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Introduction This study aims to answer the question of whether adding mobile cone-beam computed tomography (mCBCT) imaging to shape-sensing robotic-assisted bronchoscopy (ssRAB) translates into a quantifiable improvement in the tool–lesion relationship. Methods Data from 102 peripheral lung lesions with ≥2 sequential mCBCT orbital spins and from 436 lesions with 0–1 spins were prospectively captured and retrospectively analysed. The primary outcome was the tool–lesion relationship status across the first and the last mCBCT spins. Secondary outcomes included 1) the change in distance between the tip of the sampling tool and the centre of the lesion between the first and the last spins and 2) the per-lesion diagnostic yield. Results Compared to lesions requiring 0–1 spins, lesions requiring ≥2 spins were smaller and had unfavourable bronchus sign and intra-operative sonographic view. On the first spin, 54 lesions (53%) were designated as non-tool-in-lesion (non-TIL) while 48 lesions (47%) were designated as TIL. Of the 54 initially non-TIL cases, 49 (90%) were converted to TIL status by the last spin. Overall, on the last spin, 96 out of 102 lesions (94%) were defined as TIL and six out of 102 lesions (6%) were defined as non-TIL (p

Objective: Uremic pruritus (UP) is a prevalent and troublesome condition affecting individuals with end-stage renal failure, which results in intense pruritus, depression, as well as poor quality of sleep, significantly impacting their quality of life. According to previous studies, acupuncture and acupoint stimulation have been shown to provide additional benefits in treating UP in dialysis patients. In addition, using acupoints combination may yield superior effectiveness compared to utilizing a singular acupoint. To investigate the potential correlations between acupoint combinations, an association-rule analysis was employed. Materials and Methods: Apriori algorithms stand out as highly potent techniques for identifying associations in databases; this study utilized an association rule mining to examine the association rules of key acupoint groupings that could be employed for treating UP. Results: The analysis utilized information derived from the meta-analysis encompassing 40 randomized controlled trials that used acupuncture to treat UP. In total, 64 acupoints were analyzed, and 71 association rules were found. The following acupoint combinations: Auricular shenmen (TF4), Quchi (LI11), and Geshu (BL17); Auricular heart (Extra14), Sanyinjiao (SP6), and Auricular lung (CO14); and Auricular heart (Extra14), Xuehai (SP10), and Auricular lung (CO14) showed the strongest associations. Conclusion: Acupoints involving Auricular shenmen (TF4), Quchi (LI11), Geshu (BL17), Auricular heart (Extra14), Sanyinjiao (SP6), Auricular lung (CO14), and Xuehai (SP10) can be regarded as the core combination of acupuncture points for managing UP.

Background/Objectives: Obesity and metabolic conditions increase the risk of metabolic-associated steatotic liver disease (MASLD). This study examined the risk of MASLD in 137 renal transplant recipients (RTRs) from a single-center hospital on the basis of their obesity and metabolic health status. Methods: Participants were categorized into four groups: metabolically healthy nonobese (MHNO), metabolically healthy obese (MHO), metabolically abnormal nonobese (MANO), and metabolically abnormal obese (MAO). MASLD was assessed using the hepatic steatosis index (HSI), calculated as 8 × (aspartate aminotransferase/alanine aminotransferase ratio) + body mass index + 2 (if diabetic) + 2 (if woman). The HSI scores were 29.50 ± 4.55, 38.08 ± 5.44, 33.61 ± 5.23, and 39.86 ± 4.13 in the MHNO, MHO, MANO, and MAO groups, respectively (p < 0.05). Results: Overall, 25.55% of the participants (57.14% men) were classified as having MASLD (HSI > 36). A multivariate-adjusted regression analysis revealed significantly higher HSI scores in the MAO group than in the MHNO group. Both MHO and MANO groups also had significantly higher HSI scores. The odds ratios for more severe MASLD were 2.74 (95% CI: 0.88–8.52) for the MANO group and 74.59 (95% CI: 13.29–418.68) for the MAO group compared with the MHNO group. Conclusions: These findings suggest that RTRs with obesity have a higher risk of MASLD, but even those with a normal weight and metabolic abnormalities are at increased risk.

Abstract Cardiovascular disease (CVD) and its risk factors seem to be linked with deteriorated graft function and persists as the major cause of mortality in kidney transplant recipients (KTRs). Diet quality is associated with CVD prevention in the healthy population, however, less study focuses on KTRs. The study aimed to determine the association between diet quality indices and lipid profile abnormalities as risk factors for CVD in KTRs. This prospective study enrolled 106 KTRs who had functioning allografts from September 2016. Lipid profiles included low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglyceride (TG) and were based on the National Cholesterol Education Program Adult Treatment Panel III recommendations. Three-day dietary data were collected by a well-trained registered dietitian. The Alternative Healthy Eating Index-Taiwan (AHEI-Taiwan), Alternative Healthy Eating Index-2010 (AHEI-2010), and Healthy Eating Index-2015 (HEI-2015) scores were calculated and divided into quartiles and compared accordingly. KTRs’ mean LDL-C, HDL-C, TC, and TG levels were 119.8 ± 36.6 mg/dL, 52.0 ± 17.9 mg/dL, 205.8 ± 43.9 mg/dL, and 160.2 ± 121.6 mg/dL, respectively. Compared with the lowest quartile, only the highest quartile of AHEI-Taiwan had lower TC and LDL-C levels. After adjustment for age, gender, energy, Charlson comorbidity index, transplant duration, and dialysis duration, logistic regression analysis revealed that the highest quartile of AHEI-Taiwan had 82% (odds ratio [OR], 0.18; 95% confidence interval [CI] 0.04–0.72, p

The interaction between environmental stressors, such as cold exposure, and immune function significantly impacts human health. Research on effective therapeutic strategies to combat cold-induced immunosuppression is limited, despite its importance. In this study, we aim to investigate whether traditional herbal medicine can counteract cold-induced immunosuppression. We previously demonstrated that cold exposure elevated immunoglobulin G (IgG) levels in mice, similar to the effects of intravenous immunoglobulin (IVIg) treatments. This cold-induced rise in circulating IgG was mediated by the renin–angiotensin–aldosterone system and linked to vascular constriction. In our mouse model, the cold-exposed groups (4 °C) showed significantly elevated plasma IgG levels and reduced bacterial clearance compared with the control groups maintained at room temperature (25 °C), both indicative of immunosuppression. Using this model, with 234 mice divided into groups of 6, we investigated the potential of tanshinone IIA, an active compound in Salvia miltiorrhiza ethanolic root extract (SMERE), in alleviating cold-induced immunosuppression. Tanshinone IIA and SMERE treatments effectively normalized elevated plasma IgG levels and significantly improved bacterial clearance impaired by cold exposure compared with control groups injected with a vehicle control, dimethyl sulfoxide. Notably, bacterial clearance, which was impaired by cold exposure, showed an approximately 50% improvement following treatment, restoring immune function to levels comparable to those observed under normal temperature conditions (25 °C, p < 0.05). These findings highlight the therapeutic potential of traditional herbal medicine in counteracting cold-induced immune dysregulation, offering valuable insights for future strategies aimed at modulating immune function in cold environments. Further research could focus on isolating tanshinone IIA and compounds present in SMERE to evaluate their specific roles in mitigating cold-induced immunosuppression.

Background Cancer therapy–related cardiac dysfunction (CTRCD) is an important treatment‐limiting toxicity for patients with human epidermal growth factor receptor 2 (HER2)–positive breast cancer that adversely affects cancer and cardiovascular outcomes. Easy‐to‐use tools that incorporate readily accessible clinical variables for individual estimation of CTRCD risk are needed. Methods and Results From 2004 to 2013, 1440 patients with stage I to III HER2‐positive breast cancer treated with trastuzumab‐based therapy were identified. A multivariable Cox proportional hazards model was constructed to identify risk factors for CTRCD and included the 1377 patients in whom data were complete. Nine clinical variables, including age, race, body mass index, left ventricular ejection fraction, systolic blood pressure, coronary artery disease, diabetes, arrhythmia, and anthracycline exposure were built into a nomogram estimating risk of CTRCD at 1 year. The nomogram was validated for calibration and discrimination using bootstrap resampling. A total of 177 CTRCD events occurred within 1 year of HER2‐targeted treatment. The nomogram for prediction of 1‐year CTRCD probability demonstrated good discrimination, with a concordance index of 0.687. The predicted and observed probabilities of CTRCD were similar, demonstrating good model calibration. Conclusions A nomogram composed of 9 readily accessible clinical variables provides an individualized 1‐year risk estimate of CTRCD among women with HER2‐positive breast cancer receiving HER2‐targeted therapy. This nomogram represents a simple‐to‐use tool for clinicians and patients that can inform clinical decision‐making on breast cancer treatment options, optimal frequency of cardiac surveillance, and role of cardioprotective strategies.

The scarcity of dietary guidance for renal transplant recipients (RTRs) raises concerns regarding obesity and associated comorbidities, including impaired renal function. This two-stage cross-sectional study examined longitudinal changes in dietary nutrient intake in the same individuals over a 5-year interval. This study involved two stages: T1 (September 2016 to June 2018) and T2 (July 2022 to August 2023). The average duration between the two data collection stages was 6.17 ± 0.42 (range 5.20–6.87) years. The study included 227 RTRs with an average age and time since transplant of 49.97 ± 12.39 and 9.22 ± 7.91 years, respectively. Of the 35 patients who participated in both phases, fewer than half met the recommended intakes for energy, dietary fiber, and most vitamins and minerals, as set in the Dietary Reference Intakes (DRIs) or by the Dietitian Association Australia (DAA). Over half exceeded the DRI recommended intake for total protein, and more than 80% of the protein consumed per kilogram of body weight exceeded the DAA’s recommendations. In the T2 stage, the RTRs had a significantly higher blood urea nitrogen level, lower albumin level, and estimated glomerular filtration rate. These findings indicate that deteriorating dietary intake in RTRs can adversely affect their nutritional status and transplanted kidney function over a 5-year period.

Background/Purpose: Although nutrition and sarcopenia have impacts on the surgery outcome of patients who have received living donor liver transplant (LDLT), the use of the prognostic nutritional index (PNI) or psoas muscle mass index (PMI) as an indicator for five-year survival in those patients is still unclear. Methods: A total of 138 patients receiving LDLT were followed at a medical center in Taiwan. As well as analysis of clinical factors using Cox regression, time-varying PNI and PMI values as before surgery (0) and at 3-, 6-, and 12- months after LDLT were analyzed by time-dependent Cox analysis. For those 124 patients who survived after 3 months of LDLT, the values of PNI-3m, PMI-3m and their combination were further analyzed. Results: PNI and PMI were noted to be highly associated with mortality at three months post-LDLT (PNI-3m hazard ratio [HR] = 0.89, 95% confidence interval [CI]: 0.85–0.94, p

Several dietary indices assess the impacts of the Dietary Approaches to Stop Hypertension (DASH) diet on health outcomes. We explored DASH adherence and renal function among 85 Taiwanese renal transplant recipients (RTRs) in a cross-sectional study. Data collection included demographics, routine laboratory data, and 3-day dietary records. Three separate DASH indices, that defined by Camões (based on nine nutrients), that defined by Fung (using seven food groups and sodium), and that modified by Fung (as above but separated for men and women) were used. Renal function was ascertained through the estimated glomerular filtration rate (eGFR) from patients’ medical records. Participants’ mean age was 49.7 ± 12.6 years and eGFR was 54.71 ± 21.48 mL/min/1.73 m2. The three established DASH diet indices displayed significant correlations (r = 0.50–0.91) and indicated the nutritional adequacy of the diet. Multiple linear regressions indicated a significant positive association between higher DASH scores for each index and increased eGFR. In addition, RTRs in the highest DASH score tertile had higher eGFR rates than those in the lowest tertile, regardless of confounding variables. Adherence to a DASH-style diet correlated with better renal function among RTRs. Educating RTRs about the DASH diet may prevent graft function deterioration.

This study aimed to assess evidence for the effect of movement-based mind-body interventions (MMBIs) for cardiac rehabilitation (CR). Six databases were searched from January 1995 to September 2020. All randomized controlled trials (RCTs) evaluated the effect of MMBIs on heart disease (HD) patients' physical and psychological outcomes. Two reviewers independently assessed the quality of all the included studies using the revised Cochrane risk-of-bias tool for RCTs. Sixteen RCTs (5160 participants) published between 1996 and 2020 met all inclusion criteria. In total, these studies investigated the effect of MMBIs for CR. Outcome measures that emerged in these studies included physical and psychological, and/or biochemical parameters to comprehensively evaluate the effects of MMBIs on HD patients. Overall, these studies suggest that MMBIs seem to be an alternative with the optimal CR option.

BackgroundThis study investigated the association between dietary quality indices and recurrent chronic kidney disease (rCKD) in Taiwanese post-renal transplant recipients (RTRs).MethodsThis prospective study recruited RTRs aged >18 years with a functioning allograft and without any acute rejection in the past 3 months from September 2016 to June 2018. Dietary quality indices included the Alternative Healthy Eating Index (AHEI) and AHEI-2010, and the Taiwanese version of the AHEI (AHEI-Taiwan) was calculated using 3-day dietary records, and calculated scores were divided into quartiles. Laboratory data were collected from medical records. rCKD was defined as an estimated glomerular filtration rate (eGFR) of

BackgroundUremic pruritus causes sleep disturbances, poor quality of life, and increased morbidity in patients with chronic kidney disease. Acupuncture has been shown to improve uremic pruritus. There is limited evidence of the efficacy of traditional Chinese therapies. We conducted a systematic review and meta-analysis to evaluate the efficacy of acupoint stimulation therapy in patients with uremic pruritus.MethodsA systematic search of seven databases (up to Sep 2022) was conducted for randomized controlled trials that evaluated the clinical efficacy of acupuncture, acupressure, auricular acupressure, acupoint injection, acupoint thermal therapy, acupoint sticking therapy, or transcutaneous electrical acupoint stimulation in the treatment of patients with uremic pruritus. Two reviewers selected eligible articles for inclusion in the meta-analysis and evaluated the risk of bias via Cochrane Collaboration. The results of pruritus assessments and uremic pruritus-related laboratory parameters were analyzed.ResultsForty trials published between 2002 and 2022, including a total of 2,735 participants, were identified for inclusion in the meta-analysis. The effective rates for acupuncture, auricular acupressure, and the combination of acupoint injection and acupoint massage were significantly greater in patients with uremic pruritus compared to the control group. The levels of serum BUN, PTH, and histamine levels were significantly lower vs. control group.ConclusionsAcupuncture, auricular acupressure, and the combination of acupoint injection and acupoint massage seem to be effective in improving uremic pruritus in patients with chronic kidney disease. However, further investigation of these potential treatments is now warranted in larger patient populations and over a longer time frame.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022354585, identifier: PROSPERO CRD42022354585.

Acetaminophen is among the most widely used analgesics; however, the proportion and mechanism of transplacental transfer of unbound acetaminophen with actual pharmacological activity remain unknown. Our hypothesis is that acetaminophen gradually penetrates the blood-placenta barrier to reach the fetus. A multiple microdialysis coupled to liquid chromatography with photodiode array detection method was developed to monitor acetaminophen levels in the maternal blood, placenta, fetus, and amniotic fluid of a pregnant rat and investigate this hypothesis. The pharmacokinetic data indicates that acetaminophen exhibits a nonlinear behavior in the maternal blood within the dosage regimen of 100 and 300 mg/kg. In addition, acetaminophen penetrates the placenta, fetus, and amniotic fluid during treatment. The transplacental transfer ratio represented by the area under the concentration curve (AUC) ratio for the conceptus (the collective term for the fetus, placenta, and amniotic fluid) and maternal blood (AUCtissue/AUCblood) was approximately 11–23 % after acetaminophen (100 and 300 mg/kg) administration. However, the transporter of multidrug resistance-associated protein (MRP) inhibitor MK-571 did not significantly change the transplacental transfer ratio. This basic study provides constructive information for the clinical application of acetaminophen in pregnant women.

The phase of mild cognitive impairment (MCI) holds significant importance for postponing the onset of dementia. Therefore, MCI has become a central focus in research related to dementia prevention. The purpose of this study was to investigate the dietary intake and dietary patterns of MCI patients in Taiwan. In total, 40 subjects were enrolled in this cross-sectional study that was conducted from July 2019 to September 2021 at the Linkou Chang Gung Memorial Hospital. The results of the clinical dementia rating (CDR) and mini-mental state examination (MMSE) were obtained from medical records. Participants were divided into two groups: a healthy group (MMSE ≥ 26 points, CDR = 0) and an MCI group (MMSE ≥ 26 points, CDR = 0.5). Results indicated that the MCI group had significantly higher copper and lower low-fat meat intake compared to the healthy group. Furthermore, the high MIND (Mediterranean dietary approaches to stop hypertension intervention for neurodegenerative delay) diet score represented a lower risk of MCI. After adjusting for age, gender, diabetes mellitus, hypertension, and calorie intake in the multivariate regression analysis, calcium and fruit intake levels were positively associated with the MMSE, whereas low-fat meat intake was negatively associated with the CDR. In conclusion, the prevalence of MCI demonstrated a close correlation with nutrient intake, including copper and calcium. Furthermore, a MIND diet, particularly one high in n-3 polyunsaturated fatty acids, might be useful for preventing MCI. However, more extensive research with larger populations is needed to confirm this potential.

Background: The incidence of ischemic stroke (IS) is much higher among patients with chronic kidney disease (CKD) compared to the general population. Few studies have evaluated the association between the risk of IS and the use of Chinese herbal medicine (CHM) in patients with CKD. We aimed to investigate the risk of IS among patients with CKD using CHM as add-on therapy.Methods: We conducted a retrospective cohort study based on Taiwan’s National Health Insurance Research Database to assess 21,641 patients with newly diagnosed CKD between 2003 and 2012. Patients were classified as either the CHM (n = 3,149) or the non-CHM group (n = 3,149) based on whether they used CHM after first diagnosis of CKD. We used the proportional subdistribution hazards model of Fine and Gray to examine the hazard ratio (HR) of IS in propensity-score matched samples at a ratio of 1:1 for two groups.Results: The risk of IS was significantly reduced in the CHM group (adjusted HR [aHR]: 0.58, 95% confidence interval [CI]: 0.48–0.70) compared with the non-CHM group. Those who used CHM for >180 days had an even lower risk of IS than those in the non-CHM group (aHR: 0.51, 95% CI: 0.41–0.63). Additionally, frequently prescribed formulae, such as Ji-Sheng-Shen-Qi-Wan, Liu-Wei-Di-Huang-Wan, and Zhen-Wu-Tang were associated with a 30%–50% reduced risk of IS.Conclusion: Our results suggest that patients with CKD who used CHM as add-on therapy had a lower hazard of IS than those in the non-CHM group, especially for patients taking CHM for >180 days. Further experimental studies are required to clarify the causal relationship.

Summary: Background: Remdesivir was the first prodrug approved to treat coronavirus disease 2019 (COVID-19) and has the potential to be used during pregnancy. However, it is not known whether remdesivir and its main metabolite, GS-441524 have the potential to cross the blood-placental barrier. We hypothesize that remdesivir and predominant metabolite GS-441524may cross the blood-placental barrier to reach the embryo tissues. Methods: To test this hypothesis, ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) coupled with multisite microdialysis was used to monitor the levels of remdesivir and the nucleoside analogue GS-441524 in the maternal blood, fetus, placenta, and amniotic fluid of pregnant Sprague-Dawley rats. The transplacental transfer was evaluated using the pharmacokinetic parameters of AUC and mother-to-fetus transfer ratio (AUCfetus/AUCmother). Findings: Our in-vivo results show that remdesivir is rapidly biotransformed into GS-441524 in the maternal blood, which then readily crossed the placenta with a mother-to-fetus transfer ratio of 0.51 ± 0.18. The Cmax and AUClast values of GS-441524 followed the order: maternal blood > amniotic fluid > fetus > placenta in rats. Interpretation: While remdesivir does not directly cross into the fetus, however, its main metabolite, GS-441524 readily crosses the placenta and can reside there for at least 4 hours as shown in the pregnant Sprague-Dawley rat model. These findings suggest that careful consideration should be taken for the use of remdesivir in the treatment of COVID-19 in pregnancy. Funding: Ministry of Science and Technology of Taiwan.

Background: Traditional Chinese medicine and western medicine have coexisted since 1958 in Taiwan. Integrative traditional Chinese and western medicine (TC&WM) remains to be studied and promoted. In response to the documentary report of WHO Traditional Medicine Strategy 2002–2005, the present study was planned and carried out. Methods: During 2004–2008, 19 integrative TC&WM dialogue forums were held, in which 219 TC&WM scholars and professionals participated by invitation. The proceedings of the forums in Chinese were published. A study team was organized in 2009 to collect the consensus opinions, utilizing a Delphi method. The opinions collected were discussed in an international TC&WM forum held on November 1, 2014. Results: The opinions of TC&WM experts and professionals on the integrative issues and values were quite divergent. Of the 39 integrative issues, 34 (87.8%) reached consensus, agreeing that WM is excellent in the diagnosis and treatment of diseases/disorders, yet is still evolving, and not perfect without defects. TCM is patient-centered, wellness-oriented, inadequate for acute, critical and life-threatening diseases, but has a complementary and alternative role to WM. Of the 44 diseases/disorders, 36 (81.8%) reached consensus, worthy for integrative clinical use or trials. Conclusions: Integrative TC&WM, combining the best features of two systems, could be a most useful and advanced healthcare medicine in the future, requiring development of regulations and guidelines for the use of TCM and more rigorous efforts have to be made in clinical trials.

Uremic pruritus (UP), also called chronic kidney disease-associated pruritus (CKD-aP), is a bothersome symptom that causes sleep disturbance, anxiety, depression, and reduced quality of life. Pruritus often occurs in patients with end-stage renal disease. There is still no definite treatment for UP due to its unclear pathogenesis. We searched electronic databases (PubMed and Google Scholar) and gathered the latest clinical trials and pilot studies of Western and complementary alternative medicine (CAM) therapies for UP in English. These UP studies were separated into three main groups: systemic, topical, and others and CAM. Gabapentin, nalfurafine, acupuncture, and Chinese herbal bath therapy (CHBT) show antipruritic effects, with higher evidence grades in the meta-analysis. Emollients with additive compounds are more effective for reducing itch than emollients without additives. Supplements for deficient elements, such as zinc, omega-3, and omega-6, also show benefits for pruritus improvement. CAM therapies such as acupuncture, herbs, and herbal baths or creams all have good results for UP treatment. We summarize the treatments and suggest a treatment algorithm for UP according to severity. Some UP therapies are already supported by large-scale clinical evidence, and some new treatments can provide patients with new hope and treatment options. However, these new methods still need large population studies and further exploration.

Background: SARS-CoV-2 has led to a sharp increase in the number of hospitalizations and deaths from pneumonia and multiorgan disease worldwide; therefore, SARS-CoV-2 has become a global health problem. Supportive therapies remain the mainstay treatments against COVID-19, such as oxygen inhalation, antiviral drugs, and antibiotics. Traditional Chinese medicine (TCM) has been shown clinically to relieve the symptoms of COVID-19 infection, and TCMs can affect the pathogenesis of SARS-CoV-2 infection in vitro. Jing Si Herbal Drink (JSHD), an eight herb formula jointly developed by Tzu Chi University and Tzu Chi Hospital, has shown potential as an adjuvant treatment for COVID-19 infection. A randomized controlled trial (RCT) of JSHD as an adjuvant treatment in patients with COVID-19 infection is underway Objectives: This article aims to explore the efficacy of the herbs in JSHD against COVID-19 infection from a mechanistic standpoint and provide a reference for the rational utilization of JSHD in the treatment of COVID-19. Method: We compiled evidence of the herbs in JSHD to treat COVID-19 in vivo and in vitro. Results: We described the efficacy and mechanism of action of the active ingredients in JSHD to treat COVID-19 based on experimental evidence. JSHD includes 5 antiviral herbs, 7 antioxidant herbs, and 7 anti-inflammatory herbs. In addition, 2 herbs inhibit the overactive immune system, 1 herb reduces cell apoptosis, and 1 herb possesses antithrombotic ability. Conclusion: Although experimental data have confirmed that the ingredients in JSHD are effective against COVID-19, more rigorously designed studies are required to confirm the efficacy and safety of JSHD as a COVID-19 treatment.

Nicotine is a highly addictive substance and harmful to the developing foetus. However, few studies have investigated the transporter mechanism responsible for regulating the transfer of nicotine across the blood-placental interface. A multiple in-vivo microdialysis system coupled to ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed to monitor simultaneously nicotine and cotinine in the blood, placenta, foetus, and amniotic fluid of pregnant rats. The pharmacological mechanism of nicotine transfer across the placenta was investigated by co-administering corticosterone, an inhibitor of organic cation transporters (OCTs) that partly mediate the exchange of nicotine across the placenta. The results revealed that intravenously administered nicotine (1 mg/kg) was rapidly metabolised to cotinine with a transformation ratio (AUCcotinine/AUCnicotine) of 0.67 ± 0.08, 0.21 ± 0.05, 0.25 ± 0.12, 0.31 ± 0.05 in maternal blood, placenta, amniotic fluid, and foetus, respectively. The tissue transformation ratios (AUCtissue/AUCblood) were 0.83 ± 0.16, 0.65 ± 0.17, 0.57 ± 0.13 for nicotine, and 0.25 ± 0.06, 0.24 ± 0.12, 0.26 ± 0.04 for cotinine at placenta, amniotic fluid and foetus, respectively. Following the co-administration of corticosterone (2 mg/kg), the tissue transformation ratio of nicotine was significantly reduced in the placenta but was significantly increased in the foetus. Levels of cotinine were not significantly altered by the administration of corticosterone. These findings implicate OCT in mediating the transfer of nicotine across the blood-placenta barrier. Understanding the mechanism of nicotine transfer through the placenta may inform therapeutic strategies to lessen the exposure of the developing foetus to nicotine in the maternal bloodstream.

Uremic pruritus is a disturbing and refractory symptom in patients with advanced chronic kidney disease. Chinese herbal medicine has been reported to alleviate uremic pruritus. To investigate the effects of Chinese herbal medicine, we conducted a systematic review and meta-analysis on patients with uremic pruritus. We searched databases (prior to 3 May 2022) for randomized controlled trials on the effects of Chinese herbal medicine in treating uremic pruritus. Our meta-analysis included 3311 patients from 50 randomized controlled trials. In patients with uremic pruritus, adjunctive Chinese herbal medicine significantly improved overall effectiveness (risk ratio 1.29, 95% CI 1.23 to 1.35), quality of life, renal function, reduced pruritus score, and inflammatory biomarkers compared to control groups with hemodialysis alone or with anti-pruritic treatments. Chinese herbal medicine treatment showed a time-dependent tendency in improving the visual analog scale of dialysis patients. Compared to control groups, no significantly higher risk of adverse events in patients taking Chinese herbal medicine (risk ratio 0.60, 95% CI 0.22 to 1.63). Chinese herbal medicine appears to be effective and safe in complementing the treatment of patients with uremic pruritus.

Background Pneumonitis related to immune checkpoint blockade is uncommon but can be severe, fatal or chronic. Steroids are first-line treatment, however, some patients are refractory or become resistant to steroids. Like many immune-related adverse events, little is known regarding the outcomes and optimal management of patients in whom steroids are ineffective.Methods We performed a single-center retrospective cohort study at a high-volume tertiary cancer center to evaluate the clinical course, management strategies and outcomes of patients treated for immune checkpoint pneumonitis with immune modulatory medications in addition to systemic steroids. Pharmacy records were queried for patients treated with both immune checkpoint blockade and receipt of additional immune modulators. Records were then manually reviewed to identify patients who received the additional immune modulators for immune checkpoint pneumonitis.Results From 2013 to 2020, we identified 26 patients treated for immune checkpoint pneumonitis with additional immune modulators in addition to steroids. Twelve patients (46%) were steroid-refractory and 14 (54%) were steroid-resistant. Pneumonitis severity included grade 2 (42%) or grade 3–4 (58%). Additional immune modulation consisted of tumor necrosis factor-alpha inhibitor (77%) and/or mycophenolate (23%). Durable improvement in pneumonitis following initiation of additional immune modulators occurred in 10 patients (38%), including three patients (12%) in whom pneumonitis resolved and all immunosuppressants ceased. The rate of 90-day all-cause mortality/hospice referral was 50%. At last follow-up, mortality attributable to pneumonitis was 23%. In addition to mortality from pneumonitis and cancer, 3 patients (12%) died due to infections possibly associated with immunosuppression.Conclusions Steroid-refractory or -resistant immune checkpoint pneumonitis is uncommon but associated with significant morbidity and mortality. Additional immunomodulators can yield durable improvement, attained in over one third of patients. An improved understanding of the underlying biology of immune-related pneumonitis will be crucial to guide more precise and effective treatment strategies in the future.

Osteoarthritis (OA) is a common articular disease manifested by the destruction of cartilage and compromised chondrogenesis in the aging population, with chronic inflammation of synovium, which drives OA progression. Importantly, the activated synovial fibroblast (AF) within the synovium facilitates OA through modulating key molecules, including regulatory microRNAs (miR’s). To understand OA associated pathways, in vitro co-culture system, and in vivo papain-induced OA model were applied for this study. The expression of key inflammatory markers both in tissue and blood plasma were examined by qRT-PCR, western blot, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence assays. Herein, our result demonstrated, AF-activated human chondrocytes (AC) exhibit elevated NFκB, TNF-α, IL-6, and miR-21 expression as compared to healthy chondrocytes (HC). Importantly, AC induced the apoptosis of HC and inhibited the expression of chondrogenesis inducers, SOX5, TGF-β1, and GDF-5. NFκB is a key inflammatory transcription factor elevated in OA. Therefore, SC75741 (an NFκB inhibitor) therapeutic effect was explored. SC75741 inhibits inflammatory profile, protects AC-educated HC from apoptosis, and inhibits miR-21 expression, which results in the induced expression of GDF-5, SOX5, TGF-β1, BMPR2, and COL4A1. Moreover, ectopic miR-21 expression in fibroblast-like activated chondrocytes promoted osteoblast-mediated differentiation of osteoclasts in RW264.7 cells. Interestingly, in vivo study demonstrated SC75741 protective role, in controlling the destruction of the articular joint, through NFκB, TNF-α, IL-6, and miR-21 inhibition, and inducing GDF-5, SOX5, TGF-β1, BMPR2, and COL4A1 expression. Our study demonstrated the role of NFκB/miR-21 axis in OA progression, and SC75741’s therapeutic potential as a small-molecule inhibitor of miR-21/NFκB-driven OA progression.

Abstract Background Naringenin (Nar), a common dietary flavonoid abundantly present in fruits, vegetables, and Chinese herbs, is believed to possess strong anti-inflammatory properties and to modulate hepatic apolipoprotein and lipid synthesis. However, there are no reports describing Nar’s effects on the hepatitis B virus protein X (HBx) -induced hepatic steatosis, and the detailed molecular mechanisms of the compound’s effects are still unclear. Methods Nar was administered by oral gavage to HBx-transgenic mice from 4 to 6 weeks of age. Mice were sacrificed after 14 days of once-daily naringenin administration. Liver tissues and sera were collected for histopathology and biochemical analysis. Results Nar counteracted hepatic lipid accumulation and liver dysfunction in HBx-transgenic mice. In addition, Nar significantly decreased expression of adipogenic and lipogenic genes in mice, suggesting that the compound may have therapeutic effects in the early stages of HBx-mediated hepatic steatosis. These results indicated that naringenin inhibits HBx-induced expression of hepatic adipogenic and lipogenic genes through suppression of HBx-induced gene expression, including decreases in the transcriptional activity of SREBP1c, LXRα, and PPARγ in HBx-trangenic mice and HBx-transfected HepG2 cells. Conclusions Results from this study suggested that Nar may serve as a therapeutic agent for preventing HBx-infected hepatic steatosis in humans.

Abstract Background Patients with hypertension (HTN) reportedly have a higher risk of developing dementia. However, it remains unclear if use of Traditional Chinese Medicine (TCM), the most common form of complementary and alternative medicine, can help lower the risk of dementia for these patients. So the aim of the study was to investigate the effects of TCM on dementia risk among patients with hypertension. Methods This longitudinal cohort study used the Taiwanese National Health Insurance Research Database (NHIRD) to identify 143,382 newly diagnosed hypertension patients aged 20–90 years who received treatment between 1998 and 2007. Among them, 52,365 (36.52%) had received TCM after the onset of hypertension (TCM users), and the remaining 91,017 patients (63.48%) were designated as a control group (non-TCM users). All enrollees were followed until the end of 2012 to record the incidence of dementia. A Cox proportional hazards regression model was used to compute the hazard ratio (HR) of dementia in patients who received TCM. Results During the 15-year follow-up, 3933 TCM users and 10,316 non-TCM users developed dementia, representing an incidence rate of 8.41 and 11.55%, respectively, per 1000 person-years. TCM users had a significantly reduced risk of dementia compared to non-TCM users (adjusted HR = 0.76; 95% confidence interval [CI] = 0.74–0.81). The predominant effect was observed among those treated with TCM longer than 180 days (adjusted HR = 0.65; 95% CI = 0.62–0.69). Among the commonly used TCM products, Tian-Ma-Gou-Teng-Yin, Dan-Shen (Radix Salviae Miltiorrhizae), Chuan-Niu-Xi (Radix Cyathulae), Ge-Gen (Radix Puerariae), Jia-Wei-Xiao-Yao-San, and Jue-Ming-Zi (Semen Cassiae) were significantly associated with a lower risk of dementia. Conclusions Results from this population-based study support the effects of TCM on reducing dementia risk, which may provide a reference for dementia prevention strategies.

Context: Tanshinone IIA (Tan IIA) is a constituent of Danshen Salvia miltiorrhiza Bunge (Lamiaceae); however, its antifatigue activity remains unclear. Objective: To study the antifatigue properties of Tan IIA and its underlying mechanisms. Materials and methods: In program I, three mouse groups were separately subjected to three gavages with 0, 1 and 6 mg/kg Tan IIA and forced swimming test (FST) weekly for 8 weeks; in program II, one gavage with 0, 2 and 10 mg/kg Tan IIA was administered plus FST weekly for 4 weeks. Serum glucose, lactate, superoxide dismutase (SOD), malondialdehyde (MDA) and blood urea nitrogen (BUN) were determined after final FST. Results: Tan IIA significantly prolonged swimming durations in program I but not in program II. Swimming times were 3208 ± 1054 and 2443 ± 1054 s for the 1 and 6 mg/kg treatments and 856 ± 292 s for the vehicle control. The two doses significantly reduced serum glucose levels (40.3 ± 8.5 and 60.0 1 ± 11.8 mg/kg) and lactate levels (61.3 ± 27.5 and 68.8 ± 8.5 mg/kg) in treated mice compared with those in control mice (137.5 ± 38.6 mg/kg and 122.7 ± 18.2 mg/kg, respectively). However, no significant differences were observed regarding SOD, MDA or BUN levels. Discussion and conclusions: Tan IIA has antifatigue activity and is associated with reductions in serum glucose and lactate levels. Further studies should assess muscle hypertrophy and efficient aerobic glycolysis caused by Tan IIA. Tan IIA has potential as a pharmacological agent for fatigue resistance.

Insulin-like growth factors (IGFs) are mediators of growth hormones; they have an influence on cell proliferation and differentiation. In addition, IGF-binding protein (IGFBP)-3 could suppress the mitogenic action of IGFs. Interestingly, tea polyphenols could substantially reduce IGF1 and increase IGFBP3. In this study, we evaluated the effects of smoking, green tea consumption, as well as IGF1, IGF2, and IGFBP3 polymorphisms, on lung cancer risk. Questionnaires were administered to obtain the subjects' characteristics, including smoking habits and green tea consumption from 170 primary lung cancer cases and 340 healthy controls. Genotypes for IGF1, IGF2, and IGFBP3 were identified by polymerase chain reaction. Lung cancer cases had a higher proportion of smoking, green tea consumption of less than one cup per day, exposure to cooking fumes, and family history of lung cancer than controls. After adjusting the confounding effect, an elevated risk was observed in smokers who never drank green tea, as compared to smokers who drank green tea more than one cup per day (odds ratio (OR) = 13.16, 95% confidence interval (CI) = 2.96-58.51). Interaction between smoking and green tea consumption on lung cancer risk was also observed. Among green tea drinkers who drank more than one cup per day, IGF1 (CA)(19)/(CA)(19) and (CA)(19)/X genotypes carriers had a significantly reduced risk of lung cancer (OR = 0.06, 95% CI = 0.01-0.44) compared with IGF1 X/X carriers. Smoking-induced pulmonary carcinogenesis could be modulated by green tea consumption and their growth factor environment.

An all electrochemical deposition process is developed to prepare the polypyrrole nanocomposite films containing multiple layers of CdSe and CdTe. A top covering layer of polypyrrole not only further smoothed the surface but also further boosted the photoluminescence intensity of the nanocomposite film because of the enhanced radiative electron-hole recombination.

Tanshinone IIA (Tan IIA) and sinapic acid (SA) are 2 components separately isolated from 2 Asian medicinal plants, Hydnophytum formicarum Jack and Salvia miltiorrhiza Bunge. The antitumor activities of them were worth exploring, therefore, we examined their antitumor activities in A549, HCT116, HeLa, and Colo320 cancer cell lines by means of WST-1 assay. The results show that Tan IIA exerted far higher (IC50 from 1.0±0.0 to 166.3 ±24.0 µg/mL) antiproliferative activities than SA (IC50 from 2236.3 ± 484.1 to >10 000.0 µg/mL). Of the 4 cell lines, A549 cells were the most sensitive to Tan IIA; thus, we used Western blotting to explore the cytotoxic mechanisms of Tan IIA in A549 cells and found that they rely on simultaneous induction of apoptosis and necroptosis in the cells. Apoptosis was hallmarked by the induction of cleaved caspase-3 by Tan IIA and necroptosis by the necroptotic marker proteins cyclophilin A and high mobility group box 1 (HMGB1), as well as increased lactate dehydrogenase (LDH) activities. The necroptotic effect was confirmed by the necroptosis inhibitor necrostatin-1 (Nec-1), which eliminated these effects and restored cell survival rates. The levels of cyclophilin A decreased in response to the pan-caspase inhibitor z-VAD-fmk, and those of cleaved caspase-3 decreased in response to Nec-1. Conclusively, Tan IIA has the potential to prevent lung cancer and the mechanism seems to be apoptosis and necroptosis, of which the relationship is mutually interdependent. This is the first report of Tan IIA eliciting necroptosis in A549 cells. Tan IIA may be used for necroptosis-based cancer therapy, especially to overcome apoptosis resistance. [ABSTRACT FROM AUTHOR]

A general and simple procedure that allows transfer of Langmuir monolayers from the surface of water onto microscopic and planar interfaces between oil and aqueous phases is reported. The method can also be used for advanced studies of the interfacial behavior of synthetic and biological molecules at liquid-liquid interfaces.