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ObjectiveTo construct the evidence body for revision of safety information on package inserts of Chinese patent medicines in post-marketing by taking Xiaoke'an capsules as an example， so as to provide reference for the revision of instructions of Chinese patent medicines in post-marketing. MethodThe construction of the evidence body was guided by the theory of traditional Chinese medicine（TCM） and the Technical Guiding Principles for Revision of Safety Information Items in Instructions for TCMs After Marketing， and 8 categories and 25 specific items were taken as the main body of the evidence body， and information inclusion， integration， screening and improvement were carried out， then expert demonstrations were conducted， and finally modifications were made based on the opinions of the Center for Drug Evaluation to complete the revision of the safety information in the instructions of Xiaoke'an capsules. Result［Adverse reactions］ of Xiaoke'an capsules was revised to "monitoring data show that the following adverse reactions can be seen with this product：individual hypoglycemic reaction reports". ［Contraindications］ was revised to "contraindicated for those allergic to this product and its ingredients". ［Precautions］ was revised to "（1）pregnant women should use with caution， （2）elderly people should consult a physician， （3）people with spleen deficiency and dampness， spleen and stomach deficiency and cold， or those who eat less and have diarrhea should use with caution， （4）this product contains ginseng， should not be taken at the same time with TCM prescriptions or patent medicines containing veratrum and Wulingzhi， （5）pay attention to monitoring blood sugar during medication， （6）if any other discomfort occurs during medication， you should seek medical attention in time". The warning was revised to "use with caution by pregnant women， and pay attention to regular monitoring of blood sugar". ConclusionIn accordance with the content and process of the evidence body for the revision of safety information in the instructions， the revision of the safety information in the instructions of Xiaoke'an capsules has been completed， providing a strong basis for the rational and safe use of medication in the clinic.
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Resumen Presentamos el caso de una mujer joven sana, que consultó por parálisis facial periférica izquierda asociada a fiebre, tos seca, disnea y astenia de dos semanas de evolución. Al examen físico se evidenció hipoestesia en dermatomas D6 a D12 izquierdos y galactorrea bi lateral. En el laboratorio presentaba serologías virales negativas, eritrosedimentación, títulos de anticuerpos antinucleares, prolactina y hormona tiroestimulante elevados, con anticuerpos antiperoxidasa positivos. La tomografía computarizada mostró múltiples adenopatías cervicales, mediastinales e hiliares bilaterales, sin com promiso del parénquima pulmonar. El cultivo de líquido cefalorraquídeo fue negativo para gérmenes comunes, micobacterias (Xpert MTB/RIF), y la citología no mostró atipia. Se realizó una resonancia magnética con con traste endovenoso de cerebro sin hallazgos patológicos y de columna con alteración de la señal centromedular de D6 a D9 de casi la totalidad del espesor del cordón, con refuerzo con contraste endovenoso. Durante la in ternación recuperó la sensibilidad en tronco izquierdo y no repitió episodios febriles o tusígenos. Se realizó mediastinoscopía con biopsia ganglionar con anatomía patológica con presencia de numerosos granulomas no caseificantes compatibles con sarcoidosis. Se clasificó como neurosarcoidosis probable e inició tratamiento con corticoides con mejoría de los síntomas neurológi cos restantes, realizándose una resonancia magnética a los tres meses, donde la alteración de la señal se limitaba desde D7 a D8. Nuestro objetivo es destacar la presentación neurológica en múltiples sitios que obligó a descartar otras entidades más frecuentes, así como la evolución favorable incluso previo al inicio de un esquema de tratamiento de primera línea.
Abstract We present the case of a healthy young woman who consulted for left peripheral facial palsy associated with fever, dry cough, dyspnea, and asthenia of two weeks' evolution. Physical examination revealed hypoesthesia in left T6 to T12 dermatomes and bilateral galactorrhea. In the laboratory, she presented negative viral serology, elevated erythrocyte sedimentation rate, antinuclear an tibody titers, prolactin and thyroid-stimulating hormone, with positive antiperoxidase antibodies. Computed to mography showed multiple bilateral cervical, mediastinal, and hilar adenopathies, without involvement of lung parenchyma. Cerebrospinal fluid culture was negative for common germs, mycobacteria, and Xpert MTB/RIF, and cytology did not show atypia. Contrast-enhanced magnetic resonance was performed on the brain without pathological findings and on the spine with alteration of the centromedullary signal from T6 to T9 of almost the entire thickness of the cord, with posterior enhancement with gadolinium. During hospitalization, she recovered sensitivity in the left trunk and did not repeat febrile or cough episodes. She was referred to another center for mediastinoscopy with lymph node biopsy revealing the presence of numerous non-caseating granulomas compatible with sarcoidosis. It was classified as probable neurosarcoidosis and started treatment with corticoste roids with improvement of the remaining neurological symptoms. A magnetic resonance was performed three months later where the signal alteration was limited from T7 to T8. Our objective is to highlight the florid neu rological presentation that made it necessary to rule out other more frequent entities and the favorable evolution even before starting a first-line scheme of treatment.
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Abstract Happiness and achieving quality of life primarily depends on the nature of the place in which we live. The religious/spiritual factor is considered a basic factor for understanding the quality of life of individuals. The study at hand used the Arabic version of WHOQoL-SRPB to analyze the religious and spiritual factor affecting the quality of life in Islamic holy cities. The scale was applied to 671 residents of Medina with an average age of 51.6 years, of which 527 (78.5 %) are males and 144 (21.5 %) are females, and they are all Muslims. The results showed that all factors have good internal consistency, since the Alpha Cronbach value was .81 at a significant level of p < .001, and its value for the factors ranged between .75-.89, which are high values and significant at p < .001 except for the "Wholeness" factor, which was significant at p < .01. Moreover, the results of the intra-class correlations coefficients (ICC) test showed that all WHOQoL-SRPB factors are acceptable, as their values ranged between (.82-.93), and all of them were significant at p < .001.
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Buccal tablets
Diclofenac sodium
Drug release
Mucoadhesion
Mucoadhesive tablets
Release kinetics
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BACKGROUND: Spermatogonial stem cells (SSCs) are critical for sustaining spermatogenesis. Even though several regulators of SSC have been identified in rodents, the regulatory mechanism of SSC in humans has yet to be discovered. METHODS: To explore the regulatory mechanisms of human SSCs, we analyzed publicly available human testicular single-cell sequencing data and found that Ankyrin repeat and SOCS box protein 9 (ASB9) is highly expressed in SSCs. We examined the expression localization of ASB9 using immunohistochemistry and overexpressed ASB9 in human SSC lines to explore its role in SSC proliferation and apoptosis. Meanwhile, we used immunoprecipitation to find the target protein of ASB9 and verified its functions. In addition, we examined the changes in the distribution of ASB9 in non-obstructive azoospermia (NOA) patients using Western blot and immunofluorescence. RESULTS: The results of uniform manifold approximation and projection (UMAP) clustering and pseudotime analysis showed that ASB9 was highly expressed in SSCs, and its expression gradually increased during development. The immunohistochemical and dual-color immunofluorescence results displayed that ASB9 was mainly expressed in nonproliferating SSCs. Overexpression of ASB9 in the SSC line revealed significant inhibition of cell proliferation and increased apoptosis. We predicted the target proteins of ASB9 and verified that hypoxia-inducible factor 1-alpha inhibitor (HIF1AN), but not creatine kinase B-type (CKB), has a direct interaction with ASB9 in human SSC line using protein immunoprecipitation experiments. Subsequently, we re-expressed HIF1AN in ASB9 overexpressing cells and found that HIF1AN reversed the proliferative and apoptotic changes induced by ASB9 overexpression. In addition, we found that ABS9 was significantly downregulated in some NOA patients, implying a correlation between ASB9 dysregulation and impaired spermatogenesis. CONCLUSION: ASB9 is predominantly expressed in human SSCs, it affects the proliferation and apoptotic process of the SSC line through HIF1AN, and its abnormal expression may be associated with NOA.
Subject(s)
Humans , Male , Testis/metabolism , Ubiquitin-Protein Ligases/metabolism , Repressor Proteins/metabolism , Spermatogenesis/physiology , Ubiquitins/metabolism , Cell Line , Apoptosis , Cell Proliferation , Suppressor of Cytokine Signaling Proteins/metabolism , Mixed Function Oxygenases/metabolismABSTRACT
O conhecimento da anatomia e da fisiologia de uma bifurcação é essencial na área intervencionista atual. A lesão de bifurcação é uma das alterações coronárias mais desafiadoras no tratamento percutâneo. Foram investigadas muitas estratégias intervencionistas devido ao alto nível de interesse nessas lesões, mas os resultados dos procedimentos e de longo prazo foram relativamente ruins. As melhorias em implante de stents e outros procedimentos intervencionistas reduziram a probabilidade de desfechos clínicos adversos, criando o ambiente mais favorável para os stents realizarem seu trabalho. O implante de stent provisional tem sido amplamente aceito como técnica intervencionista inicial nas lesões de bifurcação coronária pela comunidade médica há mais de 15 anos. A reestenose de um grande ramo é possível após angioplastia do vaso principal utilizando uma abordagem provisional de um único stent. Embora a reestenose do ramo lateral após angioplastia de bifurcação seja menos comum nos procedimentos modernos de bifurcação, ela ainda ocorre em 5% dos casos durante o acompanhamento angiográfico baseado em sintomas. Em nossa série de casos de cinco pacientes, a reestenose grave de ramo lateral apresentou sintomas de angina recorrente, que necessitou de revascularização do vaso-alvo. Ao aplicar os princípios de bifurcação, aprimoramos a etapa do mini culotte estadiado da técnica culotte de bifurcação, tornando-a mais fácil de usar e reduzindo a exposição à radiação e o tempo de operação.
Understanding the anatomy and physiology of a bifurcation is crucial in today's interventional field. The bifurcation lesion is one of the most challenging coronary conditions to treat percutaneously. Numerous interventional strategies have been investigated because of the high level of interest in these lesions, but the relatively poor procedural and long-term results. Improvements in stenting and other interventional procedures have reduced the likelihood of adverse clinical outcomes, by creating the most favorable environment for stents to do their work. Provisional stenting has been widely accepted as the initial interventional technique for coronary bifurcation lesions by the medical community for over 15 years. Restenosis of a major branch is possible after angioplasty of the main vessel using a provisional one-stent approach. Although side branch restenosis following bifurcation angioplasty is less common with modern bifurcation procedures, it still occurs in 5% of cases during angiographic follow-up for symptoms. In our case series of five patients, severe side-branch restenosis presented with recuring anginal symptoms, which required target vessel revascularization. By applying bifurcation principles, we improved the "staged mini culotte" part of the culotte bifurcation stent technique, making it more user-friendly, and reducing exposure to radiation and operating time.
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Ensaio sobre história da Saúde Coletiva como campo científico e político. Análise das características das três áreas da Saúde Coletiva: Epidemiologia; Ciências Sociais e Humanas; e Política, Planejamento e Gestão, mediante estudo temático de Congressos da Associação Brasileira de Saúde Coletiva (Abrasco). Constatam-se conflitos de interesse e de paradigmas entre as áreas, mas também estratégias de governança para sustentar a unidade do campo da Saúde Coletiva que poderia ser sintetizada com a expressão: dialética da autonomia e integração.(AU)
This essay discusses the history of public health as a scientific and political field. We analyze the main features of the three areas of public health (epidemiology, social and human sciences, and policy, planning and management) based on a thematic study of congresses held by the Brazilian Public Health Association (Abrasco). The findings highlight a number of conflicting interests and paradigms among the areas, but also governance strategies to maintain the unity of field of public health that could be summed up with the phrase "dialectics of autonomy and integration".(AU)
Ensayo sobre historia de la Salud Colectiva como campo científico y político. Análisis de las características de las tres áreas de la Salud Colectiva: Epidemiología, Ciencias Sociales y Humanas y Política, Planificación y Gestión mediante estudio temático de Congresos de Abrasco. Se constatan conflictos de interés y de paradigmas entre las áreas, pero también estrategias de gobernanza para sustentar la unidad del campo de la Salud Colectiva que podría sintetizarse con la expresión: dialéctica de la autonomía e integración.(AU)
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@#Objective To systematically evaluate the efficacy of neoadjuvant chemoradiotherapy or chemotherapy followed by surgery versus definitive chemoradiation in stage ⅢA-N2 non-small cell lung cancer (NSCLC). Methods We searched PubMed, EMbase, Web of Science and The Cochrane Library to collect clinical studies on the efficacy comparison between neoadjuvant chemoradiotherapy or chemotherapy followed by surgery and definitive chemoradiation in stage ⅢA-N2 NSCLC from inception to September 2022. The meta-analysis was performed by using RevMan 5.3 software. Results A total of 9 studies (3 randomized controlled trials and 6 retrospective cohort studies) with 12 801 patients were included. The results of meta-analysis showed that there was no statistical difference in the progression-free survival rate between the inductive treatment followed by surgery (including lobectomy and pneumonectomy) and definitive chemoradiation (HR=0.99, 95%CI 0.86-1.15, P=0.91). Compared with definitive chemoradiation, the overall survival (OS) rate in the inductive treatment followed by surgery (including lobectomy and pneumonectomy) was lower (HR=1.24, 95%CI 1.09-1.42, P=0.001), while the OS rate in the inductive treatment followed by lobectomy was higher (HR=0.55, 95%CI 0.51-0.61, P<0.000 01). And the local recurrence rate in the inductive treatment followed by surgery was reduced (OR=0.44, 95%CI 0.36-0.55, P<0.000 01). Conclusion Neoadjuvant chemoradiotherapy or chemotherapy followed by lobectomy is superior to definitive chemoradiation in OS and it has a lower local recurrence rate, so lobectomy should be one of the multidisciplinary treatments for selected ⅢA-N2 NSCLC patients.
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Aim To investigate the impact and mechanism of Weichang'an Pill(WCA),its ethanol extract(EE),water extract(WE),and active ingredients on the contraction of isolated rat ileum smooth muscles induced by acetylcholine(ACh). Methods In vitro tissue bath experiment,WCA,EE,WE,or their active ingredients were added under the action of ACh,and then the contraction tension of isolated ileum smooth muscle from rats was recorded. The binding affinity ofthe active ingredients to the muscarinic acetylcholine M3 receptor was explored by molecular docking. Results WCA,EE,and WE were able to considerably inhibit the excitatory contraction of the ileal smooth muscles induced by ACh. Costunolide,dehydrocostus lactone,santalol,muscone,emodin,chrysophanol,physcion,crotonoside,magnolol,and honokiol were also significantly effective against ACh-induced ileal smooth muscle contraction. Conclusions WCA,EE,WE,and their active ingredients may help to promote intestinal smooth muscle relaxation by blocking the binding of the M3 receptor on the membrane of ileal smooth muscle with ACh.
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In pursuit of effective agents for hepatocellular carcinoma derived from the Artemisia species, this study built upon initial findings that an ethanol (EtOH) extract and ethyl acetate (EtOAc) fraction of the aerial parts of Artemisia dubia Wall. ex Bess. exhibited cytotoxicity against HepG2 cells with inhibitory rates of 57.1% and 84.2% (100 μg·mL-1), respectively. Guided by bioactivity, fourteen previously unidentified sesquiterpenes, artemdubinoids A-N (1-14), were isolated from the EtOAc fraction. Their structural elucidation was achieved through comprehensive spectroscopic analyses and corroborated by the comparison between the experimental and calculated ECD spectra. Single crystal X-ray diffraction provided definitive structure confirmation for artemdubinoids A, D, F, and H. Artemdubinoids A and B (1-2) represented unique sesquiterpenes featuring a 6/5-fused bicyclic carbon scaffold, and their putative biosynthetic pathways were discussed; artemdubinoid C (3) was a novel guaianolide derivative that might be formed by the [4 + 2] Diels-Alder reaction; artemdubinoids D and E (4-5) were rare 1,10-seco-guaianolides; artemdubinoids F-K (6-11) were chlorine-containing guaianolides. Eleven compounds exhibited cytotoxicity against three human hepatoma cell lines (HepG2, Huh7, and SK-Hep-1) with half-maximal inhibitory concentration (IC50) values spanning 7.5-82.5 μmol·L-1. Artemdubinoid M (13) exhibited the most active cytotoxicity with IC50 values of 14.5, 7.5 and 8.9 μmol·L-1 against the HepG2, Huh7, and SK-Hep-1 cell lines, respectively, which were equivalent to the positive control, sorafenib.
Subject(s)
Humans , Artemisia/chemistry , Sesquiterpenes/chemistry , Cell Line , Hep G2 Cells , Crystallography, X-Ray , Molecular StructureABSTRACT
OBJECTIVE To investigate the anti-inflammatory effects and mechanism of Zhuang medicine Tongfeng li’an capsules on gouty arthritis in combination with in vivo and in vitro experiments. METHODS Sixty rats were randomly divided into normal group， model group， positive control group （27 mg/kg allopurinol+0.27 mg/kg colchicine）， Tongfeng li’an capsules low- dose， medium-dose and high-dose groups （2.2， 4.5， 9.0 g/kg）， with 10 rats in each group. Except for normal group， gouty arthritis model of rats was induced in other groups. Rats in each administration group were given corresponding drugs intragastrically， and rats in the normal group and model group were given equal volume of water intragastrically for 14 consecutive days. The degree of ankle joint swelling， serum level of interleukin-1β （IL-1β） and protein expressions of nuclear factor kappa-B （NF-κB） in synovial tissue were detected， and the histopathological changes of synovium tissue in the ankle joint of rats were observed. The inflammation model was established by stimulating RAW264.7 cells with lipopolysaccharide. After Tongfeng li’an capsules （62.5， 125， 250 μg/mL） were given， the levels of nitric oxide （NO）， reactive oxygen species （ROS） and IL-1β in the cells and protein expression of NF-κB were detected， and NF-κB localization in the cells was also determined. RESULTS Results of in vivo experiment showed that compared with normal group， the swelling degree of the ankle joint， serum IL-1β level and protein expression of NF-κB in synovium tissue were all increased significantly in model group （P＜0.05）； pathological changes such as synovial hyperplasia， edema， vascular congestion， capillary hyperplasia， and increased inflammatory cells were observed. Compared with model group， the levels of above indexes were all decreased significantly in Tongfeng li’an capsules high-dose group （P＜0.05）， and most of the above indexes were significantly reduced in Tongfeng li’an capsules medium-dose and low-dose groups （P＜0.05）； synovial hyperplasia of the ankle joint improved， and the infiltration of inflammatory cells 2019BS044） decreased. Results of in vitro experiment showed that Tongfeng li’an capsule could significantly reduce the levels of NO， ROS and IL-1β and protein expression of NF-κB（P＜0.01）， and inhibit NF- κB nucleation. CONCLUSIONS Tongfeng li’ancapsules have good anti-inflammatory effect on gouty arthritis， and its mechanism may be related to the inhibition of NF-κB signaling pathway activity.
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ObjectiveTo evaluate the quality of Mori Cortex from different producing areas by the entropy weight-technique for order preference by similarity to an ideal solution（TOPSIS）， and to provide a new evaluation method for the quality control of Mori Cortex. MethodAccording to the five key indexes of color， thickness， texture， powdery and cortex remain， a subjective scoring table was designed to evaluate the appearance of Mori Cortex. High performance liquid chromatography（HPLC） was used to determine the fingerprint and the contents of multiple components（mulberroside A， chlorogenic acid， oxyresveratrol， mulberroside C， sanggenone D， sanggenone C， morusin）， and chemometrics was used to explore the differential components of Mori Cortex from different habitats. On this basis， TOPSIS was used to comprehensively evaluate the quality of Mori Cortex from different habitats， and SPSS 22.0 software was used to carry out bivariate correlation analysis between thickness and appearance color with contents of seven components of Mori Cortex. ResultThose with lighter color， thicker root bark， tougher texture， sufficient powder and less cortex remain scored higher， and the top five were all from Anhui. The established fingerprint and determination methods were stable and reliable. Partial least squares-discriminant analysis（PLS-DA） screened three components with the variable importance in the projection（VIP） value>1（mulberroside A， sanggenone D， sanggenone C）， which made an important contribution to the difference in the origin of Mori Cortex. Correlation analysis showed that there was a significantly positive correlation between mulberroside C with lightness value（L*） and total chromaticity value（E*ab） and mulberroside A with yellow-blue value（b*）（P<0.05， P<0.01）， a significantly negative correlation between sanggenone C with b* and between morusin with L*（P<0.05， P<0.01）. And there was a significantly negative correlation between mulberroside A， chlorogenic acid， and morusin with thickness（P<0.01）， a clearly negative correlation between sanggenone D with thickness（P<0.05）， a significantly positive correlation between sanggenone C with thickness（P<0.01）. TOPSIS comprehensive scores showed that the samples from Anhui had a good score and ranked high. ConclusionThere are great differences in the quality of Mori Cortex from different habitats， and those with the close habitats show similar characteristics in appearance and component content， and lighter color and less cortex were positively correlated with the quality. Among them， the quality of Mori Cortex from Anhui is relatively good.
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OBJECTIVES@#To detect the contents of Tangwei capsule main components with high performance liquid chromatography-quantitative analysis of multicomponents by single marker (HPLC-QAMS) method and to evaluate the quality with chemometrics and entropy weight-technique for order preference by similarity to an ideal solution (EW-TOPSIS).@*METHODS@#A symmetry C18 column and 0.1% formic acid-acetonitrile as mobile phase were used for HPLC of Tangwei capsule. The contents of 3'-hydroxypuerarin, puerarin, 3'-methoxypuerarin, methylnissolin-3-O-glucoside, calycosin, formononetin, rosmarinic acid, salvianolic acid B, dihydrotanshinone Ⅰ, cryptotanshinone, tanshinone Ⅰ, tanshinone ⅡA and cucurbitacin B in 15 batches of Tangwei capsule were determined simultaneously. The quality differences of 15 batches of samples were analyzed by chemometrics and EW-TOPSIS.@*RESULTS@#The HPLC-UV showed that 13 components had good linear relationships in corresponding concentration ranges (r≥0.9991). The relative standard deviations (RSD) of precision, repeatability and stability were all less than 2.00%. The average recovery rates were between 96.86% and 100.13%, and RSD were all less than 2.00%. Cluster analysis showed that 15 batches of samples were clustered into 3 groups. Partial least squares-discriminant analysis showed that salvianolic acid B, formononetin, puerarin, 3'-methoxypuerarin and rosmarinic acid were the main potential markers affecting the quality of Tangwei capsule. EW-TOPSIS analysis showed that the quality of S12-S15 was superior.@*CONCLUSIONS@#The analytical method established in this study can be used for the comprehensive evaluation of the quality of Tangwei capsule to provide laboratory support for its quality control and overall evaluation.
Subject(s)
Drugs, Chinese Herbal , Chromatography, High Pressure Liquid/methods , Chemometrics , EntropyABSTRACT
@#Stigma due to an HIV diagnosis is a well-known phenomenon and is a major barrier to accessing care.1 Over the last forty years, HIV has been transformed from a fatal disease to a manageable one, thanks to the remarkable success of antiretroviral (ARV) medication.2 When people living with HIV (PLHIV) start ARV treatment early, their life expectancy is almost completely restored. Moreover, a suppressed viral load means that PLHIV are no longer able to infect other people.3 They can have children naturally without risk to their seronegative partner or their child. PLHIV nowadays are more likely to die with HIV, not of HIV. While a cure remains elusive, the successful global rollout of ARVs means that there is no good reason for a PLHIV to die of AIDS and its complications due to lack of access to proper treatment. The Philippine AIDS Law Republic Act 8504 and its successor, Republic Act 11116 explicitly states that the State should “ensure access to HIV and AIDS-related services by eliminating the climate of stigma and discrimination that surrounds the country’s HIV and AIDS situation, and the people directly and indirectly affected by it.” Unfortunately, despite this admonition, stigma remains a significant cause of delayed HIV testing and of not seeking treatment in our country. In this issue of the journal, Dr. De Los Santos and her colleagues examine the effect of healthcare facility stigma on PLHIV accessing care in the Philippines.4 They report that 81% of their Filipino PLHIV respondents experienced stigma, which is an unacceptably high number. They identify which facilities are more likely to be correlated with stigma and make suggestions on how to address this problem. This study is very timely and comes at a time when the Department of Health is shifting first line antiretrovirals to dolutegravir-based regimens.5 Dolutegravir-based treatment is associated with fewer side effects than efavirenz-based regimens and is much more durable against resistance.6 With an HIV transmitted-drug resistance rate of 11.7%, it is imperative that PLHIV are started on more durable regimens which they are less likely to discontinue.7 Properly addressing stigma means that more people will access care. Better regimens will ensure that people stay in care. This will go a long way towards minimizing the impact of HIV and AIDS on Filipino PLHIV. Stigma among PLHIV is a complicated subject matter. Aside from the stigma associated with diagnosis, there is also stigma associated with the mode of acquisition of the disease. The most-at-risk populations are highly stigmatized. Men who have sex with men, people who inject drugs, and female sex workers experience additional stigma on top of the stigma from an HIV diagnosis.8 Aside from societal stigma, PLHIV are also prone to self-stigma.9 This phenomenon occurs when PLHIV believe they no longer deserve to live since they contracted the disease from deviant or sinful behavior. High rates of depression are found among these self-stigma sufferers. This significantly impacts the entire HIV healthcare cascade, starting from early diagnosis, to accessing treatment, and staying in care. The finding that Public Rural Health Units are the most stigmatizing healthcare facilities is very concerning since these are usually the only facilities available to PLHIV in far-flung areas. This needs to be addressed with better sensitivity training as well as concrete guidelines on avoiding stigma. It is very troubling that facilities that are supposed to cater to vulnerable populations inadvertently make it difficult for them to access care.10 Unfortunately, even facilities in urban areas are not immune to discrimination and stigmatizing behavior. I recall the experience of one of my early PLHIV patients who developed and eventually succumbed to a disseminated fungal infection.11 He told me that he had tried getting tested several years earlier but he had a traumatic experience in the government health facility that he accessed. He made a wrong turn and entered a different clinic in that hospital and when he asked for an HIV test, people recoiled from him in horror. Because of that terrible experience, he put off getting his HIV test for years until he started developing the fungal infection that eventually killed him. Had he been started on proper treatment earlier, he could have been saved. For me, it wasn’t just the fungus that killed him but it was the delay in diagnosis and care as a direct result of stigma. Addressing HIV-related stigma in our country entails a whole-of-society and a whole-of-nation approach. Mental health services to address self-stigma and depression should be standard of care not just among confirmed PLHIV but among the most-at-risk populations. Proactive education of all members of society, especially healthcare workers in facilities that diagnose and care for PLHIV is essential for ensuring sustained linkage to care. Ensuring that the majority of the PLHIV population are properly diagnosed, enrolled in treatment hubs, and have suppressed viral loads will ultimately lead to fewer transmissions and less AIDS-related deaths.
Subject(s)
HIV , Acquired Immunodeficiency SyndromeABSTRACT
Simiao Yong'an Decoction is a classic prescription for treating gangrene. Modern medical evidence has proven that Si-miao Yong'an Decoction has therapeutic effects on atherosclerosis(AS), vascular occlusion angeitides, and hypertension, while its pharmacodynamic mechanism remains unclear. The evidence of network pharmacology, molecular docking, literature review, and our previous study suggests that luteolin and kaempferol are two major flavonoids in Simiao Yong'an Decoction and can inhibit macrophage inflammation and exert anti-AS effects. However, due to lack of the metabolism studies in vivo, little is known about the metabolic characteristics of luteolin and kaempferol. This study employed ultra-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS/MS) and relevant software to identify the metabolites and metabolic pathways of luteolin and kaempferol in rat plasma, urine, and feces, after oral administration of luteolin and kaempferol, respectively. After the administration of luteolin, 10, 11, and 3 metabolites of luteolin were detected in the plasma, urine, and feces, respectively. After the administration of kaempferol, 9, 3, and 1 metabolites of kaempferol were detected in the plasma, urine, and feces, respectively. The metabolic pathways mainly involved methylation, glucuronidation, and sulfation. This study enriches the knowledge about the pharmacological mechanism of luteolin and kaempferol and supplies a reference for revealing the metabolic process of other flavonoids in Simiao Yong'an Decoction, which is of great significance for elucidating the pharmacological effects and effective substances of this decoction in vivo.
Subject(s)
Rats , Animals , Tandem Mass Spectrometry/methods , Luteolin/analysis , Drugs, Chinese Herbal/chemistry , Kaempferols/analysis , Chromatography, High Pressure Liquid/methods , Molecular Docking SimulationABSTRACT
ObjectiveTo elucidate the mechanism of Osteoking against fracture， femoral head necrosis， osteoarthritis， and lumbar disc herniation by integrating heterogeneous information network mining and experimental validation. MethodOn the basis of the disease-related database and transcriptome expression profiling dataset， as well as the ETCM database， the gene sets related to four target diseases and the candidate target spectrum of Osteoking were obtained through the integration and analysis of bioinformatics data， and a "disease-syndrome-formula-target-pathway-effect" heterogeneous information network was constructed. In addition， by functional enrichment analysis， the core targets of Osteoking in interfering with the imbalance network of four kinds of bone injury diseases， the biological pathways involved， and the corresponding clinical symptoms were screened， and they were verified in animal experiments. ResultHeterogeneous information network mining indicates that Osteoking may commonly reverse the imbalance networks of fracture， femoral head necrosis， osteoarthritis， and lumbar disc herniation via regulating cell function and activity， inhibiting inflammatory response， reducing bone destruction， and improving the immune function of the body by modulating relevant core candidate targets such as RAC-alpha serine/threonine-protein kinase （Akt1）， catenin beta-1 （CTNNB1）， epidermal growth factor receptor （EGFR）， heat shock protein 90-alpha （HSP90AA1）， and phosphatidylinositol 3-kinase catalytic subunit alpha isoform （PI3KCA）， as well as related biological pathways such as phosphatidylinositide 3-kinases/protein kinase B （PI3K/Akt）， janus kinase/signal transducer and activator of transcription （JAK/STAT）， tumor necrosis factor （TNF）， nuclear factor kappa-B （NF-κB）， and Toll-like receptors. In particular， Osteoking may improve the blood supply of the fracture end by regulating blood circulation at the target site of the disease， and it may maintain the balance of bone metabolism by regulating hormone-related pathways to promote fracture healing. In addition， Osteoking may relieve lipid metabolism disorders by targeting and regulating lipid-related pathways， accelerate bone formation and bone repair， and delay the progression of femoral head necrosis. Osteoking may relieve the symptoms of pain by acting on neurological pathways to reduce local nociceptive stimulation in patients with osteoarthritis and lumbar disc herniation. Further experimental validation demonstrates that the PI3K/Akt signaling pathway is the most significantly enriched pathway for the key network targets of Osteoking for the four diseases. The candidate target of Osteoking may have the strongest association with the network of fracture-related genes. Therefore， this study chooses fracture as the target disease to verify the efficacy of Osteoking. The results show that Osteoking can accelerate bone formation and promote fracture healing by inhibiting the activation of the PI3K/Akt signaling axis. ConclusionThe study shows that the main mechanism of "treating different diseases with an identical treatment" of four bone injury diseases with Osteoking involves cell function regulation and immune inflammation-related signaling pathways. Further experimental validation identifies that the PI3K/Akt signaling axis may be one of the key pathways of Osteoking to promote bone regeneration， bone reconstruction， and bone metabolism homeostasis.
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Objective:To investigate the medication rules of Xin'an medicine for the treatment of melancholia and further analyze the medication ideas of Xin'an physicians in the treatment of melancholia.Methods:The documents of Xin'an physicians treating melancholia in the fifth edition of the Chinese Medical Code and the online database of ancient Chinese medicine were retrieved. Excel was used to extract the prescription information to establish the database. R language was used to analyze the data regarding the medication frequency, nature and taste, association rules, and clustering of the traditional Chinese medicine used in the prescription. Results:A total of 127 effective prescriptions were sorted out, and 177 kinds of Chinese medicines were used with a total medication frequency of 1 031 times. The top three Chinese medicines with the highest frequency of use were Poria cocos (57 times), Licorice (46 times), and Paeonia Lactiflora (40 times). The main nature of herbs was plain and warm nature. The warm herbs were the most frequently used (298 times). The first five flavors of the herbs which were the most used were pungent taste (475 times, 28.70%), bitter taste (459 times, 27.73%), and sweet taste (453 times, 27.37%). The commonly used herbs with confidence coefficient > 0.800 were Licorice + Angelica sinensis, Licorice + Angelica sinensis and Paeonia Lactiflora, Licorice + Bupleurum, Licorice + Atractylodes macrocephala, Cyperus root + Ligusticum Chuanxiong, Angelica sinensis + Atractylodes macrocephala and Licorice, Paeonia Lactiflora + Angelica sinensis and Poria cocos, Licorice + Angelica sinensis and Poria cocos, Licorice + Atractylodes macrocephala and Angelica sinensis, Licorice + Bupleurum and Paeonia Lactiflora, Licorice + Atractylodes macrocephala and Ginseng, Licorice + Ginseng and Angelica sinensis, Cyperus root + Medicated leaven, Ginseng + Astragalus mongholicus, Licorice + Astragalus mongholicus.Conclusion:Xin'an medicine for the treatment of melancholia mainly uses pungent, bitter, sweet, and warm herbs. It can adjust the chill and fever, Yin and Yang of the human body, diminishes the urgency, and regulates the flow of Qi.
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Objective:To explore the mechanism of Kechuan'an Oral Liquid in treating asthma based on network pharmacology; To carry out experimental verification.Methods:The effective components and targets of Kechuan'an Oral Liquid were obtained through TCMSP and literature search. The related targets of asthma were screened by GEO database, and the intersection targets of drug and disease were selected. The PPI network was constructed by STRING database, and the GO function and KEGG pathway were enriched and analyzed for key targets by DAVID database. The rats were divided into blank control group, model group and Kechuan'an Oral Liquid group according to the method of random number table. Kechuan'an Oral Liquid group received Kechuan'an Oral Liquid 12.34 ml/kg for gavage, and blank control group and model group were perfused with distilled water of the same volume for gavage, once a day for 3 days. The asthma model of rats was prepared by atomizing the mixture of acetylcholine chloride and histamine phosphate, and HE staining was used to observe the pathological changes of lung tissue; Western blot was used to detect the protein expressions of IL-6, TLR4, MyD88 and TAK1, and the network pharmacological prediction results were verified.Results:A total of 153 active components, 1 896 targets and 2 982 differentially expressed genes of Kechuan'an Oral Liquid were screened out, and 25 intersection targets of drugs and diseases were obtained. The enrichment results showed that toll-like receptor signaling pathway, TNF signaling pathway and Nod-like receptor signaling pathway were the main mechanisms of immune inflammation. Compared with the control group, the lung tissue of rats in the model group showed morphological changes such as thickening of air duct wall and infiltration of inflammatory cells, which were significantly improved in the Kechuan'an Oral Liquid group. Compared with the control group, the expressions of IL-6, TLR4, MyD88 and TAK1 in the model group significantly increased ( P<0.01), and compared with model group, the expressions of IL-6, TLR4, MyD88 and TAK1 in Kechuan'an Oral Liquid group significantly decreased ( P<0.05 or P<0.01). Conclusion:Kechuan'an Oral Liquid can inhibit toll-like receptor signaling pathway and mediate anti-inflammatory effect to treat asthma.
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OBJECTIVE@#To study the effectiveness and feasibility of cryogenic disinfectants in different cold scenarios and analyze the key points of on-site cryogenic disinfection.@*METHODS@#Qingdao and Suifenhe were selected as application sites for the manual or mechanical spraying of cryogenic disinfectants. The same amount of disinfectant (3,000 mg/L) was applied on cold chain food packaging, cold chain containers, transport vehicles, alpine environments, and article surfaces. The killing log value of the cryogenic disinfectant against the indicator microorganisms ( Staphylococcus aureus and Escherichia coli) was used to evaluate the on-site disinfection effect.@*RESULTS@#When using 3,000 mg/L with an action time of 10 min on the ground in alpine regions, the surface of frozen items, cold-chain containers, and cold chain food packaging in supermarkets, all external surfaces were successfully disinfected, with a pass rate of 100%. The disinfection pass rates for cold chain food packaging and cold chain transport vehicles of centralized supervised warehouses and food processing enterprises were 12.5% (15/120), 81.67% (49/60), and 93.33% (14/15), respectively; yet, the surfaces were not fully sprayed.@*CONCLUSION@#Cryogenic disinfectants are effective in disinfecting alpine environments and the outer packaging of frozen items. The application of cryogenic disinfectants should be regulated to ensure that they cover all surfaces of the disinfected object, thus ensuring effective cryogenic disinfection.