Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP) is a rare autosomal dominant genetic disorder. It may also involve many other organ systems, leading to complications such as exocrine pancreatic insufficiency, liver dysfunction, lymphedema, and developmental delay. The FAM111B has been determined as the pathogenic gene associated with POIKTMP syndrome, whose protein product plays a critical role in regulating essential cellular processes including DNA repair and replication, cell cycle progression, apoptosis, nuclear transport, and telomere length maintenance. This article has provided a comprehensive review for the genetic basis of POIKTMP syndrome and its correlation with various phenotypes, which may offer insights for basic research and clinical diagnosis of this disease.
Humans ; Pulmonary Fibrosis/genetics* ; Skin Diseases, Genetic/genetics*

BACKGROUND:Hippocampal injury caused by aortic coarctation has been poorly studied,and combined detection of tumor necrosis factor α,nuclear factor κB and ionized calcium binding adaptor molecule-1 expression in aortic dissection has not been reported.OBJECTIVE:To observe histomorphologic changes in the hippocampus of a mouse model of aortic dissection and investigate the expression and significance of tumor necrosis factor alpha,nuclear factor kappaB and ionized calcium binding adaptor molecule-1 in the hippocampus of aortic dissection mice.METHODS:Sixteen healthy 3-week-old male C57BL/6 mice were randomly divided into two groups:control group and aortic dissection group,with eight mice in each group.In the aortic dissection group,mice were given β-aminopropionitrile monofumarate as drinking water for 4 weeks,and the angiotensin Ⅱ microinfiltration pump was then implanted to establish an animal model of aortic dissection.Mice in the control group were given normal diet and water.After the model was established,the maximum diameter of the ascending aorta was measured,hematoxylin-eosin staining and EVG staining were performed to evaluate the model formation rate,and the levels of inflammatory factors tumor necrosis factor α and interleukin 6 in serum were detected by enzyme-linked immunosorbent assay.The hippocampus was dissected and stained with hematoxylin-eosin to observe the pathological changes of the hippocampus in brain sections.The protein expression of tumor necrosis factor α,nuclear factor κB and ionized calcium binding adaptor molecule-1 was detected by western blot analysis.RESULTS AND CONCLUSION:(1)Compared with the control group,the maximum diameter of the ascending aorta in the aortic dissection group was significantly enlarged.(2)Hematoxylin-eosin staining of the aorta showed obvious thickening of the middle aorta and destruction and disorder of the aortic wall structure in mice.Neurons in the CA1 and CA3 regions of mice were sparsely arranged,reduced in size,and showed pyknosis with deeply stained nuclei.(3)Serum levels of inflammatory factors tumor necrosis factor α and interleukin 6 were increased in the aortic dissection group compared with the control group(P＜0.01).(4)The expression levels of tumor necrosis factor α,nuclear factor κB,phosphorylated nuclear factor κB,and ionized calcium binding adaptor molecule-1 in the hippocampus were increased in the aortic dissection group compared with the control group(P＜0.05).To conclude,microglial activation and increased expression of tumor necrosis factor α and nuclear factor κB may be involved in hippocampal neuron injury in aortic dissection mice.

BACKGROUND:Hippocampal injury caused by aortic coarctation has been poorly studied,and combined detection of tumor necrosis factor α,nuclear factor κB and ionized calcium binding adaptor molecule-1 expression in aortic dissection has not been reported.OBJECTIVE:To observe histomorphologic changes in the hippocampus of a mouse model of aortic dissection and investigate the expression and significance of tumor necrosis factor alpha,nuclear factor kappaB and ionized calcium binding adaptor molecule-1 in the hippocampus of aortic dissection mice.METHODS:Sixteen healthy 3-week-old male C57BL/6 mice were randomly divided into two groups:control group and aortic dissection group,with eight mice in each group.In the aortic dissection group,mice were given β-aminopropionitrile monofumarate as drinking water for 4 weeks,and the angiotensin Ⅱ microinfiltration pump was then implanted to establish an animal model of aortic dissection.Mice in the control group were given normal diet and water.After the model was established,the maximum diameter of the ascending aorta was measured,hematoxylin-eosin staining and EVG staining were performed to evaluate the model formation rate,and the levels of inflammatory factors tumor necrosis factor α and interleukin 6 in serum were detected by enzyme-linked immunosorbent assay.The hippocampus was dissected and stained with hematoxylin-eosin to observe the pathological changes of the hippocampus in brain sections.The protein expression of tumor necrosis factor α,nuclear factor κB and ionized calcium binding adaptor molecule-1 was detected by western blot analysis.RESULTS AND CONCLUSION:(1)Compared with the control group,the maximum diameter of the ascending aorta in the aortic dissection group was significantly enlarged.(2)Hematoxylin-eosin staining of the aorta showed obvious thickening of the middle aorta and destruction and disorder of the aortic wall structure in mice.Neurons in the CA1 and CA3 regions of mice were sparsely arranged,reduced in size,and showed pyknosis with deeply stained nuclei.(3)Serum levels of inflammatory factors tumor necrosis factor α and interleukin 6 were increased in the aortic dissection group compared with the control group(P＜0.01).(4)The expression levels of tumor necrosis factor α,nuclear factor κB,phosphorylated nuclear factor κB,and ionized calcium binding adaptor molecule-1 in the hippocampus were increased in the aortic dissection group compared with the control group(P＜0.05).To conclude,microglial activation and increased expression of tumor necrosis factor α and nuclear factor κB may be involved in hippocampal neuron injury in aortic dissection mice.

OBJECTIVE To establish a method for simultaneous determination of venetoclax， busulfan and voriconazole in plasma of patients with acute myeloid leukemia （AML）， and apply it clinically. METHODS Plasma samples were subjected to protein precipitation using acetonitrile and subsequently analyzed by liquid chromatography-tandem mass spectrometry （LC-MS/MS） using venetoclax-D 8 ， busulfan-D 8 and posaconazole as internal standards. The separation was performed on a Phenomenex Kinetex ® C 18 column with a mobile phase composed of 0.1% formic acid solution （2 mmol/L ammonium acetate）-0.1% formic acid in acetonitrile （gradient elution） at a flow rate of 0.8 mL/min. The column temperature was set at 40 ℃， the sample size was 5 μL， and the total run time was 3.10 min. An electrospray ionization source was employed， and positive ion scanning was conducted using multiple reaction monitoring mode. The ion pairs used for quantitative analysis included m/z 868.4→636.3 （venetoclax）， m/z 264.1→151.1 （busulfan）， and m/z 350.1→224.0 （voriconazole）. The above LC-MS/MS method was adopted to determine plasma concentrations of venetoclax and voriconazole in 10 AML patients， as well as plasma concentration of busulfan in 5 patients undergoing conditioning treatment for allogeneic hematopoietic stem cell transplantation. RESULTS The linear ranges of venetoclax， busulfan and voriconazole were 50-10 000， 15-3 000 and 50-10 000 ng/mL， respectively （ R 2 ≥0.999 0）， with lower limits of quantification of 50， 15 and 50 ng/mL， respectively. The RSDs of intra-day and inter-day precision tests for all three analytes were all less than 10%， with accuracy （relative errors） ranging from －10.00% to 12.96%. The average extraction recovery ranged from 92.54% to 100.95%， and the average matrix effect was 89.98%-101.49%. Dilution reliability covered all dilution factors used in the test samples， and the absolute values of relative errors in stability tests were all≤16.25%. The plasma concentrations of venetoclax， busulfan and voriconazole in enrolled patients were 496.20-4 250.45， 233.48-2 002.28 and 475.51-5 710.18 ng/mL， respectively. CONCLUSIONS The LC-MS/MS method established in this study is rapid， sensitive and easy to operate， and can be used for the therapeutic drug monitoring of venetoclax， busulfan and voriconazole.

Objective To comparatively evaluate the diagnostic value of metagenomic next-generation sequencing(mNGS)versus conventional microbial culture in spinal infections.Methods A cross-section design was conducted on 82 consecutive patients with suspected spinal infections treated between February 2022 and January 2024 at Jiangbei Branch of First Affiliated Hospital of Army Medical University(Third Military Medical University).Microbiological culture,histopathological examination,and mNGS results from infected specimens were analyzed.Clinical diagnosis,primarily based on clinical manifestations,laboratory tests and radiologic features combined with medical history,was defined as the gold standard,and then the diagnostic performance,including sensitivity and specificity,were compared between mNGS and microbial culture.Results Among the 82 patients,definitive microbiological evidence was identified in 70 cases,and mNGS demonstrated a significantly higher detection rate than microbial culture(64 vs 36 cases,78.05％vs 43.9％,P<0.05).mNGS also obtained obviously higher sensitivity,accuracy,and negative predictive value(NPV),and notably lower positive predictive value(PPV)when compared to conventional microbial culture(all P<0.05).When stratified by infection type,mNGS obtained significantly higher sensitivity and accuracy compared to microbial culture in tuberculous spinal infections(P<0.05).For non-tuberculous spinal infections,mNGS also showed superior sensitivity to microbial culture(P<0.05).Conclusion In patients with spinal infections,mNGS demonstrates a significantly higher pathogen detection rate than conventional microbial culture.This technique can provide early and broad-spectrum pathogenic microbiological evidence for spinal infection.

Objective To develop and validate a nomogram incorporating postoperative blood pressure and other multifactorial predictors for the risk of delayed cerebral ischemia(DCI)following surgical clipping in patients with aneurysmal subarachnoid hemorrhage(aSAH).Methods This retrospective cohort study consecutively enrolled 272 aSAH patients who underwent aneurysm clipping at the Department of Neurosurgery,Second Affiliated Hospital of Chongqing Medical University from January 2018 to January 2022.Demographic,clinical,and imaging data were collected.Predictors were screened using LASSO regression,and a multifactorial logistic regression-based nomogram was constructed.The dataset was randomly divided into training(n=190)and validation(n=82)sets at a 7∶3 ratio.Model discrimination,calibration,and clinical utility were evaluated using the area under the receiver operating characteristic curve(AUC),calibration curves,and decision curve analysis(DCA),respectively.Results Among 272 enrolled patients,98(36%)developed DCI.Multivariate analysis identified age(OR=0.97;95%CI:0.94～0.99;P=0.036),World Federation of Neurological Surgeons(WFNS)grade(OR=1.36;95%CI:1.02～1.82;P=0.038),Fisher grade(OR=1.44;95%CI:1.01～2.05;P=0.048),and mean arterial pressure on postoperative day 2(OR=1.06;95%CI:1.03～1.09;P<0.001)as independent risk factors for DCI.The model achieved C-indices of 0.739(95%CI:0.668～0.810)in the training set and 0.760(95%CI:0.647～0.872)in the validation set.Calibration curves demonstrated high agreement between predicted and observed probabilities(mean absolute error=0.027),while DCA confirmed significant net clinical benefit at threshold probabilities of 15%～65%.Conclusion We successfully developed a predictive model incorporating age,WFNS grade,Fisher grade,and postoperative day 2 mean arterial pressure,with elevated postoperative blood pressure identified as an early critical indicator for DCI development.

Apurinic/apyrimidinic endonuclease 1(APE 1)is a multifunctional protein that plays important roles in DNA repair and regulation of gene expression.Because APE 1 is overexpressed in various cancers,it can serve as a cancer biomarker for aiding clinical diagnosis,guiding therapy,and monitoring prognosis.On this basis,a label-free fluorescent probe was designed based on the primer exchange reaction(PER)strategy for highly sensitive detection of APE 1 activity.In the absence of APE 1,the structure of catalytic hairpin(HP)was stable and could not form G-quadruplex.Therefore,the background fluorescence of this sensing system was very low due to the dissociation of thioflavin T(ThT).In the presence of APE 1,the apurinic/apyrimidinic(AP)site of HP was cleaved by APE 1 and a short nucleic acid fragment that acted as a primer to initiate PER was generated.After PER reaction,a large number of G-quadruplex were produced,which could specifically bind with ThT and resulted in significant increase of fluorescence signal.The combination of low background design of HP and PER amplification made this biosensor had high sensitivity with a detection limit(3σ)of 0.0008 U/mL.Furthermore,the primer sequence was directly generated by the cleavage of APE 1 without additional addition,which not only increased the specificity of the reaction,but also simplified the experiment procedure.Moreover,the use of label-free fluorescence signal reduced the cost of the experiment,and realized rapid detection of APE 1.Finally,this sensor was used to detect APE 1 in human serum samples with spiked recoveries of 91%-104%,proving great potential in study of biological enzyme.

Objective To investigate the prevalence of food intolerance among children in Zhuzhou area and its relationship with age,gender,systemic diseases,and food allergies,so as to provide a basis for the scientific adjustment of children's dietary structure.Methods A retrospective analysis was conducted on totally 1 592 children who underwent food intolerance and food allergen testing in the hospital,the positive rate and distri-bution of 14 kinds of food intolerance were assessed,and their correlation with various factors was analyzed.Results Among 14 kinds of food tested,milk and eggs had the highest positive rates of intolerance,at 82.22％and 55.78％,respectively.The majority of children were intolerant to 1 to 2 kinds of food,with a de-creasing trend in the number of children intolerant to multiple kinds of food.Among the 14 types of food,ex-cept for mushrooms and pork,there were statistically significant differences in the distribution of negative,mild,moderate,and severe intolerance in other foods(P＜0.05).Children tended to have moderate or even se-vere intolerance to milk and eggs,while they tended to have mild intolerance to other foods.There was no sta-tistically significant difference in the overall food intolerance rate between boys and girls(P=0.654),but the positive rate of tomato intolerance in girls was slightly higher than that in boys(P=0.043).Except for pork,there were statistically significant differences in the positive rates of intolerance to 14 different foods among different age groups(P＜0.05).The positive rates of intolerance to cod,mushrooms,and crabs increased with age,while the positive rates of intolerance to beef decreased with age.There was a statistically significant difference in the positive rate of milk intolerance between healthy children and children with skin allergies(P＜0.05).There was a statistically significant difference in the proportion of individuals who were tolerant and not allergic to milk compared to hose who were intolerant and allergic to milk(P＜0.05).There was a statistically significant difference in the proportion of individuals who were tolerant and not allergic to eggs compared to those who were intolerant and allergic to eggs(P＜0.05).Conclusion The positive rate of food intolerance among children in Zhuzhou area is relatively high,with milk and eggs being the main intolerant foods.There are differences in the positive rate of intolerance among different gender and age groups,and in-tolerance to milk and eggs is associated with food allergies to some extent.

Objective:To explore the acupoint selection law of acupuncture and moxibustion in the treatment of broca aphasia after stroke.Methods:RCT articles about acupuncture and moxibustion treatment for broca aphasia after stroke were retrieved from CNKI, VIP, Wanfang Data, China Medical Journal Full-text Database, SinoMed, PubMed, Web of Science and Embase database from the establishment of the databases to May 31, 2024. Excel 2021, SPSS Statistics 27.0, SPSS Modeler 18.0 and Cytoscape 3.9.1 software were used to analyze the frequency of acupoint, clustering, association rules and core co-occurrence network.Results:A total of 87 articles were included, involving 100 acupuncture and moxibustion prescriptions and 101 acupoints/acupoint area, involving 6 types, including Lianquan (CV 23) (35 times), Jinjin (EX-HN12) (35 times) and Yuye (EX-HN13) (34 times). The selected acupoints were mainly distributed in the head, face, neck and lower limbs, and the meridians were mainly Governor Vessel and Conception Vessel; the specific acupoints were mainly original acupoints, followed by collaterals acupoints, and scalp acupuncture was used most frequently in special acupuncture (88 times). According to the clustering analysis of high-frequency acupoints/acupoint area, there were five effective groups, such as "Jinjin (EX-HN12)-Yuye (EX-HN13)-Lianquan (CV 23)-Baihui (GV 20)-Yamen (GV 15)". The core co-occurrence network analysis showed that the acupoints used most frequently were Lianquan (CV 23) and Jinjin (EX-HN12), and the highest correlation between the two acupoints was Jinjin (EX-HN12)-Yuye (EX-HN13).Conclusions:Acupuncture and moxibustion for the treatment of broca aphasia after stroke is often based on "awakening the brain as the outline, benefiting the marrow as the foundation, and resuscitation". Under the guidance of the theory of Zang-fu meridians and collaterals, through dredging the meridians and collaterals, tonifying the brain and opening and closing the sound, the recovery of language function can be achieved.

BACKGROUND:Ca2+expression in astrocytes has been found to be closely related to cognitive function,and the Ca2+signaling pathway regulated by inositol 1,4,5-trisphosphate receptors(IP3R2)and ryanodine receptor(RYR)2 receptors has become a hot spot in the study of cognitive disorder-related diseases. OBJECTIVE:To investigate the expression of Ca2+signals mediated by IP3R2 and RYR2 in hippocampal astrocytes in animal models of delayed encephalopathy after acute carbon monoxide poisoning,and to explore the possible pathogenesis of delayed encephalopathy after acute carbon monoxide poisoning. METHODS:C57BL mice with qualified cognitive function were selected by Morris water maze experiment and randomly divided into control group and experimental group.An animal model of delayed encephalopathy after acute carbon monoxide poisoning was established by static carbon monoxide inhalation in the experimental group,and the same amount of air was inhaled in the control group.Behavioral and neuronal changes,astrocyte specific marker glial fibrillary acidic protein,IP3R2,RYR2 receptor and Ca2+concentration in astrocytes of the two groups were detected using Morris water maze,hematoxylin-eosin staining,western blot,immunofluorescence double labeling and Ca2+fluorescence probe at 21 days after modeling. RESULTS AND CONCLUSION:In the Morris water maze,the escape latency of the experimental group was significantly longer than that of the control group(P<0.05).Hematoxylin-eosin staining results showed that in the experimental group,the number of hippocampal pyramidal cells decreased,the cell structure was disordered,and the nucleus was broken and dissolved.Immunofluorescence results showed that IP3R2 and RYR2 were co-expressed with glial fibrillary acidic protein in the hippocampus,and the expressions of IP3R2,RYR2 and glial fibrillary acidic protein were up-regulated in the hippocampus of the experimental group(P<0.05).Western blot analysis showed that the expressions of IP3R2,RYR2,and glial fibrillary acidic protein in the hippocampus of the experimental group were increased(P<0.05).Ca2+concentration in hippocampal astrocytes increased significantly in the experimental group(P<0.05).To conclude,astrocytes may affect Ca2+signals by mediating IP3R2 and RYR2 receptors,then impair the cognitive function of mice with carbon monoxide poisoning,and eventually lead to delayed encephalopathy after acute carbon monoxide poisoning.