Objective To observe the value of amide proton transfer(APT)imaging for assessing central nervous system damages in stable chronic obstructive pulmonary disease(COPD)and the correlations with MR spectroscopy(MRS)and lung function parameters.Methods Thirty-nine stable COPD patients(COPD group)and 34 healthy subjects(control group)were prospectively enrolled.Images of plain head MR,3D-APT and thalami MRS were acquired,and parameters of lung function were obtained.The basic data,outcomes of voxel-based morphometry(VBM)analysis,APT values in multiple brain regions and thalami MRS metabolite parameters were compared between groups,and the correlations of thalamus APT values with thalamus MRS metabolites parameters and lung function parameters were explored.Results Lung function parameters in COPD group were lower than those in control group,while cerebrospinal fluid volume(CSFV)and total brain volume(TIV)in COPD group were lager than those in control group(all P＜0.05).Compared with those in control group,APT values of bilateral thalami,right temporal lobe and right occipital lobe in COPD group were higher,and the peak value of N-acetyl aspartate(NAA)of bilateral thalami and NAA/creatin of right thalamus in COPD group were lower(all P＜0.05).Within COPD group,APT values of bilateral thalami were positively correlated(r=0.641),while APT values of left thalamus showed negative correlation(r=-0.435)with NAA values left thalamus and negative correlation(r=-0.432)with the forced expiratory volume in the first one second after bronchodilator administration(FEV1)(all P＜0.05).Conclusion APT values of central nervous system elevated and NAA values decreased in COPD patients.There were negative correlations between left thalamus APT and NAA values,also between APT values of left thalamus and FEV1.

Purpose The feasibility and application value of 3D amide proton transfer weighted(APTw)imaging is used to evaluate central nervous system injury in stable chronic obstructive pulmonary disease(COPD)patients.Materials and Methods A total of 36 COPD patients who attended the First Affiliated Hospital of Henan University of Chinese Medicine from January 2022 to August 2023 were selected along with 31 age-and gender-matched healthy volunteers.All subjects underwent pulmonary function tests,routine blood tests,Montreal cognitive assessment scale(MoCA)assessment and 3.0T MRI scan.The APT values of each brain region were measured independently and assessed for consistency by two observers,and the differences in APT values of each brain region were compared between the two groups to explore the correlation between the APT values of multiple brain regions and the pulmonary function,blood indices,and MoCA scores.Results The measurement consistency of APT values in multiple brain regions among observers was good(ICC>0.75).The APT values of brain regions in the COPD group were higher than those in the healthy control group,with statistically significant differences between the bilateral pallidum(t=2.490,2.168),the right thalamus(t=2.754),the nucleus accumbens(t=2.137),the temporal lobe gray matter(t=3.533)and the occipital lobe gray matter(t=2.345)compared with those in the healthy control group(all P<0.05);the APT values of the multiple brain regions were in a negative correlation(r=-0.390--0.084),with a stronger correlation between bilateral pallidum(r=-0.390,-0.370,both P<0.05);lung function indexes(forced vital capacity,forced expiratory volume in one second,forced expiratory volume in one second/forced vital capacity,forced expiratory volume in one second/prediction)in the COPD group showed a negative correlation trend with the APT values of the multibulbar areas(r=-0.339--0.010,all P>0.05),while white blood cell count,red blood cell count,hemoglobin concentration and platelet count showed a positive correlation trend with multi brain APT values(r=0.084-0.587).Conclusion As a novel MRI technology,APTw has potential application value in early detection of central nervous system damage in COPD patients and non-invasive monitoring of disease progression.

Objective:To explore the latent profile and characteristics of social isolation in patients with hematologic malignancy, and to analyze its related influencing factors, and to provide reference for improving social phobia disorder in different patients and implementing targeted intervention.Methods:This study was a cross-sectional survey. A convenient sampling method was used to select hematologic malignancy patients who were treated in Qilu Hospital of Shandong University from January 2022 to January 2023. General information questionnaire, the General Alienation Scale (GAS), and the Social Support Rating Scale(SSRS) were used for investigation. Latent profile was analyzed using the categories of social isolation in patients with hematologic malignancy, and univariate and multinomial logistic regression analysis were used to analyze relevant influencing factors.Results:A total of 195 survey subjects were included, of which 108 males and 87 females, aged (49.78 ± 13.52) years. The scores of GAS and SSRS were (43.21 ± 6.09) and (42.52 ± 6.77) respectively. The social isolation in patients with hematologic malignancy could be divided into 3 latent profiles, namely low-risk isolation 15.4% (30/195), medium-risk isolation 68.2%(133/195), and high-risk isolation16.4% (32/195). Multinomial Logistic regression analysis showed that age ( OR=0.941, 95% CI 0.894-0.990), percapita monthly income of families ( OR=0.050, 95% CI 0.004-0.657), primary caregivers (parents) ( OR=0.025, 95% CI 0.003-0.227), place of residence (town)( OR=0.170, 95% CI 0.039-0.749), disease type (leukemia) ( OR=15.610, 95% CI 2.973-81.979), disease type(lymphoma) ( OR=10.986, 95% CI 2.032-59.413) were the influencing factors of medium-risk isolation (all P<0.05). Age ( OR=0.933, 95% CI 0.880-0.988), percapita monthly income of families ( OR=0.029, 95% CI 0.002-0.525), primary caregivers (parents) ( OR=0.076, 95% CI 0.006-0.900), disease type (leukemia)( OR=19.257, 95% CI 2.580-143.723), disease type (lymphoma)( OR=9.952, 95% CI 1.290-76.763), social support ( OR=0.877, 95% CI 0.786-0.980) were the influencing factors of high-risk isolation (all P<0.05). Conclusions:The social isolation among patients with hematologic malignancy had apparent classification characteristics. It could be divided into three potential profiles. It is suggested that medical staff should take targeted social and psychological support based on different types of patients, improve their psychological and social outcomes, and utilize existing resources to implement intervention measures to help them adapt and return to society.

ObjectiveTo explore the possible mechanisms of Tongfengning （痛风宁， TFN） in treating hyperuricemia （HUA） of spleen deficiency with exuberance of dampness syndrome. MethodsTen of 60 mice were randomly selected， and were fed with regular diet as the control group， while the remaining 50 mice were fed with high-fat and high-sugar diet combined with excessive exercise and potassium oxonate-allopurinol suspension to establish an HUA animal model of syndrome of spleen deficiency with exuberance of dampness. After the successful modeling， in order to better observe the effects of TFN on the intestinal microbiota of the model mice， a mixed antibiotic suspension was administered by gavage to induce further dysbiosis of the intestinal microbiota in the model mice. Fifty sucessfully modeled mice were randomly divided into model group， TFN group， allopurinol group， probiotics group， and an allopurinol + probiotics group， 10 in each group. The TFN group was administered TFN liquid at a dosage of 19.11 g/（kg·d） by gavage. The allopurinol group was administered allopurinol suspension at a dosage of 78 mg/（kg·d） by gavage. The probiotics group was administered live combined Bifidobacterium and Lactobacillus tablets suspension at a dosage of 3 g/（kg·d） by gavage. The allopurinol + probiotics group was administered allopurinol at a dosage of 78 mg/（kg·d） and live combined Bifidobacterium and Lactobacillus tablets suspension at a dosage of 3 g/（kg·d） by gavage. The control group and model group were administered normal saline at a dosage of 19.11 ml/（kg·d） by gavage. The interventions were continued for 21 days. In order to maintain a stable high blood uric acid state， all groups but the control group continued modeling while receiving drug intervention. The changes in spleen deficiency syndrome scores， blood uric acid levels， microbial community structure， acetic acid and butyric acid content in intestinal lavage fluid， adenosine deaminase （ADA） and xanthine oxidase （XOD） content in small intestine tissue， as well as ATP-binding cassette transporter G2 （ABCG2）， glucose transporter 9 （GLUT9） protein and mRNA expression in the small intestine tissue were compared among the groups of mice. ResultsCompared with the control group， the model group showed increased spleen deficiency syndrome scores， blood uric acid levels， relative abundance of phylum Firmicutes， Firmicutes/Bacteroidetes ratio， abundance of Bacteroides genus， Klebsiella genus， and Enterococcus genus， acetic acid content in intestinal lavage fluid， ADA and XOD content in small intestine tissue， as well as GLUT9 protein and mRNA expression （P<0.05）. The number of operational taxonomic units （OTUs） of intestinal microbiota， relative abundance of Bacteroidetes phylum， abundance of Lactobacillus genus and uncultured Bacteroides genus， butyric acid content in intestinal lavage fluid， and ABCG2 protein and mRNA expression in small intestine tissue were significantly decreased （P＜0.05）. Compared with the model group， in the group treated with TFN， probiotics， and allopurinol + probiotics， the spleen deficiency syndrome score， blood uric acid level， relative abundance of Firmicutes， acetic acid content in intestinal lavage fluid， ADA and XOD content in small intestine tissue， GLUT9 protein and mRNA expression significantly decreased. The number of gut microbiota OTUs， relative abundance of proteobacteria， butyric acid content in intestinal lavage fluid， ABCG2 protein and mRNA expression in small intestine tissue significantly increased （P＜0.05）. In the probiotics group， the ratio of Firmicutes to Bacteroidetes decreased. In the TFN group， the abundance of Lactobacillus and uncultured Bacteroidetes significantly increased， while the abundance of Parabacteroides， Klebsiella， and Enterococcus significantly decreased （P＜0.05）. Compared with the TFN group， allopurinol group and the probiotics group showed elevated blood uric acid levels， abundance of Bacteroidetes， ADA and XOD levels in intestinal tissue， and GLUT9 mRNA expression. The relative abundance of Firmicutes， abundance of lactobacilli， and ABCG2 mRNA expression significantly decreased. The probiotics group showed elevated GLUT9 protein expression in intestinal tissue. The probiotics group and the allopurinol plus probiotics group showed significantly higher scores for spleen deficiency syndrome in mice， and lower levels of butyric acid in mouse intestinal lavage fluid. The allopurinol group showed decreased numbers of OTUs in mouse intestinal flora， decreased abundance of proteobacteria， and butyric acid levels in intestinal lavage fluid. The allopurinol group also showed decreased ABCG2 protein expression in intestinal tissue， increased acetic acid levels in intestinal lavage fluid， increased abundance of Klebsiella， and significantly elevated GLUT9 protein expression （P＜0.05）. ConclusionsThe treatment of HUA with TFN may be associated with the regulation of intestinal probiotics （such as lactobacilli） and pathogenic bacteria （such as Klebsiella）， as well as the production of bacterial metabolites such as acetic acid and butyric acid. It may also involve reducing the expression of ADA and XOD in the intestines， decreasing intestinal uric acid production， upregulating the expression of intestinal epithelial urate transporter ABCG2， downregulating GLUT9 expression， and promoting intestinal uric acid excretion. These factors are related to the syndrome of spleen deficiency with exuberance of dampness.

Objective:To analyze the clinical characteristics of patients with bisphosphonates related atypical femoral fractures(AFFS), thereby to facilitate early diagnosis.Methods:The clinical manifestations, biochemical indexes, imaging features and treatment follow-up of AFFS patients who were diagnosed in the Department of Osteoporosis and Bone Disease, the Sixth People′s Hospital Affiliated to Shanghai Jiaotong University from 2011 to 2019 were analyzed retrospectively, and the literature was reviewed.Results:A total of 5 cases of atypical bisphosphonate related femoral fractures were collected, all of them were female, with an average age of 68 years. All the 5 patients were treated with alendronate. Three patients were treated with 70 mg/week throughout the course, and two patients were treated with 10 mg/day at first, and changed to 70 mg/week later. The average course of treatment was 8.7 years, ranging from the shortest 5 years to the longest 17 years. Among the 5 cases, the shortest onset time was 3 years after taking medicine, and the longest was 16 years. The clinical features are as follows: all patients had prodromal pain before fracture which was characterized as dull except for case 4. Case 1 was bilateral thigh pain, the rest were unilateral thigh pain, which began to appear within 2-3 years before fracture. X-ray plain film showed thickening of the lateral bone cortex; radionuclide bone scan(ECT) showed active bone metabolism in the affected area. The abnormal manifestations of ECT were earlier than X-ray and MRI. The recognition of these features is helpful to the early diagnosis of AFFS. All 5 patients stopped bisphosphonates immediately, and continued to take calcium tablets. Active vitamin D was added to 4 cases. One case of incomplete fracture was treated conservatively with Teriparatide for one year, which was helpful to deter it from becoming complete fracture. 4 cases of complete fracture were treated with reduction and fixation, and all healed.Conclusion:Long-term use of bisphosphonates can increase the risk of AFFS. Strengthening the risk assessment during use can reduce the incidence of such fractures. Early diagnosis and reasonable treatment can improve the prognosis.

Objective:To evaluate the clinical value of prenatal molecular diagnostic technology in preventing hereditary diseases through analysis of prenatal diagnostic characteristics in 22 monogenic skeletal disorders pedigrees.Methods:This study retrospectively analyzed prenatal molecular diagnostic results of 22 pedigrees with monogenic skeletal disorders who were admitted to Department of Osteoporosis and Bone Diseases in our hospital from January 2014 to July 2021.Results:Among 22 pedigrees, there were 10 pedigrees with X-linked hypophosphatemic rickets due to PHEX gene mutations, in which 8 fetuses were found to carry pathogenic variants; 6 pedigrees with osteopetrosis, including 3 cases of CLCN7 gene mutation, 2 TCIRG1 gene mutation, and 1 CTSK gene mutation, were detected to have 2 affected fetuses and 1 carrier. There were 4 cases of osteogenesis imperfecta, including 2 cases of COL1A1 gene mutation, 1 case of COL1A2 gene mutation, and 1 case of SERPINF1 gene mutation, in which 1 affected fetus and 1 carrier were found; only one case of osteoarthritis with mild chondrodysplasia caused by COL2A1 gene mutation was found to harbor pathogenic variant in fetus; 1 case of hypophosphatasia due to ALPL gene mutation was not detected to carry pathogenic variant in fetus. By the time of follow-up, all 12 affected fetuses were terminated, and the remaining 10 fetuses except for one case still in pregnancy were born in good condition.Conclusion:Prenatal molecular diagnosis may confirm whether the fetus carries pathogenic variants at the first and second trimesters. For monogenic skeletal disorders that comply with Mendel′s law of separation, prenatal diagnosis can be determined by calculating the probability of recurrence of offspring. In addition, for families with de novo mutations in the offspring, it is necessary to pay attention to whether there are mosaic mutations in the parents.

Objective:To systematically review the qualitative researches on patients′ lived experiences of being mechanically ventilated in intensive care unit.Methods:The Cochrane Library, PubMed, Web of Science, Ovid, CNKI, VIP and Wanfang database were searched to collect qualitative studies on patients′ lived experiences of being mechanically ventilated in intensive care unit, from October 2009 to October 2019. Two reviewers independently screened the literature against the pre-determined inclusion and exclusion criteria, extracting the data, and evaluated the included studies according to JBI Critical Appraisal Tool for qualitative studies in Australia.Results:A total of fourteen studies were included. Thirty-eight complete results were grouped according to their similarities to form seven categories. These categories led to three synthesized findings: results 1: patients suffered from both physical and mental distress; results 2: they were eager for supports; results 3: patients achieved personal growth through self-adjustment and reflection.Conclusion:Discomfort experience during mechanical ventilation reduces patients′ comfort, and to a certain extent, has negative impacts on their physical or mental health and clinical outcome. As the main caregiver of patients with mechanical ventilation, not only should nurses alleviate patients′ physical distress by strengthening communication but also give them adequate psychological support. Eventually, promote the physical and mental recovery of patients.

Odontogenic keratocysts (OKCs) are common cystic lesions of odontogenic epithelial origin that can occur sporadically or in association with naevoid basal cell carcinoma syndrome (NBCCS). OKCs are locally aggressive, cause marked destruction of the jaw bones and have a propensity to recur. PTCH1 mutations (at ∼80%) are frequently detected in the epithelia of both NBCCS-related and sporadic OKCs, suggesting that PTCH1 inactivation might constitutively activate sonic hedgehog (SHH) signalling and play a major role in disease pathogenesis. Thus, small molecule inhibitors of SHH signalling might represent a new treatment strategy for OKCs. However, studies on the molecular mechanisms associated with OKCs have been hampered by limited epithelial cell yields during OKC explant culture. Here, we constructed an isogenic PTCH1 cellular model of PTCH1 inactivation by introducing a heterozygous mutation, namely, c.403C>T (p.R135X), which has been identified in OKC patients, into a human embryonic stem cell line using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system. This was followed by the induction of epithelial differentiation. Using this in vitro isogenic cellular model, we verified that the PTCH1 heterozygous mutation causes ligand-independent activation of SHH signalling due to PTCH1 haploinsufficiency. This activation was found to be downregulated in a dose-dependent manner by the SHH pathway inhibitor GDC-0449. In addition, through inhibition of activated SHH signalling, the enhanced proliferation observed in these induced cells was suppressed, suggesting that GDC-0449 might represent an effective inhibitor of the SHH pathway for use during OKC treatment.
Anilides ; pharmacology ; Basal Cell Nevus Syndrome ; Hedgehog Proteins ; genetics ; pharmacology ; Humans ; Molecular Targeted Therapy ; Odontogenic Cysts ; genetics ; physiopathology ; therapy ; Odontogenic Tumors ; genetics ; physiopathology ; therapy ; Pyridines ; pharmacology

Odontogenic keratocysts (OKCs) are common cystic lesions of odontogenic epithelial origin that can occur sporadically or in association with naevoid basal cell carcinoma syndrome (NBCCS).OKCs are locally aggressive,cause marked destruction of the jaw bones and have a propensity to recur.PTCH1 mutations (at ～80％) are frequently detected in the epithelia of both NBCCS-related and sporadic OKCs,suggesting that PTCH1 inactivation might constitutively activate sonic hedgehog (SHH) signalling and play a major role in disease pathogenesis.Thus,small molecule inhibitors of SHH signalling might represent a new treatment strategy for OKCs.However,studies on the molecular mechanisms associated with OKCs have been hampered by limited epithelial cell yields during OKC explant culture.Here,we constructed an isogenic PTCH1R135X/+ cellular model of PTCH1 inactivation by introducing a heterozygous mutation,namely,c.403C＞T (p.R135X),which has been identified in OKC patients,into a human embryonic stem cell line using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Casg) system.This was followed by the induction of epithelial differentiation.Using this in vitro isogenic cellular model,we verified that the PTCH1R135X/+ heterozygous mutation causes ligand-independent activation of SHH signalling due to PTCH1 haploinsufficiency.This activation was found to be downregulated in a dose-dependent manner by the SHH pathway inhibitor GDC-0449.In addition,through inhibition of activated SHH signalling,the enhanced proliferation observed in these induced cells was suppressed,suggesting that GDC-0449 might represent an effective inhibitor of the SHH pathway for use during OKC treatment.

Objective: To analyze the prevalence, genetic structure and evolutionary characteristics of GⅡ.17 norovirus isolated from the fecal samples of rhesus monkeys in Longhu Mountain of Guangxi Zhuang Autonomous Region. Methods: A total of 400 stool specimens were collected from wild rhesus monkeys from March to August of 2015. The GⅡ.17 norovirus named as GX213 was identified in fecal samples by high-throughput sequencing technology. Reverse transcription-polymerase chain reaction was used to confirm and screen GX213, as well as amplify its complete gene sequence. Then the sequence and phylogenetic analysis of three ORFs of GX213 were constructed by software MEGA 6.0. Results: Two out of 400 fecal samples were positive. The full-length genome of GX213 was 7 565 bp (containing PloyA tail), which was composed of three open reading frames (ORFs): ORF1(10-5112 nt), ORF2(5093-6715 nt)and ORF3(6715-7494 nt), with 20 bp overlapping between ORF1 and ORF2, and 1 bp overlapping between ORF2 and ORF3.Analysis of the complete sequence of GX213 showed that it shared the highest homology with the strain of human GⅡ.17 norovirus CUHK-NS-613 (GenBank ID: KU561248) (99.5% identity), and ORF1 and ORF3 also shared the highest homology with the strain CUHK-NS-613 [99.5% and 99.4% in nucleotide (nt); 99.5% and 99.2% in amino acid (aa), respectively], which was the main cause of human norovirus outbreaks in some regions of Asia from 2014 to 2015. ORF2 sequence analysis showed that it displayed the highest identity (99.4% in nt and 99.8% in aa) to the strain CUHK-NS-491 (GenBank ID: KP698928), only one aa mutation aa₂₄₅P→S(P1.1 region) was observed in the GX213 VP1 protein. Furthermore, the phylogenetic analysis showed that GX213 was more related to CUHK-NS-613 and CUHK-NS-491 than the strain KM1509 (GenBank ID: KX356908) of GⅡ.17 norovirus recently identified in rhesus monkeys. Conclusions GX213 belongs to the human GⅡ.17 norovirus variant causing the norovirus outbreaks from 2014 to 2015. Our research suggests that GⅡ.17 norovirus can infect not only humans but also rhesus monkeys.