ObjectiveThe theory of homotherapy for heteropathy is one of the classical rules in traditional Chinese medicine. Taking this theory as a breakthrough point， this study employed gas chromatography-mass spectrometry （GC-MS） to elucidate the mechanism underlying the therapeutic effects of Zhuyuwan on both intrahepatic cholestasis （IC） and ulcerative colitis （UC） from the viewpoint of serum metabolic homeostasis. MethodsThe rat models of α-naphthylisothiocyanate （ANIT）-induced cholestasis and 2，4，6-trinitro-benzenesulfonic acid （TNBS）-induced UC were treated with low （0.6 g·kg^-1） and high （1.2 g·kg^-1） doses of Zhuyuwan by gavage. In the experiment regarding IC， 24 Sprague-Dawley （SD） rats were randomly assigned into four groups： normal， ANIT model， low-dose Zhuyuwan， and high-dose Zhuyuwan. In the experiment regarding UC， 24 SD rats were randomly allocated into four groups： normal， TNBS model， low-dose Zhuyuwan， and high-dose Zhuyuwan. Firstly， the two disease models and the intervention effects of Zhuyuwan on the two diseases were evaluated based on serum levels of biochemical indicators ［alanine aminotransferase （ALT）， aspartate transaminase （AST）， γ-glutamyltranspeptidase （γ-GT）， and total bile acid （TBA）］， colon damage score， colon weight index， disease activity index， and histopathological changes in rats. Secondly， the rat serum samples were analyzed by gas chromatography-mass spectrometry （GC-MS） to screen the common core pathways of the two disease models， and the expression of core genes in the pathways was determined by Real-time PCR， on the basis of which the biological mechanism of the treatment of the two disease models by Zhuyuwan was ultimately elucidated. ResultsThe results of the experiment regarding IC showed that the ANIT model group had higher ALT， AST， γ-GT， and TBA levels than the normal group （P<0.01）. Compared with the ANIT model group， the low-dose Zhuyuwan group showed declined ALT and TBA levels （P<0.01） and the high-dose Zhuyuwan group showed lowered ALT， TBA， AST， and γ-GT levels （P<0.01）. The results of the experiment regarding UC showed that compared with the normal group， the TNBS model group presented increases in the colonic damage score， colon weight index， and disease activity index （P<0.01）. Compared with the TNBS model group， the low-dose Zhuyuwan group showcased declines in colon weight index （P<0.01） and disease activity index （P<0.05）， and the high-dose Zhuyuwan group showed reductions in the colon damage score， colon weight index， and disease activity index （P<0.01）. GC-MS metabolomics analysis combined with qRT-PCR demonstrated that Zhuyuwan had a similar inverse regulatory effect on arginine metabolism disruption in the above two disease models. ConclusionZhuyuwan exhibited definite therapeutic effects on both IC and UC， and the regulation of arginine biosynthesis pathway is the core mechanism for the treatment of both diseases by Zhuyuwan.

ObjectiveThe theory of homotherapy for heteropathy is one of the classical rules in traditional Chinese medicine. Taking this theory as a breakthrough point， this study employed gas chromatography-mass spectrometry （GC-MS） to elucidate the mechanism underlying the therapeutic effects of Zhuyuwan on both intrahepatic cholestasis （IC） and ulcerative colitis （UC） from the viewpoint of serum metabolic homeostasis. MethodsThe rat models of α-naphthylisothiocyanate （ANIT）-induced cholestasis and 2，4，6-trinitro-benzenesulfonic acid （TNBS）-induced UC were treated with low （0.6 g·kg^-1） and high （1.2 g·kg^-1） doses of Zhuyuwan by gavage. In the experiment regarding IC， 24 Sprague-Dawley （SD） rats were randomly assigned into four groups： normal， ANIT model， low-dose Zhuyuwan， and high-dose Zhuyuwan. In the experiment regarding UC， 24 SD rats were randomly allocated into four groups： normal， TNBS model， low-dose Zhuyuwan， and high-dose Zhuyuwan. Firstly， the two disease models and the intervention effects of Zhuyuwan on the two diseases were evaluated based on serum levels of biochemical indicators ［alanine aminotransferase （ALT）， aspartate transaminase （AST）， γ-glutamyltranspeptidase （γ-GT）， and total bile acid （TBA）］， colon damage score， colon weight index， disease activity index， and histopathological changes in rats. Secondly， the rat serum samples were analyzed by gas chromatography-mass spectrometry （GC-MS） to screen the common core pathways of the two disease models， and the expression of core genes in the pathways was determined by Real-time PCR， on the basis of which the biological mechanism of the treatment of the two disease models by Zhuyuwan was ultimately elucidated. ResultsThe results of the experiment regarding IC showed that the ANIT model group had higher ALT， AST， γ-GT， and TBA levels than the normal group （P<0.01）. Compared with the ANIT model group， the low-dose Zhuyuwan group showed declined ALT and TBA levels （P<0.01） and the high-dose Zhuyuwan group showed lowered ALT， TBA， AST， and γ-GT levels （P<0.01）. The results of the experiment regarding UC showed that compared with the normal group， the TNBS model group presented increases in the colonic damage score， colon weight index， and disease activity index （P<0.01）. Compared with the TNBS model group， the low-dose Zhuyuwan group showcased declines in colon weight index （P<0.01） and disease activity index （P<0.05）， and the high-dose Zhuyuwan group showed reductions in the colon damage score， colon weight index， and disease activity index （P<0.01）. GC-MS metabolomics analysis combined with qRT-PCR demonstrated that Zhuyuwan had a similar inverse regulatory effect on arginine metabolism disruption in the above two disease models. ConclusionZhuyuwan exhibited definite therapeutic effects on both IC and UC， and the regulation of arginine biosynthesis pathway is the core mechanism for the treatment of both diseases by Zhuyuwan.

The peripheral pulmonary lesions are located far from the central airway and close to the pleura, so it is a challenge for clinical diagnosis of their nature through biopsy. Therefore, the Ion robot-assisted bronchoscopy system which has started its commercialization in China is proposed to diagnose and treat peripheral pulmonary lesions. The Ion system can be used for navigation, registration, biopsy and treatment. In this paper, the structural principle of the Ion system is expounded, and its technical advantages such as shape perception, slender catheter and flexible operation are summarized. It represents the latest development direction of the diagnosis and treatment of peripheral pulmonary lesions. Then, the clinical application and development status of the Ion system are analyzed and discussed in detail. Finally, the development trend of the robot-assisted bronchoscopy system is prospected, which provides new ideas for realizing the "integrated and one-stop" diagnosis and treatment services for peripheral pulmonary lesions based on this system.
Bronchoscopy/instrumentation* ; Humans ; Robotics ; Robotic Surgical Procedures

OBJECTIVES: To investigate the mechanism by which transforming growth factor‑β (TGF‑β) regulates major histocompatibility complex class I (MHC-I) expression in hepatocellular carcinoma (HCC) cells and its role in immune evasion of HCC. METHODS: HCC cells treated with TGF‑β alone or in combination with SB-431542 (a TGF-β type I receptor inhibitor) were examined for changes in MHC-I expression using RT-qPCR and Western blotting. A RNA interference experiment was used to explore the role of miR-23a-3p/IRF1 signaling in TGF‑β‑mediated regulation of MHC-I. HCC cells with different treatments were co-cultured with human peripheral blood mononuclear cells (PBMCs), and the changes in HCC cell proliferation was assessed using CCK-8 and colony formation assays. T-cell cytotoxicity in the co-culture systems was assessed with lactate dehydrogenase (LDH) release and JC-1 mitochondrial membrane potential assays, and T-cell activation was evaluated by flow cytometric analysis of CD69 cells and ELISA for TNF-α secretion. RESULTS: TGF‑β treatment significantly suppressed MHC-I expression in HCC cells and reduced T-cell activation, leading to increased tumor cell proliferation and decreased HCC cell death in the co-culture systems. Mechanistically, TGF-β upregulated miR-23a-3p, which directly targeted IRF1 to inhibit MHC-I transcription. Overexpression of miR-23a-3p phenocopied TGF‑β‑induced suppression of IRF1 and MHC-I. CONCLUSIONS We reveal a novel immune escape mechanism of HCC, in which TGF‑β attenuates T cell-mediated antitumor immunity by suppressing MHC-I expression through the miR-23a-3p/IRF1 signaling axis.
Humans ; MicroRNAs/genetics* ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Interferon Regulatory Factor-1/metabolism* ; Transforming Growth Factor beta/metabolism* ; Signal Transduction ; Histocompatibility Antigens Class I/metabolism* ; Cell Line, Tumor ; Tumor Escape ; Coculture Techniques

Objective To study the clinical effect of Kinesio Tape for treating the lower limb function in children with spastic cerebral palsy accompanied by knee hyperextension.Methods Sixty children with spastic cerebral palsy treated by rehabilitation therapy in this hospital from August 2017 to December 2018 were se-lected as the study subjects and divided into the experiment group and control group,30 cases in each group.The control group adopted the conventional rehabilitation therapy,while the experiment group was combined with Kinesio Tape on the basis of conventional rehabilitation therapy.The treatment course lasted for 3 months.Before and after treatment,the children patients conducted the Gross Motor Function Measure-88(GMFM-88)scoring,Modified Ashworth Scale(MAS)grading on the triceps surae muscle in the affected side,surface electromyography,measurement of dorsiflexion angle of foot in knee extension position and meas-urement of maximum knee extension angle of knee joint.Results The GMFM-88 score,triceps surae muscle MAS grade in the affected side,foot dorsiflexion angle in Knee extension position,maximum knee extension angle in the erect position in the two groups were improved compared with those before treatment(P＜0.05).Furthermore,the above indicators in the experimental group were superior to those in the control group(P＜0.05).The surface electromyographic value had no statistical difference between the two groups(P＞0.05).No obvious adverse reactions occurred during the treatment process with good compliance.The chil-dren's parents in the experiment group filled in Kinesio Tape satisfaction questionnaire,and had 100％satis-faction.Conclusion Kinesio Tape combined with routine rehabilitation therapy could effectively improve the muscular tension,joint activity,knee excessive extension degree and exercise function in children with spastic cerebral palsy accompanied by knee hyperextension.

Epilepsy is one of common diseases of nervous system,which is mainly manifested as repeat-ed abnormal neuronal discharges in the brain.If it cannot be effectively controlled,it can cause irreversible neuronal damage in the brain.Non-coding RNAs plays an important role in the development and progression process of epilepsy and are involved in regulating autophagy,apoptosis,neuroinflammation,synaptic remode-ling and other physiological and pathological processes,especially in the regulation of autophagy in epileptic neuronal cells.This article reviews the regulatory relationship between microRNA and long non-coding RNAs,circRNAs in non-coding RNAs with autophagy in the occurrence and development of epilepsy to pro-vide a direction for the precise treatment and prevention of epilepsy.

BACKGROUND:Most of the formulas for the clinical treatment of premature ovarian insufficiency have evolved from the basic formula of Liuwei Dihuang Pills,and have achieved good therapeutic efficacy.Currently,most of the experimental studies on Liuwei Dihuang Pills focus on morphological observations and physiological and biochemical detection of in vivo animal models,while fewer studies on molecular mechanisms have been reported. OBJECTIVE:To explore the molecular mechanism of Liuwei Dihuang Pills in the treatment of premature ovarian insufficiency based on the receptor gamma coactivator-1 alpha/mitochondrial transcription factor A/reactive oxygen species pathway. METHODS:Premature ovarian insufficiency model was established in mice by intraperitoneal injection of cyclophosphamide 120 mg/kg combined with busulfan 12 mg/kg,and then Liuwei Dihuang Pill suspension was used to intervene in premature ovarian insufficiency mice.After 12 weeks of intervention,the levels of follicle-stimulating hormone,luteinizing hormone,estradiol,anti-Mullerian hormone,8-hydroxydeoxyguanosine,total antioxidant capacity and reactive oxygen species in serum of mice were detected by ELISA method.The morphological changes in mouse ovaries were observed by hematoxylin-eosin staining.The ultrastructure of mouse follicular granulosa cells and the apoptosis of granulosa cell mitochondria were observed by transmission electron microscopy.The expression levels of receptor gamma coactivator-1 alpha and mitochondrial transcription factor A in mouse ovarian granulosa cells were detected by immunohistochemistry. RESULTS AND CONCLUSION:Compared with the model group,serum levels of follicle-stimulating hormone,luteinizing hormone,reactive oxygen species,and 8-hydroxydeoxyguanosine were decreased in the experimental group(P＜0.05),and the levels of estradiol,anti-Mullerian hormone,and total antioxidant capacity were increased(P＜0.05).Hematoxylin-eosin staining showed that in the model group,there were more atretic follicles and corpus luteum forms,some secondary follicles,and interstitial fibrosis and hyperplasia;in the experimental group,a large number of atretic follicles,few corpus luteum forms,primordial follicles were observed at the edges but there were few secondary follicles and no mature follicles.Transmission electron microscopy showed that the organelles in ovarian granulosa cells of mice in the experimental groups were relatively intact.Immunohistochemical results showed that compared with the model group,the expression level of receptor gamma coactivator-1 alpha in the ovarian tissue of mice increased slightly in the experimental group at the 4th week,and there was no significant change at the 8th and 12th weeks.The expression level of mitochondrial transcription factor A in the ovarian tissues of mice in the experimental group was transiently increased at the 4th week,and then slightly decreased,which were all significantly different from those of the model group.To conclude,Liuwei Dihuang Pills inhibit ovarian granulosa cell apoptosis in mice with premature ovarian insufficiency to a certain extent through the receptor gamma coactivator-1 alpha/mitochondrial transcription factor A/reactive oxygen species signaling pathway,thereby improving the endocrine function of the ovary,enhancing the antioxidant capacity,and attenuating the degree of oxidative stress damage.

Objective:To investigate the perinatal risk factors and correlation between bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP).Methods:A retrospective analysis was performed on 173 preterm infants born at less than 32 weeks' gestation with BPD who were admitted to the neonatal intensive care unit (NICU) of the Women and Children's Hospital of Qingdao University from June 2017 to July 2022. According to the diagnostic criteria for ROP, these preterm infants were divided into the ROP group ( n=64) and the non-ROP group ( n=109). Chi-square test, two independent samples t-test, and Mann-Whitney U test were used to compare the general data, treatment, and the incidence of complications between the two groups. Multivariate logistic stepwise regression analysis was used to analyze the independent risk factors of ROP in preterm infants with BPD and the receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of independent risk factors on ROP. The correlation between the severity of BPD and the incidence of ROP was analyzed. Results:The gestational age at birth [(28.0±1.1) vs. (28.8±1.2) weeks, t=4.01], the birth weight [(1 075.9±141.4) vs. (1 143.2±168.6) g, t=2.68], the partial pressure of carbon dioxide [42.5 mmHg (1 mmHg=0.133 kPa) (34.0-51.0 mmHg) vs. 47.0 mmHg (39.0-54.0 mmHg), Z=－2.31], and the total fluid intake on the first day of birth [80.0 ml (72.3-88.7 ml) vs. 83.6 ml (76.6-92.8 ml), Z=－2.28] in the ROP group were all lower than those in the non-ROP group (all P<0.05). While the prothrombin time [15.7 s (14.1-17.7 s) vs. 14.6 s (13.1-16.7 s), Z=－2.17], activated partial thromboplastin time [64.7 s (52.9-77.9 s) vs. 55.8 s (48.4-68.9 s), Z=－2.12], the proportion of patients treated with pulmonary surfactant [71.9% (46/64) vs. 49.5% (54/109), χ 2=8.25], the total duration of oxygen supplementation [50.5 d (40.0-64.0 d) vs. 45.0 d (37.0-52.0 d), Z=－2.77], the duration of invasive ventilation [5.0 d (1.0-11.0 d) vs. 1.0 d (0.0-5.0 d), Z=－4.03], the duration of noninvasive ventilation or high-flow oxygen therapy [(31.7±12.7) vs. (26.4±13.1) d, t=－2.59], and the incidence of neonatal respiratory distress syndrome [76.6% (49/64) vs. 57.8% (63/109), χ 2=6.22] were increased in the ROP group (all P<0.05). There was no significant difference in the proportion of BPD treated with corticosteroids between the ROP and non-ROP groups [60.3% (38/63) vs. 74.3% (81/109), χ 2=3.67, P=0.055]. Multivariate logistic stepwise regression analysis showed that smaller gestational age ( OR=1.599, 95% CI: 1.126-2.272, P=0.009), less fluid intake on the first day ( OR=1.033, 95% CI: 1.004-1.062, P=0.024), and longer duration of invasive ventilation ( OR=1.076, 95% CI:1.017-1.138, P=0.011) were independent risk factors for ROP in BPD infants, while glucocorticoid treatment was an independent protective factor ( OR=0.378, 95% CI:0.173-0.827, P=0.015). Most patients with mild or moderate BPD did not develop ROP [64.6% (73/113) and 66.7% (34/51)], while those with severe BPD were more likely to be complicated by ROP (7/9) ( χ 2=6.84, P=0.033). Conclusions:BPD infants with smaller gestational age, longer duration of invasive ventilation, and less fluid intake on the first day of birth are more likely to develop ROP, while glucocorticoid therapy can reduce the incidence of ROP in this population. Severe BPD may increase the risk of ROP in infants.

OBJECTIVE To investigate the mechanism by which Ginkgo flavone aglycone （GA） reduces the cardiotoxicity of doxorubicin （DOX） based on transcriptomics and proteomics. METHODS Thirty-six mice were randomly assigned to control group （CON group， tail vein injection of equal volume of physiological saline every other day+daily intragastric administration of an equal volume of physiological saline）， DOX group （tail vein injection of 3 mg/kg DOX every other day）， and GDOX group （daily intragastric administration of 100 mg/kg GA+tail vein injection of 3 mg/kg DOX every other day）， with 12 mice in each group. The administration of drugs/physiological saline was continued for 15 days. Mouse heart tissues were collected for RNA-Seq transcriptomic sequencing and 4D-Label-free quantitative proteomic analysis to screen differentially expressed genes and proteins， which were then subjected to Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis. The expression levels of Apelin peptide （Apelin）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） mRNA and protein in mouse heart tissues， as well as the phosphorylation levels of PI3K and Akt proteins， were verified. H9c2 cardiomyocytes were divided into control group （CON group）， DOX group （2 μmol/L）， and GDOX group （2 μg/mL GA+2 μmol/L DOX） to determine cell viability and the levels of key glycolytic substances in the cells. RESULTS Six common pathways were identified from transcriptomics and proteomics， including the Apelin signaling pathway， the PI3K-Akt signaling pathway， and insulin resistance. Among them， the Apelin and PI3K-Akt signaling pathways were the most enriched in terms of gene numbers. Target validation experiments showed that compared to the CON group， the relative expression of Apelin， PI3K and Akt mRNA and protein levels， as well as the phosphorylation levels of PI3K and Akt proteins， were significantly decreased in the DOX group （P＜0.05 or P＜0.01）. The relative expression of Apelin， PI3K and Akt mRNA and the phosphorylation levels of PI3K and Akt proteins were significantly increased in the GDOX group as compared with the DOX group （P＜0.05 or P＜0.01）. Cellular experiments indicated that compared to the CON group， cell viability in the DOX group was significantly decreased （P＜0.05）， the relative uptake of glucose and the relative production of pyruvate and lactate were significantly increased （P＜0.05）， and the relative production of ATP was significantly reduced （P＜0.05）. Compared to the DOX group， cell viability in the GDOX group was significantly increased （P＜ 0.05）， and the relative production of pyruvate and lactate was significantly reduced （P＜0.05）. CONCLUSIONS GA may alleviate DOX-induced cardiotoxicity by upregulating the mRNA and protein expression of Apelin， PI3K， and Akt in heart tissues， and regulating glycolytic processes.

Hepatosplenic candidiasis (HSC) is a rare type of candidiasis that can occur in patients with hematologic malignancies, hematopoietic stem cell transplantation. At present, there is still a lack of studies on HSC in patients with hematologic disorders. Based on The Chinese Guidelines for the Diagnosis and Treatment of Invasive Fungal Disease in Patients with Hematological Disorders and Cancers (the 6th revision), We retrospectively analyzed the clinical characteristics and prognosis of patients with HSC treated in Peking University Institute of Hematology from 2008 to 2022. Finally, eighteen patients were included, with 1 (5.6%) proven, 2 (11.1%) probable, and 15 (83.3%) possible HSC. Among them, 3 (16.7%) patients occurred after haploid hematopoietic stem cell transplantation and 15 (83.3%) patients occurred after chemotherapy. 6 (33.3%) patients had positive blood cultures, including 4 cases of Candida tropicalis and 2 cases of Candida albicans. At 4 weeks of antifungal therapy, 10 (58.8%) patients achieved partial response (PR), At 8 weeks, 1 (6.3%) patients achieved complete response and 10 (62.5%) patients achieved PR. At 6 months after diagnosis, 3 (16.7%) patients died of hematopoietic recurrence, and none of them died of HSC. As a rare fungal infection disease, HSC has a low positive rate of microbiological and histological examinations, a persistent treat cycle, and has difficulty in remission, reminding us of the need for vigilance in patients with hematopoietic disorders and persistent fever.