OBJECTIVES: To reprogram human placental fibroblasts (HPFs) into chemically induced epithelioid-like cells (ciEP-Ls) using a combination of small-molecule compounds. METHODS: HPFs cultured under normoxic conditions were identified using immunofluorescence assay, PCR and chromosomal karyotyping. Under hypoxic conditions (37 ℃, 5% O₂), HPFs were cultured in a medium containing small-molecule compounds C6TSEDRVAJZ (CHIR99021, 616452, TTNPB, SAG, EPZ5676, DZNep, Ruxolitinib, VTP50469, Afuresertib, JNK-IN-8, and EZM0414), and the cell morphology was observed daily. The expression levels of epithelial cell markers in the induced cells were detected by immunofluorescence, Western blotting and PCR. Chromosomal karyotyping of the induced cells was performed and the induction efficiency was calculated. RESULTS: Before induction, HPFs showed positive expressions of fibroblast surface markers CD34 and vimentin and were negative for epithelial surface markers. PCR results showed high expressions of fibroblast-specific genes S100A4 and COL1A1 in HPFs with a normal human diploid karyotype. After one day of induction, the HPFs underwent morphological changes from a multinodular spindle shape to a round or polygonal shape, which was morphologically characteristic of ciEP-Ls. On day 4 of induction, the cells exhibited high expressions of the epithelial cell markers E-cadherin and Lin28A. RT-qPCR results also showed that the cells expressed the epithelial markers Smad3, GLi3, PAX8, WT1, KRT19, and KRT18 with significantly down-regulated expressions of all the fibroblast surface markers and a normal human diploid karyotype. The reprogramming efficiency of HPFs into ciEP-Ls ranged from (64.53±2.8)% to (68.10±3.6)%. CONCLUSIONS The small-molecule compound combination C6TSEDRVAJZ is capable of inducing HPFs into ciEP-Ls under hypoxic conditions with a high induction efficiency.
Humans ; Fibroblasts/drug effects* ; Pregnancy ; Female ; Cell Differentiation/drug effects* ; Pyrimidines/pharmacology* ; Placenta/cytology* ; Cells, Cultured ; Pyridines/pharmacology* ; Pyrazoles/pharmacology* ; Epithelial Cells/cytology*

ObjectiveTo reveal the active substances and mechanisms of modified Qing'e formula （MQEF） in delaying skin photoaging by ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry （UPLC-Q-TOF-MS），network pharmacology， and cell experiments. MethodsUPLC-Q-TOF-MS and a literature review were employed to analyze the transdermally absorbed components in mice after the topical application of MQEF. The potential targets of MQEF in treating skin photoaging were retrieved from databases.The compound-potential target network and protein-protein interaction network were constructed to screen the key components and core targets. A photoaging cell model was established by irradiating HaCaT cells with medium-wave ultraviolet B （UVB）. The safe doses of bakuchiol （BAK） and salvianolic acid B （SAB） for treating HaCaT cells and the effects of BAK and SAB on the viability of cells exposed to UVB irradiation were determined by the cell counting kit-8 （CCK-8） method.The reactive oxygen species （ROS） fluorescent probe was used to measure the ROS production in the cells treated with BAK and SAB.The expression levels of genes related to oxidative stress，inflammation，collagen metabolism，and circadian rhythm clock were measured by Real-time PCR. ResultsA total of 24 transdermally absorbed components of MQEF were identified，which acted on 367 potential targets，and 417 targets related to skin photoaging were screened out，among which 47 common targets were predicted as the targets of MQEF in treating skin photoaging. MQEF exerted the anti-photoaging effect via key components such as BAK and SAB，which acted on core proteins such as serine/threonine kinase 1 （Akt1） and mitogen-activated protein kinase 3 （MAPK3） and intervened in core pathways such as the tumor necrosis factor （TNF） and phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt） signaling pathways.Compared with the model group，the administration of BAK and SAB increased the survival rate of HaCaT cells （P<0.01），down-regulated the mRNA levels of cyclooxygenase-2 （COX-2），interleukin-6 （IL-6），tumor necrosis factor-α （TNF-α），matrix metalloproteinase-1 （MMP-1），and matrix metalloproteinase-9 （MMP-9） （P<0.01），and up-regulated the mRNA levels of heme oxygenase-1 （HO-1） and NAD（P）H quinone dehydrogenase 1 （NQO-1） （P<0.05，P<0.01） in photoaged HaCaT cells.In addition，it eliminated excess ROS production induced by UVB and up-regulated the mRNA levels of brain and muscle ARNT-like 1 （BMAL1） and circadian locomotor output cycles kaput （CLOCK） associated with circadian clock （P<0.05，P<0.01）. ConclusionMQEF delays skin photoaging through the coordinated effects of various components，multiple targets，and diverse pathways.The key components BAK and SAB in MQEF exhibit anti-photoaging properties，which involve inhibiting oxidative stress，preventing collagen degradation，mitigating inflammation，and maintaining normal skin circadian rhythms by regulating clock gene expression.

Coronary heart disease is a chronic and lifelong disease， which places a dual burden on the physiological and psychological well-being of patients， and can easily lead to psychological distress and affect their prognosis and quality of life. This article provides a systematic review， in which the current status， evaluation tools， influencing factors and intervention methods of psychological distress in patients with coronary heart disease are explored， aiming to provide key information beneficial for identifying and preventing psychological distress， and to improve the overall management and treatment effectiveness of coronary heart disease patients. In this paper， 18 articles were included， and the demographic， physiological， psychological and social factors affecting the psychological distress of patients with coronary heart disease were systematically analyzed， thus to provide a deeper understanding of psychological distress and offering references for formulating targeted intervention strategies.

Objective To investigate the influence of oxygen supply flow rate in high-flow nasal cannula(HFNC)oxygen therapy on pressure distributions in the upper airway.Methods A three-dimensional(3D)model of the upper airway was reconstructed using CT images from an adult male,and then coupled with a high-flow nasal cannula model to establish a coupled model of the nasal cannula and the upper airway.Subsequently,a physical model of this upper airway,which was combined with a head model,artificial lungs,and a monitoring system was created by 3D printing technology to form a physical simulation platform in vitro.Computational and physical simulations were carried out respectively to determine the air pressure at typical locations in the upper airway under different oxygen supply flow rates.Results Pressures at typical upper airway locations obtained by computational and physical simulations turned out to be in good agreement;both peak inspirational pressure(PIP)and positive end-expiratory pressure(PEEP)increased quadratically with the increase of oxygen supply flow rate;and the air pressure distribution was more uniform in the laryngeal cross-section as compared to the nasal part of the upper airway.Conclusions This study may provide a theoretical support for optimization of the setting of oxygen suppy flow rate and the selection of PEEP effect assessment position in the clinical application of HFNC oxygen therapy.

Objective:To investigate the effect of preoperative systemic inflammatory response index (SIRI) on prognosis in patients with resectable colorectal cancer.Methods:The clinical data of 355 colorectal cancer patients underwent radical resection from January 2018 to December 2022 in the Second Affiliated Hospital of Harbin Medical University were retrospectively analyzed. The basic information, pathological data and laboratory test results were recorded, and SIRI was calculated. The patients followed up to December 2023 or death, and the overall survival (OS) and disease-free survival (DFS) were recorded. The receiver operating characteristic (ROC) curve was drawn, the optimal critical value of SIRI in patients with colorectal cancer was determined according to the maximum Yoden index, and the patients were grouped based on this. Multivariate Cox regression analysis was used to analyze the independent risk factors of prognosis in patients with colorectal cancer. Kaplan-Meier survival curve was drawn, and the log-rank test was used for comparison.Results:ROC curve analysis result showed that the optimal critical value of SIRI was 0.99, and the area under the curve was 0.556. Among the 355 patients with colorectal cancer, SIRI<0.99 was in 229 cases (low SIRI group), and SIRI≥0.99 was in 126 cases (high SIRI group). There were no statistical difference in gender composition, age, body mass index (BMI), preoperative carcinoembryonic antigen, preoperative cancer antigen 19-9 (CA19-9), tumor location, T stage, N stage, tumor stage, degree of differentiation, tumor long diameter, lymphatic invasion, vascular invasion, operating time and intraoperative blood loss between two groups ( P>0.05). The incidence of anastomotic leakage in high SIRI group was significantly higher than that in low SIRI group: 20.6% (26/126) vs. 12.2% (28/229), and there was statistical difference ( P<0.05). The median follow-up time of 355 patients was 21.7 months. The mortality and recurrence rate in high SIRI group were significantly higher than those in low SIRI group: 28.6% (36/126) vs. 19.2% (44/229) and 13.5% (17/126) vs. 6.1% (14/229), and there were statistical differences ( P<0.05). Kaplan-Meier survival curve analysis result showed that the median OS and DFS in high SIRI group were significantly lower than those in low SIRI group (17.3 months vs. 23.3 months and 15.1 months vs. 21.9 months), and there were statistical differences ( P<0.05). Multivariate Cox regression analysis result showed that the tumor stage Ⅲ to Ⅳ, preoperative CEA>5 μg/L and SIRI>0.99 were independent risk factors of OS and DFS in patients with colorectal cancer (OS: HR = 2.447, 1.951 and 1.923; 95% CI 1.461 to 4.099, 1.266 to 3.456 and 1.003 to 2.655; P<0.05. DFS: HR = 2.982, 1.782 and 1.529; 95% CI 1.663 to 4.754, 1.147 to 2.651 and 1.198 to 2.021; P<0.05). Conclusions:The preoperative SIRI is an independent risk factor of prognosis in patients with colorectal cancer. The patients with low SIRI have longer postoperative OS and DFS. The preoperative SIRI has guiding value in the prognosis assessment and treatment selection in patients with colorectal cancer.

Objective To investigate the expression of the circular RNA circ-PHC3 in cervical cancer tissues and its regulatory mechanisms in the proliferation,migration,and invasion of cervical cancer cells.Methods The expression levels of circ-PHC3 in cervical cancer tissues and adjacent non-tumor tissues were analyzed using the GEO database.The correlation between circ-PHC3 expression and the clinical stage as well as prognosis of cervical cancer patients was also evaluated.The expression of circ-PHC3 in cervical cancer cell lines HCC94,C33A,HeLa,HCC1106,and SiHa was detected by real-time quantitative polymerase chain reaction(qRT-PCR).The cell line with the highest circ-PHC3 expression was selected for transfection with a circ-PHC3 inhibitor.The interaction between circ-PHC3 and miR-1179 was validated using a dual luciferase reporter gene assay.The expression levels of miR-1179 in transfected cells were further assessed by qRT-PCR.Functional assays,including colony formation,flow cytometry,wound healing,and Transwell assays,were conducted to evaluate cell proliferation,cell cycle progression,migration,and invasion,respectively.Western blot analysis was performed to determine the expression of key proteins associated with proliferation,migration,and invasion in circ-PHC3-modulated cells.Finally,in vivo experiments were carried out to investigate the impact of circ-PHC3 silencing on the growth and metastasis of cervical cancer cells in animal models.Results The expression level of circ-PHC3 in cervical cancer tissues was significantly higher than that in adjacent normal tissues(P<0.01).Furthermore,circ-PHC3 expression was significantly associated with the clinical stage of cervical cancer(P<0.01).Patients with high circ-PHC3 expression exhibited a notably lower survival rate compared to those with low circ-PHC3 expression(P<0.01).In cervical cancer cell lines including HCC94,C33A,HeLa,HCC1106,and SiHa,circ-PHC3 expression was markedly upregulated(all P<0.01),with the highest expression observed in HCC1106 cells(P<0.01).Circ-PHC3 was found to directly interact with miR-1179(P<0.01),and silencing circ-PHC3 significantly increased miR-1179 expression(P<0.01).Transfection of HCC1106 cells with a circ-PHC3 inhibitor significantly suppressed cell proliferation,migration,and invasion(all P<0.01),and induced cell cycle arrest(P<0.01);these effects were partially reversed by co-transfection with a miR-1179 inhibitor(all P<0.05).In HCC1106 cells with circ-PHC3 knockdown,the expression levels of key proteins associated with proliferation,migration,and invasion—Cyclin E,CDK2,MMP-9,and N-cadherin—were significantly reduced(all P<0.01),and this reduction was partially attenuated by miR-1179 inhibition(all P<0.01).In vivo experiments further demonstrated that circ-PHC3 knockdown significantly inhibited tumor growth and metastasis of HCC1106 cells(all P<0.01).Conclusions Circ-PHC3 is highly expressed in cervical cancer tissues,and its overexpression is significantly correlated with poor prognosis in patients with cervical cancer.Knockdown of circ-PHC3 upregulates the expression of miR-1179 and suppresses the proliferation,migration,and invasion of cervical cancer cells.

Objective:To describe the prevalence of perinatal death in Tongzhou District of Beijing,and to estimate the association between maternal periconceptional supplementation of folic acid or multiple micronutrients containing folic acid and perinatal mortality rate.Methods:A retrospective cohort study was conducted based on the maternal and child care system in Tongzhou District of Beijing.The subjects were 94 490 perinatal who were born during January 2013 to December 2018.The information on perina-tal outcomes and maternal periconceptional supplementation of folic acid or multiple micronutrients contai-ning folic acid were collected.The Poisson log-linear model was used to estimate the association between maternal periconceptional folic acid or multiple micronutrients supplementation and perinatal mortality rate.Results:The overall perinatal mortality rate was 2.71‰.The perinatal mortality rates for maternal nutrients supplementation containing folic acid and no supplementation during periconceptional period were 2.63‰ and 3.43‰,respectively,and the difference in rates was not statistically significant[crude risk ratio(cRR)=0.77,95％CI:0.54-1.14].After adjusting for potential confounding factors in-cluding ethnicity,age,education level,occupation,household registration,parity,numbers of fetuses,gestational age,pregnant with assisted reproductive technology,delivery year and pre-pregnancy body mass index,the rates remained not statistically significant[adjusted risk ratio(aRR)=0.93,95％CI:0.77-1.13].The perinatal mortality rates were 2.23‰ and 2.99‰ for pure folic acid and multi-nutrients supplements containing folic acid,respectively,and the difference in rates was statistically sig-nificant(cRR=1.34,95％CI:1.02-1.76).The rates difference remained statistically significant after adjusting for potential confounders(aRR=1.31,95％CI:1.06-1.62).Additionally,the peri-natal mortality rates differences among the non-supplementation group and the supplementation group with variate timing of initiation(pre-conception or post-conception)or frequency of supplementation(low-frequency or high-frequency)were not statistically significant,regardless of adjusting for confounders.Conclusion:The overall perinatal mortality rate was lower than the national average level in Tongzhou District of Beijing.Maternal periconceptional supplementation of pure folic acid or micronutrients contai-ning folic acid had no impact on perinatal mortality.The association between maternal periconceptional supplementation of multiple micronutrients containing folic acid and perinatal mortality rate need further research.

Objective To investigate the auditory effects of cochlear implantation in quiet and noisy environ-ments in children with different bilateral intervention modes,as well as the factors influencing these effects.Methods A total of 185 children with bilateral severe to profound sensorineural hearing loss were divided into three groups:bimodal hearing mode group(BIM,n=55),simultaneous bilateral cochlear implantation group(SCI,n=70),and sequential bilateral cochlear implantation group(SBCI,n=60).The Parents' Evaluation of Aural/Oral Performance of Children(PEACH)was used to assess the PEACH scores of the three groups in quiet and noisy environments one year after binaural hearing aid intervention.Additionally,the effects of cochlear implantation age,preoperative residual hearing,hearing aid usage,rehabilitation training mode,family system,and other factors on auditory per-formance in quiet and noisy environments were analyzed.Results The PEACH scores in quiet environments were higher than those in noisy environments for all three groups(all P＜0.05).The SCI group had higher PEACH scores in both quiet and noisy environments compared to the BIM group(P＜0.05).Multifactorial analysis revealed differences in factors influencing auditory performance in quiet and noisy environments among the three groups.First cochlear implantation before 3 years of age,preoperative hearing aid usage,and home-based rehabilitation training mode were common favourable influencing factors for auditory performance in both environments.Preopera-tive residual hearing below 95 dB HL was an favourable influencing factor for auditory performance in quiet environ-ments in the BIM group.The higher the level of parental education,the better auditory performance in both quiet and noisy environments for the SCI and SBCI groups.Implantation interval of 24 months or less and hearing aid usage during the inter-implantation period were favourable influencing factors for auditory performance in both envi-ronments for the SBCI group.Conclusion Children with severe to profound prelingual deafness after simultaneous bilateral CI implantation had better hearing performance than bimodal listening in quiet and noise environments.Ear-ly implantation,preoperative or inter-implantation hearing aid usage are recommended to improve auditory perform-ance in noisy environments,regardless of the bilateral intervention mode.The interval between bilateral cochlear im-plantations should be less than 12 months.

Objective Based on the Ancient and Modern Medical Record Cloud Platform,the medication rules of Chinese herbal medicine for the treatment of polycystic ovary syndrome(PCOS)of liver stagnation type were explored.Methods From database inception till December 2023,the medical records of TCM in treating PCOS of liver stagnation type were retrieved from the databases of China National Knowledge Infrastructure(CNKI),China Science and Technology Journal Database(VIP),Wanfang Data Knowledge Service Platform(Wangfang).After that,the data of prescription and TCM syndrome type were extracted,and then a database was constructed.The Ancient and Modern Medical Record Cloud Platform(V2.3.7)was used to conduct statistical analysis of relevant types of liver stagnation,occurrence frequency of Chinese herbal medicines,and the properties and efficacy of Chinese herbal medicines,as well as correlation analysis and clustering analysis for Chinese herbal medicines.The core prescriptions were mined by complex network analysis.Results A total of 108 prescriptions were included in this study,involving 174 Chinese herbal medicines.The syndrome of kidney deficiency and liver stagnation was most frequently seen,and Angelicae Sinensis Radix and Bupleuri Radix were the Chinese herbal medicines used most frequently.The Chinese herbal medicines usually have the meridian tropism of liver,spleen and kidney meridians,and most of them were mild and sweet in the proterties.The Chinese herbal medicines usually have the actions of soothing liver and alleviating depression.A total of 17 herbal groups such as"Angelicae Sinensis Radix-Paeoniae Radix Alba"and"Bupleuri Radix-Paeoniae Radix Alba"were obtained after association analysis,and the cluster analysis yielded four clustering combinations of Chinese herbal medicine.The core prescription was composed of Bupleuri Radix,Paeoniae Radix Alba,Angelicae Sinensis Radix,Poria,Glycyrrhizae Radix et Rhizoma,Cuscutae Semen,Rehmanniae Radix Praeparata,Cyperi Rhizoma,and Atractylodis Macrocephalae Rhizoma.Conclusion Chinese medicine treatment for PCOS of liver stagnation type focuses on soothing liver and invigorating spleen,nourishing liver and kidney,thus to harmonize qi and blood,and thoroughfare vessel and conception vessel.

Objective To investigate the effects of modified Simiao San combined with Metronidazole Tablets on immune factors,inflammatory factors,and oxidative stress in patients with bacterial vaginosis(BV).Methods Eighty BV patients treated at Dongguan Hospital of Guangzhou University of Chinese Medicine(Dongguan Traditional Chinese Medicine Hospital)from March 2023 to April 2024 were equally randomly divided into a control group(40 cases,treated with Metronidazole Tablets)and a study group(40 cases,treated with modified Simiao San plus Metronidazole Tablets).The treatment for the two groups lasted for 7 days.Serum immunologic factors[immunoglobulin(Ig)A,IgG,and IgM],inflammatory factors[C-reactive protein(CRP),tumor necrosis factor α(TNF-α),and interleukin-6(IL-6)],and oxidative stress markers[superoxide dismutase(SOD),malondialdehyde(MDA),and glutathione peroxidase(GSH-Px)]in the two groups were measured before and after treatment.After treatment,symptom resolution time,clinical efficacy,and the incidence of total adverse reactions were compared between the two groups.Results(1)After 7 days,the total effective rate was 95.00%(38/40)in the study group versus 77.50%(31/40)in the control group(tested by chi-square test,P＜0.05).(2)The study group showed significantly shorter time to the resolution of profuse or scanty leukorrhea,odor of leukorrhea,vulvar itching,vaginal pain,and vaginal mucosal hyperemia(all P＜0.01)than the control group.(3)After treatment,both groups exhibited increased IgA,IgG,and IgM(P＜0.05)compared to those before treatment,with greater improvements in the study group(P＜0.01).(4)After treatment,serum levels of inflammatory factors of CRP,TNF-α,and IL-6 in both groups decreased(P＜0.05),with superior reductions in the study group(P＜0.01).(5)After treatment,serum levels of oxidative stress markers of SOD and GSH-Px levels rose(P＜0.05),while MDA declined(P＜0.05)in both groups,and the study group demonstrated more pronounced improvements(P＜0.01).(6)Adverse reaction rates were 5.00%(2/40)and 15.00%(6/40)in the study group and control group,respectively,the differentce being no statistical significance between the two groups(P＞0.05).Conclusion Modified Simiao San combined with Metronidazole Tablets significantly alleviates BV symptoms,improves immune function,and inhibits inflammatory response and oxidative stress,demonstrating satisfactory efficacy and high safety.