BACKGROUND: Bile acids (BAs) facilitate the progression of gastric intestinal metaplasia (GIM). Long non-coding RNAs (lncRNAs) dysregulation was observed along with the initiation of gastric cancer. However, how lncRNAs function in GIM remains unclear. This study aimed to explore the role and mechanism of lncRNA PVT1 in GIM, and provide a potential therapeutic target for GIM treatment. METHODS: We employed RNA sequencing (RNA-seq) to screen dysregulated lncRNAs in gastric epithelial cells after BA treatment. Bioinformatics analysis was conducted to reveal the regulatory mechanism. PVT1 expression was detected in 21 paired biopsies obtained under endoscopy. Overexpressed and knockdown cell models were established to explore gene functions in GIM. Molecular interactions were validated by dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (Ch-IP). The levels of relative molecular expression were detected in GIM tissues. RESULTS: We confirmed that lncRNA PVT1 was upregulated in BA-induced GIM model. PVT1 promoted the expression of intestinal markers such as CDX2 , KLF4 , and HNF4α . Bioinformatics analysis revealed that miR-34b-5p was a putative target of PVT1 . miR-34b-5p mimics increased CDX2 , KLF4 , and HNF4α levels. Restoration of miR-34b-5p decreased the pro-metaplastic effect of PVT1 . The interactions between PVT1 , miR-34b-5p, and the downstream target HNF4α were validated. Moreover, HNF4α could transcriptionally activated PVT1 , sustaining the GIM phenotype. Finally, the activation of the PVT1 /miR-34b-5p/ HNF4α loop was detected in GIM tissues. CONCLUSIONS BAs facilitate GIM partially via a PVT1/miR-34b-5p/HNF4α positive feedback loop. PVT1 may become a novel target for blocking the continuous development of GIM and preventing the initiation of gastric cancer in patients with bile reflux.
Humans ; RNA, Long Noncoding/metabolism* ; MicroRNAs/metabolism* ; Hepatocyte Nuclear Factor 4/genetics* ; Bile Acids and Salts ; Kruppel-Like Factor 4 ; Metaplasia/metabolism*

Cardiovascular disease (CVD) is the leading cause of death worldwide. As the key pathological basis of CVD, arteriosclerosis holds great significance for early screening. However, existing clinical and homecare detection devices have many shortcomings; for instance, the commonly used non-invasive indicator PWV (pulse wave velocity) is easily interfered by blood pressure.This study developed a homecare arteriosclerosis monitoring system, which integrates the measurement functions of cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI). The hardware design of the system includes an integrated structure of flexible silver ion electrodes and clip-type cuffs, a contact heart sound sensor, and a stepped deflation blood pressure measurement module. Meanwhile, a high-precision analog-to-digital conversion module and the STM32F405 main control chip are used to realize the synchronous acquisition of multiple signals.In terms of software, the underlying driver program was designed through MDK (Keil5), and a user interface was built on the Visual Studio platform to achieve functions such as data acquisition, display, and storage. At the algorithm level, the system adopted algorithms like the Pan-Tompkins algorithm to identify key feature points of physiological signals, and then calculate CAVI and ABI.System test results show that the ECG input noise of the system is less than 20 μV, the common-mode rejection ratio is 95 dB, and the blood pressure measurement error does not exceed 2 mmHg, which meets the design goals. Clinical data analysis indicates that CAVI is highly positively correlated with pulse wave velocity (PWV) ( r=0.85, P<0.001), but CAVI is less affected by blood pressure fluctuations. In addition, with the increase of risk factors (such as hypertension, hyperlipidemia, coronary heart disease, etc.) and age, arteriosclerosis indicators (CAVI, PWV, ABI) all show an upward trend.In conclusion, the homecare arteriosclerosis monitoring system proposed in this study not only overcomes the problems of traditional devices that rely on professional operation and are susceptible to blood pressure interference, but also provides a reliable tool for arteriosclerosis screening in home scenarios, and has important reference value for clinical diagnosis.
Humans ; Cardio Ankle Vascular Index ; Home Care Services ; Atherosclerosis/diagnosis* ; Ankle Brachial Index ; Algorithms ; Pulse Wave Analysis ; Arteriosclerosis/diagnosis* ; Monitoring, Physiologic/instrumentation*

Cantharidin (CTD), a natural compound used to treat multiple tumors in the clinic setting, has been limited due to acute kidney injury (AKI). However, the major cause of AKI and its underlying mechanism remain to be elucidated. Serum creatinine (SCr) and blood urea nitrogen (BUN) were detected through pathological evaluation after CTD (1.5 mg/kg) oral gavage in mice in 3 days. Kidney lipidomics based on ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to investigate lipids disorder after CTD exposure in mice. Then, spatial metabolomics based on matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) was used to detect the kidney spatial distribution of lipids. Integrative analysis was performed to reveal the spatial lipid disorder mechanism and verify key lipids in vitro. The results showed that the levels of SCr and BUN were increased, and tubular necrosis was observed in mouse kidneys, resulting in acute tubular necrosis (ATN) in CTD-induced AKI. Then, lipidomics results revealed that after CTD exposure, 232 differential lipid metabolites and 11 pathways including glycerophospholipid (GP) and sphingolipid (SL) metabolism were disrupted. Spatial metabolomics revealed that 55 spatial differential lipid metabolites and nine metabolic pathways were disturbed. Subsequently, integrative analysis found that GP metabolism was stimulated in the renal cortex and medulla, whereas SL metabolism was inhibited in the renal cortex. Up-regulated lysophosphatidylcholine (LysoPC) (18:2(9Z,12Z)), LysoPC (16:0/0:0), glycerophosphocholine, and down-regulated sphingomyelin (SM) (d18:0/16:0), SM (d18:1/24:0), and SM (d42:1) were key differential lipids. Among them, LysoPC (16:0/0:0) was increased in the CTD group at 1.1196 μg/mL, which aggravated CTD-induced ATN in human kidney-2 (HK-2) cells. LysoPC acyltransferase was inhibited and choline phosphotransferase 1 (CEPT1) was activated after CTD intervention in mice and in HK-2 cells. CTD induces ATN, resulting in AKI, by activating GP metabolism and inhibiting SL metabolism in the renal cortex and medulla, LysoPC (16:0/0:0), LysoPC acyltransferase, and CEPT1 may be the therapeutic targets.

Objective:To discuss the inhibitory effect of chelerythrine(CHE)on the migration,invasion,and epithelial-mesenchymal transition(EMT)of the human ovarian cancer SKOV3 cells,and to clarify the associated mechanism.Methods:The SKOV3 cells were cultured in vitro and divided into control group and 2.5,5.0,10.0,20.0,and 40.0 μmol·L-1 CHE groups.Methylthiazolydiphenyl-tetrazolium(MTT)assay was used to detect the inhibitory rates of proliferation of the cells in various groups.The SKOV3 cells were cultured in vitro and divided into control group,transforming growth factor-β1(TGF-β1)group,TGF-β1+5 μmol·L-1 CHE group,and TGF-β1+10 μmol·L-1 CHE group.Cell scratch assay was used to detect the migration rates of the cells in various groups;Transwell chamber assay was used to detect the numbers of migration and invasion cells in various groups;Western blotting method was used to detect the expression levels of E-cadherin,N-cadherin,and Vimentin proteins in the cells in various groups;immunofluorescence staining method was used to detect the fluorescence intensities of E-cadherin and N-cadherin in the cells in various groups.Results:The MTT assay results showed that compared with control group,the inhibitory rates of proliferation of the cells in 5.0,10.0,20.0,and 40.0 μmol·L-1 CHE groups were significantly increased(P<0.05 or P<0.01).The cell scratch assay results showed that compared with control group,the migration rate of the cells in TGF-β1 group was increased(P<0.01);compared with TGF-β1 group,the migration rates of the cells in TGF-β1+5 μmol·L-1 CHE group and TGF-β1+10 μmol·L-1 CHE group were significantly decreased(P<0.01).The Transwell chamber assay results showed that compared with control group,the numbers of migration and invasion cells in TGF-β1 group were significantly increased(P<0.05);compared with TGF-β1 group,the numbers of migration and invasion cells in TGF-β1+5 μmo·l L-1 CHE group and TGF-β1+10 μmo·l L-1 CHE group were significantly decreased(P<0.01).The Western blotting results showed that compared with control group,the expression level of E-cadherin protein in the cells in TGF-β1 group was significantly decreased(P<0.01),while the expression levels of N-cadherin and Vimentin proteins were increased(P<0.05 or P<0.01);compared with TGF-β1 group,the expression levels of E-cadherin protein in the cells in TGF-β1+5 μmol·L-1 CHE group and TGF-β1+10 μmol·L-1 CHE group were significantly increased(P<0.01),and the expression levels of N-cadherin and Vimentin proteins were significantly decreased(P<0.01).The immunofluorescence staining results showed that compared with control group,the fluorescence intensity of E-cadherin in the cells in TGF-β1 group was decreased,and the fluorescence intensity of N-cadherin was increased;compared with TGF-β1 group,the fluorescence intensities of E-cadherin in the cells in TGF-β 1+5 μmol·L-1 CHE group and TGF-β1+10 μmol·L-1 CHE group were significantly increased,and the fluorescence intensities of N-cadherin were decreased.Conclusion:CHE can inhibit the proliferation,migration,invasion,and EMT of the human ovarian cancer SKOV3 cells.

Objective To analyze the distribution of common allergens in children with allergic rhinitis(AR)in Hangzhou,and to provide reference for its prevention and treatment.Methods From January 2020 to December 2022,13 521 children who were diagnosed with AR and underwent in vitro serum specific immunoglobulin E(sIgE)detection in Affiliated Hangzhou First People's Hospital,School of Medicine,Westlake University were selected as the research objects.The positive rates of allergens in children with AR of different genders,ages and seasons were compared.Results Among 13 521 children,the positive rate of sIgE was 54.49%(7367/13 521),of which 64.82%were allergic to only one allergen.Among the 19 common allergens,the top three overall positive rates were household dust mite(44.27%),milk(14.62%),and mixed grass(4.82%).The positive rates of allergens of house dust mites,cat hair dander,mulberry,mold combination,tree pollen combination,amaranth,cockroach,milk,shrimp,crab,pineapple,shellfish and mango in male children were significantly higher than those in female children(P<0.05).The positive rates of allergens of house dust mite,mixed grass,cat hair dander,mulberry,mold combination,egg white,shrimp,crab,pineapple,cashew nuts and shellfish in different age groups were statistically significant(P<0.05).July and August were the two months with the highest allergen positive rate.The allergen positive rates of house dust mite,dog and cat hair dander were the highest in summer,and the allergen positive rate of plants was consistent with the flowering season.The sIgE concentration of house dust mite(77.87%)was mainly grade 3 and above.The sIgE concentration of other allergens was mainly grade 1 and 2.Conclusion Dust mites and milk are the most common allergens in children with AR in Hangzhou,and the distribution of allergens varies with gender,age and season.Allergen detection can provide a more accurate plan for the diagnosis,prevention and treatment of AR.

Based on the discussions in the The Inner Canon of Yellow Emperor （《黄帝内经》）， it is proposed that in the course of the disease， "bind" represents the initial stage of pulmonary nodules， while "accumulation" represents the final form. In terms of the pathogenesis， "two colds interacting" represented by "body cold" and "cold fluid retention" are the prerequisites for the formation of pulmonary nodules， while "disorder of qi" represented by "fainting" is the core of the formation. The specific manifestation is the disturbance of pivot of shaoyang （少阳） or shaoyin （少阴）， resulting in a complex of cold and heat， and then phlegm and stasis are suddenly generated and further formed into nodules. Therefore， the treatment principle should be to regulate the cardinal mechanism， dissolve phlegm and blood stasis. Depending on the complex degree of cold and heat， it is suggested to use Chaihu Guizhi Decoction （柴胡桂枝汤）， Chaihu Guizhi Ganjiang Decoction （柴胡桂枝干姜汤）， or Chaihu Xianxiong Decoction （柴胡陷胸汤） for disturbance of shaoyang pivot， while for shaoyin pivot dysfunction， modified Mahuang Fuzi Xixin Decoction （麻黄附子细辛汤） or Shengjiang Powder （升降散） can be used.

OBJECTIVE: To explore the toxicological mechanism of drug-induced liver injury(DILI) in rats induced by cantharidin(CTD). METHODS: SD rats were exposed to different doses of CTD(0.061 4, 0.092 1, 0.184 1 mg·kg−1) by oral gavage for 28 d. Liver index and serum liver function indictors were detected. HE staining was used to evaluate the pathological changes of liver. Then the proteins in endoplasmic reticulum stress(ERS), autophagy, and apoptosis-pathway were detected by Western blotting. RESULTS: The liver index was increased in CTD groups. The ALT, AST, LDH, ALP and T-Bil were increased by CTD with a dose-dependent manner. Disrupted hepatic architecture and dilatation of central vein were observed after CTD intervention. The protein expression levels of GRP78, CHOP, ATF4, Beclin-1, LC3, Caspase-3, Caspase-8, and Bax/Bcl-2 were increased after CTD intervention. Molecular docking results revealed that GRP78, ATF4, and Beclin-1 could directly interconnect with CTD. CONCLUSION CTD can activate ERS, autophagy and synergistically inducing downstream apoptosis in rat, providing a novel insight into the mechanism of CTD-induced DILI.

Objective:To explore the repair strategy of chest radiation ulcer after radical mastectomy for breast cancer and its clinical effect.Methods:The study was a retrospective observational study. From September 2020 to September 2023, 27 female patients (aged 37-83 years) with chest radiation ulcers after radical mastectomy for breast cancer who met the inclusion criteria were admitted to Beijing Jishuitan Hospital Affiliated to Capital Medical University, of which 7 patients developed significant pain in the chest region. Various examinations were completed to accurately assess the presence of tumors and depth of radiation ulcers. After tumor recurrence was ruled out, the ulcer wounds were thoroughly debrided (the wound size after debridement was 8 cm×7 cm to 18 cm×18 cm). At the same time, pathological examination of the wound tissue and bacterial culture of the wound tissue/exudate samples were performed. The wound repair surgery was performed at the same time after debridement or one week after vacuum sealing drainage (VSD) treatment. Based on the location and size of the wound, the age and overall condition of the patient, as well as the principle of minimizing damage to the donor site, the most suitable tissue flap was selected to repair the wound. The donor site wound was transplanted with a split-thickness skin graft or sutured together. The level and tissue structure of radiation injury, and the type and size of transplanted tissue flap were recorded. The results of postoperative pathological examination of wound tissue and bacterial culture of wound tissue/exudate samples, pain relief, survival of tissue flap, and wound healing were recorded. During the follow-up, the shape of the tissue flap, whether the ulcer recurred, the wound healing of the donor site, and whether the abdominal wall hernia occurred in the donor site of the rectus abdominis myocutaneous flap were observed.Results:Radiation injury involved ribs and costal cartilage in 21 cases, ribs, sternum, and clavicle in 4 cases, and clavicle and subclavian artery in 2 cases. Twelve patients were transplanted with rectus abdominis myocutaneous flap, eight patients with latissimus dorsi myocutaneous flap, three patients with internal thoracic artery perforator flap, three patients with superior epigastric artery perforator flap, and one patient with free deep inferior epigastric perforator flap. The size of tissue flap was 14 cm×8 cm to 20 cm×20 cm. After surgery, no tumor component was found in the pathological examination of wound tissue; 25 patients were positive and 2 patients were negative in bacterial culture results of wound tissue/exudate samples; the pain of 7 patients was completely relieved. The tissue flaps of 25 patients survived completely after surgery, and the wounds healed. Two patients had partial necrosis at the tip of the rectus abdominis myocutaneous flap, which healed after debridement and tissue flap repair. The patients were followed up for 6 months to 2 years. The appearance of the tissue flaps was good, and no ulcer recurred. The linear scar was left on the donor site, and no abdominal wall hernia occurred in the donor site of the rectus abdominis myocutaneous flap.Conclusions:Thorough debridement and VSD treatment after accurate assessment of the extent of damage, and the selection of appropriate tissue flap to repair the wound based on the patient's general condition, the wound characteristics, and the principle of minimizing damage to the donor site are good repair strategies for the chest radiation ulcers after radical mastectomy for breast cancer. By using the strategies, the wounds could be closed as soon as possible, preventing ulcer recurrence and having a good prognosis.

Objective:To explore the clinical effects of chimeric perforator flaps in repairing wounds with bone or internal fixation exposure and wounds with osteomyelitis.Methods:This study was a retrospective observational study. From January 2018 to December 2022, 20 patients with wounds with bone or internal fixation exposure and wounds with osteomyelitis who met the inclusion criteria were admitted to Beijing Jishuitan Hospital Affiliated to Capital Medical University, including 19 males and 1 female, aged from 21 to 73 years. Among the 21 wounds, there were 5 wounds with bone exposure, 12 wounds with osteomyelitis, and 4 wounds with internal fixation exposure. After the debridement in the first stage, the wound area was 6 cm×3 cm to 22 cm×10 cm. Then vacuum sealing drainage was carried out for 5 to 7 days. In the second stage, the wounds were covered with pedicled chimeric medial sural artery perforator flap, pedicled chimeric posterior tibialis artery perforator flap, free chimeric perforator flap pedicled with descending branch of lateral circumflex femoral artery, free chimeric medial sural artery perforator flap or free chimeric deep circumflex iliac artery perforator flap with incision area of 7 cm×5 cm to 25 cm×12 cm. The chimeric muscle flap was used to fill and cover irregular deep cavities. The wounds in the flap donor sites were sutured directly or repaired with medium-thickness skin grafts from the thigh. The survival of flap and the healing of wound in flap donor site were observed after operation. The recurrence of infection was followed up.Results:Among the 18 free chimeric perforator flaps, 16 flaps survived successfully; one flap experienced a venous crisis on the day of surgery and survived completely after emergency exploration and re-anastomosis; another one flap had partial distal necrosis, which healed after dressing changes. All the wounds in the flap donor sites healed evenly. All 3 pedicled chimeric perforator flaps survived; one of them developed sub-flap infection but healed after debridement and bone cement placement. The wound in the donor site of 1 flap developed incision dehiscence, which healed successfully after redebridement and suturing. The donor site wounds of the rest 2 flaps healed well. During 3 to 12 months of follow-up, the patients with wounds with bone or internal fixation exposure showed no signs of abnormal exudation or infection, and no infection recurrence was observed in patients with wounds with osteomyelitis.Conclusions:The application of chimeric perforator flaps is effective in covering wounds, filling dead spaces, and controlling infection in wounds with bone or internal fixation exposure and wounds with osteomyelitis. Moreover, this method minimizes the damage to the donor site.

ObjectiveTo systematically explore the roles and contributions of the sovereign drug Gypsum Fibrosum contained in Baihu Guizhitang （BHGZT） against rheumatoid arthritis （RA） with heat syndrome from property-efficacy association by an approach integrating transcriptomics with gene regulatory network analysis. MethodA total of 20 male Lewis rats were randomly assigned into 4 groups： a control group （n=5）， a group of adjuvant-induced arthritis rat model with heat syndrome （AIA-H， n=5）， an AIA-H + BHGZT group （BHGZT， 21.4 g·kg^-1， n=5）， and an AIA-H + BHGZT without Gypsum Fibrosum group （BHGZT-GYP， 10.7 g·kg^-1， n=5）. We combined the gene expression profiling based on AIA-H rat model and "disease-gene-drug effective target" network analysis to predict the major function of Gypsum Fibrosum contained in BHGZT against RA with heat syndrome. Furthermore， in vivo experiments with the AIA-H rat model were performed to validate the therapeutic effects on the severity of arthritis based on the representative images of arthritis， limb diameter， infrared thermography， pain thresholds， and joint injury， as well as at the level of immunity-inflammation imbalance. Oil Red O staining was employed for the differentiation of 3T3-L1 pre-adipocytes in the AIA-H rats treated by BHGZT， BHGZT-GYP， and GYP. ResultGene expression profiling and network analysis demonstrated that Gypsum Fibrosum mainly regulated the energy metabolism disorders and the immunity-inflammation imbalance during the development and progression of RA. In vivo experiments showed that both BHGZT and BHGZT-GYP reduced the disease severity of AIA-H rats （P<0.01） by relieving joint redness and distortion， decreasing arthritis score and limb diameter， elevating pain thresholds， alleviating joint erosion， joint inflammation， and bone destruction （P<0.05）. Notably， BHGZT outperformed BHGZT-GYP （P<0.05）. Both BHGZT and BHGZT-GYP inhibited the pathological changes and decreased the indexes of thymus and spleen （P<0.05）， and down-regulated the expression of inflammatory cytokines including Toll-like receptor 4 （TLR4）， tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， IL-12， IL-1β， and IL-18 （P<0.05）. In addition， BHGZT and GYP significantly inhibited the adipogenic differentiation of 3T3-L1 cells， with the performance superior to that of BHGZT-GYP. ConclusionThe sovereign drug Gypsum Fibrosum contained in BHGZT played a crucial role in reversing energy metabolism disorders and immunity-inflammation imbalance， which may be associated with its cold property and function of clearing heat and purging fire.