Based on the traditional Chinese medicine theory that "all pain， itching， and sores are related to the heart"， this paper proposes treating recurrent aphthous ulcers from the perspective of the heart. It suggests that excessive heart fire and tissue erosion due to flaming fire in the heart meridian constitute the core pathogenesis of this condition. Hyperactive heart fire is identified as the key pathogenic factor， while heart yin deficiency， obstruction of the heart collaterals， and malnourishment of the heart spirit are considered significant contributing factors. Clinically， the treatment follows the principle of clearing heart fire as the main strategy， supplemented by nourishing yin， activating collaterals， and calming the spirit. The self-formulated Qingxin Yuchuang Formulation （清心愈疮方） serves as the base prescription， with flexible modifications incorporating the Yuyin Formulation （育阴方）， Huoxue Formulation （活血方）， and Yu'an Formulation （郁安方） to address specific syndromes involving heart yin deficiency， collateral blockage， and emotional disturbance.

Objective: To compare the changes in the concentration of relevant growth factors released from platelet-rich plasma (PRP) stored at -80℃ by cryopreservation and at 4℃ by refrigerated lyophilization over 2 years, aiming to provide a theoretical basis for prolonging PRP storage duration. Methods: PRP (n=15) was separated using a blood cell separator and stored under -80℃ cryopreservation (F-PRP group) and 4℃ refrigerated freeze-drying conditions (FD-PRP group). The contents of growth factors (PDGF-AA, PDGF-BB, EGF, TGF-β1, and VEGF) in both groups were measured by ELISA at 1, 3, 6, 9, 12 and 24 months. Results: PDGF-AA and VEGF maintained good stability in both groups for up to 24 months. PDGF-BB and TGF-β1 showed high stability in the first 12 months but their stability decreased gradually from 12th to 24th months. EGF demonstrated good stability in the first 6 months, and its stability gradually decreased from the 9th to 24th months. Comparing the F-PRP and FD-PRP groups, the concentrations of the five growth factors in the FD-PRP group were either not statistically different or higher than those in the F-PRP group at all time points. Specifically, the concentrations of EGF were significantly higher in the FD-PRP group at all time points. Conclusion: Both -80℃ freezing and 4℃ freeze-drying enable long-term preservation of PRP. Freeze-drying imposes less stringent storage requirements and facilitates growth factor compared to frozen storage.

ObjectiveTo explore the mechanism of action of Wuwei Shenqintang in improving pulmonary fibrosis by using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF-MS） for metabolomic analysis of lung tissue and feces. MethodsA rat model with pulmonary fibrosis was established by intratracheal injection of 5 mg·kg^-1 bleomycin. The successfully modeled rats were randomly divided into a blank group， a model group， a prednisone （3.15 mg·kg^-1） group， and low-dose， medium-dose， and high-dose groups of Wuwei Shenqintang （4.586， 9.172， 18.344 g·kg^-1）. The rats were given intragastric administration once a day for 28 consecutive days. Hematoxylin-eosin （HE） staining was used to measure the pathological changes in lung and colon tissue， and Masson staining was used to detect the degree of pulmonary fibrosis. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression of interleukin-1β （IL-1β）， IL-6， IL-8， tumor necrosis factor-α （TNF-α）， and secretory immunoglobulin A （SIgA） in bronchoalveolar lavage fluid and intestinal mucus. Immunohistochemistry and reverse transcription quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of type Ⅰ collagen （Col-Ⅰ）， fibronectin （FN）， and alpha smooth muscle actin （α-SMA） in lung tissue. UPLC-Q-TOF-MS was used to study the changes in the metabolic network of lung tissue and feces in rats with pulmonary fibrosis treated with Wuwei Shenqintang， screen potential biomarkers for the treatment of pulmonary fibrosis by Wuwei Shenqintang， and perform pathway enrichment analysis. ResultsCompared with the blank group， the model group showed extensive inflammatory cell infiltration and continuous fibrotic lesions in lung tissue， colonic mucosal damage， and connective tissue hyperplasia. The expression of IL-6， IL-8， IL-1β， TNF-α， and SIgA in bronchoalveolar lavage fluid and intestinal mucus was significantly increased （P<0.01）. The expression of Col-Ⅰ， FN， and α-SMA proteins and mRNAs in lung tissue was significantly upregulated （P<0.01）. Compared with the model group， the groups of Wuwei Shenqintang exhibited significantly reduced inflammatory infiltration and blue collagen deposition in lung tissue， alleviated colonic damage， decreased expression of IL-6， IL-8， IL-1β， TNF-α， and SIgA in bronchoalveolar lavage fluid and intestinal mucus （P<0.01）， and reduced average absorbance values and mRNA expression of Col-Ⅰ， FN， and α-SMA in lung tissue （P<0.05， P<0.01）， with the prednisone group and the medium-dose and high-dose groups of Wuwei Shenqintang showing the most significant effects. The metabolomics results for lung tissue showed that compared with the blank group， the model group had 19 significantly different compounds （P<0.05， P<0.01）. Wuwei Shenqintang could normalize 17 of these compounds compared with the model group （P<0.05， P<0.01）. Fecal metabolomics results showed that compared with those in the blank group， there were 42 compounds with significant differences in the model group （P<0.05， P<0.01）. Compared with the model control group， Wuwei Shenqintang could normalize 41 of these compounds （P<0.05， P<0.01）. The combined analysis results indicated that Wuwei Shenqintang might inhibit pulmonary fibrosis by regulating the biosynthesis of phenylalanine， tyrosine， and tryptophan as well as the retinol metabolism pathway. ConclusionWuwei Shenqintang can ameliorate pulmonary fibrosis， which may be related to the regulation of the "lung-intestine axis".

ObjectiveTo explore the mechanism of action of Wuwei Shenqintang in improving pulmonary fibrosis by using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF-MS） for metabolomic analysis of lung tissue and feces. MethodsA rat model with pulmonary fibrosis was established by intratracheal injection of 5 mg·kg^-1 bleomycin. The successfully modeled rats were randomly divided into a blank group， a model group， a prednisone （3.15 mg·kg^-1） group， and low-dose， medium-dose， and high-dose groups of Wuwei Shenqintang （4.586， 9.172， 18.344 g·kg^-1）. The rats were given intragastric administration once a day for 28 consecutive days. Hematoxylin-eosin （HE） staining was used to measure the pathological changes in lung and colon tissue， and Masson staining was used to detect the degree of pulmonary fibrosis. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression of interleukin-1β （IL-1β）， IL-6， IL-8， tumor necrosis factor-α （TNF-α）， and secretory immunoglobulin A （SIgA） in bronchoalveolar lavage fluid and intestinal mucus. Immunohistochemistry and reverse transcription quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of type Ⅰ collagen （Col-Ⅰ）， fibronectin （FN）， and alpha smooth muscle actin （α-SMA） in lung tissue. UPLC-Q-TOF-MS was used to study the changes in the metabolic network of lung tissue and feces in rats with pulmonary fibrosis treated with Wuwei Shenqintang， screen potential biomarkers for the treatment of pulmonary fibrosis by Wuwei Shenqintang， and perform pathway enrichment analysis. ResultsCompared with the blank group， the model group showed extensive inflammatory cell infiltration and continuous fibrotic lesions in lung tissue， colonic mucosal damage， and connective tissue hyperplasia. The expression of IL-6， IL-8， IL-1β， TNF-α， and SIgA in bronchoalveolar lavage fluid and intestinal mucus was significantly increased （P<0.01）. The expression of Col-Ⅰ， FN， and α-SMA proteins and mRNAs in lung tissue was significantly upregulated （P<0.01）. Compared with the model group， the groups of Wuwei Shenqintang exhibited significantly reduced inflammatory infiltration and blue collagen deposition in lung tissue， alleviated colonic damage， decreased expression of IL-6， IL-8， IL-1β， TNF-α， and SIgA in bronchoalveolar lavage fluid and intestinal mucus （P<0.01）， and reduced average absorbance values and mRNA expression of Col-Ⅰ， FN， and α-SMA in lung tissue （P<0.05， P<0.01）， with the prednisone group and the medium-dose and high-dose groups of Wuwei Shenqintang showing the most significant effects. The metabolomics results for lung tissue showed that compared with the blank group， the model group had 19 significantly different compounds （P<0.05， P<0.01）. Wuwei Shenqintang could normalize 17 of these compounds compared with the model group （P<0.05， P<0.01）. Fecal metabolomics results showed that compared with those in the blank group， there were 42 compounds with significant differences in the model group （P<0.05， P<0.01）. Compared with the model control group， Wuwei Shenqintang could normalize 41 of these compounds （P<0.05， P<0.01）. The combined analysis results indicated that Wuwei Shenqintang might inhibit pulmonary fibrosis by regulating the biosynthesis of phenylalanine， tyrosine， and tryptophan as well as the retinol metabolism pathway. ConclusionWuwei Shenqintang can ameliorate pulmonary fibrosis， which may be related to the regulation of the "lung-intestine axis".

Familial hemophagocytic lymphohistiocytosis （FHL） with central nervous system involvement as the initial clinical manifestation is very rare and has atypical clinical manifestations， which often leads to difficulties in early diagnosis and misdiagnosis. This article reports two cases of FHL confirmed by genetic testing in Department of Neurology， Women and Children’s Hospital of Qingdao University. One patient was a boy with 1‒3 years of age， while the other patient was a girl of pre-school age； both patients had the main clinical manifestations of unstable walking and dysarthria. Brain MRI findings of the boy suggested multiple abnormal signals in the bilateral hemispheres and the cerebellum， and brain MRI findings of the girl suggested multiple symmetrical hyperintensities in the bilateral frontal lobes， the periventricular region， and the basal ganglia. Both children were found to have PRF1 gene mutations. This article reviews relevant literature to improve the understanding of this disease among clinicians， and the possibility of this disease should be considered in case of unexplained central nervous system involvement. For suspected cases， it is recommended to conduct comprehensive examinations and genetic testing， so as to achieve early diagnosis， start treatment in a timely manner， and improve prognosis.
Ataxia

Objective To investigate the value of thrombomodulin(TM),thrombin-antithrombin complex(TAT),α2 plasmin inhibitor-plasmin complex(PIC)and tissue plasminogen activator-inhibitor complex(t-PAIC)in the diagnosis and prognosis of neonatal disseminated intravascular coagulation(DIC).Methods Eighty-seven DIC neonates(the observation group)were included and divided into the survival group(66 cases)and the death group(21 cases)based on their outcomes at discharge.And 50 healthy newborns born in the same period were selected as the control group.The clinical data of neonates were collected,and risk factors of neonatal DIC were analyzed by Logistic regression.The differences of TM,TAT,PIC and t-PAIC levels in different groups were analyzed.The receiver operating characteristic(ROC)curve was used to analyze values of TM,TAT,PIC and t-PAIC in the diagnosis and prognosis of neonatal DIC.Results The incidence of low Apgar score,birth asphyxia,IVH,sepsis and maternal pregnancy induced hypertension syndrome(PIH)were higher in the observation group than those in the control group(P＜0.05).Multivariate Logistic regression analysis showed that low Apgar score,birth asphyxia,sepsis and PIH were independent risk factors for neonatal DIC.TM,TAT,PIC and t-PAIC levels were higher in the observation group than those in the control group(P＜0.05).ROC curve showed that the combined diagnosis value of TM,TAT,PIC and t-PAIC was better than that of single diagnosis of neonatal DIC.TM and TAT levels were higher in the death group than those in the survival group(P＜0.05),and there were no significant differences in PIC and t-PAIC levels between the two groups.Multivariate Logistic regression analysis showed that elevated TAT level was an independent risk factor for neonatal DIC prognosis.ROC curve showed that when TAT was 21.72 μg/L,the area under the curve for predicting neonatal DIC prognosis was 0.772(95%CI:0.666-0.878),and the sensitivity and specificity were 76.2%and 71.2%,respectively.Conclusion The combined application of TM,TAT,PIC and t-PAIC has important clinical value in diagnosis and prognosis evaluation of neonatal DIC.

Objective To analyze the spatiotemporal distribution characteristics of respiratory bacterial infections in Sanmenxia City from 2012 to 2022, and explore key areas for respiratory infection prevention and control. Methods Respiratory bacterial infection cases admitted to our hospital from 2012 to 2022 was collected, use OpenGeoDal software for spatial autocorrelation analysis, and SaTScan software for spatiotemporal scanning analysis. Results From 2012 to 2022, 8762 cases of respiratory bacterial infection were reported in Sanmenxia , with an average annual incidence of 173.47/100 000 and a standardized incidence of 132.63/100 000，and the overall incidence showed a downward trend (χ²=48.093，P<0.01). The incidence of respiratory tract bacterial infection has gender characteristics,the incidence of respiratory tract bacterial infection is the highest among people aged 50 years and above (P<0.05). There was no global spatial autocorrelation, and local autocorrelation results showed that the "high-high" clustering area was mainly located in Yima City. The spatiotemporal scanning results showed that the first level aggregation area was located in Yima City, with a time span of 2020-2022 and a radiation radius of 4.57 km (LLR=40.19, RR=3.27, P<0.001). Conclusion The overall trend of respiratory bacterial infections in Sanmenxia City is decreasing, and Yima City is a ^“high- high^” gathering area, which is a key region to prevention and control.

Microglia, originating from primitive macrophages in the yolk sac, serves as both immune system defenders and regulators of homeostasis. These cells exhibit two primary polarization states: conventionally activated(M1)and alternatively activated(M2). The polarization of microglia plays a crucial role in influencing inflammatory disorders, metabolic imbalances, and neural degeneration. This process is implicated in various aspects of ocular diseases, especially age-related macular degeneration(AMD), including inflammation, oxidative stress and pathological angiogenesis. The distinct functional phenotypes of microglia impact disease progression and prognosis. Thus, regulating the polarization or functional phenotype of microglia at different stages of AMD holds promise for personalized therapeutic approaches. This comprehensive review outlines the involvement of microglia polarization in both physiological and pathological conditions, emphasizing its relevance in AMD. The discussion underscores the potential of polarization as a foundation for personalized treatment strategies for AMD.

ObjectiveTo investigate the mechanism of anti-pulmonary fibrosis of cannabidiol by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）. MethodSD rats were randomly divided into blank group， model group， prednisone group（3.15 mg·kg^-1） and cannabidiol low， medium and high dose groups（12， 36， 108 mg·kg^-1）， with 8 rats in each group. The rat model of pulmonary fibrosis was established by intratracheal injection of bleomycin（5 mg·kg^-1）， which was administered continuously for 28 days after successful modeling. The pathological changes of rat lung tissue were observed， and enzyme-linked immunosorbent assay（ELISA） was used to detect the expression levels of matrix metalloproteinase-7（MMP-7）， type Ⅱ alveolar cell surface antigen（KL-6）， pulmonary surfactant-associated protein A（SP-A） and SP-D in serum. The expression levels of type Ⅰ collagen（Col-Ⅰ） and fibronectin（FN） in lung tissues were detected by immunohistochemistry， and the expression of mucin 5 subtype AC（MUC5AC） was detected by immunofluorescence. UPLC-Q-TOF-MS was used to search for potential biomarkers and related metabolic pathways of cannabidiol in treating pulmonary fibrosis. ResultCompared with the blank group， there were a large number of inflammatory cell infiltration and continuous fibrosis lesions in the lung tissue of rats in the model group. Compared with the model group， the inflammatory infiltration and blue collagen deposition in the lung tissue of rats in the prednisone and cannabidiol groups were reduced. Compared with the blank group， the expressions of MMP-7， KL-6， SP-A and SP-D in serum of the model group were significantly increased（P<0.01）， while the expressions of MMP-7， KL-6， SP-A and SP-D in the prednisone and cannabidiol high dose groups were significantly decreased by comparing with the model group（P<0.05， P<0.01）. Compared with the blank group， the expression levels of Col-Ⅰ and FN in the lung tissues of the model group were significantly increased， and the fluorescence intensity of MUC5AC was significantly increased（P<0.01）. Compared with the model group， the expression levels of Col-Ⅰ and FN in the lung tissues of the prednisone and cannabidiol high dose groups were significantly decreased（P<0.05， P<0.01）， and the expression of MUC5AC was significantly decreased（P<0.01）. Compared with the blank group， a total of 18 differential compounds were screened out in the model group， which could be used as potential biomarkers， and cannabidiol could call back 16 of them， mainly involving 4 metabolic pathways（linoleic acid metabolism， phenylalanine， tyrosine and tryptophan biosynthesis， arachidonic acid metabolism， and niacin and niacinamide metabolism）. Compared with the blank group， the relative contents of potential biomarkers arachidonic acid and linoleic acid were significantly increased in the model group（P<0.05， P<0.01）， while the relative contents of 5，6-EET， L-tyrosine and niacinamide were significantly decreased（P<0.01）. Compared with the model group， cannabidiol could significantly reduce the relative contents of arachidonic acid and linoleic acid， and significantly increase the relative contents of 5，6-EET， L-tyrosine and niacinamide（P<0.01）. ConclusionCannabidiol has an intervention and remission effect on pulmonary fibrosis， and its mechanism may be related to linoleic acid metabolism， phenylalanine， tyrosine and tryptophan biosynthesis， arachidonic acid metabolism， niacin and niacinamide metabolism.

Objective:To confirm the potential etiological factors of congenital aortic stenosis(AS)by genetic analysis on prenatal diagnostic results of the fetus with AS.Methods:Amniocentesis for chromosomal G-band karyotyping combinated with single nucleotide polymorphism array(SNP-array)analysis was conducted on the amniotic fluid collected from a 25-week pregnant woman diagnosed as"fetus AS";chromosome karyotyping was also performed on the peripheral blood of the fetal parents.Results:The fetal karyotype analysis showed a chimeric Y-chromosome isobaric double-adherent granules.The SNP-array analysis results revealed a 11.2 Mb duplication in the Yp11.31q11.21 region and a 14.8 Mb deletion in the Yq11.21q11.23 region.Both the parents presented a normal karyotype,suggesting it was a newfound mutation.After extensive genetic counseling,the pregnant woman and her family chose to terminate the pregnancy locally.Conclusion:The chromosomal karyotype of the chimeric Y-chromosome isobaric double-adherent granules may be a contributing factor to the AS phenotype in the male fetus.The combined use of chromosomal karyotyping and SNP-array analysis on the amniotic cells is instrumental in the early diagnosis of the disease.