Weeks Of Drug Treatment Research Articles

Features of diagnosis and treatment of a child with choledochal cyst IС type

Choledochal cysts are congenital cystic dilatations of the extrahepatic and/or intrahepatic bile ducts. Diagnosis and choice of treatment tactics for this pathology often cause difficulties. A case report of a choledochal cyst in a 2-year-old patient with symptoms of recurrent jaundice, cholangitis, and pancreatitis, which required laparoscopic cholecystostomy and cholangiography during preparation for radical surgery, was retrospectively analyzed. The child was re-admitted to the pediatric surgical department with complaints of hyperthermia up to 39°C, resumption of periodic abdominal pain, nausea, and increased icterus of the sclera and skin. Laboratory and ultrasound examination indicated biliary and pancreatic hypertension. Choledochal cyst, cholestasis syndrome, acute cholecystopancreatitis was diagnosed. Owing to the existing clinical symptoms and laboratory and ultrasound data, laparoscopic cholecystostomy was urgently performed. Against the background of conservative therapy, within 2 days after laparoscopic cholecystostomy, clinically, laboratory and according to control ultrasound examination, biliary and pancreatic hypertension were stopped. The child underwent cholangiography through a cholecystostomy without additional anesthesia, which revealed a fusiform dilatation of the common hepatic and bile ducts. After 2 weeks of drug treatment against the background of laparoscopic cholecystostomy, the child underwent excision of the common bile duct cyst, and cholecystectomy with hepatic enteroanastomosis on a Roux-en-Y loop. The postoperative period was smooth. No other complaints or complications were noted within 24 months. In the reported case, recurrent obstructive jaundice was caused by a choledochal cyst. Laparoscopic cholecystostomy enabled the quick and successful relief of biliary hypertension, preparation of the patient for radical surgical treatment, and safe informative cholangiography through cholecystostomy. Hepatic enteroanastomosis with a disconnected loop according to Roux-en-Y was an effective surgical treatment method for choledochal cyst.

New Psychometric Strategies for the Evaluation of Affective, Cognitive, and Psychosocial Functioning in Unipolar versus Bipolar Depression: Impact of Drug Treatment.

Different studies have been conducted to understand how patients with unipolar and bipolar depression differ in terms of cognitive and affective symptoms as well as in psychosocial function. Furthermore, the impact of antidepressants, second-generation antipsychotics, and mood stabilizers on these dimensions needs to be characterized, as well as the best psychometric approach to measure changes after pharmacological treatment. This study aims to analyze the impact of psychotropic drugs on cognitive, affective, and psychosocial functioning in MDD and BD patients; to test the sensitivity of psychometric tools for measuring those changes; also, to understand how psychosocial abilities are associated with affective and cognitive dimensions in patients with MDD and BD. A total of 22 patients with MDD and 21 patients with BD in the depressive phase were recruited. Several psychometric tests were administered to assess affective, cognitive, and psychosocial symptoms before and after 12 weeks of drug treatment (T0 and T1) with different psychotropic drugs including second-generation antidepressants, second-generation antipsychotics and mood stabilizers (lamotrigine). MDD patients showed significant improvement in MoCA, Delayed Recall of Rey's 15 Words and HDRS, while a significant worsening was detected on Digit Span Backwards and on FAST scores. Instead, patients with BD showed significant improvements in the MoCA as the MDD patients, but only a trend of improvement (non-statistically significant) on the BDI-II. A positive correlation was detected in both groups between FAST and HDRS and BDI-II scores, especially in BD patients. Our results demonstrate that drug treatment with psychotropic drugs can improve cognitive and affective symptoms, but not all psychometric tools may be equally sensitive to detect those changes in MDD vs. BD patients. Moreover, we found that affective and cognitive dimensions can be considered as different psychopathological dimensions both in unipolar and bipolar depression.

Autophagy inhibitor 3-methyladenine attenuates renal injury in streptozotocin-induced diabetic mice.

To investigate whether 3-methyladenine (3-MA) can protect the kidney of streptozotocin (STZ) - induced diabetes mice, and explore its possible mechanism. STZ was used to induce diabetes in C57BL/6J mice. The mice were divided into normal control group (NC), diabetes group (DM), and diabetes+3-MA intervention group (DM+3-MA). Blood glucose, water consumption, and body weight were recorded weekly. At the end of the 6th week of drug treatment, 24-hour urine was collected. Blood and kidneys were collected for PAS staining to evaluate the degree of renal injury. Sirius red staining was used to assess collagen deposition. Blood urea nitrogen (BUN), serum creatinine, and 24-hour urine albumin were used to evaluate renal function. Western blot was used to detect fibrosis-related protein, inflammatory mediators, high mobility group box 1 (HMGB1)/NF-κB signal pathway molecule, vascular endothelial growth factor (VEGF), and podocin, and immunohistochemistry (IHC) was used to detect the expression and localization of autophagy-related protein and fibronectin. Compared with the kidney of normal control mice, the kidney of diabetes control mice was more pale and hypertrophic. Hyperglycemia induces renal autophagy and activates the HMGB1/NF-κB signal pathway, leading to the increase of inflammatory mediators, extracellular matrix (ECM) deposition, and proteinuria in the kidney. In diabetic mice treated with 3-MA, blood glucose decreased, autophagy and HMGB1/NF-κB signaling pathways in the kidneys were inhibited, and proteinuria, renal hypertrophy, inflammation, and fibrosis were improved. 3-MA can attenuate renal injury in STZ-induced diabetic mice through inhibition of autophagy and HMGB1/NF-κB signaling pathway.

Value of Chuanjin Qinggan decoction in improving the depressive state of patients with herpes zoster combined with depression.

Western medicine is beneficial for the recovery of neurological function in patients with depression, but some patients experience side effects such as headaches, dizziness, nausea, gastrointestinal symptoms, insomnia, and cardiac dysfunction. In recent years, integrative medicine has achieved positive results in the treatment of various diseases. To study Chuanjin Qinggan decoction combined with selective serotonin reuptake inhibitors (SSRIs) in patients with herpes zoster complicated by depression. Patients with herpes zoster complicated by depression who were treated at the Yantai Hospital of Traditional Chinese Medicine from January 2021 to December 2022 were retrospectively selected as research participants. Among them, 43 patients with herpes zoster complicated by depression who received SSRI treatment between January and December 2021 were assigned to the Western medicine group, while those who received combined treatment of traditional Chinese and Western medicine between January and December 2022 were assigned to the combined group. Both groups were treated for eight weeks. The degree of pain, effect of herpes zoster treatment, degree of improvement in depressive symptoms, serum neurotransmitter levels, sleep quality, and occurrence of adverse reactions were compared between the two groups. We found that after eight weeks of drug treatment, the two treatment schemes achieved differing efficacy. In further comparison, we found that, compared with patients treated with SSRIs alone, patients treated with Chuanjin Qinggan decoction combined with SSRIs showed more significant improvement in depression and a greater increase in dopamine and 5-hydroxytryptamine levels after treatment (P < 0.05). Patients treated with Chuanjin Qinggan decoction combined with SSRIs also experienced lower pain, better treatment efficacy for herpes zoster, better sleep quality, and a lower incidence of adverse reactions compared to those treated with SSRIs alone (P < 0.05). All minor adverse reactions occurring during treatment were resolved after symptomatic treatment. The treatment scheme of Chuanjin Qinggan decoction combined with SSRIs can improve the psychological state of patients with herpes zoster complicated by depression and alleviate adverse reactions.

Effects and mechanisms of total flavones of Abelmoschus manihot in inhibiting podocyte necroptosis and renal fibrosis in diabetic kidney disease

Previous studies have shown that high blood glucose-induced chronic microinflammation can cause inflammatory podocyte injury in patients with diabetic kidney disease(DKD). Therein, necroptosis is a new form of podocyte death that is closely associated with renal fibrosis(RF). To explore the effects and mechanisms in vivo of total flavones of Abelmoschus manihot(TFA), an extract from traditional Chinese herbal medicine Abelmoschus manihot for treating kidney diseases, on podocyte necroptosis and RF in DKD, and to further reveal its scientific connotation with multi-pathway and multi-target, the authors randomly divided all rats into four groups: a namely normal group, a model group, a TFA group and a rapamycin(RAP) group. After the modified DKD rat models were successfully established, four group rats were given double-distilled water, TFA suspension and RAP suspension, respectively by gavage every day. At the end of the 4th week of drug treatment, all rats were sacrificed, and the samples of their urine, blood and kidneys were collected. And then, the various indicators related to podocyte necroptosis and RF in the DKD model rats were observed, detected and analyzed, respectively. The results indicated that, general condition, body weight(BW), serum creatinine(Scr), urinary albumin(UAlb), and kidney hypertrophy index(KHI) in these modified DKD model rats were both improved by TFA and RAP. Indicators of RF, including glomerular histomorphological characteristics, fibronectin(FN) and collagen type Ⅰ(collagen Ⅰ) staining extent in glomeruli, as well as the protein expression levels of FN, collagen Ⅰ, transforming growth factor-β1(TGF-β1) and Smad2/3 in the kidneys were improved respectively by TFA and RAP. Podocyte damage, including foot process form and the protein expression levels of podocin and CD2AP in the kidneys was improved by TFA and RAP. In addition, tumor necrosis factor-α(TNF-α)-mediated podocyte necroptosis in the kidneys, including the morphological characteristics of podocyte necroptosis, the extent and levels of the protein expression of TNF-α and phosphorylated mixed lineage kinase domain like pseudokinase(p-MLKL) was improved respectively by TFA and RAP. Among them, RAP had the better effect on p-MLKL. More importantly, the activation of the receptor interacting serine/threonine protein kinase 1(RIPK1)/RIPK3/MLKL signaling axis in the kidneys, including the expression levels of its key signaling molecules, such as phosphorylated receptor interacting serine/threonine protein kinase 1(p-RIPK1), p-RIPK3, p-MLKL and cysteinyl aspartate specific proteinase-8(caspase-8) was improved respectively by TFA and RAP. Among them, the effect of TFA on p-RIPK1 was superior. On the whole, in this study, the authors demonstrated that TFA alleviates podocyte necroptosis and RF in DKD through inhibiting the activation of the TNF-α-mediated RIPK1/RIPK3/MLKL signaling axis in diabetic kidneys. The authors' findings provide new pharmacological evidence to reveal the scientific connotation of TFA in treating RF in DKD in more depth.

Focused ultrasound: a novel therapy for improving vaginal microecology in patients with high-risk HPV infection

Objectives To investigate changes in vaginal microecology in women with high-risk human papillomavirus (HR-HPV) infection after focused ultrasound (FU) treatment. Materials and methods We collected vaginal secretions at the time of admission and 3 months after FU treatment from 169 women who received FU treatment for cervical HR-HPV infection between July 2020 and September 2022. Among them, there were 101 patients with cute vaginitis, we also collected their vaginal secretions after one week of drug treatment. These samples were evaluated for vaginal microecology and HPV-DNA examination. Results Of the 169 patients, 101 (59.7%) suffered from acute vaginitis at the time of admission. After one week of targeted antibiotics drug treatment, there were no pathogens or pus cells on the field of microscopic vision, but there was no significant difference(p > 0.05) in the diversity and density of vaginal flora, the proportion and function of Lactobacillus (H2O2 negative rate) between one week after treatment and at the time of admission. At the time of admission of the 169 patients, the normal flora rate was 40.3%, which increased to 93.5% three months after FU treatment. The differences in vaginal secretion parameters at the time of admission and 3 months after FU treatment were as follows: H2O2 negative rate (37.3% vs. 3.6%), leukocyte esterase positive rate (54.4% vs. 5.9%), sialidase positive rate (38.5% vs. 4.1%), bacterial vaginitis positive rate (55% vs. 4.7%), fungal vaginitis positive rate (44.4% vs. 5.9%), and trichomonal vaginitis positive rate (7.1% vs. 0). The difference was statistically significant (p < 0.01). The pH value and Nagent score at the time of admission were significantly higher than those three months after FU. Three months after FU, the positive rate of HPV was 5.8% in the group of patients with normal vaginal microecology at the time of admission and post-FU; it was 6.7% in the group of patients with abnormal vaginal microecology at the time of admission and normal vaginal microecology post-FU; and it was 100% in the group patients with abnormal vaginal microecology at the time of admission and post-FU. A significant difference was observed among the three groups (p < 0.01). Conclusion FU is an effective treatment for patients with cervical HR-HPV infection. FU does not interfere with the vaginal microecology of HR-HPV positive patients with normal vaginal microecology.FU followed by antibiotic drug therapy for pathogens is beneficial to restore the function of Lactobacillus vaginalis in HR-HPV positive patients with acute vaginitis,so as to improve the vaginal microecology of HR-HPV positive patients with abnormal vaginal microecology.

Levosimendan Reverses Cardiac Malfunction and Cardiomyocyte Ferroptosis During Heart Failure with Preserved Ejection Fraction via Connexin 43 Signaling Activation.

In recent decades, the occurrence of heart failure with preserved ejection fraction (HFpEF) has outweighed that of heart failure with reduced ejection fraction by degrees, but few drugs have been demonstrated to improve long-term clinical outcomes in patients with HFpEF. Levosimendan, a calcium-sensitizing cardiotonic agent, improves decompensated heart failure clinically. However, the anti-HFpEF activities of levosimendan and underlying molecular mechanisms are unclear. In this study, a double-hit HFpEF C57BL/6N mouse model was established, and levosimendan (3 mg/kg/week) was administered to HFpEF mice aged 13 to 17 weeks. Different biological experimental techniques were used to verify the protective effects of levosimendan against HFpEF. After four weeks of drug treatment, left ventricular diastolic dysfunction, cardiac hypertrophy, pulmonary congestion, and exercise exhaustion were significantly alleviated. Junction proteins in the endothelial barrier and between cardiomyocytes were also improved by levosimendan. Among the gap junction channel proteins, connexin 43, which was especially highly expressed in cardiomyocytes, mediated mitochondrial protection. Furthermore, levosimendan reversed mitochondrial malfunction in HFpEF mice, as evidenced by increased mitofilin and decreased ROS, superoxide anion, NOX4, and cytochrome C levels. Interestingly, after levosimendan administration, myocardial tissue from HFpEF mice showed restricted ferroptosis, indicated by an increased GSH/GSSG ratio; upregulated GPX4, xCT, and FSP-1 expression; and reduced intracellular ferrous ion, MDA, and 4-HNE levels. Regular long-term levosimendan administration can benefit cardiac function in a mouse model of HFpEF with metabolic syndromes (namely, obesity and hypertension) by activating connexin 43-mediated mitochondrial protection and sequential ferroptosis inhibition in cardiomyocytes.

Isorhynchophylline alleviates cartilage degeneration in osteoarthritis by activating autophagy of chondrocytes

ContextOsteoarthritis is a common degenerative disease, the cause of it is still unknown, and the treatment mainly focuses on improving symptoms. Studies have found that Isorhynchophylline (Isorhy) has antioxidant, anti-inflammatory, antiproliferative and neuroprotective effects.ObjectiveThis study investigates the role and mechanism of Isorhy in OA.MethodsThe destabilized medial meniscus model was used to mimic OA. Fifteen male Sprague Dawley rats were partitioned into three portions: Normal group, OA group (surgery; normal saline treatment) and OA + Isorhy group (surgery; 50 μM Isorhy treatment) were performed on the first day of every week from the 5th to the 8th week after surgery. After 4 weeks of drug treatment, the rats have been processed without debridement of the knee specimens and fixed using 4% paraformaldehyde for two days. The morphological analysis was performed by H&E, Safranin O-Fast green staining and micro-CT analysis. The specimens were researched employing Micro-CT. In the part of the aggregate methods that were evaluated by qRT-PCR and western blot of the following proteins LC3II/LC3I, Beclin-1, ATG5, ATG7, MMP3 andMMP13. Akt/PI3K signaling related proteins (p-AKT, AKT, p-PI3K, PI3K, p-mTOR, mTOR) were detected by Western blot. BECLIN1 and MMP3 were detected by Immunofluorescence assay.ResultsIn this present research, it was proved that autophagy-related and cartilage matrix-related proteins in osteoarthritis could be regulated by Isorhynchophylline treatment. The transcriptome sequencing results suggested the regulation was closely associated with PI3K/AKT/mTOR pathway, thereby alleviating osteoarticular inflammation. In-depth study showed that Isorhy could also affect OA in rat OA models, that was indicated by H&E, Safranin O-Fast green staining, and also micro-CT analysis.ConclusionOur findings indicated that Isorhy could be regarded as a prospective candidate for OA treatment.

Raspberry Ketone Protects Kidney Damage in Diabetic Nephropathy by Improving Kidney Mitochondrial Dysfunction

Mitochondrial dysfunction and oxidative stress play essential roles in the pathogenesis of diabetic nephropathy (DN). The respiratory oxygen consumption and oxidative stress status of kidney mitochondria are closely associated with the development of DN. In this study, raspberry ketone (RK), the predominant bioactive component extracted from raspberry, was applied to treat the established DN mice model. This study investigated whether RK protects the kidneys of high-fat and high-sugar/streptozotocin (STZ)-induced diabetic rats by inhibiting oxidative stress and ameliorating mitochondrial dysfunction. Besides, the DN mice models were established by injecting high-fat and high-sugar/STZ (130 mg/kg, intraperitoneal injection). The animals were randomly divided into the control group (normal saline, ig), DN group (normal saline, ig), DN + RK group (200 mg/kg RK + normal saline, ig), DN + RK group (400 mg/kg RK + normal saline, ig), and DN + Metformin (Met) (200 mg/kg Met + normal saline, ig). Regular monitoring of fasting blood glucose (FBG) levels was observed in mice. After 10 weeks of drug treatment, the kidneys of mice in each group were analyzed using ultrasound, and the mice were euthanized humanely. Kidney weight (KW)/body weight (BW) and kidney injury, mitochondrial function, and oxidative stress indicators were determined. The histopathological changes in renal tissue were observed after hematoxylin and eosin (H&amp;E) staining. The results recommended that RK has a renoprotective function on DN mice by improving mitochondrial dysfunction and inhibiting oxidative stress.

Serum metabolomic profiling revealed potential diagnostic biomarkers in patients with panic disorder

BackgroundCurrently, specific metabolites and diagnostic biomarkers of panic disorder (PD) patients have not been identified in clinical practice. The aim of this study was to explore metabolites and metabolic pathways in serum through a metabolomics method. MethodsFifty-five PD patients who completed 2 weeks of inpatient treatment and 55 healthy control subjects (HCs) matched for age, sex and BMI were recruited. Ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) was used to detect metabolites in serum. Multivariate Statistical Analysis was used to identify differential metabolites. The relevant biometabolic pathways were further identified by the online tool MetaboAnalyst 5.0. Results43 different metabolites in PD patients compared to HCs (P < 0.05) were screened. Pathway analysis showed that these small molecules were mainly associated with amino acid metabolism. 14 metabolites were significantly changed after 2 weeks of drug treatment (P < 0.05), which were mainly associated with tryptophan metabolism. ConclusionIn conclusion, our analysis of metabolomics of PD patients at baseline and two weeks after treatment screened for differential metabolites that could be potential diagnostic biomarkers involved in PD pathogenesis and influence some biometabolic pathways such as phenylalanine metabolism and tryptophan metabolism. In the future, we can summarize and observe the dynamic changes of differential metabolites that appear more frequently in similar studies to further explore the underlying mechanisms of PD evolution.

A case report of multiple Mycobacterium Kansasii bone infection with pathological fracture of T11 vertebral body and thoracic spinal cord injury

Rationale: Cases of vertebral infection with bone destruction and spinal cord injury caused by Mycobacterium kansasii infection are rarely reported, and the infection is usually associated with severe immunosuppression. Patient concerns: A 62-year-old male patient was hospitalized for 10 days due to recurrent low back pain with diminished skin sensation below the umbilical level. Diagnosis: The patient had no underlying disease. MRI showed multiple bone destruction lesions throughout the body, pathological fractures of the T11 vertebral body, and compression and degeneration of the thoracic spinal cord. Complete back abscess puncture examination, CT-guided vertebral puncture examination, metagenomic next-generation sequencing and bone marrow puncture and other examinations to confirm the diagnosis of Mycobacterium kansasii infection. Intervention: According to the drug susceptibility test of pathogenic bacteria, combined antiinfective treatment was given. After 3 weeks of drug treatment, the patient underwent thoracic posterior debridement, spinal canal decompression, and pedicle screw internal fixation. Outcome: The skin sensation of the patient’s lower limbs was improved 1 month after the operation compared with that before the operation. After adhering to oral drug treatment, the inflammatory index decreased steadily. Four months after the operation, the skin sensation of the patient’s lower extremities returned to normal. Lessons: Regular, adequate, and full course of drug treatment is the key to the treatment of Mycobacterium kansasii infection. Next-generation metagenomic sequencing can improve the efficiency and accuracy of the detection of Mycobacterium kansasii. For patients with abscesses and spinal nerve compression, surgical decompression and abscess removal are effective treatment options.

Comparison of Clinical Efficacy of Sodium Nitroprusside and Urapidil in the Treatment of Acute Hypertensive Cerebral Hemorrhage.

This paper mainly studies the clinical efficacy of sodium nitroprusside and urapidil in the treatment of acute hypertensive intracerebral hemorrhage and analyzes the brain CT image detection based on a deep learning algorithm. A total of 132 cases of acute hypertension admitted to XXX hospital from XX 2019 to XX 2020 were retrospectively analyzed. The diseases of all patients were clinically confirmed, and patients were divided into groups according to the differences in treatment methods. Urapidil was used for group 1; sodium nitroprusside was used for group 2; and urapidil combined with sodium nitroprusside was used for group 3. A convolutional neural network in deep learning is used to construct intelligent processing to classify brain CT images of patients. The network performance of AlexNet, GoogLeNet, and CNN3 is predicted. The results show that GoogLeNet has the highest prediction accuracy of 0.83, followed by AlexNet with 0.80 and CNN3 with 0.74. The results of the performance parameter curve show that the GoogLeNet has the highest performance parameter of 0.89, followed by AlexNet and CNN3 network. The performance parameter curve of machine learning is above 0.80. After five weeks of drug treatment, the hematoma volume was (3.8 ± 2.6) mL in group1, (7.6 ± 2.8) mL in group 2, and (2.8 ± 1.5) mL in group 3. After 5 days of treatment, the patients' heart rate changed compared with before treatment. Compared with group 2, there were significant differences between groups 1 and 3 (P < 0.01), indicating that the therapeutic effect of the combination group was significantly better than that of the other groups alone. In summary, the combination of sodium nitroprusside and urapidil has a significantly better effect than that of urapidil alone. A convolutional neural network based on deep learning improves the recognition accuracy of medical images.

Mechanism of Yifei Decoction Combined with MitoQ on Inhibition of TGFβ1/NOX4 and PDGF/ROCK Signal Pathway in Idiopathic Pulmonary Fibrosis.

Background Rho-related coiled helix forming protein kinase (Rho-ROCK) and another important fibrogenic factor-PDGF play a critical role in collagen deposition in rat lung tissue. Yifei decoction (YFT), a Chinese herbal decoction, has been used to treat idiopathic pulmonary fibrosis (IPF) in clinical practice and has produced positive outcomes; however, convincing evidence is currently lacking. The present study aimed to investigate the effects of YFT combined with MitoQ in rats with IPF and to explore the underlying mechanism. Methods Rat IPF model was established by endotracheal injection of 5 mg/kg BleomycinA5 into the specific pathogen-free SD rats. MitoQ (6.5 μmol/kg once daily), YFT (10 ml/kg once daily), and MitoQ + YFT (6.5 μmol/kg + 10 ml/kg once daily) were used to treat the rat model for 4 weeks, respectively. The normal rats without IPF were used as the controls. After 4 weeks of drug treatment, lung histopathology was assessed. Immunohistochemistry was used to detect the expression of fibronectin and collagen IV in lung tissue. The expression of IL-6, IL-1β, TNF-α, GSH-Px, SOD, MDA, and hydroxyproline was determined by enzyme-linked immunosorbent assay. The expressions of TGFβ1, NOX4, PDGFR-β, and ROCK1 were determined using real-time quantitative PCR and Western blot. Results After 4 weeks of drug treatment, comparison of the MitoQ + YFT group with the IPF group showed that lung injury scores, W/D, lung tissue hydroxyproline, fibronectin, collagen IV content, and IL-6, IL-1β, TNF-α, and MDA levels were significantly lower (P < 0.05), as well as the expression of TGFβ1, NOX4, PDGFR-β, and ROCK1, but the activity of GSH-Px and SOD was higher (P < 0.05). Conclusion MitoQ combined with YFT can improve lung injury in rats with pulmonary fibrosis by reducing the secretion of proinflammatory cytokines and inhibiting TGFβ1/NOX4 and PDGF/ROCK signaling pathways. It may provide a new method for the treatment of pulmonary fibrosis.

Chemically-Modified Tetraiodothyroacetic Acid (Tetrac) Induces Cancer Cell Apoptosis and Facilitates Clearance of Apoptotic Debris (Efferocytosis)

Tetraiodothyroaetic acid (tetrac) is a derivative of L-thyroxine with anticancer properties. By multiple molecular mechanisms, tetrac and chemically-modified tetrac induce apoptosis in a variety of human cancer cells in vitro and in xenografts. The anticancer activities of tetrac are initiated at the thyroid hormone analogue receptor on the extracellular domain of plasma membrane integrin αvβ3 (PJ Davis et al., Physiol Rev 101:319-352, 2021). Induction of apoptosis in glioblastoma xenograft with chemically modified tetrac (P-bi-TAT) has yielded 90% in volume of grafts that continues after discontinuation of tetrac. In the present study, we show that human glioblastoma xenograft shrinkage in response to P-bi-TAT is associated with local appearance of phagocytic monocytes and clearance of apoptotic debris (efferocytosis). Primary culture xenograft of glioblastoma cells (GBM 052814, kindly provided by the University of Pittsburgh Medical Center, Department of Neurosurgery) and U87-luc (ATCC, Manassas, VA) xenografts were generated in 5-member groups of nude mice for each tumor cell type and for controls. Five days post-implantation, injection of animals was begun with PBS (control) or P-bi-TAT (10 mg/kg body weight). Injection was continued X21 days and animals were then maintained off-treatment for an additional 21 days. Tumors were harvested, formalin-fixed and slide-mounted, then analyzed by TUNEL assay for apoptosis and by anti-CD68 staining for monocytic macrophage content. Histologic analysis (H&E staining) was also carried out. TUNEL analysis and histopathology of both xenograft models revealed more than 90% apoptotic change with 21-days of P-bi-TAT treatment (P <0.001) and persistence of 40% apoptotic change 3 weeks post-discontinuation of drug (P<0.001 vs. end of treatment change). By H&E histology and CD68 analysis, monocytes accounted for more than 90% of the viable cells after 3 weeks’ drug treatment. Sixty percent of the end-of-treatment monocyte population persisted 3 weeks after discontinuation of P-bi-TAT (P <0.001). Histology revealed negligible cell debris after 3 weeks of drug treatment and at 3 weeks post-discontinuation of P-bi-TAT. Thus, the anticancer/pro-apoptotic action of tetrac-containing P-bi-TAT is associated with efferocytosis that contributes to the frank tumor shrinkage that results from P-bi-TAT treatment of human glioblastoma xenografts. This is the first documentation of efferocytosis regulated from the thyroid hormone analogue receptor on tumor cell integrin αvβ3.

The Effectiveness of Sovodak in the Treatment of Patients with Chronic Hepatitis C

Background: Recently, interferon-free treatment has been considered for the treatment of chronic hepatitis C due to their high therapeutic success and lack of serious side effects. The combination of Sofosbuvir and Daclatasvir is effective in the treatment of the disease because of its pan-genotype. In the present study, the effectiveness of Sovodak, which is a combination of the aforementioned two drugs in one tablet, in the treatment of patients with chronic hepatitis C and cirrhosis was investigated.&#x0D; Methods: Patients with chronic hepatitis C whose diagnosis was confirmed by HCV RNA–PCR test were included in the study. These patients received one Sovodak tablet daily (for 12 weeks for non-cirrhotic patients and 24 weeks for cirrhotic patients). Sustained virologic response (SVR) was assessed by PCR test 12 weeks after the end of the treatment and one year later. Also, serum levels of liver enzymes, platelet count, and liver stiffness (using elastography method) were measured and their levels were compared before and after treatment in patients.&#x0D; Results: Findings related to the PCR test in patients showed that the level of SVR was 100% in patients 12 weeks after treatment (SVR-12). In three cirrhotic patients who received only 12 weeks of drug treatment, the disease recurred a year later. According to the results, ALT and AST serum levels were significantly decreased (P &lt; 0.001), and platelet count level was increased (P &lt; 0.001) one year after the end of the treatment period. Also, the liver stiffness index measured using FibroScan was significantly decreased in patients 12 weeks after the end of the treatment (P &lt; 0.001).&#x0D; Conclusion: The results of this study, in line with other studies, showed the effective role of Sovodak in completely eliminating the HCV virus in patients with chronic hepatitis C. Cirrhotic patients need to receive treatment for at least six months.&#x0D; Key words: Sovodak, hepatitis C, sustained virologic response, effectiveness, liver cirrhosis

Fourteen-day PET/CT imaging to monitor drug combination activity in treated individuals with tuberculosis.

Early bactericidal activity studies monitor daily sputum bacterial counts in individuals with tuberculosis (TB) for 14 days during experimental drug treatment. The rate of change in sputum bacterial load over time provides an informative, but imperfect, estimate of drug activity and is considered a critical step in development of new TB drugs. In this clinical study, 160 participants with TB received isoniazid, pyrazinamide, or rifampicin, components of first-line chemotherapy, and moxifloxacin individually and in combination. In addition to standard bacterial enumeration in sputum, participants underwent 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography and computerized tomography ([18F]FDG-PET/CT) at the beginning and end of the 14-day drug treatment. Quantitating radiological responses to drug treatment provided comparative single and combination drug activity measures across lung lesion types that correlated more closely with established clinical outcomes when combined with sputum enumeration compared to sputum enumeration alone. Rifampicin and rifampicin-containing drug combinations were most effective in reducing both lung lesion volume measured by CT imaging and lesion-associated inflammation measured by PET imaging. Moxifloxacin was not superior to rifampicin in any measure by PET/CT imaging, consistent with its performance in recent phase 3 clinical trials. PET/CT imaging revealed synergy between isoniazid and pyrazinamide and demonstrated that the activity of pyrazinamide was limited to lung lesion, showing the highest FDG uptake during the first 2 weeks of drug treatment. [18F]FDG-PET/CT imaging may be useful for measuring the activity of single drugs and drug combinations during evaluation of potential new TB drug regimens before phase 3 trials.

Effect of Danhong Injection () on Improving Coronary Microcirculation Injury after Percutaneous Coronary Intervention.

To explore the effectiveness of Danhong Injection () on improving microcirculatory injury after percutaneous coronary intervention (PCI) in patients with coronary heart disease (CHD). A randomized controlled trial was conducted and 90 patients were enrolled. A random sequence was generated using statistical analysis software. Patients with microcirculatory injuries after PCI were randomly divided into 3 groups for treatment (30 subjects in each group): Danhong Injection group: after PCI, Danghong Injections were given with intravenous administration with 40 mL twice a day for a week; statins intensive group: after PCI, atorvastatin calcium tablets were given oral medication with 80 mg once, and then atorvastatin 40 mg daily for 1 week; the control group: after PCI, atorvastatin calcium tablets were given oral medication with 10-20 mg daily for 1 week. The index of microcirculation resistance (IMR) was used to assess microcirculatory injury during PCI. The IMR of the target vessel was reexamined after 1 week of drug treatment. After one week's drug treatment, IMR was significantly decreased in both statins intensive group and Danhong Injection group compared with the control group (P<0.01), but no difference was found between statins intensive group and Danhong injection group (14.03 ± 2.54 vs. 16.03 ± 5.72 U, P=0.080). The efficacy of Danhong Injection is non-inferior to statin. Early use of Danhong Injection after PCI can effectively improve coronary microcirculation injury after PCI.

Improvement effect and mechanism of ethanol extract from Citri Reticulatae Pericarpium on triglyceride in hyperlipidemia model rat

The aim of this paper was to study the improvement effect of ethanol extract from Citri Reticulatae Pericarpium(CRP) on triglyceride of hyperlipidemia model rats, and to explore the possible mechanism. SD rats were randomly divided into normal group, model group, positive control group, and high, medium and low-dose CRP ethanol extract groups, with 10 rats in each group. During the experiment, except for the normal group that was fed with distilled water and ordinary feed, rats in the other groups were given different concentrations of alcohol and fed with high-sugar and fat diets. All rats were given free diets. While being modeled, each group was administered with 0.01 mL·g~(-1) by gavage once a day for six weeks. Blood samples were collected after two weeks, four weeks and six weeks of drug treatment. After the completion of the experiment, blood, liver and adipose tissue were collected. Triglyceride(TG), alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP) in serum, TG in liver tissue and TG in fecal were detected. Free fatty acid(FFA) and triglyceride-related hydrolase, such as adipose tiglyceride lipase(ATGL), lipoprotein lipase(LPL), hepatic lipase(HL), hormone-sensitive triglyceride lipase(HSL) were detected by ELISA. The mRNA expressions of peroxisome proliferators-activated receptors(PPARγ), sterol regulatory element binding protein 1 c(SREBP-1 c) and farnesoid X receptor(FXR) were determined by RT-PCR. Compared with the model group, each administration group could reduce TG levels in serum and liver to varying degrees, reduce serum ALT, AST, ALP activities, significantly reduce free fatty acid content in serum, significantly increase triglyceride metabolism-related enzymes, including fat ATGL, LPL and liver HL content, and significantly reduced the content of fat HSL. According to the study of transcriptional regulation genes relating to triglyceride metabolism, extract from CRP could significantly increase the mRNA expressions of PPARγ and FXR. In conclusion, ethanol extract from CRP could ob-viously reduce the TG level of hyperlipidemia model rats, and might reduce plasma TG content by increasing PPARγ-LPL/ATGL and FXR-HL triglyceride hydrolysis pathways.

Effects of Genetic Polymorphisms of Drug Transporter ABCB1 (MDR1) and Cytochrome P450 Enzymes CYP2A6, CYP2B6 on Nicotine Addiction and Smoking Cessation

ObjectivesTo determine the effects of genetic polymorphisms of ABCB1 (MDR1), CYP2A6, CYP2B6 on smoking status, and clinical outcomes of smoking cessation therapies in a Turkish population.Methods130 smokers and 130 non-smokers were recruited. Individuals who never smoked were described as non-smokers. 130 smokers were treated with nicotine replacement therapy (NRT) (n = 40), bupropion (n = 47), bupropion + NRT (n = 15), and varenicline (n = 28). Smokers were checked by phone after 12 weeks of treatment whether they were able to quit smoking or not. Genotyping and phenotyping were performed.ResultsCessation rates were as follows; 20.0% for NRT, 29.8% for bupropion, 40.0% for bupropion + NRT, 57.1% for varenicline (p = 0.013). The frequency of ABCB1 1236TT-2677TT-3435TT haplotype was significantly higher in non-smokers as compared to smokers (21.5% vs. 10.8, respectively; p = 0.018). Neither smoking status nor smoking cessation rates were associated with genetic variants of CYP2A6 (p = 0.652, p = 0.328, respectively), or variants of CYP2B6 (p = 0.514, p = 0.779, respectively).ConclusionGenetic variants of the drug transporter ABCB1 and the 1236TT-2677TT-3435TT haplotype was significantly associated with non-smoking status. Neither ABCB1 nor CYP2A6, CYP2B6 genetic variants were associated with smoking cessation rates at the 12th week of drug treatment.

Therapeutic effects of various renin angiotensin modulators on hyperglycemia-induced cataract formation in Sprague Dawley rats.

Our previous research work reported the beneficial effects of angiotensin receptor blockers (ARBs) for the treatment of diabetes associated cataract which was induced by streptozotocin (STZ). The current study, evaluated the effects of topical administration of various renin angiotensin modulators on STZ-induced cataracts in rats. Single dose of STZ (60 mg/kg, i.p.) was administered in the rats to induce diabetes. Animals were divided into normal and diabetic rats. Normal rats were administered with single dose of sodium citrate buffer (0.1 M, 10ml/kg, i.p.). Diabetic animals were divided into various treatment groups, each group contains six animals and received aliskiren, olmesartan, enalapril, and angiotensin 1-7 at a dose of 0.5% w/v topically on the cornea of the eye for a period of 8 weeks. During experimental protocol morphology of the eyes and lenticular opacity were monitored. Animals were sacrificed after 8 weeks of drug treatment, and various cataractogenic biochemical parameters were assessed. Topical administrations with aliskiren, enalapril, olmesartan, and angiotensin 1-7 showed non-significant alterations in the blood glucose level, but significantly decreased lenticular opacity, restored antioxidant level, restored MDA level and Nitrite content, and decreased the onset of cataract formation. Overall, our findings suggest that topical treatment with renin angiotensin modulators delayed the onset of diabetes-induced cataract formation.