ObjectiveTo investigate the effect of mucin 1 (MUC1) on the proliferation and apoptosis of nasopharyngeal carcinoma (NPC) and its regulatory mechanism. MethodsThe 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital. The expression of MUC1 was measured by real-time quantitative PCR (qPCR) in the patients with PNC. The 5-8F and HNE1 cells were transfected with siRNA control (si-control) or siRNA targeting MUC1 (si-MUC1). Cell proliferation was analyzed by cell counting kit-8 and colony formation assay, and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells. The qPCR and ELISA were executed to analyze the levels of TNF-α and IL-6. Western blot was performed to measure the expression of MUC1, NF-кB and apoptosis-related proteins (Bax and Bcl-2). ResultsThe expression of MUC1 was up-regulated in the NPC tissues, and NPC patients with the high MUC1 expression were inclined to EBV infection, growth and metastasis of NPC. Loss of MUC1 restrained malignant features, including the proliferation and apoptosis, downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells. ConclusionDownregulation of MUC1 restrained biological characteristics of malignancy, including cell proliferation and apoptosis, by inactivating NF-κB signaling pathway in NPC.

Photodynamic therapy (PDT) is a new modality for cancer therapy, which has been used in the clinical treatment for various tumors, such as skin cancer, bladder cancer and prostate cancer. Most photosensitizers have the disadvantages of hydrophobic, low bioavailability and the limited tumor targeting ability. The nanoscale delivery systems can improve the solubility of photosensitizers and enhance their accumulation at the tumor sites. The multifunctional nano-delivery systems are prepared in combination with other anti-tumor drugs to enhance the anti-tumor effect. In addition to addressing the issues of poor solubility and the insufficient tumor targeting ability, the nanoscale delivery systems need to improve the pharmacokinetic properties of photosensitizers, facilitating their rapid accumulation at the tumor sites and quick elimination in vivo, and reducing the skin phototoxicity. This review summarizes the recent clinical application of PDT of cancer, the development of photosensitizers, the delivery systems for photosensitizers and the combinatorial application with other therapeutic methods. The goal is to present an understanding of knowledge on the design of new types of photosensitizers and its clinical application in PDT of cancer.

BACKGROUND: Butylphthalide (NBP) and edaravone (EDV) injection are common acute ischemic stroke medications in China, but there is a lack of large real-world safety studies on them. This study aimed to determine the incidence of adverse events, detect relevant safety signals, and assess the risk factors associated with these medications in real-world populations. METHODS: In this study, data of acute ischemic stroke patients were extracted from the electronic medical record database of six tertiary hospitals between January 2019 and August 2021. Baseline confounders were eliminated using propensity score matching. The drugs' safety was estimated by comparing the results of 24 laboratory tests standards on liver function, kidney function, lipid level, and coagulation function. The drugs' relative risk was estimated by logistic regression. A third group with patients who did not receive NBP or EDV was constructed as a reference. Prescription sequence symmetry analysis was used to evaluate the associations between adverse events and NBP and EDV, respectively. RESULTS: 81,292 patients were included in this study. After propensity score matching, the NBP, EDV, and third groups with 727 patients in each group. Among the 15 test items, the incidence of adverse events was lower in the NBP group than in the EDV group, and the differences were statistically significant. The multivariate logistic regression equation revealed that NBP injection was not a promoting factor for abnormal laboratory test results, whereas EDV had statistically significant effects on aspartate transaminase, low-density lipoprotein cholesterol and total cholesterol. Prescription sequence symmetry analysis showed that NBP had a weak correlation with abnormal platelet count. EDV had a positive signal associated with abnormal results in gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, prothrombin time, and platelet count. CONCLUSIONS In a large real-world population, NBP has a lower incidence of adverse events and a better safety profile than EDV or other usual medications.

The mortality of female breast cancer in Shandong Province has increased since the 1970. The differential decomposition analysis found that the slight decline in the crude mortality of breast cancer among women was entirely due to non-demographic factors during the 1970-1990, and the significant increase in the crude mortality was due to a combination of demographic and non-demographic factors since the 1990. The contribution rate of demographic factor has gradually increased from 53.5% in 2004-2005 to 59.5% in 2011-2013, while that of non-demographic factor has decreased from 46.5% to 40.5%. The women aged 45-64 years old were the major population of female breast cancer deaths, accounting for 40%-60% of total breast cancer deaths in different times, and then the mortality in female aged 55-64 years old increased rapidly, with increases of 52.12%, 115.19% and 29.01% in 2011-2013 over the 1970-1974, 1990-1992 and 2004-2005, respectively (Z=-7.342,P<0.001). Compared with 1970-1974, the age-standardized mortality rate of rural women increased by 41.86% in 2011-2013 (Z=-17.933, P<0.001), and that of urban women increased by 18.62% in 2011-2013 (Z=-25.642, P<0.001). The age-standardized mortality rate of breast cancer in urban women was higher than that in rural women in different times (all P<0.05). The spatial scan analysis found that eastern Shandong Province was found to be a sustained high-risk area for death, and other high-risk areas were transferred from north to southwest of Shandong between 1970 and 2013.
Breast Neoplasms/epidemiology* ; Female ; Humans ; Middle Aged ; Rural Population ; Spatial Analysis

In this study, dexamethasone (DXMS) and captopril (CAP) were co-loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles with a surface coating of a phospholipid bilayer, and then the core-shell nanoparticles were modified with polyethylene glycol and integrin α8 antibody to obtain immunoliposome-nanoparticle hybrids (DXMS/CAP@PLGA-ILs). The role of nanoparticles on the renal targeting, anti-inflammatory effects, and macrophage differentiation were investigated. The results showed that the particle size of the nanoparticles was 115.9 ± 2.89 nm, and the core-shell structure could be observed under an electron microscope. The drug loading capacity of DXMS and CAP was 5.72% ± 0.37% and 7.51% ± 0.07%, respectively. The results of in vitro experiments showed that DXMS/CAP@PLGA-ILs could reduce the secretion of specific cytokines and the mRNA expression of markers in M2-type macrophages, thus promoting the differentiation of M2-type macrophages in the direction of unpolarized macrophages. In vivo experiments in mice showed that DXMS/CAP@PLGA-ILs had a significant renal targeting effect, which could restore the renal index, serum creatinine, and urea nitrogen levels of mesangial proliferative glomerulonephritis in mice. Moreover, DXMS/CAP@PLGA-ILs could reduce both the secretion of inflammatory cytokines and the mRNA expression levels of M1 and M2 macrophage markers in the kidney. All the animal experiments were in accordance with the regulations of Animal Ethics Committee of Sichuan Agricultural University. In conclusion, renal-targeting DXMS/CAP@PLGA-ILs could effectively regulate the polarization of macrophages and had an "anti-inflammatory/anti-fibrosis" therapeutic effect, providing a new strategy and basis for the targeted therapy of glomerulonephritis.

Humans ; ST Elevation Myocardial Infarction/diagnostic imaging* ; Percutaneous Coronary Intervention

Hypertension is the most important risk factor for cardiovascular and cerebrovascular diseases， affecting the structures and functions of important organs of the body， such as the heart， brain， and kidney. At present， the prevalence of hypertension in China remains high. How to effectively curb the incidence of hypertension and reduce target organ damage in patients with hypertension is an urgent challenge that needs to be addressed. Traditional Chinese medicine （TCM）， by virtue of its unique efficacies and advantages， is increasingly applied around the world. In TCM， "wind" is considered as a major constant factor in the development of hypertension. Some scholars believe that hypertension is located in collaterals， and the lesions of collaterals are also important reasons for the occurrence and development of hypertension. Collateral diseases and pathogenic wind are closely related to the development of hypertension as well as target organ damage in the heart， brain， and kidney. From the six-meridian syndrome differentiation for febrile diseases， "collateral" and "wind" are closely related to the Jueyin， with collateral diseases classified into Jueyin diseases and pathogenic wind beginning in the Jueyin. The occurrence， development， and persistence of hypertension are closely related to Jueyin diseases. The present study analyzed the pathogenesis and treatment of hypertension from "collateral" and "wind" of the Jueyin， and specifically discussed the relationship between hypertension and "collateral" and "wind" of the Jueyin. It is believed that the internal depression of wind and fire in the Jueyin results in the upward impulse of liver fire， and the deficiency of Jueyin can trigger the internal movement of liver wind and stirring wind due to collateral deficiency. External contraction in the Jueyin due to the induction of external wind is the important pathogenesis of the development of hypertension and the damage to target organs such as the heart， brain， and kidney. The therapeutic methods for both "collateral" and "wind" were also discussed based on the primary prescription for Jueyin， Wumei Pills. Six-meridian syndrome differentiation can guide the therapeutic principles for all diseases and inspire posterity. Exploring the pathogenesis and treatment of hypertension from “collateral" and "wind" of the Jueyin is of great significance in guiding the prevention and treatment of hypertension， reducing target organ damage in patients with hypertension， and improving the prognosis of cardiovascular and cerebrovascular diseases.

ObjectiveTo establish a traditional Chinese medicine （TCM） syndrome model with yin deficiency and internal heat， discuss the rationality of model evaluation， and analyze differentially expressed genes in multiple dimensions to explore the molecular mechanism-signaling pathways as well as key targets of Baihe Dihuangtang （BHDH） in treating depression with Yin deficiency and internal heat. MethodForty male SD rats were randomly divided into a blank control group，a model group，a fluoxetine group （positive drug），a BHDH group， and a Zhibai Dihuangtang group （positive drug for Yin deficiency and internal heat）. The depression model with Yin deficiency and internal heat was induced by chronic unpredictable mild stress （CUMS）combined with Chinese herbal drugs with warm and heat nature. The model established was comprehensively evaluated by the detection of the basic condition， behavioral performance， and biochemical indicators of rats in each group. The differentially expressed genes were screened out by mRNA sequencing and underwent Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analyses. The protein-protein interaction （PPI） network was plotted and key genes were analyzed to explore the underlying mechanism of BHDH in treating depression with Yin deficiency and internal heat. ResultThe comparison of basic conditions， behavioral assays， energy metabolism， endocrine hormones， cytokines， and neurotransmitters showed that the model was properly induced. BHDH could significantly improve depression with Yin deficiency and internal heat by regulating the pathways related to the nervous system， endocrine system， and inflammatory and immune system. The key genes of the PPI network were Fos， Epha8， Npy2r， Htr2c， and Nr4a1. ConclusionUnder the guidance of TCM theories of treatment based on syndrome differentiation and etiology and pathogenesis，this study established a depression model with yin deficiency and internal heat in animals and evaluation system in accordance with the symptoms and signs of emotional diseases， and further confirmed the scientificity of the modeling method and the underlying mechanism of BHDH in interfering with depression with Yin deficiency and internal heat based on the results of mRNA sequencing.

OBJECTIVE: To observe the effect of electroacupuncture (EA) at back-shu points of five zang on fatigue status, quality of life and motor cortical excitability in patients with chronic fatigue syndrome (CFS), so as to explore the possible mechanism of EA for CFS. METHODS: A total of 72 patients with CFS were randomized into an EA group (36 cases, 4 cases dropped off) and a sham EA group (36 cases, 3 cases dropped off). In the EA group, EA at Ganshu (BL 18), Xinshu (BL 15), Pishu (BL 20), Feishu (BL 13) and Shenshu (BL 23) was adopted, with continuous wave, 2 Hz in frequency. In the sham EA group, sham EA at non-acupoints (1.5-2.0 cm lateral to back-shu points of five zang) was applied, with shallow needling, and no current was connected. The treatment in the both groups was 20 min each time, once every other day, 2 weeks as one course, 3 courses were required. Before and after treatment, the scores of fatigue scale-14 (FS-14) and the MOS 36-item short form health survey (SF-36) were observed, and cortical excitability (the resting motor threshold [RMT], amplitude of motor-evoked potential [MEP-A] and latency of motor-evoked potential [MEP-L]) was detected in the two groups. RESULTS: After treatment, the physical fatigue score, mental fatigue score and total score of FS-14, as well as RMT of motor cortex in the EA group were decreased compared with those before treatment (P<0.01), the physical fatigue score and total score of FS-14 in the sham EA group were decreased compared with those before treatment (P<0.05); each item score and total score of FS-14 and RMT of motor cortex in the EA group were lower than those in the sham EA group (P<0.01, P<0.05). After treatment, each item score and total score of SF-36 and MEP-A of motor cortex in the EA group were increased compared with those before treatment (P<0.01), which were higher than those in the sham EA group (P<0.01, P<0.05). CONCLUSION EA at back-shu points of five zang can effectively improve the fatigue status and quality of life in patients with CFS, its mechanism may be related to the up-regulating excitability of cerebral motor cortex.
Humans ; Electroacupuncture ; Fatigue Syndrome, Chronic/therapy* ; Acupuncture Points ; Quality of Life ; Cortical Excitability

Objective:To establish the ultraperformance liquid chromatography （UPLC） fingerprint of Pipa Qingfeiyin substance benchmark， and to establish a quantitative analysis method for simultaneous determination of the contents of five index components， so as to provide reference for the quality control and evaluation of this famous classical formula. Method:ACQUITY UPLC^® CSH^TM C₁₈ column （2.1 mm×100 mm， 1.7 μm） was used with mobile phase of acetonitrile （A）-0.1% formic acid aqueous solution （B） for gradient elution （0-7 min， 5%-7%A； 7-11 min， 7%-8%A； 11-22 min， 8%-14%A； 22-30 min， 14%-15%A； 30-35 min， 15%-25%A； 35-42 min， 25%-40%A； 42-45 min， 40%-50%A； 45-50 min， 50%-60%A）， the flow rate was 0.35 mL·min^-1， the column temperature was 25 ℃， the detection wavelengths were 278 nm and 248 nm. UPLC fingerprints of 15 batches of Pipa Qingfeiyin substance benchmark were established， and the "Similarity Evaluation System of Chromatographic Fingerprint of Traditional Chinese Medicine" software （2012 edition） was used for similarity analysis， and the common peaks were assigned. Cluster analysis （CA）， principal component analysis （PCA） and orthogonal partial least squares discriminant analysis （OPLS-DA） were used to evaluate the fingerprint data. UPLC fingerprint method was used to simultaneously determine the contents of five components in the substance benchmark. Result:The method validation of fingerprint and determination method was good， the similarities between 15 batches of Pipa Qingfeiyin substance benchmark and their control fingerprint were ≥0.997， 23 common peaks were identified and 11 chromatographic peaks were identified. CA， PCA and OPLS-DA divided 15 batches of the substance benchmark into two groups. The linear relationship of phellodendrine hydrochloride， chlorogenic acid， berberine hydrochloride， palmatine hydrochloride and ammonium glycyrrhizinate was good in a certain range of concentration （R²>0.999）， their average recovery was 96.47%-101.16%， and the contents of these five components in the substance benchmark were 0.87-2.00， 1.53-5.95， 18.45-33.97， 3.87-6.29， 1.02-4.12 mg·g^-1， respectively. Conclusion:The established UPLC fingerprint and multi-index component content determination methods have strong specificity， good resolution and high sensitivity， it can be characterized except for the Ginseng Radix et Rhizoma flavor， which can provide reference for the quality control and evaluation of Pipa Qingfeiyin compound preparation.