Machine learning enabled multiplex detection of periodontal pathogens by surface-enhanced Raman spectroscopy.

Periodontitis is a chronic inflammation of the periodontium caused by a persistent bacterial infection, resulting in destruction of the supporting structures of teeth. Analysis of microbial composition in saliva can inform periodontal status. Actinobacillus actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), and Streptococcus mutans (Sm) are among reported periodontal pathogens, and were used as model systems in this study. Our atomic force microscopic (AFM) study revealed that these pathogens are biological nanorods with dimensions of 0.6-1.1 µm in length and 500-700 nm in width. Current bacterial detection methods often involve complex preparation steps and require labeled reporting motifs. Employing surface-enhanced Raman spectroscopy (SERS), we revealed cell-type specific Raman signatures of these pathogens for label-free detection. It overcame the complexity associated with spectral overlaps among different bacterial species, relying on high signal-to-noise ratio (SNR) spectra carefully collected from pure species samples. To enable simple, rapid, and multiplexed detection, we harnessed advanced machine learning techniques to establish predictive models based on a large set of raw spectra of each bacterial species and their mixtures. Using these models, given a raw spectrum collected from a bacterial suspension, simultaneous identification of all three species in the test sample was achieved at 95.6 % accuracy. This sensing modality can be applied to multiplex detection of a broader range and a larger set of periodontal pathogens, paving the way for hassle-free detection of oral bacteria in saliva with little to no sample preparation.

Distinctive structure, composition and biomechanics of collagen fibrils in vaginal wall connective tissues associated with pelvic organ prolapse.

Collagen is the predominant structural protein within connective tissues. Pelvic organ prolapse (POP) is characterized by weakening of the pelvic floor connective tissues and loss of support for pelvic organs. In this study, we examined the multiscale structure, molecular composition and biomechanics of native collagen fibrils in connective tissues of the posterior vaginal fornix collected from healthy women and POP patients, and established the correlation of these properties with clinical POP quantification (POP-Q) scores. The collagen characteristics, including collagen amount, ratio of Collagen I and Collagen III, collagen fibril d-period, alignment and stiffness, were found to change progressively with the increase of the clinical measurement of Point C, a measure of uterine descent and apical prolapse. The results imply that a severe prolapse is associated with stiffer collagen fibrils, reduced collagen d-period, increased fibril alignment and imbalanced collagen synthesis, degradation and deposition. Additionally, prolapse progression appears to be synchronized with deterioration of the collagen matrix, suggesting that a POP-Q score obtained via a non-invasive clinical test can be potentially used to quantitatively assess collagen abnormality of a patient's local tissue. STATEMENT OF SIGNIFICANCE: Abnormal collagen metabolism and deposition are known to associate with connective tissue disorders, such as pelvic organ prolapse. Quantitative correlation of the biochemical and biophysical characteristics of collagen in a prolapse patient's tissue with the clinical diagnostic measurements is unexplored and unestablished. This study fills the knowledge gap between clinical prolapse quantification and the individual's cellular and molecular disorders leading to connective tissue failure, thus, provides the basis for clinicians to employ personalized treatment that can best manage the patient's condition and to alert pre-symptomatic patients for early management to avoid unwanted surgery.

Role of photobleaching process of indocyanine green for killing neuroblastoma cells.

Indocyanine green (ICG) is an FDA-approved near infrared (NIR) imaging agent for diagnosis and imaging guided surgery. It also exhibits phototoxicity under high-dose NIR irradiation, expanding its application as a photo-therapeutic agent. Since ICG's efficiency as a type II photosensitizer has been controversial due to its low triplet state yield, other mechanisms have been explored. While claims of toxic decomposition products, accompanied by irreversible ICG photobleaching, were proposed as the main mechanism, evidences from systemic studies are lacking. In this work, we aimed to unravel the factors affecting ICG photobleaching and the associated photo-killing effect on neuroblastoma, one of the most common pediatric tumors but often escapes therapy. Specifically, we examined how albumin-induced ICG stabilization affects the ICG photobleaching process, and the effect of photobleached ICG on cell proliferation and viability of neuroblastoma cells. It was found that ICG photobleaching was significant only under aerobic conditions and was more efficient in solutions with higher concentration ICG monomers, which were stabilized from aggregates by the presence of BSA while increasing photobleaching and associated oxygen consumption. Photobleached ICG inhibited cell proliferation, indicating another effect of tumor treatment by ICG. Taken together, while enhanced photobleaching by BSA-bound ICG monomers may reduce the photodynamic effect targeting cellular components, the photoproducts directly contribute to tumor growth inhibition and assist in a secondary mechanism to stop tumor growth.

Electrospun Silk Fibroin-CNT Composite Fibers: Characterization and Application in Mediating Fibroblast Stimulation.

Electrospinning is a simple, low-cost, and highly efficient technique to generate desirable nano/microfibers from polymer solutions. Silk fibroin (SF), a biopolymer found in Bombyx mori cocoons, has attracted attention for various biomedical applications. In this study, functionalized CNT was incorporated in SF to generate biocomposite fibers by electrospinning. The electrospun (E-spun) fibers were well aligned with morphology mimicking the locally oriented ECM proteins in connective tissues. While as-spun fibers dissolved in water in just two minutes, ethanol vapor post-treatment promoted ß-sheet formation leading to improved fiber stability in an aqueous environment (>14 days). The addition of a minute amount of CNT effectively improved the E-spun fiber alignment and mechanical strength while retained high biocompatibility and biodegradability. The fibers' electrical conductivity increased by 13.7 folds and 21.8 folds, respectively, in the presence of 0.1 w% and 0.2 w% CNT in SF fibers. With aligned SF-CNT 0.1 % fibers as a cell culture matrix, we found electrical stimulation effectively activated fibroblasts from patients of pelvic organ prolapse (POP), a connective tissue disorder. The stimulation boosted the fibroblasts' productivity of collagen III (COLIII) and collagen I (COLI) by 74 folds and 58 folds, respectively, and reduced the COLI to COLIII ratio favorable for tissue repair. The developed material and method offer a simple, direct, and effective way to remedy the dysfunctional fibroblasts of patients for personalized cell therapeutic treatment of diseases and health conditions associated with collagen disorder.

Clinical progress and advanced research of red blood cells based drug delivery system.

Red blood cells (RBCs) are biocompatible carriers that can be employed to deliver different bioactive substances. In the past few decades, many strategies have been developed to encapsulate or attach drugs to RBCs. Osmotic-based encapsulation methods have been industrialized recently, and some encapsulated RBC formulations have reached the clinical stage for treating tumors and neurological diseases. Inspired by the intrinsic properties of intact RBCs, some advanced delivery strategies have also been proposed. These delivery systems combine RBCs with other novel systems to further exploit and expand the application of RBCs. This review summarizes the clinical progress of drugs encapsulated into intact RBCs, focusing on the loading and clinical trials. It also introduces the latest advanced research based on developing prospects and limitations of intact RBCs drug delivery system (DDS), hoping to provide a reference for related research fields and further application potential of intact RBCs based drug delivery system.

[Application of Hydrashift 2/4 daratumumab assay in eliminating interference of daratumumab on serum immunofixation electrophoresis].

Objective: To investigate the interference of daratumumab on immunofixation electrophoresis after treating plasma cell diseases and methods to eliminate the interference. Methods: Serum samples of eight patients with plasma cell diseases treated with daratumumab in Peking University People's Hospital from April 2020 to March 2021 were collected for standard immunofixation electrophoresis and Hydrashift 2/4 daratumumab assay. Results: After treatment, 81.3% (13/16) of the samples showed drug-induced monoclonal antibodies (IgG-κ) . The samples without drug-induced monoclonal bands were related to individual differences, administration intervals, and immunoglobulin levels. Among the samples with IgG-κ monoclonal bands, 76.9% (10/13) could be directly identified as endogenous or exogenous monoclonal bands by immunofixation electrophoresis, and the others (3/13) could be identified by Hydrashift 2/4 daratumumab assay. Conclusion: Hydrashift 2/4 daratumumab assay can remove the band of daratumumab on the immunofixation electrophoresis and help with efficacy evaluation.

Maf1 suppression of ATF5-dependent mitochondrial unfolded protein response contributes to rapamycin-induced radio-sensitivity in lung cancer cell line A549.

mTOR is well known to promote tumor growth but its roles in enhancing chemotherapy and radiotherapy have not been well studied. mTOR inhibition by rapamycin can sensitize cancer cells to radiotherapy. Here we show that Maf1 is required for rapamycin to increase radio-sensitivity in A549 lung cancer cells. In response to ionizing radiation (IR), Maf1 is inhibited by Akt-dependent re-phosphorylation, which activates mitochondrial unfolded protein response (UPRmt) through ATF5. Rapamycin suppresses IR-induced Maf1 re-phosphorylation and UPRmt activation in A549 cells, resulting in increased sensitivity to IR-mediated cytotoxicity. Consistently, Maf1 knockdown activates ATF5-transcription of mtHSP70 and HSP60, enhances mitochondrial membrane potential, reduces intracellular ROS levels and dampens rapamycin's effect on increasing IR-mediated cytotoxicity. In addition, Maf1 overexpression suppresses ethidium bromide-induced UPRmt and enhances IR-mediated cytotoxicity. Supporting our cell-based studies, elevated expression of UPRmt makers (mtHSP70 and HSP60) are associated with poor prognosis in patients with lung adenocarcinoma (LAUD). Together, our study reveals a novel role of Maf1-UPRmt axis in mediating rapamycin's enhancing effect on IR sensitivity in A549 lung cancer cells.

Aligned Collagen-CNT Nanofibrils and the Modulation Effect on Ovarian Cancer Cells.

Fibrillar collagen is a one-dimensional biopolymer and is the most abundant structural protein in the extracellular matrix (ECM) of connective tissues. Due to the unique properties of carbon nanotubes (CNTs), considerable attention has been given to the application of CNTs in developing biocomposite materials for tissue engineering and drug delivery. When introduced to tissues, CNTs inevitably interact and integrate with collagen and impose a discernible effect on cells in the vicinity. The positive effect of the collagen-CNT (COL-CNT) matrix in tissue regeneration and the cytotoxicity of free CNTs have been investigated extensively. In this study, we aimed to examine the effect of COL-CNT on mediating the interaction between the matrix and SKOV3 ovarian cancer cells. We generated unidirectionally aligned collagen and COL-CNT nanofibrils, mimicking the structure and dimension of collagen fibrils in native tissues. AFM analysis revealed that the one-dimensional structure, high stiffness, and low adhesion of COL-CNT greatly facilitated the polarization of SKOV3 cells by regulating the ß-1 integrin-mediated cell-matrix interaction, cytoskeleton rearrangement, and cell migration. Protein and gene level analyses implied that both collagen and COL-CNT matrices induced the epithelial-mesenchymal transition (EMT), and the COL-CNT matrix prompted a higher level of cell transformation. However, the induced cells expressed CD44 at a reduced level and MMP2 at an increased level, and they were responsive to the chemotherapy drug gemcitabine. The results suggested that the COL-CNT matrix induced the transdifferentiation of the epithelial cancer cells to mature, less aggressive, and less potent cells, which are inapt for tumor metastasis and chemoresistance. Thus, the presence of CNT in a collagen matrix is unlikely to cause an adverse effect on cancer patients if a controlled dose of CNT is used for drug delivery or tissue regeneration.

[Analysis of clinical characteristics of 21 cases of acute fibrinous and organizing pneumonia].

Objective: To summarize the clinical features of 21 cases of acute fibrinous and organizing pneumonia (AFOP) confirmed by pathology, thereby improving clinicians' understanding of this disease and avoiding misdiagnosis in clinical practice. Methods: Twenty-one patients diagnosed pathologically with AFOP from January 2016 to April 2019 were analyzed retrospectively. The clinical symptoms, laboratory examination results, imaging features, treatments and outcomes were analyzed comprehensively. Results: There were 10 males and 11 females, with an average age of (58±10) years. All the cases presented subacute disease onset. The main symptoms were cough, expectoration and fever. The results from laboratory examination showed that the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were significantly higher than the normal levels. The total number of leukocytes, the percentage of neutrophils, and procalcitonin were also higher than the normal levels. Among these patients, 4 cases showed positive sputum bacteriology. Nine patients were found to have probable etiological factors (infections in 4, tumors in 4 cases, and connective tissue disease in 1 case). Twelve patients had no confirmed etiological factors. As to radiological findings, the patterns were multiple patchy infiltrates(16/21), solitary mass (3/21) and multiple nodules in both lungs (2/21). Most lesions were subpleural in distribution (15/21), with air bronchogram sign (11/21), pleural effusion (9/21), and cavity (4/21). Three patients received anti-infective therapy only. The infiltration in lung disappeared within 2 months in one patient, but the lesion still existed in one case after three years of follow-up. However, one patient were lost during the follow-up. Eighteen patients were treated with oral glucocorticoids, and about 50% of the patients showed significant improvement in symptoms and imaging findings within one month. The average follow-up time was (22±10) months, and there was no death. Conclusions: The clinical and imaging findings of AFOP are nonspecific. The exact mechanism of its pathogenesis is not clear. Infection and tumor may be related to the pathogenesis of AFOP. AFOP with subacute onset has a good response to glucocorticoid treatment with a better prognosis.

Outcome of Kidney Transplantation From Donor After Cardiac Death: Reanalysis of the US Mycophenolic Renal Transplant Registry.

BACKGROUND: Kidney transplantation is limited by the shortage of donor kidneys. Donation after cardiac death (DCD) has been explored to alleviate this problem. To better understand the outcome of DCD kidney transplantation, we reanalyzed the Mycophenolic Renal Transplant (MORE) Registry. METHODS: We compared delayed graft function (DGF), biopsy-proved acute rejection (BPAR), graft loss, and patient death between DCD and donation after brain death (DBD) kidney transplantations. Recipients were further stratified into depleting and nondepleting induction groups for exploratory analysis. RESULTS: There were 548 patients who received kidney transplants from deceased donor in the MORE Registry. Among them, 133 received grafts from DCD donors and 415 received from DBD donors. The incidence of DGF was 29.4% and 23.5% in the DCD group and the DBD group, respectively (P = .1812), and the incidence of BPAR at 12 months was 9.0% and 9.9% respectively (P = .7713). The 1-year graft loss rate in the DCD group was higher than that in the DBD group (7.5% vs 3.1%, P = .0283), and the 4-year graft loss rate and patient death rate were not significantly different between the 2 groups. CONCLUSIONS: The DCD kidney transplant group had acceptable short-term outcomes and good long-term outcomes as compared with the DBD kidney transplant group.

CUNR scoring system for the prediction of lateral lymph node metastasis in papillary thyroid carcinoma.

OBJECTIVE: Our present study aimed to evaluate and compare the number and rate of central lymph node metastases (LNMs) for the prediction of lateral LNM (LLNM) in papillary thyroid carcinoma (PTC) and to develop a scoring system. RESULTS: Capsule invasion, tumor location in the upper portion of the thyroid, an ipsilateral central compartment LNM number ≥3, and an ipsilateral central compartment LNM rate of ≥56% were identified as significant independent predictors of ipsilateral lateral LNM in PTC. The predictive ability of an ipsilateral central compartment LNM rate ≥56% (area under the curve (AUC) = 0.802) was better than that of an ipsilateral central compartment LNM number ≥3 (AUC = 0.755). The ROC curves identified the best index point (CUNR) to distinguish the presence or absence of ipsilateral LLNM as 11, which has a high sensitivity (0.860) and a low false-negative rate (0.100, 1-Specificity). These findings were supported by the validation cohort. CONCLUSIONS: Patients with a CUNR index point equal to or greater than 11 and ipsilateral lateral lymph node dissection should be considered for a diagnosis of LLNM. PATIENTS AND METHODS: A total of 1,281 PTC patients were included and divided into two groups: those with a presence of LLNM (n = 222) and those with an absence of LLNM (n = 1059). Univariate and multivariate analyses were performed to detect the risk factors for LLNM, and receiver operating characteristic (ROC) curves were used to detect the best cutoff values of these predictors. Additionally, a scoring system for the odds ratio (OR) of independent factors was developed and validated in an independent cohort of PTC patients (n = 560).

Perioperative Antiemetic Therapy for Fast-Track Laparoscopic Bariatric Surgery.

BACKGROUND: Postoperative nausea and vomiting (PONV) is problematic in bariatric surgery patients and has negative impacts on perioperative outcome. Antiemetic prophylaxis may reduce PONV. Perioperative antiemetic prophylaxis or therapy is crucial and may enhance fast-track bariatric surgery. This study examined the impact of intraoperative multimodal antiemetic prophylaxis on fast-track bariatric surgery. METHODS: This prospective observational clinical study explored the perioperative data of 400 consecutive laparoscopic bariatric surgery patients, over a 6-year period. Perioperative outcomes and variables were analyzed and compared between different intraoperative antiemetic modes. RESULTS: The mean BMI was 49, mean age was 42, and male:female ratio was 1:4. About 70% of patients received intraoperative multimodal antiemetic, comprising combinations of prochlorperazine, dexamethasone, ondansetron, or cyclizine. PONV occurred in 19.5% of patients. Intraoperative multimodal antiemetic was associated with significantly less PONV, shorter post-anesthesia care unit duration, earlier postoperative drinking, and shorter hospital stay (p = 0.001). Compared to other multimodal antiemetic modes, dexamethasone + cyclizine + prochlorperazine provided the best prophylaxis and outcome: p = 0.002. CONCLUSION: PONV is a common and peculiar problem in bariatric surgery patients. However, intraoperative multimodal antiemetic prophylaxis effectively minimizes PONV. Intraoperative multimodal antiemetic enhances fast-track bariatric surgical care, patient satisfaction, and perioperative outcomes.

[Application of p16/Ki-67 immunocytochemistry in triage of patients with atypical squamous cells of undetermined significance].

Objective: To investigate the clinical value of p16/Ki-67 immunocytochemistry in patients with atypical squamous cells of undetermined significance(ASC-US). Methods: One hundred and seventy-one cases of thin-prep cytology test (TCT) diagnosed as ASC-US underwent p16/Ki-67 immunocytochemistry. All patients had colposcopy and biopsy from March 2015 to January 2016. Ninety of the 171 cases underwent high-risk HPV test at the same time. Results: p16/Ki-67 immunocytochemistry was positive in 43.9% (75/171) of the 171 cytology samples; the sensitivity and specificity of p16/Ki-67 immunocytochemistry were 77.6%(52/67) and 77.9%(81/104) in detecting CIN2+ , and the positive and negative predictive value were 69.3%(52/75) and 84.4%(81/96), respectively. The sensitivity and specificity in diagnosing CIN2+ were 100.0%(34/34) and 10.7%(6/56) for HPV test, and the positive and negative predictive value were 40.5%(34/84) and 6/6. p16/Ki-67 immunocytochemistry showed lower sensitivity but obviously higher specificity than high-risk HPV detection. Conclusion: p16/Ki-67 immunocytochemistry is a good triage test for identifying CIN2+ in ASC-US specimens.

Tumor-secreted anterior gradient-2 binds to VEGF and FGF2 and enhances their activities by promoting their homodimerization.

The importance of the tumor microenvironment in targeted anticancer therapies has been well recognized. Various protein factors participate in the cross-talk between tumor cells and non-malignant cells. Anterior gradient-2 (AGR2) is overexpressed in diverse human adenocarcinomas and it exists in both intracellular and extracellular spaces. Although intracellular AGR2 has been intensively investigated, the function of secreted AGR2, especially its exact mechanism of action is still poorly understood. Here we report that the secreted AGR2 promotes the angiogenesis and the invasion of vascular endothelial cells and fibroblasts by enhancing the activities of vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2). Further study indicated that AGR2 directly binds to these extracellular signaling molecules, and enhances their homodimerization. The extracellular AGR2 activity can be blocked to reduce angiogenesis and inhibit tumor growth in vitro and in vivo by a monoclonal antibody targeting the AGR2 self-dimerization region, and combined treatment with bevacizumab produced maximum inhibition effect. In conclusion, our investigation reveals a mechanism that directly links the secreted AGR2 with extracellular signaling networks, and we propose that the secreted AGR2 is a blockable molecular target, which acts as a chaperon-like enhancer to VEGF and FGF2.

Obstructive sleep apnea and postoperative complications among patients undergoing gynecologic oncology surgery.

OBJECTIVE: To investigate the prevalence of obstructive sleep apnea (OSA), physiological or risk factors associated with OSA, and OSA-associated postoperative complications among patients undergoing gynecologic oncology surgery. METHODS: A prospective observational study enrolled gynecologic oncology patients undergoing abdominal surgery at a center in the UK between August 2009 and January 2013. All patients underwent perioperative sleep oximetry for the diagnosis of OSA. Data assessed included the body mass index, the STOP-Bang score, the Epworth Sleepiness Scale score, the apnea-hypopnea index, and postoperative complications. Associations were determined between preoperative OSA and postoperative OSA, postoperative complications, and risk factors such as body mass index, age, STOP-Bang score, and Epworth score. RESULTS: Among 160 participants, 72 (45.0%) were obese and 80 (50.0%) had OSA. Obesity, older age (more than 65 years), and a neck circumference of 40 cm or more were significantly associated with OSA. Overall, 58 (36.3%) patients had postoperative complications; 21 (13.1%) had surgical complications and 37 (23.1%) had medical complications. Complications were not associated with OSA (P=0.612). Four (2.5%) patients died; mortality was not associated with OSA (P=0.810). CONCLUSION: OSA is common among gynecologic oncology patients. Portable sleep oximetry identifies gynecology patients who have OSA or require postoperative critical care. Obesity is associated with OSA, but OSA is not associated with postoperative complications in gynecologic oncology patients.

Perioperative Analgesia for Fast-Track Laparoscopic Bariatric Surgery.

BACKGROUND: Postoperative pain and analgesia present challenges in bariatric surgery patients. Multimodal analgesia may provide better efficacy, less complications and expedite fast-track bariatric surgical care. There are no studies of the broader topic of perioperative analgesia and the overall impact. This study highlights the impact of multimodal intraoperative analgesia on fast-track bariatric surgery. METHODS: This observational study examined the perioperative outcome data of 412 consecutive laparoscopic bariatric surgery patients over a 6-year period. Perioperative outcome and variables were analysed and compared between different intraoperative analgesia types. RESULTS: Mean BMI was 49, mean age was 42 and male:female ratio was 1:4. About 82% of patients received multimodal intraoperative analgesia, comprising various combinations of bupivacaine infiltration and intravenous acetaminophen, morphine, tramadol, parecoxib or diclofenac. Morphine was administered in 83% of patients and tramadol in 17%. Multimodal intraoperative analgesia provided better postoperative analgesia, shorter postanaesthesia care unit (PACU) duration, lower postoperative opioid requirement, less postoperative vomiting, earlier postoperative oral intake, earlier ambulation and shorter hospital stay compared to unimodal intraoperative morphine analgesia (p = 0.0001). Multimodal analgesia comprising tramadol + acetaminophen + diclofenac provided better postoperative analgesia, shorter PACU duration, lower postoperative opioid requirement, earlier ambulation, shorter hospital stay and less postoperative hypopnoea compared to patients who received morphine (p = 0.0001). CONCLUSIONS: Multimodal intraoperative analgesia provides better postoperative analgesia, less complications and better perioperative outcomes and facilitates fast-track bariatric surgical care. Tramadol is suitable, efficacious and safe and associated with the best perioperative outcomes in bariatric surgery patients.

Determination of Ginkgolides A, B, C, J and Bilobalide in Plasma by LC-ESI (-)/MS/MS (QQQ) and its Application to the Pharmacokinetic Study of Ginkgo Biloba Extract in Rats.

A simple, rapid, and specific high-performance liquid chromatograph coupled with a tandem mass spectrometry method has been developed and validated for the quantification of ginkgolides in rat plasma, and the main pharmacokinetic parameters of ginkgolides after oral administration of Ginkgo biloba extract (GBE) was acquired. Methods: Plasma samples were pretreated with ethyl acetate extraction. Sulfamethoxazole was used as the internal standard (IS). Chromatographic separation was achieved on an Eclipse XDB-C18 column (2.1 mm×150 mm, 5 µm) with a mobile phase consisting of methanol/0.1% formic acid water (gradient elution: 0~25 min (77:23)→(60:40), V/V) at a flow rate of 0.3 mL·min-1. The detection was performed on a triple quadruple tandem mass spectrometer using an electrospray ionization (ESI) source for 25 min. The detection was operated by multiple reaction monitoring(MRM) under negative ionization mode of the transitions of m/z 325→163 for BB, 469→423 for GJ, 439→125 for GC, 453→351 for GA, 423→367 for GB and of m/z 252→156 for sulfamethoxazole (IS) respectively. Results: The pharmacokinetic properties of BB, GJ, GA, GB and GC were in line with the open 2-compartment model after oral administration of GBE in rats; The pharmacokinetic parameters of various lactones were calculated, and drugs-time curve and the curve fitting diagram of 5 ginkgolides were drew; The absorption and distribution rate of BB, GJ, GA, GB and GC were fast in rats in vivo, and half-life of absorption was less than 3 h. Conclusion: The developed LC-ESI (-)/MS/MS (QQQ) method was successfully applied to assess the pharmacokinetic parameters and oral bioavailability of ginkgolides in rats after administration of GBE, which can provide basis for further clinical efficacy studies.

[Fine needle aspiration cytology of thyroid nodules: a cytopathologic study of 2 043 cases].

OBJECTIVE: To evaluate the clinical value of thyroid fine needle aspiration cytology(FNAC) and the Bethesda system for reporting thyroid cytopathology(TBSRTC). METHODS: FNAC was performed for 2 043 cases and cytopathological data were retrospectively analyzed. Cytopathological diagnoses according to TBSRTC were classified as non-diagnostic, benign, atypia of undetermined significance/follicular lesion of undetermined significance(AUS/FLUS), follicular neoplasm/suspicious for follicular neoplasm(FN/SFN), suspicious for malignancy(SM) and malignancy. The results of 234 FNAC samples in which surgery was performed were compared with the histological diagnoses. RESULTS: Of the 2 043 FNAC samples, 15.7%(320/2 043)were non-diagnostic, 51.2%(1 047/2 043)were benign, 16.6%(339/2 043) were AUS/FLUS, 2.3%(46/2 043)were FN/SFN, 8.6%(176/2 043)were SM and 5.6%(115/2 043)were malignant. In 234 cases, there was follow-up histology. Rates of malignancy were as follows: non-diagnostic, 18.2%(2/11); benign(2.2%, 1/45); AUS/FLUS(25.6%, 10/29); FN/SFN(12.1%, 10/39); SM(91.8%, 56/61); malignant(100.0%, 45/45). The sensitivity, specificity, false positive rate, false negative rate and overall accuracy of FNAC in the diagnosis of thyroid nodules was 87.1%(101/116), 95.3%(102/107), 4.7%(5/107), 12.9%(15/116), 91.0%(203/223). CONCLUSIONS: FNAC is a reliable diagnostic method for evaluation of thyroid disease. TBSRTC is a accurate and effective reporting system for cytopathological diagnoses, so it is worthy of being widely popularized in clinical application.

Electromyographical characteristics and muscle utilization in hemiplegic patients during sit-to-stand activity: an observational study.

BACKGROUND: Sit-to-stand is an important process in daily activity, and stroke patients have difficulty completing this task due to many reasons. AIM: To investigate the characteristic of muscle utilization of lower limb muscles between healthy participants and hemiplegic patients during sit-to-stand activity. DESIGN: This is an observational study. SETTING: Inpatients at a rehabilitation hospital. POPULATION: Thirty-two stroke patients and 36 healthy participants. METHODS: The participants were evaluated on sit-to-stand movement. Muscle strength was assessed by measuring maximal voluntary contraction (MVC) bilaterally in quadriceps, hamstrings, tibialis anterior and gastrocnemius. Amplitude (average and maximal) and area under the curve (AUC) of quadriceps, hamstring, tibialis anterior, and gastrocnemius of both sides were recorded during this activity. RESULTS: The average and maximal amplitudes of paretic muscles were significantly less than non-paretic muscles and healthy controls (P<0.05). AUC of paretic muscles was significantly less than non-paretic muscles (P<0.05) but not statistically different from healthy controls. The area under the curve of non-paretic muscles was significantly greater than healthy controls (P<0.05), except for tibialis anterior (P=0.07). The area under the curve/maximal voluntary contraction ratios of quadriceps and hamstrings in both sides of patients were significantly larger than healthy controls (P<0.05), except for paretic quadriceps (P=0.078). The muscle utilization ratio (MUR) of the patients was significantly higher than that of the healthy participants. CONCLUSIONS: This study demonstrated electromyographical features of sit-to-stand activity in hemiplegic patients. During sit-to-stand, stroke patients' muscle utilization of both sides increased and MUR of the paretic side is similar to the non-paretic side. CLINICAL REHABILITATION IMPACT: Muscle utilization ratio might help to understand how patients fulfill the sit-to-stand task. Using this information might improve our training strategy. Through customized training, paretic patients could fulfill the task with less muscle utilization.

A novel cyclic helix B peptide inhibits dendritic cell maturation during amelioration of acute kidney graft rejection through Jak-2/STAT3/SOCS1.

We recently synthesized a novel proteolysis-resistant cyclic helix B peptide (CHBP) that exhibits promising renoprotective effects. Dendritic cells (DCs) play an activation role in acute rejection (AR). Thus, the present study was designed to investigate the effects of CHBP on DCs in a rat renal transplantation model. The left kidney was harvested from male Lewis rats and then transplanted into male Wistar rats with or without CHBP treatment. Five successive treatment doses of CHBP after transplantation significantly ameliorated AR with lower histological injury, apoptosis and CD4(+) and CD8(+) T-cell infiltration in renal allografts. CHBP reduced IFN-γ and IL-1ß levels but increased IL-4 and IL-10 levels in the serum. The number of mature DCs was significantly decreased in renal allografts treated with CHBP. In addition, incubating DCs with CHBP in vitro led to reduction in TNF-α, IFN-γ, IL-1ß and IL-12 levels and increase of IL-10 expression at the protein level in the supernatant. Mechanistically, CHBP inhibited TLR activation-induced DC maturation by increasing SOCS1 expression through Jak-2/STAT3 signaling. In conclusion, CHBP suppresses renal allograft AR by inhibiting the maturation of DCs via Jak-2/STAT3/SOCS1 signaling, suggesting that CHBP may be an potential therapeutic drug for treating renal AR.