ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， network pharmacology and molecular docking techniques， to explore the pharmacodynamic material basis and mechanism of Renshen Wuweizi Tang in treating spleen-lung Qi deficiency syndrome. MethodsThe chemical components in the decoction of Renshen Wuweizi Tang were systematically characterized and identified by UPLC-Q-TOF-MS/MS， and network pharmacology was used to screen potential active ingredients， collect component targets and gene sets related to spleen-lung Qi deficiency syndrome， and obtain protein interaction relationships through STRING. Cytoscape 3.9.1 was used to construct a "formula-syndrome" association network and calculate topological feature values. Gene ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis were performed on core genes to explore potential pharmacodynamic links， the average shortest path between the formula-drug target network and the pharmacodynamic link gene network was calculated to discover dominant pharmacodynamic links， and MCODE plugin was used to identify core gene clusters from the dominant pharmacodynamic links， which were validated using Gene Expression Omnibus（GEO）， and molecular docking was performed between key components and core targets. ResultsOne hundred and thirty-seven components were identified in the negative ion mode， and eighty components were identified in the positive ion mode. After deduplication， a total of 185 components were identified， mainly composed of triterpenoid saponins（49） and flavonoids（54）. Based on the "formula-syndrome" correlation network analysis， energy metabolism was determined to be the dominant pharmacodynamic link of Renshen Wuweizi Tang in the treatment of spleen-lung Qi deficiency syndrome. The results of molecular docking showed that 7 components（adenosine， atractylenolide Ⅱ， atractylenolide Ⅲ， ginsenoside Rg₁， glycyrrhizin B₂， glycyrrhizin E₂ and campesterol） from 4 medicinal materials（Ginseng Radix et Rhizoma， Atractylodis Macrocephalae Rhizoma， Glycyrrhizae Radix et Rhizoma and Poria） in this formula might regulate energy metabolism by acting on 6 targets， namely cyclic adenosine monophosphate-response element binding protein 1（CREB1）， glyceraldehyde-3-phosphate dehydrogenase（GAPDH）， interleukin（IL）-6， nuclear transcription factor（NF）-κB1， peroxisome proliferator-activated receptor α（PPARα）， and tumor necrosis factor（TNF）， thus improving the symptoms of diseases related to spleen-lung Qi deficiency syndrome. ConclusionThis study established a UPLC-Q-TOF-MS/MS for rapid characterization and identification of chemical components in the decoction of Renshen Wuweizi Tang， expanding the understanding of the material composition of this formula， and found that 7 components might act on the key advantageous pharmacodynamic link "energy metabolism" through 6 targets to improve the related symptoms of spleen-lung Qi deficiency syndrome. This can provide a reference for the subsequent exploration of the material benchmark and mechanism of the famous classical formula.

This article reported a case of neurodevelopmental disorder accompanied by spastic diplegia and visual impairment with the manifestation of small fetal head circumference. Prenatal ultrasonography performed at 33 +5 weeks of pregnancy revealed small fetal head circumference (-2.61SD) and oligohydramnios. Whole-exome sequencing identified a heterozygous frameshift variation of c.1623_1624insA (p.R542Tfs*30) in the CTNNB1 gene (NM_001904.4) of the fetus. No phenotypic abnormalities or corresponding gene variations were detected in the parents, suggesting it was a de novo variation. Based on the clinical manifestations, the fetus was diagnosed with a neurodevelopmental disorder accompanied by spastic diplegia and visual defects. Following genetic counseling, the pregnant woman chose to terminate the pregnancy.

Osteoporosis (OP) is a systemic disease characterized by decreased bone mass, increased bone fragility due to damage to the microstructure of bone tissue, and susceptibility to fractures.At present, it mainly relies on pharmacologic treatment.Because the occurrence of OP and some eye diseases are associated with a series of age-related pathological mechanisms, and OP therapeutic drugs also have anti-non-infectious inflammation, antioxidant, anti-apoptosis, and sex hormone-regulating effects, there is a certain correlation with the pathogenesis of some ophthalmic diseases, and thus affect the onset and progression of eye diseases.The application of OP therapeutic drugs such as vitamin D and its derivatives, estrogen, bisphosphonates, and desuximab may increase the risk of age-related macular degeneration, dry eye, and ocular inflammation, and may also play a preventive role in some eye diseases such as dry eye, cataract, glaucoma, and choroidal neovascularization.Therefore, when OP therapeutic drugs are used clinically, the changes of related eye diseases should be regularly monitored.This article reviews the research on the effects of OP therapeutic drugs on eye diseases.

ObjectiveTo improve the quality standard of Yuanhu Zhitong oral liquid in order to strengthen the quality control of this oral liquid. MethodThin layer chromatography（TLC） was used for the qualitative identification of Corydalis Rhizoma and Angelicae Dahuricae Radix in Yuanhu Zhitong oral liquid by taking tetrahydropalmatine， corydaline reference substances and Corydalis Rhizoma reference medicinal materials as reference， and cyclohexane-trichloromethane-methanol（5∶3∶0.5） as developing solvent， Corydalis Rhizoma was identified using GF254 glass thin layer plate under ultraviolet light（365 nm）. And taking petroleum ether（60-90 ℃） -ether-formic acid（10∶10∶1） as developing solvent， Angelicae Dahuricae Radix was identified using a silica gel G TLC plate under ultraviolet light（305 nm）. High performance liquid chromatography（HPLC） was performed on a Waters XSelect HSS T3 column（4.6 mm×250 mm， 5 μm） with acetonitrile（A）-0.1% glacial acetic acid solution（adjusted pH to 6.1 by triethylamine）（B） as the mobile phase for gradient elution（0-10 min， 20%-30%A； 10-25 min， 30%-40%A； 25-40 min， 40%-50%A； 40-60 min， 50%-60%A）， the detection wavelength was set at 280 nm， then the fingerprint of Yuanhu Zhitong oral liquid was established， and the contents of tetrahydropalmatine and corydaline were determined. ResultIn the thin layer chromatograms， the corresponding spots of Yuanhu Zhitong oral liquid， the reference substances and reference medicinal materials were clear， with good separation and strong specificity. A total of 12 common peaks were identified in 10 batches of Yuanhu Zhitong oral liquid samples， and the peaks of berberine hydrochloride， dehydrocorydaline， glaucine， tetrahydropalmatine and corydaline. The similarities between the 10 batches of samples and the control fingerprint were all >0.90. The results of determination showed that the concentrations of corydaline and tetrahydropalmatine had good linearity with paek area in the range of 0.038 6-0.193 0， 0.034 0-0.170 0 g·L^-1， respectively. The methodological investigation was qualified， and the contents of corydaline and tetrahydropalmatine in 10 batches of Yuanhu Zhitong oral liquid samples were 0.077 5-0.142 9、0.126 1-0.178 2 g·L^-1， respectively. ConclusionThe established TLC， fingerprint and determination are simple， specific and reproducible， which can be used to improve the quality control standard of Yuanhu Zhitong oral liquid.

ObjectiveThe mechanisms underlying therapeutic efficacies of Detumescence Analgesic Plaster was analyzed based on "effect-target" associations. MethodBased on CNKI and PubMed databases， the chemical components of Artemisia seed， bastard speedwell， and menthol in Detumescence Analgesic Plaster were collected. The capacity of transdermal absorption was predicted based on the Encyclopedia of Traditional Chinese Medicine （ETCM 2.0）. Golden Triangle of compounds with Accepted used for candidate target prediction based on the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP v2.0）according to the similarity of chemical structures. At the same time， the SoFDA data platform was employed to collect the symptoms related to the efficacy of Detumescence Analgesic Plaster and its related genes information. In addition， based on the interaction between the above-mentioned candidate targets and their efficacy-related genes， the "effect-target" interaction network of Detumescence Analgesic Plaster was constructed. The key targets by topological features calculation， and functional mining was carried out to explain the efficacy mechanism of Detumescence Analgesic Plaster. ResultA total of 165 candidate targets were obtained based on ETCM 2.0 and TCMIP v2.0 databases， and symptoms related to the efficacy of clearing heat， detumescence， and relieving pain， as well as 1 744 related genes were collected based on the SoFDA database. Network construction and analysis showed that the core effect targets of Detumescence Analgesic Plaster were mainly involved in regulating the "immune-inflammation" balance of the body and maintaining the homeostasis of material and energy metabolism， blood circulation， and nervous system functions， and they were closely related to the efficacy of this prescription in clearing heat， reducing detumescence， and relieving pain. Among them， the heat clearing group of Detumescence Analgesic Plaster had the functions of heat clearing， detoxifying， antibacteria， and anti-inflammation. The biological function of its key effect target group was related to correcting the imbalance of "immune-inflammation" induced by pathogens. The detumescence group of Detumescence Analgesic Plaster had the functions of reducing water and swelling and resolving hard lumps， and the biological function of its core effect target group was related to improving microcirculation disturbance. The pain relieving group of Detumescence Analgesic Plaster had the functions of removing stasis， promoting blood circulation， and relieving pain， and its core effect target group was related to correcting the nervous system and the disorder of material and energy metabolism. ConclusionThe heat clearing， swelling reducing， and pain relieving effects of Detumescence Analgesic Plaster may be closely related to its act on related candidate targets， so as to correct the imbalance of "nerve-immunity-vascular-axis"， regulate neuronal excitability and inflammatory response， and intervene in material and energy metabolism. The relevant research results lay a theoretical foundation for clarifying the advantages of Detumescence Analgesic Plaster and assisting its clinical precise positioning.

ObjectiveA rapid method for identification of chemical constituents in Baoyuantang reference sample was established in order to clarify the material basis of this formula. MethodBased on ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） and self-established database information， the chemical components in Baoyuantang were systematically characterized and identified. The chromatography was performed on a Waters ACQUITY UPLC HSS T3 column（2.1 mm×100 mm， 1.8 μm） with mobile phase of 0.1% formic acid aqueous solution（A）-0.1% formic acid acetonitrile solution（B） for gradient elution（0-3 min， 2%-19%B； 3-8 min， 19%B； 8-8.1 min， 19%-22%B； 8.1-14 min， 22%-29%B； 14-16 min， 29%B； 16-32 min， 29%-45%B； 32-32.1 min， 45%-90%B； 32.1-35 min， 90%-95%B； 35-36 min， 95%-98%B； 36-37 min， 98%-2%B； 37-40 min， 2%B）. Based on electrospray ionization（ESI）， continuum data format was collected in both positive and negative ion modes with a scanning range of m/z 50-1 500. Chemical constituents in the decoction of Baoyuantang were systematically analyzed by UNIFI 1.9.4 software matching， control comparison， The Encyclopedia of Traditional Chinese Medicine（ETCM） database search and literature reports. ResultA total of 229 components were identified under negative ion mode and 181 under positive ion mode， with a total of 322 components after removing duplicates， including 116 triterpene saponins， 66 flavonoids， 19 organic acids， 6 gingerphenols， 6 gingerols， 5 gingerones， 10 amino acids， 7 saccharides， 5 coumarins and 82 other components. Among them， 83， 141， 39， 35 and 38 components were attributed to Ginseng Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， Astragali Radix， Cinnamomi Cortex and Zingiberis Rhizoma Recens， respectively. ConclusionIn this study， the rapid characterization and identification of multi-class components in Baoyuantang was realized， and it was confirmed that the material basis of this formula was mainly triterpenoid saponins， flavonoids， gingerols and organic acids， and the chemical composition was attributed and analyzed， which provided a reference for the subsequent quality control research.

Background Dibutyl phthalate (DBP) is one of the most commonly used plasticizers, and has been found to relate to allergic asthma. However, mechanisms behind the phenomenon linking DBP and allergic asthma are still not well comprehended. Objective To investigate the role of endoplasmic reticulum stress in DBP-exacerbated allergic asthma. Methods Thirty-two male mice were divided into four groups at random, eight mice in each group: control group, allergic asthma model group (ovalbumin, OVA), OVA+40 mg·kg⁻¹ DBP exposure group (OVA+DBP), and OVA+40 mg·kg⁻¹ DBP+50 mg·kg⁻¹ 4-phenyl butyric acid (4-PBA) group (OVA+DBP+4-PBA). The control group mice were treated with saline via intraperitoneal injection on day 21, 35, 42, and 49, and atomized saline for 30 min per day from day 54 to 60. The OVA group mice were injected with 0.3 mL OVA sensitizing solution via intraperitoneal injection on day 21, 35, 42, and 49, and atomized with 1% OVA solution from day 54 to 60. The OVA+DBP group was treated in the same way as the OVA group to build an allergic asthma model, and was orally exposed to 40 mg·kg⁻¹ DBP from day 1 to 53, plus atomized with 1% OVA solution from day 54 to 60. In order to verify the role of endoplasmic reticulum stress in DBP-exacerbated allergic asthma, 4-PBA was injected intraperitoneally every 2 d from day 1 to 53 in the OVA+DBP+4-PBA group mice. The pathological changes such as airway remodeling, inflammatory cell infiltration, and airway mucous hyperplasia in lung tissues were observed after hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) staining. The contents of total immunoglobulin E (T-IgE) and ovalbumin immunoglobulin E (OVA-IgE) levels in serum, and interleukin (IL)-4, IL-5, IL-13, and IL-17A in alveolar lavage fluid (BALF) were detected by Enzyme-Linked ImmunoSorbent Assay(ELISA). The expression levels of endoplasmic reticulum stress-related proteins including inositol-requiring enzyme 1α (IRE1α), protein kinase R-like endoplasmic reticulum kinase (PERK), and activating transcription factor 6 (ATF6) were detected by immunohistochemistry. Results Compared to the control mice, the OVA mice showed significant asthma-like symptoms, including inflammatory cell infiltration, increased inflammatory cytokines, airway remodeling, and mucous hyperplasia. Compared to the OVA group, long-term exposure to DBP aggravated airway pathological changes in the OVA+DBP mice, and increased the serum T-IgE and OVA-IgE levels (P<0.01), the Th2 (IL-4, IL-5, IL-13) and Th17 (IL-17A) cytokines in BALF (P<0.01), and the expression levels of endoplasmic reticulum stress-related proteins IRE1α, PERK and ATF-6 (P<0.01). In addition, after the 4-PBA treatment, it was found that compared with the OVA+DBP group, the expression levels of endoplasmic reticulum stress-related proteins (IRE1α, PERK and ATF-6) were down-regulated in the OVA+DBP+4-PBA group (P<0.01), the levels of cytokines (IL-4, IL-5, IL-13, and IL-17A) in BALF and T-IgE and OVA-IgE in serum were decreased (P<0.01), and airway remodeling and mucous hyperplasia were significantly alleviated. Conclusion Long-term exposure to DBP could aggravate allergic asthma by activating the endoplasmic reticulum stress pathway. This worsening effect is accompanied by the increase of immunoglobulin IgE levels and the release of Th2 and Th17 cytokines, which in turn leads to lung histopathological changes that affect lung function.

AIM:To compare the effects of 0.01% with 0.05% atropine eye drops on pupil diameter(PD)and intraocular pressure(IOP)in myopic children.METHODS: Prospective non-randomized controlled study. A total of 232 myopic children who treated at the Department of Ophthalmology, the Second People's Hospital of Puyang from March 2021 to February 2022 were included. They were divided into 0.01% atropine eye drops group(81 cases), 0.05% atropine eye drops group(77 cases), and control group(74 cases)according to patients' will, respectively. The control group received placebo eye drops(isotonic excipient). The PD and IOP of the three groups of patients were measured before medication and at 6 and 12 mo after medication.RESULTS: Finally, 181 cases(181 eyes)(with all right eye data included in the study)completed a 1-year follow-up, with a loss to follow-up rate of 22.0%(51/232). Among them, 62 cases(62 eyes)belonged to the 0.01% atropine eye drops group, 54 cases(54 eyes)belonged to the 0.05% atropine eye drops group, and 65 cases(65 eyes)belonged to the control group. There was no significant difference in baseline PD and IOP among the three groups(all P<0.05). After 12 mo of medication, the changes in PD among the 0.01% atropine eye drops group, 0.05% atropine eye drops group, and control group were 0.79±0.70, 1.29±0.66, and 0.06±0.74 mm, respectively(P<0.001). The change in PD in the 0.05% atropine eye drops group was significantly greater than that in both the 0.01% atropine eye drops group and the control group. Similarly, the change in PD in the 0.01% atropine eye drops group was significantly greater than that in the control group(all P<0.05). After 12 mo of medication, the changes in IOP among the 0.01% atropine eye drops group, 0.05% atropine eye drops group, and control group were -0.70±1.94, -0.22±1.79, and 0.25±2.03 mmHg, respectively(P<0.05). The changes in IOP in the 0.05% atropine eye drops group showed statistically significant difference compared to both the 0.01% atropine eye drops group and the control group(all P>0.05), and the changes in IOP in the 0.01% atropine eye drops group were statistically significant compared to the control group(P<0.05). Multivariate linear regression analysis revealed that baseline refractive error and baseline PD were significant factors influencing the change in PD among children treated with atropine eye drops(β=0.230, 95%CI: 0.005-0.455, SE=0.114, t=2.025, P=0.045; β=-0.562, 95%CI: -0.729--0.396, SE=0.084, t=6.697, P<0.001). Additionally, baseline IOP was significant factor influencing the change in IOP among children in the atropine eye drop groups(β=-0.285, 95%CI: -0.439--0.131, SE=0.078, t=3.662, P<0.001).CONCLUSION: The PD of myopic children increased after using 0.01% and 0.05% atropine eye drops, and the change in PD after using 0.05% atropine eye drops was significantly greater than that of 0.01% atropine eye drops. No risk was found in the use of 0.01% and 0.05% atropine eye drops and elevated IOP.

OBJECTIVE To establish the specific chromatogram of Qianghuo Shengshi Tang(QHSS) reference sample, clarify the key quality attributes of QHSS, providing reference for the quality evaluation of QHSS reference sample. METHODS The SilGreen C18 column(4.6 mm×250 mm, 5 μm) was used. The mobile phase consisted acetonitrile and 0.2% formic acid aqueous solution. The detection wavelength was 328 nm. Established an HPLC characteristic spectrum analysis method for the reference sample of QHSS. A variety of chromatographic columns and different instruments were applied to investigate the adaptability of the system. HPLC-LTQ-Orbitrap MS was used to identify the specific peaks of the QHSS reference samples in positive ion mode. RESULTS There were 14 peaks in the specific chromatogram, which belonged to Notopterygii Rhizoma Et Radix, Angelicae Pubescentis Radix, Ligustici Rhizoma Et Radix, Chuanxiong Rhizome, Viticis Fructus, respectively. Ferulic acid(peak 3) was reference peak. A total of 22 compounds were identified by mass spectrometry, including coumarin and flavonoids. CONCLUSION The established specific chromatogram method of QHSS is simple, stable and reproducible. The material basis of QHSS reference sample is basically determined, providing a reference for the development and quality control of QHSS.

Objective To explore the clinical features and prognostic factors of gastric cancer patients liver metastasis.Methods Data from 7055 patients with gastric cancer were retrieved from Surveillance,Epidemiology and End Results(SEER)database between 2010 and 2015.The patients were divided into the liver metastases group(901 cases)and the non-liver metastases group(6154 cases)according to whether liver metastasis occurred.Univariate and multivariate Cox regression were used to analyze the prognostic risk factors,and the Kaplan-Meier method was used for survival analysis.Results There was a significant difference in age,gender,race,T stage,N stage,primary surgery,radiotherapy and tumor size between the two groups(P<0.05),and the median survival time of patients in the liver metastases group was 6 months,non-liver metastases group was 25 months.Cox regression analysis showed that age(P=0.009),tumor grade(P<0.001),surgery(P<0.001)and chemotherapy(P<0.001)were the main factors affecting the prognosis of gastric cancer with liver metastases.Conclusion Age,tumor grade,surgery and chemotherapy were the prognostic risk factors for gastric cancer with liver metastases.A nomogram based on age,tumor grade,surgery and chemotherapy has a good survival prediction significance for gastric cancer with liver metastases.