and analyzed.Whole-genome sequencing was used to analyze the distribution of resistance genes,virulence genes,and capsular serotypes of the strains.The sequences of 7 housekeeping genes of CRKP genome were uploaded to the Klebsiella pneumoniae(KPN)multilocus sequence typing(MLST)database to determine the sequence types(STs)of the strains. Results:The age of the 40 ICU CRKP-infected patients was(69.03±17.82)years old,with various underlying diseases,and there were 20 patients with improved clinical outcome and 20 patients with death.The isolated strains primarily originated from mid-stream urine and bronchoalveolar lavage fluid.Whole-genome sequencing results revealed that the strains predominantly carried blaKPC-1(29 strains,72.5%)and blaNDM-1(6 strains,15.0%),with 5 strains carrying both blaKPC-1 and blaNDM-1.Various virulence genes were detected,among which the carriage rates of genes such as entA,entB,entE,entS,fepA,fepC,fepG,yag/ecp,and ompA reached 100%,while the carriage rates of genes such as entD,fimB,iroB,iroD,fes,and pla were low.The CRKP strains isolated from ICU were predominantly ST11(27 cases,67.5%),with KL64 being the main capsular serotype(29 cases,72.5%).A total of 23 ST11-KL64 CRKP strains were detected,accounting for 57.5%. Conclusion:The main type of ICU CRKP is ST11-KL64,carrying various virulence genes,primarily those related to iron absorption.Furthermore,blaKPC has shifted from blaKPC-2 to blaKPC-1.Therefore,close monitoring of the molecular epidemiological changes of CRKP is necessary,and strict control measures should be implemented to effectively curb the occurrence of CRKP infections.

Objective:To identify and characterize one Yokenella regensburgei strain(designated as CXLZQ123) isolated from a case of perionychial abscess. Methods:Strain CXLZQ123 was isolated from a patient with periungual abscess at the Dermatology Department of San County Central Hospital in June 2, 2023. The strain was initially identified through morphological and biochemical tests, followed by mass spectrometry identification, 16S rRNA sequencing and whole-genome sequencing. MEGA 11.0 was used to compare and analyze the strain′s genetic relationship with relevant species in GenBank, and a phylogenetic tree was constructed based on genetic distance to analyze its genetic evolution. Meanwhile, the average nucleotide identity between its genome and similar strains were compared.Results:The strain was identified as a Gram-negative rod. MicroScan WalkAway biochemical tests indicated that the strain was either Yokenella regensburgei (91.47%) or Hafnia alvei (8.53%). MALDI-TOF mass spectrometry confirmed it as Yokenella regensburgei. Based on 16S rRNA gene sequence analysis, the strain showed the highest similarity(99.37%) to CIP 105435 (sequence number NR_104934.1). The 16S rRNA gene sequence of the isolated strain Yokenella regensburgei was submitted to the National Center for Biotechnology Information (NCBI) with the GenBank sequence number of OR230248.1. The whole-genome of CXLZQ123 were sequenced and uploaded (NCBI, SRA sequence number: SRR26510420). The average nucleotide identity between CXLZQ123 and Yokenella regensburgei strains W13 and UU2206353 were 98.82% and 99.04%, respectively. Conclusions:Through morphological observation, biochemical identification, mass spectrometry identification, 16S rRNA and whole-genome sequencing, this pathogenic strain is identified as Yokenella regensburgei. This rare bacterium is sensitive to most detected antibiotics. This study provides diagnostic and treatment experience for Yokenella regensburgei-related infections.

Objective:To assess the efficacy of a novel spatial-temporal polyp detection system in colonoscopy.Methods:This research was a retrospective comparative study. Eight hundred and thirty-three participants who underwent computer-aided detection (CADe) colonoscopy at the First Medical Center of Chinese PLA General Hospital between March and June 2023 were enrolled to the experimental group, while 770 individuals who received conventional colonoscopy from March to June 2022, in the identical operation room were to the control group. The primary outcome was the adenoma detection rate (ADR), and the secondary outcomes were the polyp detection rate (PDR), adenomas per colonoscopy (APC), and polyps per colonoscopy (PPC).Results:The ADR [29.3% (244/833) VS 21.7% (167/770), χ2=12.133, P<0.001] and PDR [47.9% (399/833) VS 37.9% (292/770), χ2=16.241, P<0.001] were significantly higher in the experimental group than those in the control group. Adenomas ≤5 mm [23.5% (196/833) VS 16.1% (124/770), χ2=13.808, P<0.001] and flat-type adenomas [15.1% (126/833) VS 7.3% (56/770), χ2=24.519, P<0.001] were detected in a significantly higher proportion of subjects in the experimental group than those in the control group. There were significant difference in APC [0 (0,1) VS 0 (0,1), Z=-3.698, P<0.001] and PPC [0 (0,1) VS 0 (0,1), Z=-4.424, P<0.001] between the experimental and control groups. The use of CADe system significantly increased both ADR [29.5% (167/566) VS 18.9% (89/472), χ2=15.709, P<0.001] and PDR [47.3% (268/566) VS 33.3% (157/472), χ2=21.123, P<0.001] in junior endoscopists. However, in senior endoscopists, there was no statistical significant difference in ADR [28.8% (77/267) VS 26.2% (78/298), χ2=0.502, P=0.479] or PDR [49.1% (131/267) VS 45.3% (135/298), χ2=0.800, P=0.371] with or without CADe system. Conclusion:The use of CADe system significantly increases overall polyp and adenoma detection in clinical practice, especially in the detection of diminutive and flat-type lesions. Junior endoscopists gain greater advantages from the use of CADe system than their senior peers.

Objective:To detect the levels of γ-glutamyl transferase (GGT) in the amniotic fluid of normal pregnancies at 19-23 +6 gestational weeks and to analyze the changes in GGT level with gestational age. Methods:This study retrospectively collected the amniotic fluid supernatant from 383 singleton pregnant women (102, 103, 82, 68 and 28 cases at 19-19 +6, 20-20 +6, 21-21 +6, 22-22 +6, 23-23 +6 weeks of gestation, respectively) who underwent amniocentesis for prenatal diagnosis but had normal genetic diagnosis results in Cheeloo Hospital of Shandong University from January 2021 to September 2022. The levels of GGT in the amniotic fluid supernatant were tested and the statistical parameters including xˉ± s, min-max, median ( M), P1, P2.5, P5, P95, P97.5 and P99 values of GGT levels at each gestational week were calculated. GGT were non-normal data and converted into natural logarithms (lnGGT), and a least square linear regression equation was established to analyze the relationship between lnGGT and gestational week. Results:At 19-19 +6, 20-20 +6, 21-21 +6, 22-22 +6, and 23-23 +6 gestational weeks, the xˉ± s of amniotic fluid GGT were (385.8±235.7), (331.8±219.4), (253.7±197.9), (226.7±166.4), and (155.3±96.8) U/L, and the weekly declines were 14.0%, 23.5%, 10.6%, and 31.5%, respectively; the M values were 311.0, 288.0, 199.0, 160.5, and 105.5 U/L, and the weekly declines were 7.4%, 30.9%, 19.3%, and 34.3%, respectively; the P1- P99 were 67.1-1 404.5, 63.2-1 189.1, 36.0-849.8, 44.0-787.3, and 32.0-375.6 U/L, respectively. lnGGT was negatively correlated with gestational age ( R 2=0.148, P<0.001). Conclusions:In normal pregnancies at 19-23 +6 gestational weeks, GGT levels in amniotic fluid decrease with gestational age. Therefore, gestational age should be considered when establishing the reference value for amniotic fluid GGT in normal pregnancies.

Post-stroke cognitive impairment (PSCI) refers to a clinical syndrome that occurs after a stroke and meets the diagnostic criteria for cognitive impairment, lasting for more than 6 months, and seriously affecting the daily life of patients. The complement system has been confirmed to be associated with PSCI. This article reviews the correlation between complement system and PSCI, as well as the possibility of complement system as an intervention target for PSCI.

Objective:To investigate the mechanism of human placenta derived mesenchymal stem cells (hPMSCs) in the inhibition of TNF-α secretion in CD4 + IFN-γ + T cells (Th1) through CD73/nuclear factor-erythroid 2-related factor 2(Nrf2) pathway to reduce liver injury in mice with graft versus-host disease (GVHD). Methods:Flow cytometry (FCM) was used to analyze the expression of TNF-α in Th1 cells and the expression of PD-1 on CD4 + IFN-γ + TNF-α + T cells (TNF-α + Th1 cells) isolated from peripheral blood and liver tissues of mice with GVHD. Hematoxylin-hosin (HE) staining, Masson staining and immunofluorescence staining were used to observe the pathological changes in liver tissues of GVHD mice in each group. HE staining was also used to observe the pathological changes in skin and lung tissues of GVHD mice. A nonconditional protocol to induce the differentiation of peripheral blood mononuclear cells (PBMCs) into Th1 cells in vitro was established. The proportion of TNF-α + Th1 cells and the mean fluorescence intensity (MFI) of Nrf2 and phosphorylated nuclear factor-kappa B (p-NF-κB) in this T cell subgroup were detected. Results:Compared with the normal control group, the proportion of TNF-α + Th1 cells and the expression of PD-1 on this T cells in peripheral blood and liver tissues of mice in the GVHD high group increased significantly ( P<0.01). The proportion of TNF-α + Th1 cells in peripheral blood and liver tissues decreased after hPMSCs treatment ( P<0.001), but the expression of PD-1 on this T cell subset was promoted in peripheral blood and liver tissues ( P<0.01, P<0.001). However, the intervention effects of shCD73 on TNF-α + Th1 cells in peripheral blood and liver tissues were significantly weakened ( P<0.05, P<0.01). Liver histopathological analysis showed that the proportion of TNF-α + Th1 cells in liver was positively correlated with Suzuki′s score, collagen area and the MFI of α-SMA ( P<0.001). Similarly, histopathological analysis of skin and lung tissues also showed that the proportion of TNF-α + Th1 cells in peripheral blood was positively correlated with skin Marina score and lung Shukai Qiao score ( P<0.001). In vitro experiment also showed that hPMSCs down-regulated the proportion of TNF-α + Th1 cells ( P<0.01) and up-regulated the expression of PD-1 on them ( P<0.05). Further analysis showed that hPMSCs could enhance the MFI of Nrf2 ( P<0.05) and weaken the MFI of p-NF-κB ( P<0.01) in TNF-α + Th1 cells. Conclusions:hPMSCs could up-regulate the expression of PD-1 through CD73/Nrf2 pathway to inhibit the formation of TNF-α + Th1 cells, thereby alleviating liver injury in GVHD mice.

Abstract By reviewing the advocacy framework and implementation path of global adolescent health promotion, summarizing the main health problems of adolescents worldwide and current status of adolescent health care services in China, an ecological model of adolescent health care was concluded according to the demands of adolescents towards health care services. A comprehensive intervention strategy, ie. multi sector cooperation, community participation and integration of hospital, school, community and family, etc, has been put forward to promote the health and sustainable development of adolescents.

Objective:To establish the normal values of water-perfused high resolution esophageal manometry (HREM)(GAP-36A) at resting period, water swallowing, semisolid swallowing and solid swallowing in Chinese population.Methods:From September 1, 2019 to June 30, 2020, 91 healthy volunteers receiving water-perfused HREM (GAP-36A) at resting period, water swallowing, semisolid swallowing and solid swallowing were selected from 9 hospitals (Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; the First Affiliated Hospital of Dalian Medical University; the Second Hospital of Hebei Medical University; the Second Affiliated Hospital, Naval Medical University; the First Affiliated Hospital, Sun Yat-sen University; the First Affiliated Hospital, University of Science and Technology of China; Aviation General Hospital of China Medical University; the Affiliated Hospital of Medical School of Nanjing University and the First People′s Hospital of Yichang). Parameters included the position of the upper and lower edges of the upper esophageal sphincter (UES) and lower esophageal sphincter (LES), the length of the LES and UES, the position of the pressure inversion point (PIP), the resting pressure of UES and LES and swallow-related parameters such as the distal contraction integral (DCI), 4 s integrated relaxation pressure (IRP), distal latency (DL) and UES residual pressure. One-way analysis of variance, post-hoc test and sum rank test were used for statistical analysis.Results:A total of 87 healthy volunteers were enrolled, including 40 males and 47 females, aged (38.5±14.2) years old (ranged from 19 to 65 years old). The position of the upper and lower edges of the LES was (42.7±2.8) and (45.6±2.8) cm, respectively, the length of the LES was (2.9±0.4) cm, and the position of PIP was (43.3±2.8) cm. The position of the upper and lower edges of the UES was (18.1±3.0) and (22.6±2.0) cm, respectively, and the length of the UES was (4.8±1.0) cm. The resting pressure of LES and UES was (17.4±10.7) and (84.1±61.1) mmHg (1 mmHg=0.133 kPa), respectively. The DCI value at solid swallowing was higher than those at water swallowing and semisolid swallowing ((2 512.4±1 448.0) mmHg·s·cm vs. (2 183.2±1 441.2) and (2 150.8±1 244.8) mmHg·s·cm), and the differences were statistically significant ( t=-4.30 and -3.74, both P<0.001). The values of 4 s IRP at semisolid swallowing and solid swallowing were lower than that at water swallowing ((4.6±4.1) and (4.9±3.9) mmHg vs. (5.4±3.9) mmHg), and the differences were statistically significant ( t=3.38 and 2.09, P=0.001 and 0.037). The DL at water swallowing was shorter than those at semisolid swallowing and solid swallowing ((8.5±1.8) s vs. (9.8±2.2) and (10.6±2.8) s), and the DL at semisolid swallowing was shorter than that at solid swallowing, and the differences were statistically significant ( t=-10.21, -13.91 and -4.68, all P<0.001). The UES residual pressure at water swallowing was higher than those at semisolid swallowing and solid swallowing (9.5 mmHg, 6.5 to 12.3 mmHg vs. 8.0 mmHg, 4.5 to 11.7 mmHg and 5.5 mmHg, 2.0 to 9.3 mmHg), and the UES residual pressure at semisolid swallowing was higher than that at solid swallowing, and the differences were statistically significant ( t=3.48, 10.30 and 6.35, all P<0.001). Conclusions:The normal values of water-perfused HREM (GAP-36A) in Chinese population at resting period, water swallowing, semisolid swallowing and solid swallowing can provide a reference basis for clinical diagnosis and treatment for patients receiving water-perfused HREM examination.