There are different views on the theory of “spleen governs time”， which is still a hot spot in the study of Zangxiang （藏象） theory. Based on Zangxiang time-space view， it is found that the thinking mode of the spleen governing time theory follows space-time logic. It is believed that the different time views of the spleen governing time are all formed based on the space view that the spleen belongs to earth and resides in the center， and the zang time theory is developed with the unified time and space logic. Guided by Zangxiang time-space view， the origin of the spleen belonging to earth and residing in the center is traced， and the theoretical connotation and its clinical application of spleen governing time under different time-space logic are explored with reference to the four season and five zang theory， five season and five zang theory， six season and six zang theory， and eight season and eight zang theory.

Objective To investigate the effects of kuwanon G(KG)on proliferation,apoptosis,migration and invasion of gastric cancer cells and the molecular mechanisms.Methods The effects of KG on proliferation and growth of gastric cancer cells were assessed with CCK-8 assay and cell clone formation assay,by observing tumor formation on the back of nude mice and using immunohistochemical analysis of Ki-67.The effect of KG on cell apoptosis was analyzed using Annexin V-FITC/PI apoptosis detection kit,Western blotting and TUNEL staining.The effects of KG on cell migration and invasion were detected using Transwell migration and invasion assay and Western blotting for matrix metalloproteinase(MMP).The role of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway in KG-mediated regulation of gastric cancer cell proliferation,migration,and invasion was verified by Western blotting and rescue assay.Results KG significantly inhibited proliferation and reduced clone formation ability of gastric cancer cells in a concentration-dependent manner(P<0.05).KG treatment also increased apoptosis,enhanced the expressions of cleaved caspase-3 and Bax,down-regulated Bcl-2,lowered migration and invasion capacities and inhibited the expression of MMP2 and MMP9 in gastric cancer cells(P<0.05).Mechanistic validation showed that KG inhibited the activation of the PI3K/AKT/mTOR pathway,and IGF-1,an activator of the PI3K/AKT/mTOR pathway,reversed the effects of KG on proliferation,migration and invasion of gastric cancer cells(P<0.05).Conclusion KG inhibits proliferation,migration and invasion and promotes apoptosis of gastric cancer cells at least in part by inhibiting the activation of the PI3K/AKT/mTOR pathway.

Objective To investigate the effects of kuwanon G(KG)on proliferation,apoptosis,migration and invasion of gastric cancer cells and the molecular mechanisms.Methods The effects of KG on proliferation and growth of gastric cancer cells were assessed with CCK-8 assay and cell clone formation assay,by observing tumor formation on the back of nude mice and using immunohistochemical analysis of Ki-67.The effect of KG on cell apoptosis was analyzed using Annexin V-FITC/PI apoptosis detection kit,Western blotting and TUNEL staining.The effects of KG on cell migration and invasion were detected using Transwell migration and invasion assay and Western blotting for matrix metalloproteinase(MMP).The role of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway in KG-mediated regulation of gastric cancer cell proliferation,migration,and invasion was verified by Western blotting and rescue assay.Results KG significantly inhibited proliferation and reduced clone formation ability of gastric cancer cells in a concentration-dependent manner(P<0.05).KG treatment also increased apoptosis,enhanced the expressions of cleaved caspase-3 and Bax,down-regulated Bcl-2,lowered migration and invasion capacities and inhibited the expression of MMP2 and MMP9 in gastric cancer cells(P<0.05).Mechanistic validation showed that KG inhibited the activation of the PI3K/AKT/mTOR pathway,and IGF-1,an activator of the PI3K/AKT/mTOR pathway,reversed the effects of KG on proliferation,migration and invasion of gastric cancer cells(P<0.05).Conclusion KG inhibits proliferation,migration and invasion and promotes apoptosis of gastric cancer cells at least in part by inhibiting the activation of the PI3K/AKT/mTOR pathway.

Objective:To explore the characteristics and typology of self-care behavior among patients with chronic heart failure (CHF), and analyze their influencing factors.Methods:A cross-sectional study was used. A total of 318 patients with CHF who were hospitalized in the Heart Center of Zhongshan Hospital, Fudan University from November 2022 to July 2023 were selected by continuous enrollment method. The General Information Questionnaire, Heart Failure Self-care Index Scale, Brief Illness Perception Questionnaire, Self-efficacy for Managing Chronic Disease 6-item Scale, Perceived Social Support Scale, Atlanta Heart Failure Knowledge Test-V2 and Self-Care Confidence Scale were used to investigate. Latent profile analysis was utilized to delineate the characteristics and subtypes of self-care behaviors in CHF patients and examine the influencing factors.Results:A total of 291 patients were included in this study, including 190 males and 101 females, aged 67 (61, 74) years old. The analysis identified three latent categories of self-care behaviors among CHF patients: 26 cases in high self-care group, 131 cases in moderate self-care with deficiencies in maintenance and symptom perception group, and 134 cases in low self-care group.Ordered multicategorical Logistic regression analysis revealed that age ( OR=1.023, 95% CI 1.001-1.046, P<0.05), self-care confidence ( OR=0.859, 95% CI 0.817-0.904, P<0.01), and social support ( OR=0.966, 95% CI 0.940-0.993, P<0.05) were the factors influencing the potential categories of self-care behavior in CHF patients. Conclusions:The study identifies distinct categorical characteristics of self-care behaviors in patients with CHF. Healthcare professionals can leverage these findings to identify the self-care behavior characteristics and influencing factors for each patient category at an early stage, thereby providing personalized and precise support strategies to help patients enhance self-care behaviors.

The survival rate of cancer patients was improved due to the development of cancer treatment techniques, and thus the fertility protection for young female cancer patients has attracted increasing attention. Radiotherapy, as one of the comprehensive cancer treatment, could cause ovarian damage in adolescent and child-bearing women, which leads to fertility decline and a series of side effects. Radiation can cause ovarian damage not only by acting on biological macromolecules directly, but also by increasing oxidative stress between oocytes and ovarian granulosa cells indirectly. At present, the fertility preservation of female cancer patients undergoing radiotherapy mainly includes physical protection, drug protection and biological protection. Recently, the development of new technologies for the preservation of fertility in female cancer patients has also brought new hope, including factors such as protective effects, patient age, and the selection of specific cancer treatment measures, which are the main considerations in the selection process of fertility preservation measures. This article reviews the research progress on radiation-induced ovarian damage, with a focus on the introduction of the fertility preservation measures and new technologies for young female tumor patients receiving radiotherapy.

Objective:To investigate efficacy and advantages of combined local flaps in repairing large defects in patients with nasal and perinasal non-melanoma skin cancers after Mohs micrographic surgery.Methods:From March 2018 to November 2020, 11 patients with nasal and perinasal non-melanoma skin cancers, who underwent Mohs micrographic surgery followed by repair with combined local flaps, were collected from Department of Dermatology, the Second Hospital of Hebei Medical University. According to the location and size of postoperative defects, flaps were designed based on the nasal aesthetic subunit principle. For large defects that could not be directly sutured or covered by a single local flap, 2 or 3 kinds of flaps were applied in combination, such as kite flap, modified diamond flap, nasolabial skin flap, bilobed skin flap, etc.Results:Among the 11 patients, 10 were diagnosed with basal cell carcinoma and 1 with squamous cell carcinoma, and the area of defects ranged from 2.0 cm × 2.3 cm to 2.7 cm × 3.6 cm. After Mohs micrographic surgery combined with local skin flap repair, all skin flaps survived well without blood supply obstruction, the texture, color and contour of the skin flaps were similar to those of the surrounding normal skin, and no obvious scars were formed. During the postoperative follow-up of 4 to 32 months, no recurrence of the tumors occurred, and the patients was satisfied with the appearance.Conclusion:To repair large defects using combined skin flaps of 2 or 3 kinds after Mohs micrographic surgery in patients with nasal and perinasal non-melanoma skin cancers can maintain the normal nasal or perinasal morphological structure and aesthetic appearance, and yield a satisfactory cosmetic effect.

Black carbon (BC) is the most strongly light-absorbing component of particulate matter and is largely emitted from the incomplete combustion of fossil and biomass fuels. It has a graphite structure with less carbonized, irregular, microcrystalline, and heterogeneous components, which is determined by pyrolysis conditions. BC can be absorbed by human body via inhalation or ingestion route and then be transported to various organs through the blood circulation system in human body. When crossing different biological barriers (such as blood-brain barrier, placenta barrier, and blood-testis barrier), BC may further act on these targets and induce various toxicities. This review first distinguished between BC and carbon black, and then introduced analytical methods of BC in various environmental samples: microscopic observation, chemothermal oxidation methods, other chemical oxidation methods, and molecular marker analysis. We summarized the principles, technical characteristics, and application to environmental samples of these methods, and discussed the ideas and perspectives of determination of BC in biological samples for human biomonitoring.

OBJECTIVE: To investigate the serum microRNA (miRNA) expression and examine the impact of miRNA expression profiles on T helper type 17 (Th17)/regulatory T cells (Treg) imbalance among patients with cystic echinococcosis, so as to provide insights into the illustration of the mechanisms underlying chronic Echinococcus granulosus infections, and long-term pathogenesis. METHODS: Total RNA was extracted from the sera of cystic echinococcosis patients and healthy controls, and subjected to high-throughput sequencing with the Illumina sequencing platform. Known miRNAs were annotated and new miRNAs were predicted using the miRBase database and the miRDeep2 tool, and differentially expressed miRNAs were identified. The target genes of differentially expressed miRNAs were predicted using the software miRanda and TargetScan, and the intersection was selected for Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Among the differentially expressed miRNAs with the 20 highest fold changes, miRNAs that targeted genes relating to key transcription factors RORC and FOXP3 that determine the production of Th17 and Treg cells or their important regulatory pathways (PI3K-Akt and mTOR pathways) were matched. RESULTS: A total of 53 differentially expressed miRNAs were screened in sera of cystic echinococcosis patients and healthy controls, including 47 up-regulated miRNAs and 6 down-regulated miRNAs. GO enrichment analysis showed that these differentially expressed miRNA were involved DNA transcription and translation, cell components, cell morphology, neurodevelopment and metabolic decomposition, and KEGG pathway analysis showed that the differentially expressed miRNA were mainly involved in MAPK, PI3K-Akt and mTOR signaling pathways. Among the differentially expressed miRNAs with the 20 highest fold changes, there were 3 miRNAs that had a potential for target regulation of RORC, and 15 miRNAs that had a potential to target the PI3K-Akt and mTOR signaling pathways. CONCLUSIONS Significant changes are found in serum miRNA expression profiles among patients with E. granulosus infections, and differentially expressed miRNAs may lead to Th17/Treg imbalance through targeting the key transcription factors of Th17/Treg or PI3K-Akt and mTOR pathways, which facilitates the long-term parasitism of E. granulosus in hosts and causes a chronic disease.
Echinococcosis/genetics* ; Gene Expression Profiling ; Humans ; MicroRNAs/metabolism* ; Phosphatidylinositol 3-Kinases/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; T-Lymphocytes, Regulatory ; TOR Serine-Threonine Kinases/genetics* ; Th17 Cells ; Transcription Factors/genetics*

Background:Based on the effect of seasonal changes on human visceral function,this study investigated the impact of seasonal photoperiod of the pineal body on hypothalamic-pituitary-adrenal axis-hippo-campal-receptor in rats,aiming to reveal the mechanism by which pineal gland melatonin regulates the seasonal secretion of hippocampal neurotransmitters.Methods:Vernal equinox,summer solstice,autumn equinox,and winter solstice were selected as four experimental time points,and rats were randomly divided into normal control group,sham operation group,and pinealectomized group.The seasonal changes in corticotropin-releasing hormone(CRH),adrenocorticotropic hormone(ACTH),corticosterone,hypothalamic melatonin receptor(MTR),and hippocampal corticosterone receptor(CORTR)were examined by enzyme-linked immunosorbent assay.Results:Comparing the same group between different seasons,we showed that in the normal control group,CRH,ACTH,corticosterone,and MTR were higher,while CORTR was lower in autumn and winter than in spring(all P＜.05).Compared with the normal control group,the pinealectomized group showed higher levels of corticosterone(P=.01),MTR(P=.01),and CORTR(P=.03)during spring;reduced levels of MTR and CORTR(both P＜.001)during summer;higher levels of ACTH(P=.001)and MTR(P＜.001),and lower levels of CRH(P=.001),corticosterone(P＜.001),and CORTR(P=.003)during autumn;and lower levels of CRH(P＜.001)and MTR(P=.004),and higher level of ACTH(P＜.001)in winter.Conclusions:Seasonal photoperiod acts on the pineal gland to secrete different levels of melatonin,resulting in seasonal changes in the hypothalamic-pituitary-adrenal axis-hippocampal-receptor,which may be the pathophysiological basis for the onset of seasonal affective disorder.

Objective:To explore the heterogeneity of behavioral problems and cognitive function of three subtypes of attention deficit hyperactivity disorder(ADHD), and to analyze the related factors of cognitive function.Methods:The outpatients with ADHD were evaluated by Wechsler children′s intelligence test (C-WISC), SNAP-Ⅳ parental rating scale (SNAP-Ⅳ), Conners parental symptom questionnaire (PSQ) and 12 online cognitive function tests. The differences of behavioral problems and cognitive function of children with different subtypes of ADHD, and the correlation between their intelligence level, PSQ, SNAP-Ⅳ and cognitive function were compared by SPSS 22.0 software.Results:The results of PSQ questionnaire showed that ADHD-C ((1.11±0.59), (1.59±0.58), (1.62±0.50)) had higher behavior problems, impulse-hyperactivity and hyperactivity index than ADHD-I ((0.64±0.27), (1.01±0.54), (1.09±0.32)) and ADHD-HI ((0.75±0.35), (1.22±0.58), (1.05±0.38)) ( F=9.374, F=7.644, F=15.176, P<0.05), while ADHD-C (2.01±0.55) had higher learning problems than ADHD-I (1.66±0.58) and ADHD-HI (1.16±0.43) ( F=11.709, P<0.05). In terms of cognitive function, there were differences in language understanding ability, digital reasoning ability, sequence relationship and short-term memory ability ( χ2=6.734, 7.192, 7.822, 8.646, all P<0.05) among the three groups of ADHD children. ADHD-HI (4.00(4.00, 5.00), 5.00(4.25, 6.00), 5.00(4.00, 7.00)) had better language understanding ability, digital reasoning ability and sequence relationship than ADHD-I (3.00(2.00, 5.00), 3.00(2.50, 6.00), 4.00(3.00, 5.50)). The short-term memory ability of ADHD-HI (5.00(4.00, 6.00)) and ADHD-C (5.00(4.00, 6.00)) were better than that of ADHD-I (4.00(3.00, 5.00)). The intellectual structure of ADHD children was positively correlated with spatial cognitive ability, sequential relationship, Raven reasoning test, short term memory span and Wisconsin card sorting test ( r=0.25-0.57, all P<0.05). Children′s learning problems and psychosomatic problems were negatively correlated with their digital comprehension ability ( r=-0.26, -0.25, both P<0.05). Conclusion:The behavioral problems and cognitive function of children with different subtypes of ADHD are different and have a certain correlation.