RESUMEN
INTRODUCTION: Upper urinary tract stones combined with parenchymal infiltrative renal pelvic cancer are challenging to detect on imaging and to evaluate the differential diagnosis. CASE PRESENTATION: The symptoms and diagnoses in three cases of parenchymal infiltrative renal pelvic cancer and upper urinary tract stones that occurred between June 2019 and June 2022 were reviewed. Primary symptoms of lumbar discomfort and hematuria were evident in all 3 patients. Preoperative computed tomography (CT) abdominal imaging revealed that all three cases had hydronephrosis along with renal stones, while the other two cases only had localized hypoenhancement of the renal parenchyma, which was only thought to be limited inflammatory changes in the renal cortex as a result of the combination of renal pelvis infection. After percutaneous nephrolithotomy or ureteroscopic lithotripsy, a combined renal pelvis tumor was discovered in all of these instances. Radical tumor surgery was later performed. One patient who had several tumor metastases passed away 6 months after surgery. A case with multiple metastases was discovered 15 months after surgery and survived with the help of the current chemotherapy. A case with a bladder tumor recurrence was discovered 16 months after surgery and had transurethral bladder tumor electrosurgery and routine bladder perfusion chemotherapy. CONCLUSION: Upper urinary tract stones and parenchymal infiltrative pyel carcinoma have atypical imaging, easily confused with infectious diseases. CT or computed tomography urography (CTU) must be considered by urologists. Patients who have a CT with local renal parenchyma density should be suspected of having parenchymal invasive renal pelvis carcinoma; a needle biopsy ought to be performed; and repeat biopsies may be performed if necessary. High-risk individuals need multiple, sufficient biopsies as needed and a comprehensive intraoperative assessment of the renal pelvic mucosa.
Asunto(s)
Neoplasias Renales , Pelvis Renal , Humanos , Neoplasias Renales/complicaciones , Neoplasias Renales/patología , Pelvis Renal/patología , Pelvis Renal/diagnóstico por imagen , Persona de Mediana Edad , Masculino , Femenino , Cálculos Renales/complicaciones , Anciano , Tomografía Computarizada por Rayos XRESUMEN
This study aims to systematically review the efficacy and safety of Shufeng Jiedu Capsules in the treatment of influenza. The randomized controlled trial(RCT) of Shufeng Jiedu Capsules alone or in combination with conventional western medicine for treating influenza were retrieved from PubMed, EMbase, Cochrane Library, Web of Science, SinoMed, CNKI, VIP, Wanfang, and ClinicalTrails.gov. The data analysis was performed in RevMan 5.4.1. The Cochrane risk of bias assessment tool was used to evaluate the quality of the involved RCT, and GRADEpro GDT to assess the quality of the evidence. A total of 11 RCTs involving 1 836 patients were included in this study. Compared with conventional western medicine, Shufeng Jiedu Capsules/Shufeng Jiedu Capsules + conventional western medicine improved the response rate(RR=1.09, 95%CI[1.03, 1.15], P=0.002), shortened the time to relief of cough, and increased the 3-day sore throat relief rate, whereas there was no significant difference in the time to fever abatement, the time to relief of sore throat, 3-day cough relief rate, or 3-day runny nose relief rate. Subgroup-analysis showed that Shufeng Jiedu Capsules + conventional western medicine improved the response rate(RR=1.11, 95%CI[1.08, 1.15], P<0.000 01), shortened the time to relief of cough, and increased the 3-day relief rate of symptoms(cough, sore throat, and runny nose) compared with conventional western medicine alone, while there was no significant difference in the time to fever abatement or the time to relief of sore throat. Shufeng Jiedu Capsules alone could not improve the response rate(RR=0.97, 95%CI[0.93, 1.02], P=0.19). In addition, Shufeng Jiedu Capsules/Shufeng Jiedu Capsules + conventional western medicine vs conventional western medicine were no significant difference in adverse reactions(RR=0.98, 95%CI[0.57, 1.69], P=0.95). The available evidence suggests that Shufeng Jiedu Capsules is effective and safe in the treatment of influenza, and the combination of Shufeng Jiedu Capsules with conventional western medicine can accelerate the relief of symptoms. However, since the number and quality of the included studies were low, the above findings remained to be further verified by multicenter RCT with large sample sizes.
Asunto(s)
Medicamentos Herbarios Chinos , Gripe Humana , Faringitis , Humanos , Gripe Humana/tratamiento farmacológico , Medicamentos Herbarios Chinos/efectos adversos , Cápsulas , Tos/tratamiento farmacológico , Tos/inducido químicamente , Rinorrea , Estudios Multicéntricos como AsuntoRESUMEN
BACKGROUND The development of artificial dermis provides a new therapeutic method for full-thickness skin defects. However, the slow regeneration of blood vessels in the wound site still cannot be solved perfectly. In our study, we combined platelet-rich plasma (PRP) with Lando® artificial dermal scaffold to promote vascular regeneration and wound healing in pigs. MATERIAL AND METHODS First, PRP was compounded with the artificial dermal scaffold. Then, this material was co-cultured with human vascular endothelial cells (HUVECs) and the growth and proliferation of HUVECs were assessed. Bama miniature pigs wound models were fabricated, the materials were transplanted into the skin defect, and wound healing and blood vessel regeneration were assessed by HE staining and CD31 immunohistochemistry. RESULTS Scanning electron microscopy (SEM) showed that PRP formed round particles on the surface of the artificial dermis material. Cell co-culture experiments showed that the PRP composite artificial dermal scaffold can promote the growth and proliferation of HUVECs. CCK8 experiments demonstrated that the number of cells in the PRP composites group on days 2, 3, 4, and 5 was higher than that in the material alone group (P<0.01). The results of animal experiments showed that PRP composite artificial dermal material can promote wound healing. Histological staining and immunohistochemical staining indicated that the PRP composites group promoted epithelial tissue thickening and blood vessel regeneration in wounds (P<0.001). CONCLUSIONS Our experimental results showed that the artificial dermal scaffold loaded with platelet-rich plasma can promote the revascularization of wounds and accelerated wound healing.
Asunto(s)
Plasma Rico en Plaquetas , Piel Artificial , Animales , Células Endoteliales , Piel/lesiones , Porcinos , Cicatrización de HeridasRESUMEN
BACKGROUND: Osteitis fibrosa cystica is a rare, benign and osteolytic lesion attributed to hyperparathyroidism. The high level of parathyroid hormone cause rapid bone loss. CASE PRESENTATION: The patient is a 50-year-old male complaining of severe and persistent pain in the right knee joint. Imaging studies were suspicious for a benign tumor in the right distal femur. Biopsy under CT guidance showed numerous osteoclast aggregation and hemosiderin deposition around the bone trabeculae. Blood tests disclosed significantly elevated parathyroid hormone, serum calcium, serum alkaline phosphatase. Parathyroid ultrasonography and CT scan showed a solid mass in front of the trachea at the thoracic entrance plane. After resection of the mass, the clinical symptoms were relieved and the radiological results were significantly improved, which further confirmed the diagnosis. CONCLUSIONS: Metabolic diseases-associated bone lesions require a comprehensive diagnosis of multiple inspection items. An interprofessional team approach to the diagnosis and treatment of osteitis fibrosa cystica will provide the best outcome.
Asunto(s)
Neoplasias Óseas , Hiperparatiroidismo , Osteítis Fibrosa Quística , Neoplasias de las Paratiroides , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/diagnóstico por imagen , Fémur/diagnóstico por imagen , Fémur/patología , Fémur/cirugía , Humanos , Hiperparatiroidismo/complicaciones , Masculino , Persona de Mediana Edad , Osteítis Fibrosa Quística/diagnóstico por imagen , Osteítis Fibrosa Quística/etiología , Neoplasias de las Paratiroides/diagnóstico , Neoplasias de las Paratiroides/diagnóstico por imagenRESUMEN
BACKGROUND: Mechanical obstruction is the most common cause of shunt failure for hydrocephalic patients. However, the diagnosis is extremely challenging and often requires invasive testing methods. Thus, a simple and non-invasive technique is in urgent need to predict the intracranial pressure (ICP) of hydrocephalic patients during their post-surgical follow-up, which could help neurosurgeons to determine the conditions of the shunt system. MATERIALS AND METHODS: Two groups of patients were enrolled in the current study. In group I, patients were enrolled as they were diagnosed with high ICP hydrocephalus and received shunt surgery. The shunt valve pressures were taken for their post-surgical ICP. Meanwhile, the participants of group II exhibited abnormally increased lumbar puncture opening pressure (LPOP; from 180 to 400 mmH2O). Both the ICP and LPOP were used to match with their corresponding tympanic membrane temperature (TMT). RESULTS: When patients' ICP were in the normal range (group I, from 50 to 180 mmH2O), the TMT correlated with ICP in a linear regression model (R2 = 0.59, p < 0.001). Interestingly, when patients exhibited above-normal ICP (LPOP was from 180 to 400 mmH2O), their TMT fit well with the ICP in a third-order polynomial regression (R2 = 0.88). When the ICP was 287.98 mmH2O, the TMT approached the vertex, which was 38.54 °C. Based on this TMT-ICP algorithm, we invented a non-invasive ICP monitor system. Interestingly, a tight linear correlation was detected between the ICP data drawn from the non-invasive device and Codman ICP monitoring system (R2 = 0.93, p < 0.01). CONCLUSIONS: We believe the TMT-ICP algorithm (the Y-Jiang model) could be used for preliminary prediction of shunt malfunction as well as monitoring ICP changes.
Asunto(s)
Hidrocefalia , Presión Intracraneal , Humanos , Invenciones , Hidrocefalia/diagnóstico , Hidrocefalia/cirugía , Monitoreo Fisiológico , Derivaciones del Líquido CefalorraquídeoRESUMEN
OBJECTIVE: To investigate the protective effect of dexmedetomidine (Dex) preconditioning against ischemia-reperfusion (IR) injury after testicular torsion in rats. METHODS: Fifty-six adult male rats, were randomly divided into seven groups: sham control, 1h IR, 2h IR, 4h IR, 1h IR + Dex, 2h IR + Dex, and 4h IR + Dex. The torsion model was established in the latter six groups by a counterclockwise 720° left spermatic cord torsion lasting 1, 2 and 4 hours, respectively, and the rats in the last three groups injected intraperitoneally with Dex at 100 µg/kg 30 minutes before testicular reduction. At 4 hours after testicular reduction, the testes were removed for biochemical examination of the tissue homogenate and assessment of the testicular damage based on the results of HE staining and Johnsen testicular biopsy scores. RESULTS: Lower levels of catalase and total superoxide dismutase were associated with longer time of ischemia (P<0.05) and higher in the IR than in the IR + Dex groups with the same duration of ischemia (P<0.05). The levels of malondialdehyde, nitric oxide and myeloperoxidase were all significantly increased in the IR and IR + Dex groups compared with those in the sham control group (P<0.05), higher with longer time of ischemia (P<0.05), but lower in the IR + Dex than in the IR group with the same length of time of ischemia (P<0.05). Histopathological examination revealed edema in the testis tissue, damage to the seminiferous tubules and germ cells and interstitial hemorrhage, more severe in the IR and IR + Dex groups than in the sham control group (P<0.05), which were all remarkably improved in the 1h IR + Dex and 2h IR + Dex groups compared with the 1h IR and 2h IR groups (P<0.05) but showed no statistically significant difference between the 4h IR and 4h IR + Dex groups (P > 0.05). CONCLUSIONS: Dexmedetomidine protects the rat testis against testicular torsion-induced early ischemia-reperfusion injury, but it is less effective for longer ischemia than 4 hours.
Asunto(s)
Dexmedetomidina , Daño por Reperfusión , Torsión del Cordón Espermático , Animales , Dexmedetomidina/farmacología , Dexmedetomidina/uso terapéutico , Masculino , Ratas , Daño por Reperfusión/complicaciones , Daño por Reperfusión/prevención & control , Torsión del Cordón Espermático/complicaciones , Superóxido DismutasaRESUMEN
The aim of this study is to investigate the effects of betulinic acid (BA) on triple-negative breast cancer MDA-MB-231 cells and observe the ultrastructural changes. The concentration of BA required to induce apoptosis in MDA-MB-231 cells has been previously reported. In this study, a cell counting kit-8 proliferation assay was used to measure cell viability and the apoptosis rate. Western blotting was performed to observe the protein expression levels of Bcl-2. Cell morphology and changes in cell density were observed by microscopy. Electron microscopy revealed pyknotic nuclei as well as vacuoles. Collectively, our results showed the morphological mechanisms by which BA impairs the ultrastructure of MDA-MB-231 cells.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias de la Mama Triple Negativas/patología , Triterpenos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Femenino , Humanos , Microscopía Electrónica de Transmisión , Triterpenos Pentacíclicos , Ácido BetulínicoRESUMEN
This paper explores the connection between paclitaxel, a chemotherapeutic agent, and gastric cancer cells. In this experiment, it is demonstrated that paclitaxel triggers autophagy and inhibits proliferation of gastric cancer cells. An 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was used to detect cell viability and the IC50 of paclitaxel. Western blot was used to detect the expression levels of P62, and to measure the protein expression of autophagy. Immunofluorescence was used to reveal the appearance of punctate structures in the cytoplasm-this ultrastructure associated with autophagy was observed by microscopy. Electron microscopy revealed the formation of double-membrane autophagosomes, a typical structure of autophagy. In conclusion, our research indicates that paclitaxel may influence gastric cancer BGC823 cells by way of inducing autophagy.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Autofagia/efectos de los fármacos , Paclitaxel/farmacología , Neoplasias Gástricas/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , HumanosRESUMEN
Allylation and benzylation of p-quinones was achieved through an unusual redox chain reaction. Mechanistic studies suggest that the existence of trace hydroquinone initiates a redox chain reaction that consists of a Lewis acid catalyzed Friedel-Crafts alkylation and a subsequent redox equilibrium that regenerates hydroquinone. The electrophiles could be various allylic and benzylic esters. The addition of Hantzsch ester as an initiator improves the efficiency of the reaction.
RESUMEN
The objective of this study was to evaluate the impact of finasteride on the progression of prostate intraepithelial neoplasia and levels of prostate-specific antigen (PSA) in patients. A total of 120 patients with high-grade prostatic intraepithelial neoplasia were included in this study from January 2013 to January 2018. All patients underwent prostate biopsies. Among them, 60 patients were assigned to the observation group and received a daily dosage of 5 mg finasteride for 60 months, while the remaining 60 patients were assigned to the control group and did not receive finasteride. PSA levels were measured every six months, and imaging scans were conducted throughout the five-year study period. Additional biopsies were performed if PSA levels exceeded 10 ng/mL or imaging suggested the presence of prostate cancer. Statistical analysis was applied to the collected data. In total, 25 cases of prostate cancer were identified in this study. Of these cases, 7 patients belonged to the observation group, whereas the remaining 18 patients were from the control group. The observation group exhibited significantly lower levels of total serum PSA (p < 0.001) and Gleason scores (p < 0.001) compared to the control group. Our study, which involved 120 participants, demonstrated that finasteride effectively reduces serum PSA levels and mitigates the severity of prostate cancer. These findings suggest that finasteride holds potential as a treatment option for patients with -high-grade prostatic intraepithelial neoplasia.
Asunto(s)
Neoplasia Intraepitelial Prostática , Neoplasias de la Próstata , Masculino , Humanos , Neoplasia Intraepitelial Prostática/diagnóstico , Neoplasia Intraepitelial Prostática/tratamiento farmacológico , Finasterida/farmacología , Finasterida/uso terapéutico , Antígeno Prostático Específico , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/tratamiento farmacológico , Progresión de la EnfermedadRESUMEN
OBJECTIVE: To evaluate the effectiveness and safety of Chinese medicine (CM) in the treatment of coronavirus disease 2019 (COVID-19) in China. METHODS: A multi-center retrospective cohort study was carried out, with cumulative CM treatment period of ⩾3 days during hospitalization as exposure. Data came from consecutive inpatients from December 19, 2019 to May 16, 2020 in 4 medical centers in Wuhan, China. After data extraction, verification and cleaning, confounding factors were adjusted by inverse probability of treatment weighting (IPTW), and the Cox proportional hazards regression model was used for statistical analysis. RESULTS: A total of 2,272 COVID-19 patients were included. There were 1,684 patients in the CM group and 588 patients in the control group. Compared with the control group, the hazard ratio (HR) for the deterioration rate in the CM group was 0.52 [95% confidence interval (CI): 0.41 to 0.64, P<0.001]. The results were consistent across patients of varying severity at admission, and the robustness of the results were confirmed by 3 sensitivity analyses. In addition, the HR for all-cause mortality in the CM group was 0.29 (95% CI: 0.19 to 0.44, P<0.001). Regarding of safety, the proportion of patients with abnormal liver function or renal function in the CM group was smaller. CONCLUSION: This real-world study indicates that the combination of a full-course CM therapy on the basic conventional treatment, may safely reduce the deterioration rate and all-cause mortality of COVID-19 patients. This result can provide the new evidence to support the current treatment of COVID-19. Additional prospective clinical trial is needed to evaluate the efficacy and safety of specific CM interventions. (Registration No. ChiCTR2200062917).
RESUMEN
It is now 40 years since bisphosphonates (BPs) were first used in the clinic. So, it is timely to provide a brief review of what we have learned about these agents in bone disease. BPs are bone-specific and have been classified into two major groups on the basis of their distinct molecular modes of action: amino-BPs and non-amino-BPs. The amino-BPs are more potent and they inhibit farnesyl pyrophosphate synthase (FPPS), a key enzyme of the mavalonate/cholesterol biosynthetic pathway, while the non-amino-BPs inhibit osteoclast activity, by incorporation into non-hydrolyzable analogs of ATP. Both amino-BPs and non-amino-BPs can protect osteoblasts and osteocytes against apoptosis. The BPs are widely used in the clinic to treat various diseases characterized by excessive bone resorption, including osteoporosis, myeloma, bone metastasis, Legg-Perthes disease, malignant hyperparathyroidism, and other conditions featuring bone fragility. This review provides insights into some of the adverse effects of BPs, such as gastric irritation, osteonecrosis of the jaw, atypical femoral fractures, esophageal cancer, atrial fibrillation, and ocular inflammation. In conclusion, this review covers the biochemical and molecular mechanisms of action of BPs in bone, particularly the discovery that BPs have direct anti-apoptotic effects on osteoblasts and osteocytes, and the current situation of BP use in the clinic.
Asunto(s)
Enfermedades Óseas/tratamiento farmacológico , Difosfonatos/uso terapéutico , Difosfonatos/efectos adversos , Difosfonatos/farmacocinética , Humanos , Distribución TisularRESUMEN
OBJECTIVE: To analyze the variations of glycerol-3-phosphate dehydrogenase 1 like gene (GPD1-L) and address the association with sudden manhood death syndrome (SMDS). METHODS: The genomic DNA was extracted from blood samples of the SMDS group and the normal control group. The exons, exon-intron boundaries and 3'-UTRs of coding region of GPD1-L were PCR amplified and DNA sequenced directly to confirm the types of variations. The genotype frequency and allele frequency were analyzed statistically. RESULTS: There were two variants in the SMDS group, c.465C>T and c.*18G>T, the latter existed certain degree difference of genotype distribution and allele frequency between the SMDS group and the control group, but there was no statistically significant (P > 0.05). CONCLUSION: The relation between gene mutation of GPD1-L and the occurrence of Chinese SMDS deserves a further research.
Asunto(s)
Muerte Súbita/etiología , Glicerolfosfato Deshidrogenasa/genética , Mutación , Adolescente , Adulto , Pueblo Asiatico/genética , Secuencia de Bases , Estudios de Casos y Controles , Análisis Mutacional de ADN , Cartilla de ADN/genética , Exones , Frecuencia de los Genes , Genotipo , Glicerolfosfato Deshidrogenasa/sangre , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo de Nucleótido Simple , Adulto JovenRESUMEN
The methylation of the lysine residue can affect some fundamental biological processes, and specific biological effects of the methylations are often related to product specificity of methyltransferases. The question remains concerning how active-site structural features and dynamics control the activity as well as the number (1, 2, or 3) of methyl groups on methyl lysine products. SET domain containing protein 3 (SETD3) has been identified recently as the ß-actin histidine73-N3 methyltransferase, and also, it has a weak methylation activity on the H73K ß-actin peptide for which the target H73 residue is mutated into K73. Interestingly, the K73 methylation activity of SETD3 increases significantly as a result of the N255 â A or N255 â F/W273 â A mutation, and the N255A product specificity also differs from that of wild-type. Here, we performed QM/MM molecular dynamics and potential of mean force (PMF) simulations for SETD3 and its mutants (N255A and N255F/W273A) to study how SETD3 and its mutants could have different product specificities and activities for the K73 methylation. The PMF simulations show that the barrier for the first methylation of K73 is higher compared to the barrier of the H73 methylation in SETD3. Moreover, the second methylation of K73 has been found to have a barrier from the free energy simulation that is higher by 2.2 kcal/mol compared to the barrier of the first methyl transfer to K73, agreeing with the suggestion that SETD3 is a monomethylase. For the first, second, and third methylations of K73 in the N255A mutant, the barriers obtained from the PMF simulations for transferring the second and third methyl groups are found to be lower relative to the barrier for the first methyl transfer. Thus, N255A can be considered as a trimethyl lysine methyltransferase. In addition, for the first K73 methylation, the activities from the PMF simulations follow the order of N255F/W273A > N255A > WT, in agreement with experiments. The examination of the structural and dynamic results at the active sites provides better understanding of different product specificities and activities for the K73 methylations in SETD3 and its mutants. It is demonstrated that the existence of well-balanced interactions at the active site leading to the near attack conformation is of crucial importance for the efficient methyl transfers. Moreover, the presence of potential interactions (e.g., the C-H···O and cation-π interactions) that are strengthening at the transition state can also be important. Furthermore, the activity as well as product specificity of the K73 methylation also seems to be controlled by certain active-site water molecules which may be released to provide extra space for the addition of more methyl groups on K73.
Asunto(s)
Actinas , N-Metiltransferasa de Histona-Lisina , Metilación , N-Metiltransferasa de Histona-Lisina/genética , N-Metiltransferasa de Histona-Lisina/química , Actinas/química , Lisina/química , Simulación de Dinámica Molecular , Péptidos/metabolismoRESUMEN
Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, in Fig. 2A on p. 8311, portraying the results of immunostaining experiments for osterix, the 'GIOP' and 'GIOP+TMP (20)' data panels contained overlapping data, such that these images were derived from apparently the same original source, where they were intended to show the results from differently performed experiments. Moreover, in Fig. 3A on p. 8312 showing the results from ALP staining and Alizarin Red S staining experiments, two pairs of apparently overlapping data panels were identified in the Dex 106 M / TMP 50 µM, 100 µM and 200 µM data panels. After having reexamined their original data, the authors have realized that the data featured in Figs. 2A and 3A were assembled incorrectly in these figures. Revised versions of Fig. 2 and 3, now containing replacement data for the experiments shown in Figs. 2A and 3A, are shown on the next page. Note that these errors did not adversely affect either the results or the overall conclusions reported in this study. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this. They also wish to apologize to the readership of the Journal for any inconvenience caused. [Molecular Medicine Reports 16: 83078314, 2017; DOI: 10.3892/mmr.2017.7610].
RESUMEN
The SETD3 enzyme has been identified as the methyltransferase for the His73 methylation in ß-actin, and such methylation plays an important role in regulating the actin's biochemical properties and fine-tuning the protein's cellular roles. Further studies have demonstrated that SETD3 may be able to methylase some other residues, including lysine and methionine, that substitute His73 in the ß-actin peptide. The activity of SETD3 on the Met73 peptide is low without turnover. Interestingly, it has been shown that the N255V and N255A mutations of SETD3 can increase the activity by about 3-fold for the methionine methylation, while such mutations lead to a significant reduction of kcat for the His73 methylation. The detailed mechanism that leads to such increase of the activity for the Met73 methylation as a result of the mutations has not been understood. In this work, QM/MM molecular dynamics (MD) and potential of mean force (PMF) free energy simulations are undertaken for investigating structural, dynamic, and energetic properties involving the complex of SETD3 and Met73 peptide and to study the SETD3-catalyzed methionine methylation and the effects of the N255V mutation. It is demonstrated that the free energy barrier in the case of the methionine methylation in SETD3 is about 10 kcal/mol higher than that for the histidine methylation. Moreover, the free energy barrier for the methionine methylation in the N255V mutant is about 1 kcal/mol lower than that in the wild-type enzyme. These results agree with previous experimental observation. The origin of the free-energy barrier changes as a result of the H to M substitution on the ß-actin peptide and the N255V mutation of SETD3 is discussed based on the data obtained from the simulations.
Asunto(s)
Actinas , Lisina , Metilación , Histona Metiltransferasas/química , Histona Metiltransferasas/genética , Histona Metiltransferasas/metabolismo , Actinas/química , Actinas/genética , Actinas/metabolismo , Histidina/química , Histidina/metabolismo , Metionina , Metiltransferasas/metabolismo , Racemetionina , Péptidos , CatálisisRESUMEN
OBJECTIVE: To investigate the effect and mechanism of acupoint injection with 0.1% vitamin C+vitamin B complex solution (VC+VBCo) at "Tiantu" (CV 22), "Quchi" (LI 11) and "Zusanli" (ST 36) in mouse model of pneumonia induced by influenza A virus (A/PR/8/34 [H1N1], PR8). METHODS: Sixty male ICR mice were randomized into 6 groups, i.e. control group, model group, acupoint injection group, intraperitoneal injection group, non-target point group and ribavirin group, 10 mice in each one. Except the control group, the pneumonia models were induced by slow nasal dripping PR8 virus in the other groups. On the 2nd day of experiment, VC+VBCo solution, 40 µL was injected at "Tiantu" (CV 22), "Quchi" (LI 11, left) and "Zusanli" (ST 36, left) in the acupoint injection group; VC+VBCo solution, 120 µL was injected intraperitoneally in the intraperitoneal injection group; VC+VBCo solution, 40 µL was injected at non-target acupoints (0.5 cm away from "Tiantu" [CV 22] to the left side, "Quchi" [LI 11, left] and "Zusanli" [ST 36, left]) in the non-target point group; and ribavirin solution, 120 µL was injected intraperitoneally in the ribavirin group. The intervention was delivered once daily, for consecutive 7 days. Three parallel experiments were undertaken. The mean death rate and survival time were assessed in each group, the body mass and lung index were compared among groups. Using HE staining, the morphology of lung tissue was observed; and with real-time fluorescence quantitative PCR, viral load in lung tissue was detected. The concentrations of inflammatory factors (tumor necrosis factor α [TNF-α], interleukin [IL]-1ß, IL-10) were detected in lung tissue of each group using ELISA; and those of oxidative stress markers (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px], malondialdehyde [MDA]) were detected with chemiluminescence method. RESULTS: Compared with the control group, the body mass was decreased and lung index was increased in the model group (P<0.01). In comparison with the model group, body mass was increased in the acupoint injection group (P<0.05), lung index was reduced in the acupoint injection group the and ribavirin group (P<0.05); the mean death rate was decreased and the mean survival time prolonged in the mice of the acupoint injection group (P<0.01, P<0.05); and the mean death rate was reduced in the mice of the ribavirin group (P<0.05). In the model group, the alveolar structure was not integral, the alveolar septum was thickened, inflammatory cells were infiltrated and red blood cells exudated seriously (P<0.01). Compared with the model group, in the acupoint injection group and the ribavirin group, the alveolar structure was integral, the thickened alveolar septum was alleviated; and the infiltration of inflammatory cells and the exudation of red blood cells were reduced remarkably. The viral load was reduced in the mice of the ribavirin group when compared with the model group (P<0.01). Compared with the control group, the concentrations of TNF-α, IL-1ß and MDA in lung tissue were increased and those of IL-10, SOD and GSH-Px were reduced in the model group (P<0.01). In the acupoint injection group and the ribavirin group, the concentrations of TNF-α, IL-1ß and MDA were reduced in lung tissue and those of IL-10, SOD and GSH-Px were increased (P<0.05, P<0.01) when compared with the model group. CONCLUSION: Acupoint injection with VC+VBCo solution may alleviate inflammatory responses and oxidative stress in lung tissue of the PR8-induced pneumonia mice, improve survival rate and prolong the survival time in the case of no effect of the viral load.
Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Virus de la Influenza A , Neumonía , Puntos de Acupuntura , Animales , Interleucina-10 , Masculino , Ratones , Ratones Endogámicos ICR , Ribavirina/uso terapéutico , Superóxido Dismutasa , Factor de Necrosis Tumoral alfaRESUMEN
BACKGROUND: The present study aimed to explore the effectiveness of electro-acupuncture (EA) in combination with a local anesthetic used in Western medicine in preventing the side effects of gastroscopy. METHODS: A sample group of 150 patients were divided into three groups based on treatment methods: an EA group, a dyclonine hydrochloride mucilage group, and a combined treatment group. In the EA group, EA stimulation was given at the Hegu, Neiguan, and Zusanli acupoints; in the dyclonine hydrochloride mucilage group, patients took 10 mL of dyclonine hydrochloride mucilage orally; in the combined treatment group, prevention of side effects was attempted by administration of both acupuncture and oral local anesthetic. The incidences of nausea, emesis, salivation, cough, restlessness, and breath holding during gastroscopy were observed and recorded for the three groups. Mean arterial pressure, heart rate, and oxygen saturation were recorded before the examination, and changes in these measures were recorded as the gastroscope passed through the pylorus and after the examination. The visual analogue scale (VAS) values of nausea and emesis, the rate of successful first-pass intubation, and the time of gastroscopy were also recorded. Statistical analysis was performed using R-3.5.3 software. RESULTS: Incidences of side effects (e.g., nausea, emesis, salivation, restlessness, and breath holding) during the examination were lower in the combined treatment group than in the EA group and the dyclonine hydrochloride mucilage group (P<0.05 and P<0.01, respectively). Furthermore, the changes in heart rate and oxygen saturation when the gastroscope passed through the pylorus and after the examination were better in the combined treatment group than in the EA group and dyclonine hydrochloride mucilage group (P<0.01). The VAS values of nausea and emesis, the first-pass success rate, and examination duration were also better for the combined treatment group than for the other two groups (P<0.05 and P<0.01). CONCLUSIONS: EA combined with local anesthesia with dyclonine hydrochloride mucilage can alleviate side effects during gastroscopy, reduce patient pain, and improve the efficiency of the procedure.
Asunto(s)
Terapia por Acupuntura , Propiofenonas , Puntos de Acupuntura , Gastroscopía , HumanosRESUMEN
OBJECTIVE: To systematically evaluate the efficacy and safety of Tanreqing Injection (, TRQI) combined with conventional treatment on clinical outcomes in the treatment of patients with influenza. METHODS: The electronic databases searched were Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE (PubMed), EMbase (OvidSP), Chinese Bio-medical Literature and Retrieval System (Sinomed), China National Knowledge Infrastructure Database (CNKI), China Science and Technology Journal Database (VIP) and WanFang Data Knowledge Service Platform, and we checked the reference sections of the retrieved articles as well. The search was performed in October 2018, and we used the randomized controlled trials (RCTs) that corresponded to the new diagnostic criteria for influenza. Two review authors independently screened the internalized articles in accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) statement checklist. We evaluated the quality of the articles and extracted the data from the studies using the Revmen5.3 software. RESULTS: We included 12 RCTs of over 882 cases in this meta-analysis. Compared to conventional treatment, TRQI combined with conventional treatment could increase the total effective rate [9 RCTs, n=648, odds ratio (OR): 4.92, 95% confidence interval (CI): 2.94, 8.24, P<0.0001, random effects model], decrease the average time for fever clearance [7 RCTs, n=564, mean difference (MD): -1.08, 95% CI: -1.68, -0.48, P=0.0004, random effects model] and decrease the time for resolution of cough (5 RCTs, n=362, MD: -1.76, 95% CI: -2.63, -0.90, P<0.0001, random effects model). CONCLUSION: Based on this meta-analysis of RCTs, TRQI combined with conventional treatment had a statistically significant benefit in increasing the total effective treatment rate and reducing the time for fever clearance as well as time for resolution of cough.
Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Gripe Humana/tratamiento farmacológico , Tos/tratamiento farmacológico , Quimioterapia Combinada , Fiebre/tratamiento farmacológico , Humanos , Inyecciones , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVES: Although COVID-19 is known to be caused by human-to-human transmission, it remains largely unclear whether ambient air pollutants and meteorological parameters could promote its transmission. METHODS: A retrospective study was conducted to study whether air quality index (AQI), four ambient air pollutants (PM2.5, PM10, NO2 and CO) and five meteorological variables (daily temperature, highest temperature, lowest temperature, temperature difference and sunshine duration) could increase COVID-19 incidence in Wuhan and XiaoGan between Jan 26th to Feb 29th in 2020. RESULTS: First, a significant correlation was found between COVID-19 incidence and AQI in both Wuhan (R2=0.13, p<0.05) and XiaoGan (R2=0.223, p<0.01). Specifically, among four pollutants, COVID-19 incidence was prominently correlated with PM2.5 and NO2 in both cities. In Wuhan, the tightest correlation was observed between NO2 and COVID-19 incidence (R2=0.329, p<0.01). In XiaoGan, in addition to the PM2.5 (R2=0.117, p<0.01) and NO2 (R2=0.015, p<0.05), a notable correlation was also observed between the PM10 and COVID-19 incidence (R2=0.105, p<0.05). Moreover, temperature is the only meteorological parameter that constantly correlated well with COVID-19 incidence in both Wuhan and XiaoGan, but in an inverse correlation (p<0.05). CONCLUSIONS: AQI, PM2.5, NO2, and temperature are four variables that could promote the sustained transmission of COVID-19.