Effectiveness of a comprehensive package based on electronic medication monitors at improving treatment outcomes among tuberculosis patients in Tibet: a multicentre randomised controlled trial.

BACKGROUND: WHO recommends that electronic medication monitors, a form of digital adherence technology, be used as a complement to directly observed treatment (DOT) for tuberculosis, as DOT is inconvenient and costly. However, existing evidence about the effectiveness of these monitors is inconclusive. Therefore, we evaluated the effectiveness of a comprehensive package based on electronic medication monitors among patients with tuberculosis in Tibet Autonomous Region (hereafter Tibet), China. METHODS: This multicentre, randomised controlled trial recruited patients from six counties in Shigatse, Tibet. Eligible participants had drug-susceptible tuberculosis and were aged 15 years or older when starting standard tuberculosis treatment. Tuberculosis doctors recruited patients from the public tuberculosis dispensary in each county and the study statistician randomly assigned them to the intervention or control group based on the predetermined randomised allocation sequence. Intervention patients received an electronic medication monitor box. The box included audio medication-adherence reminders and recorded box-opening data, which were transmitted to a cloud-based server and were accessible to health-care providers to allow remote adherence monitoring. A linked smartphone app enabled text, audio, and video communication between patients and health-care providers. Patients were also provided with a free data plan. Patients selected a treatment supporter (often a family member) who was trained to support patients with using the electronic medication monitor and app. Patients in the control group received usual care plus a deactivated electronic medication monitor, which only recorded and transmitted box-opening data that was not made available to health-care providers. The control group also had no access to the app or trained treatment supporters. The primary outcome was a binary indicator of poor monthly adherence, defined as missing 20% or more of planned doses in the treatment month, measured using electronic medication monitor opening data, and verified by counting used medication blister packages during consultations. We recorded other secondary treatment outcomes based on national tuberculosis reporting data. We analysed the primary outcome based on the intention-to-treat population. This trial is registered at ISRCTN, 52132803. FINDINGS: Between Nov 17, 2018, and April 5, 2021, 278 patients were enrolled into the study. 143 patients were randomly assigned to the intervention group and 135 patients to the control group. Follow-up ended when the final patient completed treatment on Oct 4, 2021. In the intervention group, 87 (10%) of the 854 treatment months showed poor adherence compared with 290 (37%) of the 795 months in the control group. The corresponding adjusted risk difference for the intervention versus control was -29·2 percentage points (95% CI -35·3 to -22·2; p<0·0001). Five of the six secondary treatment outcomes also showed clear improvements, including treatment success, which was found for 133 (94%) of the 142 individuals in the intervention arm and 98 (73%) of the 134 individuals in the control arm, with an adjusted risk difference of 21 percentage points (95% CI 12·4-29·4); p<0·0001. INTERPRETATION: The interventions were effective at improving tuberculosis treatment adherence and outcomes, and the trial suggests that a comprehensive package involving electronic medication monitors might positively affect tuberculosis programmes in high-burden and low-resource settings. FUNDING: TB REACH.

Pterostilbene could alleviate diabetic cognitive impairment by suppressing TLR4/NF-кB pathway through microbiota-gut-brain axis.

Diabetic cognitive impairment (DCI) is a serious neurodegenerative disorder caused by diabetes, with chronic inflammation being a crucial factor in its pathogenesis. Pterostilbene is a well-known natural stilbene derivative that has excellent anti-inflammatory activity, suggesting its potential medicinal advantages for treating DCI. Therefore, this study is to explore the beneficial effects of pterostilbene for improving cognitive dysfunction in DCI mice. A diabetic model was induced by a high-fat diet plus streptozotocin (40 mg·kg-1 ) for consecutive 5 days. After the animals were confirmed to be in a diabetic state, they were treated with pterostilbene (20 or 60 mg·kg-1 , i.g.) for 10 weeks. Pharmacological evaluation showed pterostilbene could ameliorate cognitive dysfunction, regulate glycolipid metabolism disorders, improve neuronal damage, and reduce the accumulation of ß-amyloid in DCI mice. Pterostilbene alleviated neuroinflammation by suppressing oxidative stress and carbonyl stress damage, astrocyte and microglia activation, and dopaminergic neuronal loss. Further investigations showed that pterostilbene reduced the level of lipopolysaccharide, modulated colon and brain TLR4/NF-κB signaling pathways, and decreased the release of inflammatory factors, which in turn inhibited intestinal inflammation and neuroinflammation. Furthermore, pterostilbene could also improve the homeostasis of intestinal microbiota, increase the levels of short-chain fatty acids and their receptors, and suppress the loss of intestinal tight junction proteins. In addition, the results of plasma non-targeted metabolomics revealed that pterostilbene could modulate differential metabolites and metabolic pathways associated with inflammation, thereby suppressing systemic inflammation in DCI mice. Collectively, our study found for the first time that pterostilbene could alleviate diabetic cognitive dysfunction by inhibiting the TLR4/NF-κB pathway through the microbiota-gut-brain axis, which may be one of the potential mechanisms for its neuroprotective effects.

Combination of UHPLC-Q Exactive-Orbitrap MS, Bioinformatics and Molecular Docking to Reveal the Mechanism of Huan-Lian-Jie-Du Decoction in the Treatment of Diabetic Encephalopathy.

Diabetic encephalopathy (DE) is a serious complication of diabetes, which affects patients' quality of life. We aimed to explore HLJDD in the treatment of DE by LC/MS and bioinformatics. UPLC-Q Exactive-Orbitrap MS was employed to clarify the compounds. The modules and hub targets of DE were gained from WGCNA. Subsequently, an Herb-Compound-Target network was constructed and enrichment analysis was used. In addition, a protein-protein interaction (PPI) network was constructed and molecular docking was used to verify the above analysis. As result, 138 compounds and 10 prototypes in brain were identified. In network pharmacology, 8 modules and 5692 hub targets were obtained from WGCNA. An Herb-Compound-Target network was constructed by 4 herbs, 10 compounds and 56 targets. The enrichment analysis showed that the treatment of DE with HLJDD involve oxidative stress and neuroprotection. Beside, SRC, JUN, STAT3, MAPK1 and PIK3R1 were identified and as hub targets of HLJDD in treating DE. Moreover, Molecular docking showed that five hub targets had strong affinity with the corresponding alkaloids. Therefore, we explored the underlying mechanisms of HLJDD in the treatment of DE and to provide the theoretical and scientific basis for subsequent experimental studies and clinical applications.

Evaluation of a package of risk-based pharmaceutical and lifestyle interventions in patients with hypertension and/or diabetes in rural China: A pragmatic cluster randomised controlled trial.

BACKGROUND: Primary prevention of cardiovascular disease (CVD) requires adequate control of hypertension and diabetes. We designed and implemented pharmaceutical and healthy lifestyle interventions for patients with diabetes and/or hypertension in rural primary care, and assessed their effectiveness at reducing severe CVD events. METHODS AND FINDINGS: We used a pragmatic, parallel group, 2-arm, controlled, superiority, cluster trial design. We randomised 67 township hospitals in Zhejiang Province, China, to intervention (34) or control (33). A total of 31,326 participants were recruited, with 15,380 in the intervention arm and 15,946 in the control arm. Participants had no known CVD and were either patients with hypertension and a 10-year CVD risk of 20% or higher, or patients with type 2 diabetes regardless of their CVD risk. The intervention included prescription of a standardised package of medicines, individual advice on lifestyle change, and adherence support. Control was usual hypertension and diabetes care. In both arms, as usual in China, most outpatient drug costs were out of pocket. The primary outcome was severe CVD events, including coronary heart disease and stroke, during 36 months of follow-up, as recorded by the CVD surveillance system. The study was implemented between December 2013 and May 2017. A total of 13,385 (87%) and 14,745 (92%) participated in the intervention and control arms, respectively. Their mean age was 64 years, 51% were women, and 90% were farmers. Of all participants, 64% were diagnosed with hypertension with or without diabetes, and 36% were diagnosed with diabetes only. All township hospitals and participants completed the 36-month follow-up. At 36 months, there were 762 and 874 severe CVD events in the intervention and control arms, respectively, yielding a non-significant effect on CVD incidence rate (1.92 and 2.01 per 100 person-years, respectively; crude incidence rate ratio = 0.90 [95% CI: 0.74, 1.08; P = 0.259]). We observed significant, but small, differences in the change from baseline to follow-up for systolic blood pressure (-1.44 mm Hg [95% CI: -2.26, -0.62; P < 0.001]) and diastolic blood pressure (-1.29 mm Hg [95% CI: -1.77, -0.80; P < 0.001]) in the intervention arm compared to the control arm. Self-reported adherence to recommended medicines was significantly higher in the intervention arm compared with the control arm at 36 months. No safety concerns were identified. Main study limitations include all participants being informed about their high CVD risk at baseline, non-blinding of participants, and the relatively short follow-up period available for judging potential changes in rates of CVD events. CONCLUSIONS: The comprehensive package of pharmaceutical and healthy lifestyle interventions did not reduce severe CVD events over 36 months. Improving health system factors such as universal coverage for the cost of essential medicines is required for successful risk-based CVD prevention programmes. TRIAL REGISTRATION: ISRCTN registry ISRCTN58988083.

Renewable and robust biomass waste-derived Co-doped carbon aerogels for PMS activation: Catalytic mechanisms and phytotoxicity assessment.

Developing monolithic carbon-based catalyst with low cost, easy separation and high performance to degrade pollutants via PMS activation is crucial. In this work, a series of novel monolithic Me-CA catalysts based on biomass derived carbon aerogel were prepared by hydrothermal method using waste watermelon peel as raw material. Co-CA catalyst showed excellent performance to activate PMS for 2, 4-DCP degradation in different temperature and different water matrices. Different pollutants, such as ciprofloxacin (CIP), bisphenol A (BPA), and 2, 4-dichlorophenoxyacetic acid (2, 4-D) could also be removed in the Co-CA/PMS system. As expected, Co-CA could be easily separated from degraded solution, and show high stability and reusability for PMS activation with a lower cobalt leaching. Based on the results of the quenching tests, electron paramagnetic resonance (EPR) spectra, Chronoamperometric test (i-t curves) and electro-chemical impedance spectroscopy (EIS), the PMS activation mechanism was proposed. The phytotoxicity assessment determined by germination situation of mung bean indicated that PMS activation could eliminate the hazards of 2, 4-D. Therefore, this study provides a low cost, efficient and environmental-friendly monolithic biomass carbon aerogel catalyst for different pollutants degradation, which further advances monolithic catalyst for practical wastewater treatment.

Long-term outcomes of an educational intervention to reduce antibiotic prescribing for childhood upper respiratory tract infections in rural China: Follow-up of a cluster-randomised controlled trial.

BACKGROUND: Inappropriate antibiotic prescribing causes widespread serious health problems. To reduce prescribing of antibiotics in Chinese primary care to children with upper respiratory tract infections (URTIs), we developed an intervention comprising clinical guidelines, monthly prescribing review meetings, doctor-patient communication skills training, and education materials for caregivers. We previously evaluated our intervention using an unblinded cluster-randomised controlled trial (cRCT) in 25 primary care facilities across two rural counties. When our trial ended at the 6-month follow-up period, we found that the intervention had reduced antibiotic prescribing for childhood URTIs by 29 percentage points (pp) (95% CI -42 to -16). METHODS AND FINDINGS: In this long-term follow-up study, we collected our trial outcomes from the one county (14 facilities and 1:1 cluster randomisation ratio) that had electronic records available 12 months after the trial ended, at the 18-month follow-up period. Our primary outcome was the antibiotic prescription rate (APR)-the percentage of outpatient prescriptions containing any antibiotic(s) for children aged 2 to 14 years who had a primary diagnosis of a URTI and had no other illness requiring antibiotics. We also conducted 15 in-depth interviews to understand how interventions were sustained. In intervention facilities, the APR was 84% (1,171 out of 1,400) at baseline, 37% (515 out of 1,380) at 6 months, and 54% (2,748 out of 5,084) at 18 months, and in control facilities, it was 76% (1,063 out of 1,400), 77% (1,084 out of 1,400), and 75% (2,772 out of 3,685), respectively. After adjusting for patient and prescribing doctor covariates, compared to the baseline intervention-control difference, the difference at 6 months represented a 6-month intervention-arm reduction in the APR of -49 pp (95% CI -63 to -35; P < 0.0001), and compared to the baseline difference, the difference at 18 months represented an 18-month intervention-arm reduction in the APR of -36 pp (95% CI -55 to -17; P < 0.0001). Compared to the 6-month intervention-control difference, the difference at 18 months represented no change in the APR: 13 pp (95% CI -7 to 33; P = 0.21). Factors reported to sustain reductions in antibiotic prescribing included doctors' improved knowledge and communication skills and focused prescription review meetings, whereas lack of supervision and monitoring may be associated with relapse. Key limitations were not including all clusters from the trial and not collecting returned visits or sepsis cases. CONCLUSIONS: Our intervention was associated with sustained and substantial reductions in antibiotic prescribing at the end of the intervention period and 12 months later. Our intervention may be adapted to similar resource-poor settings. TRIAL REGISTRATION: ISRCTN registry ISRCTN14340536.

Cost-effectiveness analysis of a multi-dimensional intervention to reduce inappropriate antibiotic prescribing for children with upper respiratory tract infections in China.

BACKGROUND: We developed a multifaceted intervention to reduce antibiotic prescription rate for children with upper respiratory tract infections (URTIs) among primary care doctors in township hospitals in China. The intervention achieved a 29% (95% CI 16-42) absolute risk reduction in antibiotic prescribing. This study was to assess the cost-effectiveness of our intervention at reducing antibiotic prescribing in rural primary care facilities as measured by the intervention's effect on the antibiotic prescription rates for childhood URTIs. METHODS: We took a healthcare provider perspective, measuring costs of consultation (time cost of doctor), prescription monitoring process and peer-review meetings (time cost of participants) and medication costs. Costs on provider side were collected through a bespoke questionnaire from all 25 township hospitals in December 2016, while medication costs were collected prospectively in the trial. Incremental cost-effectiveness ratios were calculated by dividing the mean difference in cost of the two trial arms by the mean difference in antibiotic prescribing rate. RESULTS: This showed an incremental cost of $0.03 per percentage point reduction in antibiotic prescribing. In addition to this incremental cost, the cost of implementing the intervention, including training and materials delivered by township hospitals, was $390.65 (SD $145.68) per healthcare facility. CONCLUSIONS: This study shows that a multifaceted intervention programme, when embedded into routine practice, is very cost-effective at reducing antibiotic prescribing in primary care facilities and has the potential of scale up in similar resource limited settings.

Impact of China's essential medicines scheme and zero-mark-up policy on antibiotic prescriptions in county hospitals: a mixed methods study.

OBJECTIVE: To evaluate the impact of the national essential medicines scheme and zero-mark-up policy on antibiotic prescribing behaviour. METHODS: In rural Guangxi, a natural experiment compared one county hospital which implemented the policy with a comparison hospital which did not. All outpatient and inpatient records in 2011 and 2014 were extracted from the two hospitals. Primary outcome indicator was antibiotic prescribing rate (APR) among children aged 2-14 presenting in outpatients with a primary diagnosis of upper respiratory tract infection (URTI). We organised independent physician reviews to determine inappropriate prescribing for inpatients. Difference-in-difference analyses based on multivariate regressions were used to compare APR over time after adjusting potential confounders. We conducted 12 in-depth interviews with paediatricians, hospital directors and health officials. RESULTS: A total of 8219 and 4142 outpatient prescriptions of childhood URTIs were included in the intervention and comparison hospitals, respectively. In 2011, APR was 30% in the intervention and 88% in the comparison hospital. In 2014, the intervention hospital significantly reduced outpatient APR by 21% (95% CI:-23%, -18%), intravenous infusion by 58% (95% CI: -64%, -52%) and prescription cost by 31 USD (95% CI: -35, -28), compared with the controls. We collected 251 inpatient records, but did not find reductions in inappropriate antibiotic use. Interviews revealed that the intervention hospital implemented a thorough antibiotics stewardship programme containing training, peer review of prescriptions and restrictions for overprescribing. CONCLUSION: The national essential medicines scheme and zero-mark-up policy, when implemented with an antimicrobial stewardship programme, may be associated with reductions in outpatient antibiotic prescribing and intravenous infusions.

Diagnostic and treatment delays of multidrug-resistant tuberculosis before initiating treatment: a cross-sectional study.

OBJECTIVE: Shandong Province has implemented the standardised treatment of multidrug-resistant tuberculosis (MDR-TB) supported by the Global Fund. The study aimed to understand the managements and delays of patients with MDR-TB before initiating their treatments. METHODS: All patients with MDR-TB who had completed intensive phase treatment from January 2010 to May 2012 were interviewed using a structured questionnaire. Delays and treatments were analysed. Diagnosis delay is defined as the period between having sputum smear results and drug susceptibility test (DST) results. Treatment delay was defined as starting MDR-TB treatment more than 2 days after receiving the diagnosis of MDR-TB. Total delay is the sum of diagnosis delay and treatment delay. RESULTS: In total, 110 patients with MDR-TB participated in the study. Median delay for diagnosis was 102 days. Over 80% of patients had a diagnosis delay longer than 90 days. MDR-TB treatments commenced after a median of 9 days after DST results, and over 37% of the patients with MDR-TB experienced treatment delays. Chronic cases or patients with indifferent attitude had significantly longer treatment delay than other groups (P = 0.03 and 0.03, respectively). During their delays, of 44 patients with retreatment failures, 12 (27.3%) were treated through adding single second line drugs (SLDs) to first-line regimens, and 25 (56.8%) were treated with first-line drugs. A high proportion of initial treatment failure/relapsed/returned cases (37%) and new cases (43%) were administered with SLDs. CONCLUSIONS: Most of the patients with MDR-TB experienced prolonged diagnosis delay, which was the most important factor contributing to the total delay. Misuse of SLDs during the days was common, so necessary training should be given to prevent irrational prescription of medications.

Evaluation of a systematic cardiovascular disease risk reduction strategy in primary healthcare: an exploratory study from Zhejiang, China.

BACKGROUND: In China, cardiovascular disease (CVD) risk reduction strategies are not systematically implemented in primary healthcare (PHC). We conducted an exploratory study to evaluate the preliminary effectiveness of our systematic CVD risk reduction package in one township hospital of Zhejiang. METHODS: Using the Asian Equation, we selected subjects aged 40-74 years with a calculated 10-year CVD risk of 20% or higher from the existing resident health records and research checkup. The subjects were provided, as appropriate, with the low-dose combination of CVD-preventive drugs (antihypertensive drugs, aspirin, statin), lifestyle modification and adherence strategies monthly. The intervention was piloted for three months in 2012, preceding the conduct of a cluster-based randomized controlled trial (RCT). RESULTS: A total of 153 (40%) subjects were recruited, with an average total 10-year risk of CVD of 28.5 ± 7.9%. After intervention, the appointment rate was up to 90%. An upward trend was observed for the use of CVD-preventive drugs. The smoking rates significantly reduced from 38 to 35%, with almost no change for salt reduction. The systolic blood pressure (BP) and diastolic BP decreased slightly. CONCLUSION: A holistic CVD risk reduction approach shows preliminary effects in a rural PHC setting of Zhejiang, China. However, further understanding is needed regarding its long-term effectiveness and feasibility in PHC practices. Our cluster-based RCT will provide the highest level of evidence for the policy development of preventing CVD in a rural PHC of China.

Protective effects of Huang-Qi-Ge-Gen decoction against diabetic liver injury through regulating PI3K/AKT/Nrf2 pathway and metabolic profiling.

ETHNOPHARMACOLOGICAL RELEVANCE: Huang-Qi-Ge-Gen decoction (HGD) is a traditional Chinese medicine prescription that has been used for centuries to treat "Xiaoke" (the name of diabetes mellitus in ancient China). However, the ameliorating effects of HGD on diabetic liver injury (DLI) and its mechanisms are not yet fully understood. AIM OF THE STUDY: To elucidate the ameliorative effect of HGD on DLI and explore its material basis and potential hepatoprotective mechanism. MATERIALS AND METHODS: A diabetic mice model was induced by feeding a high-fat diet and injecting intraperitoneally with streptozotocin (40 mg kg-1) for five days. After the animals were in confirmed diabetic condition, they were given HGD (3 or 12 g kg-1, i. g.) for 14 weeks. The effectiveness of HGD in treating DLI mice was evaluated by monitoring blood glucose and blood lipid levels, liver function, and pathological conditions. Furthermore, UPLC-MS/MS was used to identify the chemical component profile in HGD and absorption components in HGD-treated plasma. Network pharmacology and molecular docking were performed to predict the potential pathway of HGD intervention in DLI. Then, the results of network pharmacology were validated by examining biochemical parameters and using western blotting. Lastly, urine metabolites were analyzed by metabolomics strategy to explore the effect of HGD on the metabolic profile of DLI mice. RESULTS: HGD exerted therapeutic potential against the disorders of glucose metabolism and lipid metabolism, liver dysfunction, liver steatosis, and fibrosis in a DLI model mice induced by HFD/STZ. A total of 108 chemical components in HGD and 18 absorption components in HGD-treated plasma were preliminarily identified. Network pharmacology and molecular docking results of the absorbed components in plasma indicated PI3K/AKT as a potential pathway for HGD to intervene in DLI mice. Further experiments verified that HGD markedly reduced liver oxidative stress in DLI mice by modulating the PI3K/AKT/Nrf2 signaling pathway. Moreover, 19 differential metabolites between normal and DLI mice were detected in urine, and seven metabolites could be significantly modulated back by HGD. CONCLUSIONS: HGD could ameliorate diabetic liver injury by modulating the PI3K/AKT/Nrf2 signaling pathway and urinary metabolic profile.

Exploring opportunities to strengthen rural tuberculosis health service delivery: a qualitative study with health workers in Tibet autonomous region, China.

OBJECTIVES: This qualitative study aimed to explore opportunities to strengthen tuberculosis (TB) health service delivery from the perspectives of health workers providing TB care in Shigatse prefecture of Tibet Autonomous Region, China. DESIGN: Qualitative research, semi-structured in-depth interviews. SETTING: The TB care ecosystem in Shigatse, including primary and community care. PARTICIPANTS: Participants: 37 semi-structured interviews were conducted with village doctors (14), township doctors and nurses (14), county hospital doctors (7) and Shigatse Centre for Disease Control staff (2). RESULTS: The three main themes reported include (1) the importance of training primary and community health workers to identify people with symptoms of TB, ensure TB is diagnosed and link people with TB to further care; (2) the need to engage community health workers to ensure retention in care and adherence to TB medications; and (3) the opportunity for innovative technologies to support coordinated care, retention in care and adherence to medication in Shigatse. CONCLUSIONS: The quality of TB care could be improved across the care cascade in Tibet and other high-burden, remote settings by strengthening primary care through ongoing training, greater support and inclusion of community health workers and by leveraging technology to create a circle of care. Future formative and implementation research should include the perspectives of health workers at all levels to improve care organisation and delivery.

Rapid and accurate quality evaluation of Angelicae Sinensis Radix based on near-infrared spectroscopy and Bayesian optimized LSTM network.

The authentic traditional Chinese medicines (TCMs) including Angelicae Sinensis Radix (ASR) are the representative of high-quality herbals in China. However, ASR from authentic region being adulterated or counterfeited is frequently occurring, and there is still a lack of rapid quality evaluation methods for identifying the authentic ASR. In this study, the color features of ASR were firstly characterized. The results showed that the authentic ASR cannot be fully identified by color characteristics. Then near-infrared (NIR) spectroscopy combined with Bayesian optimized long short-term memory (BO-LSTM) was used to evaluate the quality of ASR, and the performance of BO-LSTM with common classification and regression algorithms was compared. The results revealed that following the pretreatment of NIR spectra, the optimal NIR spectra combined with BO-LSTM not only successfully distinguished authentic, non-authentic, and adulterated ASR with 100 % accuracy, but also accurately predicted the adulteration concentration of authentic ASR (R2 > 0.99). Moreover, BO-LSTM demonstrated excellent performance in classification and regression compared with common algorithms (ANN, SVM, PLSR, etc.). Overall, the proposed strategy could quickly and accurately evaluate the quality of ASR, which provided a reference for other TCMs.

Substrate-free dissolving microneedles with barbed shape to increase adhesion and drug-delivery efficiency to skin.

Microneedle drug delivery has recently emerged as a clinical method, and dissolving microneedles (DMNs) offer exclusive simplicity and efficiency, compared to the other kinds of microneedles. The tips of most currently available DMNs are cone/house-shaped to result in a lower penetration force. Penetration of the needle tips into the skin relies mainly on the back tape or external pressure, and their adhesion to the skin is relatively low. In addition, only the drug in the part of tips that are pierced into the dermis can be dissolved, resulting in drug waste. Inspired from the barbed structure of the honeybee stinger, we reported substrate-free DMNs with a barbed structure by a dual-molding process, which is suitable for mass production. Those DMNs showed 3-fold greater adhesion force between the needle tips and the skin, better dissolution and deeper penetration than house-shaped DMNs in vivo under the same conditions. For the in situ treatment of psoriasis in mice, the barbed DMNs required only the half dose of house-shaped DMNs to achieve similar efficacy.

Wireless facial biosensing system for monitoring facial palsy with flexible microneedle electrode arrays.

Facial palsy (FP) profoundly influences interpersonal communication and emotional expression, necessitating precise diagnostic and monitoring tools for optimal care. However, current electromyography (EMG) systems are limited by their bulky nature, complex setups, and dependence on skilled technicians. Here we report an innovative biosensing approach that utilizes a PEDOT:PSS-modified flexible microneedle electrode array (P-FMNEA) to overcome the limitations of existing EMG devices. Supple system-level mechanics ensure excellent conformality to the facial curvilinear regions, enabling the detection of targeted muscular ensemble movements for facial paralysis assessment. Moreover, our apparatus adeptly captures each electrical impulse in response to real-time direct nerve stimulation during neurosurgical procedures. The wireless conveyance of EMG signals to medical facilities via a server augments access to patient follow-up evaluation data, fostering prompt treatment suggestions and enabling the access of multiple facial EMG datasets during typical 6-month follow-ups. Furthermore, the device's soft mechanics alleviate issues of spatial intricacy, diminish pain, and minimize soft tissue hematomas associated with traditional needle electrode positioning. This groundbreaking biosensing strategy has the potential to transform FP management by providing an efficient, user-friendly, and less invasive alternative to the prevailing EMG devices. This pioneering technology enables more informed decision-making in FP-management and therapeutic intervention.

Factors Influencing Medication Adherence in Elderly Patients with Hypertension: A Single Center Study in Western China.

Purpose: To develop and empirically test a conceptual model that explains the factors influencing antihypertensive medication adherence behavior in elderly patients in a city in western China. Patients and Methods: The conceptual model was based on the Theory of Planned Behavior and the Health Belief Model and was empirically tested using cross-sectional survey data from Nanchong City, a city in western China, collected between October and December 2020. Data were analyzed using structural equation modeling. Results: Behavioral intentions were the main predictor of medication adherence behavior (path coefficient of 0.353). Perceived benefits and perceived barriers directly (path coefficient = 0.201 and -0.150, respectively), and indirectly (path coefficient = 0.118 and -0.060) through behavioral intentions, influenced medication adherence behavior. Perceived susceptibility (path coefficient = 0.390) and perceived severity (path coefficient = 0.408) influenced behavioral attitudes, which influenced behavioral intentions (path coefficient = 0.298). Conclusion: The conceptual model demonstrates a robust ability to predict and explain medication adherence behavior among elderly patients with hypertension, facilitating the adoption and maintenance of changes in adherence behavior and the potential for preventing disease progression and improving quality of life.

Comparative study on Angelica sinensis after different processing with yellow rice wine in color, aromas, chemical components, and antioxidant activities.

This study aimed to explore the differences in raw Angelica Sinensis (RAS), wine washing AS (WAS), and wine stir-frying AS (WSAS). The results showed there were differences among the three AS in color and aroma, and 34 aroma compounds were identified. The content determination results revealed the ferulic acid and Z-ligustilide levels of RAS decreased after processing, and those in WAS were higher than in WSAS. Furthermore, 85 representative common components and 37 unique components were tentatively identified in three AS. Finally, the free radical scavenging assay results indicated the antioxidant capacity of RAS was reduced after processing, and the antioxidant capacity of WAS was better than WSAS. Collectively, the RAS undergoes significant changes in color, aromas, components, and antioxidant ability after processing, and the different processing methods also result in significant differences between WAS and WSAS.

Customized flexible hollow microneedles for psoriasis treatment with reduced-dose drug.

Microneedles, especially hollow microneedles (HMNs), play an important role in drug delivery, but most of the current HMNs are manufactured based on silicon microfabrication (lithography, etching, etc.), which are slightly conservative due to the lack of low-cost, batch-scale and customized preparation approach, especially for the HMNs with flexible substrate. For the first time, we propose the use of a high-precision 3D printed master mold followed by a dual-molding process for the preparation of HMNs with different shapes, heights, and inner and outer diameters to satisfy different drug delivery needs. The 3D printed master mold and negative mold can be reused, thereby significantly reducing the cost. HMNs are based on biocompatible materials, such as heat-curing polymers or light-curing resins. The thickness and rigidity/flexibility characteristics of the substrate can be customized for different applications. The drug delivery efficiency of the fabricated HMNs was verified by the in situ treatment of psoriasis on the backs of mice, which required only a 0.1-fold oral dose to achieve similar efficacy, and the associated side effects and drug toxicity were reduced. Thus, this dual-molding process can reinvigorate HMNs development.

Adaptive estimation of continuous gait phase based on capacitive sensors.

Continuous gait phase plays an important role in robotic prosthesis control. In this paper, we have conducted the offline adaptive estimation (at different speeds and on different ramps) of continuous gait phase of robotic transtibial prosthesis based on the adaptive oscillators. We have used the capacitive sensing method to record the deformation of the muscles. Two transtibial amputees joined in this study. Based on the strain signals of the prosthetic foot and the capacitive signals of the residual limb, the maximum and minimum of estimation errors are 0.80 rad and 0.054 rad, respectively, and their corresponding ratios in one gait cycle are 1.27% and 0.86%, respectively. This paper proposes an effective method to estimate the continuous gait phase based on the capacitive signals of the residual muscles, which provides a basis for the continuous control of robotic transtibial prosthesis.

A Low-Cost Flexible Perforated Respiratory Sensor Based on Platinum for Continuous Respiratory Monitoring.

Monitoring sleep conditions is of importance for sleep quality evaluation and sleep disease diagnosis. Accurate respiration detection provides key information about sleep conditions. Here, we propose a perforated temperature sensor that can be worn below the nasal cavity to monitor breath. The sensing system consists of two perforated temperature sensors, signal conditioning circuits, a transmission module, and a supporting analysis algorithm. The perforated structure effectively enhances the sensitivity of the system and shortens the response time. The sensor's response time is 0.07 s in air and sensitivity is 1.4‱°C-1. The device can achieve a monitoring respiratory temperature range between normal room temperature and 40 °C. The simple and standard micromachining process ensures low cost and high reproducibility. We achieved the monitoring of different breathing patterns, such as normal breathing, panting, and apnea, which can be applied to sleep breath monitoring and exercise information recording.