Levodopa improved different motor symptoms in patients with Parkinson's disease by reducing the functional connectivity of specific thalamic subregions.

BACKGROUND: The thalamus is an important relay station for the motor circuit of human. Levodopa can reverse the clinical manifestations by modulating the function of motor circuits, but its detailed mechanisms are still not fully understood. We aimed to explore (1) the mechanism by which levodopa modulates the functional connectivity (FC) in the subregions of the thalamus; (2) the relationship between the changed FC and the improvement of motor symptoms in Parkinson's disease (PD) patients. METHODS: Resting-state functional MRI was used to scan 36 PD patients and 37 healthy controls. The FC between the subregions in the thalamus and the whole brain was measured and compared under different medication states of PD patients. The correlation between the improvement of motor symptoms and changes in FC in the thalamus subregions was examined. RESULTS: The PD on state exhibited decreased FC between the right pre-motor thalamus and the right postcentral gyrus, as well as the right lateral pre-frontal thalamus and the right postcentral gyrus. These decreases were positively correlated with the improvement of resting tremor. The PD on state also exhibited decreased FC between the left lateral pre-frontal thalamus and right paracentral lobule, which was positively correlated with the improvement of bradykinesia. CONCLUSIONS: This study demonstrates that levodopa treats PD by decreasing the FC between the thalamus subregions and pre/post-central cortex. Our results provide a basis for further exploration of the functional activity of thalamic subregions and offer new insights into the precision treatment in PD patients.

Inflammatory microenvironment in gastric premalignant lesions: implication and application.

Gastric precancerous lesions (GPL) are a major health concern worldwide due to their potential to progress to gastric cancer (GC). Understanding the mechanism underlying the transformation from GPL to GC can provide a fresh insight for the early detection of GC. Although chronic inflammation is prevalent in the GPL, how the inflammatory microenvironment monitored the progression of GPL-to-GC are still elusive. Inflammation has been recognized as a key player in the progression of GPL. This review aims to provide an overview of the inflammatory microenvironment in GPL and its implications for disease progression and potential therapeutic applications. We discuss the involvement of inflammation in the progression of GPL, highlighting Helicobacter pylori (H. pylori) as a mediator for inflammatory microenvironment and a key driver to GC progression. We explore the role of immune cells in mediating the progression of GPL, and focus on the regulation of inflammatory molecules in this disease. Furthermore, we discuss the potential of targeting inflammatory pathways for GPL. There are currently no specific drugs for GPL treatment, but traditional Chinese Medicine (TCM) and natural antioxidants, known as antioxidant and anti-inflammatory properties, exhibit promising effects in suppressing or reversing the progression of GPL. Finally, the challenges and future perspectives in the field are proposed. Overall, this review highlights the central role of the inflammatory microenvironment in the progression of GPL, paving the way for innovative therapeutic approaches in the future.

Morusinol Extracted from Morus alba Inhibits Cell Proliferation and Induces Autophagy via FOXO3a Nuclear Accumulation-Mediated Cholesterol Biosynthesis Obstruction in Colorectal Cancer.

The incidence rate of colorectal cancer (CRC) has been increasing significantly in recent years, and it is urgent to develop novel drugs that have more effects for its treatment. It has been reported that many molecules extracted from the root bark of Morus alba L. (also known as Cortex Mori) have antitumor activities. In our study, we identified morusinol as a promising anticancer agent by selecting from 30 molecules extracted from Morus alba L. We found that morusinol treatment suppressed cell proliferation and promoted apoptosis of CRC cells in vitro. Besides this, we observed that morusinol induced cytoprotective autophagy. The GO analysis of differentially expressed genes from RNA-seq data showed that morusinol affected cholesterol metabolism. Then we found that key enzyme genes in the cholesterol biosynthesis pathway as well as the sterol regulatory element binding transcription factor 2 (SREBF2) were significantly downregulated. Furthermore, additional cholesterol treatment reversed the anti-CRC effect of morusinol. Interestingly, we also found that morusinol treatment could promote forkhead box O3 (FOXO3a) nuclear accumulation, which subsequently suppressed SREBF2 transcription. Then SREBF2-controlled cholesterol biosynthesis was blocked, resulting in the suppression of cell proliferation, promotion of apoptosis, and production of autophagy. The experiments in animal models also showed that morusinol significantly impeded tumor growth in mice models. Our results suggested that morusinol may be used as a candidate anticancer drug for the treatment of CRC.

Experimental research on the evaluation of left ventricular systolic function by layered speckle tracking before and after berberine treatment in a cardiac hypertrophy rat model.

Background: To evaluate the effect of berberine (BBR) intervention on left ventricular hypertrophy and systolic function in rats by ultrasound layered strain imaging and cardiac hypertrophy model. Methods: Eighty healthy male Sprague-Dawley (SD) rats were randomly divided into four groups: group A (normal saline control group), group B [isoproterenol (ISO) induced model group], group C (BBR hydrochloride 5 mg/kg + ISO group) and group D (BBR hydrochloride 10 mg/kg + ISO group). Echocardiography was performed on days 1, 7 and 14, respectively. The myocardial tissue was taken for pathological examination. The key proteins of Rho/ROCK signaling pathway were quantified by immunohistochemical staining. Results: On day 7, compared with group A, peripheral strain values of the subendocardium and middle myocardium of rats in groups B, C and D were significantly decreased. The absolute value of circumferential strain (CS) in subendocardium and middle myocardium in group B was significantly lower than that in groups C and D (-24.21 vs. -26.68 vs. -27.69; -14.90 vs. -16.48 vs. -17.69). Pathological results showed that compared with the myocardial cells in control group A, the myocardial cells in group B had significantly increased cross-sectional area, and obvious myocardial interstitial fibrosis. Compared with group B, BBR intervention reduced the deposition of fibrosis in groups C and D, group D was more obvious. Immunohistochemical results showed that compared with group A, the protein expression levels of ROCK, RhoA and Bax in groups B, C and D were significantly increased, while the protein expression levels of Bcl-2 were significantly decreased. Conclusions: Ultrasound layered strain imaging could evaluate the early left ventricular systolic function in isoprenaline-induced hypertrophy rat model. BBR might inhibit oxidative stress through the Rho/ROCK signaling pathway and slow down the progression of myocardial fibrosis after the formation of cardiac hypertrophy. This provides reference and direction for clinical decision-making and further research.

Association of smoking, alcohol, and coffee consumption with the risk of ovarian cancer and prognosis: a mendelian randomization study.

OBJECTIVE: Currently, the association between smoking, alcohol, and coffee intake and the risk of ovarian cancer (OC) remains conflicting. In this study, we used a two-sample mendelian randomization (MR) method to evaluate the association of smoking, drinking and coffee consumption with the risk of OC and prognosis. METHODS: Five risk factors related to lifestyles (cigarettes per day, smoking initiation, smoking cessation, alcohol consumption and coffee consumption) were chosen from the Genome-Wide Association Study, and 28, 105, 10, 36 and 36 single-nucleotide polymorphisms (SNPs) were obtained as instrumental variables (IVs). Outcome variables were achieved from the Ovarian Cancer Association Consortium. Inverse-variance-weighted method was mainly used to compute odds ratios (OR) and 95% confidence intervals (Cl). RESULTS: The two-sample MR analysis supported the causal association of genetically predicted smoking initiation (OR: 1.15 per SD, 95%CI: 1.02-1.29, P = 0.027) and coffee consumption (OR: 1.40 per 50% increase, 95%CI: 1.02-1.93, P = 0.040) with the risk of OC, but not cigarettes per day, smoking cessation, and alcohol consumption. Subgroup analysis based on histological subtypes revealed a positive genetical predictive association between coffee consumption and endometrioid OC (OR: 3.01, 95%CI: 1.50-6.04, P = 0.002). Several smoking initiation-related SNPs (rs7585579, rs7929518, rs2378662, rs10001365, rs11078713, rs7929518, and rs62098013), and coffee consumption-related SNPs (rs4410790, and rs1057868) were all associated with overall survival and cancer-specific survival in OC. CONCLUSION: Our findings provide the evidence for a favorable causal association of genetically predicted smoking initiation and coffee consumption with OC risk, and coffee consumption is linked to a greater risk of endometrioid OC.

Clinical Significance of Neuregulin 4, Afamin, and SERPINB1 in Gestational Diabetes Mellitus and Their Relationship with Insulin Resistance.

Objective: This study aims to explore the serum levels of neuregulin 4 (NRG4), afamin (AFM), and serpin family B member 1 (SERPINB1) in gestational diabetes mellitus (GDM) patients and their relationship with insulin resistance. Method: Serum levels of AFM, SERPINB1, and NRG4 were measured in GDM (n = 58), and non-GDM women (n = 60) using enzyme-linked immunosorbent assay (ELISA) kits. Besides, the serum insulin and glucose levels were also measured followed by calculating the homeostatic model assessment of insulin resistance (HOMA-IR). The correlation was performed using the Pearson analysis. Results: The increased serum levels of AFM and SERPINB1 were revealed in GDM patients as compared with non-GDM women, accompanied by the lower NRG4 serum level. ROCs for AFM concentrations showed an AUC of 0.629 (95% CI: 0.527∼0.731), 0.832 (95% CI: 0.754∼0.909) for the SERPINB1 serum level, and 0.626 (95% CI: 0.524∼0.728) for the NRG4 serum level. The threshold was 108.05 mg/L, 8.75 ng/mL, and 96.25 ng/mL of AFM, SERPINB1, and NRG4. Moreover, the combined ROC of AFM, SERPINB1, and NRG4 serum levels showed higher sensitivity (72.41%) and specificity (85.00%) for the diagnosis of GDM (AUC = 0.839; 95% CI: 0.764∼0.913). In GDM patients, the Pearson analysis revealed a significant correlation between AFM and SERPINB1 (r = 0.776), AFM and NRG4 (r = -0.799), as well as SERPINB1 and NRG4 (r = -0.783). Moreover, AFM and SERPINB1 serum concentrations in GDM patients were positively related to insulin levels, fasting glucose levels, and HOMA-IR values. However, the SERPINB1 serum level was negatively correlated with serum insulin and glucose levels and HOMA-IR. Conclusion: Abnormal serum levels of NRG4, AFM, and SERPINB1, as highly sensitive diagnostic tools, are closely related to insulin resistance in GDM patients.

Transcutaneous Electrical Acupoint Stimulation Improved Preoperative Blood Pressure in Gynecological Malignant Tumor Patients With Hypertension: A Randomized, Controlled Trial.

Objective: Gynecological malignant tumor patients with hypertension, even if blood pressure is well controlled, are prone to hypertension before surgery. We plan to verify the effect of transcutaneous electrical acupoint stimulation (TEAS) on stabilizing blood pressure before operation. Methods: We enrolled 91 patients and randomly divided them into TEAS group (n=46) and control group (n=45). Patients in TEAS group received TEAS at acupoints Hegu and Neiguan. Patients in control group received transcutaneous electrical stimulation at the nonacupoint position of the upper limbs. After entering the operating room, the blood pressure before and after induction was measured. The main results were the occurrence of preinduction hypertension and postinduction hypotension. Results: There was no difference in the general information of the two groups. There were four cases (9%) of preinduction hypertension in TEAS group and 13 cases (29%) in control group. The incidence in TEAS group was significantly lower (P=0.013). There were five cases (11%) of postinduction hypotension in TEAS group and eight cases (18%) in control group. There was no significant difference between the two groups (P=0.346). The systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP) of the highest blood pressure before induction in TEAS group were lower than those in control group (P=0.002, 0.002, and 0.001). There was no difference in SBP, DBP, or MBP between the two groups on the day before the operation. There was no difference in the lowest blood pressure before operation between the two groups after induction. Conclusion: TEAS can prevent preinduction hypertension in patients with gynecological malignant tumors. Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=143276, identifier ChiCTR2100054336.

The Trend of 2D Transistors toward Integrated Circuits: Scaling Down and New Mechanisms.

2D transition metal chalcogenide (TMDC) materials, such as MoS2 , have recently attracted considerable research interest in the context of their use in ultrascaled devices owing to their excellent electronic properties. Microprocessors and neural network circuits based on MoS2 have been developed at a large scale but still do not have an advantage over silicon in terms of their integrated density. In this study, the current structures, contact engineering, and doping methods for 2D TMDC materials for the scaling-down process and performance optimization are reviewed. Devices are introduced according to a new mechanism to provide the comprehensive prospects for the use of MoS2 beyond the traditional complementary-metal-oxide semiconductor in order to summarize obstacles to the goal of developing high-density and low-power integrated circuits (ICs). Finally, prospects for the use of MoS2 in large-scale ICs from the perspectives of the material, system performance, and application to nonlogic functionalities such as sensor circuits and analogous circuits, are briefly analyzed. The latter issue is along the direction of "more than Moore" research.

Geraniol enhances inhibitory inputs to the paraventricular thalamic nucleus and induces sedation in mice.

BACKGROUND: Plant extracts with sedative effects have a long history of clinical use for treating insomnia and epilepsy. Geraniol (GE), a plant-derived acyclic monoterpene, reduces locomotion and prolongs barbiturate-induced anesthesia in rats. However, the mechanisms of GE in sedation remain elusive. PURPOSE: This study aimed to investigate the mechanisms of GE in sedation in mice. METHODS: GE was administered systemically by nebulization and intraperitoneal injection. Open field tests, acute seizure tests, and electroencephalogram (EEG) recordings were performed to examine the sedative effects of GE in mice. The time of loss of the righting reflex and return of the righting reflex were recorded in anesthesia experiments to examine the effect of GE on anesthesia. In vitro c-Fos staining and in vivo fiber photometry recordings were performed to detect the activity change of the paraventricular thalamic nucleus (PVT). Microinjection of GE into PVT and related behavioral tests were performed to confirm that PVT was a critical target for GE. Whole-cell recordings were performed to dissect the effects of GE on PVT neurons via GABAA receptors. Molecular docking was performed to examine the interaction between GE and GABAA receptor subunits. RESULTS: We found that GE reduced locomotion, relieved acute seizures, altered the EEG, and facilitated general anesthesia in mice. Next, we found that GE decreased c-Fos expression and suppressed the calcium activity in PVT. Microinjection of GE into PVT reduced locomotion and facilitated anesthesia. Furthermore, electrophysiology results showed that GE induced dramatic membrane hyperpolarization and suppressed the activity of PVT neurons, mainly by prolonging spontaneous inhibitory postsynaptic currents and inducing tonic inhibitory currents. Molecular docking results indicated that the ß3 subunit might be a potential target for GE. CONCLUSION: By combined using behavioral tests, immunohistochemistry, calcium recording, and electrophysiology, we systematically revealed that GE inhibits PVT and induces sedation in mice. Essential oils have long been considered part of traditional medicine, and they are playing a critical role in aromatherapy. Since GE has a comparatively ideal safety property and multiple delivery methods, GE has great application potential in aromatherapy. Our study also provides a potential candidate for further development of sedatives and anaesthetics.

Anti-tumor effect of Yanggan Huayu granule by inducing AKT-mediated apoptosis in hepatocellular carcinoma.

ETHNOPHARMACOLOGICAL RELEVANCE: Yanggan Huayu granule (YGHY) is a formula of traditional Chinese medicine that has been widely used to treat patients with liver cancer. But its working mechanism is still poorly understood. AIM OF THE STUDY: To investigate the anti-tumor effect of YGHY and its working mechanisms in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: H22 mouse xenograft model was used to detect the effect of YGHY on hepatocellular carcinoma (HCC). MTT and CCK8 assays were performed to assess the effect of YGHY on HCC cell growth. Transwell assay was performed to detect the invasion and migration activities of HCC cells. Effect of YGHY drug-contained serum on apoptosis was detected by flow cytometry. Western blot was performed to detect the protein expressions. RESULTS: Results showed that YGHY inhibited tumor volume and weight, induced the apoptosis of HepG2 and SMMC-7721 cells and increased the protein expressions of Cleaved-Caspase3 and Cleaved-PARP. Furthermore, YGHY significantly down-regulated the protein expression of p-AKT. SC79, as an activator of AKT signaling, was able to increase the expression of p-AKT, and regulate the protein expressions of Cleaved-Caspase3, Cleaved-PARP, BCL-2 and BAX. YGHY drug-contained serum negated the protein expression change provided by SC79. CONCLUSIONS: Taken together, this data indicates that YGHY could inhibit HCC growth by inducing apoptosis, operating through AKT signaling.

Effectiveness of self-myofascial release combined with biofeedback and electrical stimulation for the management of myofascial pelvic pain: A randomized controlled trial.

BACKGROUND: Myofascial pelvic pain (MFPP) caused by myofascial trigger points (MTrPs) is a major contributor to chronic pelvic pain in women. However, the effect of the patient's self-myofascial release (SMFR) is unclear. This study aimed to investigate the effect of SMFR combined with biofeedback and electrical stimulation (BES) therapy in comparison with BES alone in patients with MFPP. METHODS: A prospective randomized controlled study was conducted. Sixty-eight patients were randomly allocated into BES-SMFR group (n = 34) and BES group (n = 34). Every patient received 4 weeks of treatment, evaluated at baseline (T0), 4 weeks post-intervention (T4) and 12-week follow-up (T12). The primary outcome was pain intensity. The secondary outcomes were degree of activation of MTrPs, surface electromyography (sEMG) levels and Patient Global Impression of Improvement (PGI-I). RESULTS: Compared with the effect of BES, BES-SMFR treatment significantly decreased pain intensity and the degree of activation of MTrPs in the levator ani (p = 0.02) and obturator internus (p = 0.03), as well as the sEMG levels of the pre-test resting baseline and post-test resting baseline (all p < 0.01). The degree of activation of MTrPs in the piriformis and coccygeus (all p > 0.05) and the sEMG levels of the quick flicks and endurance contraction were not significantly different. The BES-SMFR treatment improved the PGI-I scale at T4 (p = 0.02) but not at T12 (p = 0.40). CONCLUSIONS: This study confirmed that the addition of SMFR to BES treatment resulted in superior outcomes compared with those with BES alone in patients with MFPP. SIGNIFICANCE STATEMENT: Myofascial pelvic pain (MFPP) is a major contributor of female chronic pelvic pain. Myofascial release has been used commonly for better pain release; however, poor therapeutic effect due to poor patient compliance is common in clinical practice. Therefore, in future research, there is a need to investigate the effect of patient's self-myofascial release (SMFR) technique, which can eliminate the need for frequent office visits and improve patient compliance to some extent, in patients with MFPP.

Insights into spatiotemporal variations of the water quality in Taihu Lake Basin, China.

Taihu Lake Basin is highly developed but suffers from perennial water shortages due to pollution. Most studies have been limited to examining the water quality in specific areas, but few have investigated the entire basin. This study was based on official water quality data obtained from 565 sites in the monitoring network, thereby covering the entire basin. The water quality spatiotemporal variations were explored by statistical analysis, and the precise spatial distribution of the main pollutants was analyzed by heat maps. Only 29.09% of the water quality assessment results showed "drinkable," whereas 28.63% showed "moderate" and "severe" pollution. The "severe" proportion had a significant declining trend (R2 = 0.933) and was affected by the variations of nitrogen that was related to rainfall and anthropogenic activities. The water quality spatial variation was most likely related to anthropogenic influence and land use. The water quality in the developed and densely populated urban areas was poor, especially in downtown Shanghai. NH3-N, TN, TP, BOD5, COD, CODMn, and DO were the main pollutants that affected the water quality. NH3-N and TN were major reduction targets. NH3-N was the main pollutant that deteriorated the water quality in most densely populated urban areas. Many lakes and reservoirs were highly polluted with TN. Controlling domestic sewage may be effective to improve the water quality. This study makes up for the limited research on the water quality spatiotemporal variations in the entire Taihu Lake Basin and provides beneficial information and suggestions for decision-making regarding the water management.

The impact of COVID-19 on palliative care for people with Parkinson's and response to future pandemics.

Introduction: Although in some countries, palliative care (PC) still remains poorly implemented, its importance throughout the course of Parkinson's disease (PD) is increasingly being acknowledged. With an emergence of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic, growing emphasis has been placed on the palliative needs of people with Parkinson's (PwP), particularly elderly, frail, and with comorbidities.Areas covered: The ongoing COVID-19 pandemic poses an enormous challenge on aspects of daily living in PwP and might interact negatively with a range of motor and non-motor symptoms (NMS), both directly and indirectly - as a consequence of pandemic-related social and health care restrictions. Here, the authors outline some of the motor and NMS relevant to PC, and propose a pragmatic and rapidly deployable, consensus-based PC approach for PwP during the ongoing COVID-19 pandemic, potentially relevant also for future pandemics.Expert opinion: The ongoing COVID-19 pandemic poses a considerable impact on PwP and their caregivers, ranging from mental health issues to worsening of physical symptoms - both in the short- and long-term, (Long-COVID) and calls for specific, personalized PC strategies relevant in a lockdown setting globally. Validated assessment tools should be applied remotely to flag up particular motor or NMS that require special attention, both in short- and long-term.

Melatonin alleviates angiotensin-II-induced cardiac hypertrophy via activating MICU1 pathway.

Mitochondrial calcium uptake 1 (MICU1) is a pivotal molecule in maintaining mitochondrial homeostasis under stress conditions. However, it is unclear whether MICU1 attenuates mitochondrial stress in angiotensin II (Ang-II)-induced cardiac hypertrophy or if it has a role in the function of melatonin. Here, small-interfering RNAs against MICU1 or adenovirus-based plasmids encoding MICU1 were delivered into left ventricles of mice or incubated with neonatal murine ventricular myocytes (NMVMs) for 48 h. MICU1 expression was depressed in hypertrophic myocardia and MICU1 knockdown aggravated Ang-II-induced cardiac hypertrophy in vivo and in vitro. In contrast, MICU1 upregulation decreased cardiomyocyte susceptibility to hypertrophic stress. Ang-II administration, particularly in NMVMs with MICU1 knockdown, led to significantly increased reactive oxygen species (ROS) overload, altered mitochondrial morphology, and suppressed mitochondrial function, all of which were reversed by MICU1 supplementation. Moreover, peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α)/MICU1 expression in hypertrophic myocardia increased with melatonin. Melatonin ameliorated excessive ROS generation, promoted mitochondrial function, and attenuated cardiac hypertrophy in control but not MICU1 knockdown NMVMs or mice. Collectively, our results demonstrate that MICU1 attenuates Ang-II-induced cardiac hypertrophy by inhibiting mitochondria-derived oxidative stress. MICU1 activation may be the mechanism underlying melatonin-induced protection against myocardial hypertrophy.

Effectiveness and safety of electroacupuncture for insomnia: A protocol for an overview of systematic reviews and meta-analysis.

BACKGROUND: Insomnia is a common disease characterized by difficulty falling and/or staying asleep, and accompanied by irritability or fatigue during wakefulness. It is widely reported that insomnia is one of the most extensive mental disorders which the incidence rate is estimated to be about 10%. Insomnia can have serious influences on patients health and quality of life. Electro acupuncture (EA) is reported to be efficacious and widely used for the treatment of insomnia in China. This overview aims to summarize the available evidence from current systematic reviews for the efficacy of electroacupuncture therapy for insomnia. METHODS: We will make a comprehensive retrieval in 7 databases as following:The time is limited from the construction of the library to August 2020. We will use the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) tool to evaluate methodological quality. Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols (PRISMA-P) will be used in the report checklist to assess the quality of reports in the study. The Grading of the Classification of Recommendations, Evaluation, Development and Evaluation (GRADE) will be used to evaluate the included SRs and meta-analysis. Our reviewers will conduct systematic reviews, qualification evaluation, data extraction, methodological quality and evidence quality screening in pairs. The outcomes of interest include: The Pittsburgh Sleep Quality Index (PSQI), The Insomnia Severity Index (ISI), Athens Insomnia Scale, Sleep parameters measured by either subjective or objective approaches, such as actigraphy, polysomnogram, and electroencephalogram. Or any other scale used to assess the level of illness. The evidence will be synthesized where appropriate based on patient subgroups and outcomes. RESULTS: The results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: INPLASY202080087. CONCLUSION: This overview will provide comprehensive evidence of EA for patients with insomnia.

Falls prevention interventions for community-dwelling older people living in mainland China: a narrative systematic review.

BACKGROUND: Falls in community-dwelling older people have been recognised as a significant public health issue in China given the rapidly growing aged population. Although there are several reviews documenting falls prevention programs for community-dwelling older adults, no systematic reviews of the scope and quality of falls prevention interventions in Mainland China exist. Therefore, the aim of this study was to systematically review falls prevention interventions for community-dwelling older people living in Mainland China. METHODS: We systematically reviewed literature from Chinese and English databases. All types of randomised controlled trials (RCTs) and quasi-experimental studies published from 1st January 1990 to 30th September 2019 were included. Observational studies and studies in care facilities and hospitals were excluded. Narrative synthesis was performed to summarise the key features of all included studies. Quality assessment was conducted using the Cochrane Risk of Bias Tool and ROBINS-I tool for randomised and non-randomised studies respectively. RESULTS: A total of 1020 studies were found, and 101 studies were included in the analysis. Overall, very few high quality studies were identified, and there was insufficient rigor to generate reliable evidence on the effectiveness of interventions or their scalability. Most interventions were multiple component interventions, and most studies focused on outcomes such as self-reported falls incidence or awareness of falls prevention. CONCLUSION: There is an opportunity to undertake an evaluation of a rigorously-designed, large-scale falls prevention program for community-dwelling older people in Mainland China. To help mitigate the rising burden of falls in Mainland China, recommendations for future falls prevention interventions have been made. These include: (1) target disadvantaged populations; (2) incorporate personalised interventions; and (3) investigate the effectiveness of those under-explored interventions, such as psychological, social environment, management of urinary incontinence, fluid or nutrition therapy and surgery. The study results will also potentially provide a useful evidence base for other low-and-middle income countries in a similar situation.

42 cases of coronavirus disease 2019 of the ordinary type with the adjuvant treatment of heat-sensitive moxibustion 42.

OBJECTIVE: To observe the clinical therapeutic effect of adjuvant treatment with heat-sensitive moxibustion for coronavirus disease 2019 (COVID-19) of the ordinary type. METHODS: A total of 42 patients with COVID-19 of the ordinary type were adopted. Shénquè ( CV8) and Tianshu ( ST25) were selected. Heat-sensitive moxibustion was operated according to the required standard, 40 min to 60 min each time, once daily. Before and after moxibustion, the improvements in clinical symptoms were evaluated, such as chest oppression, poor appetite, lassitude and negative emotions. RESULTS: (1) The number of cases and the incidence was 21 cases (50.0%), 24 cases (57.1%) and 26 cases (61.9%) for chest oppression, poor appetite and lassitude before heat-sensitive moxibustion. The number of cases was reduced to be 10 cases (23.8%), 7 cases (16.7%) and 4 cases (9.5%) after the 1st treatment of heat-sensitive moxibustion for chest oppression, poor appetite, and lassitude. It was reduced to be 11 cases (26.2%), 8 cases (19.0%) and 4 cases (9.5%) after the 2nd treatment of moxibustion and it was reduced to be 18 cases (42.9%), 10 cases (23.8%) and 6 cases (14.3%) after the 3rd treatment of moxibustion. The incidences of the symptoms were all reduced obviously as compared with those before treatment. (2) Before treatment with heat-sensitive moxibustion, there were 24 cases of negative emotions (57.1%). It was reduced to be 16 cases (38.1%), 11 cases (26.2%) and 3 cases (7.1%) after the 1st, 2nd and 3rd treatment of heat-sensitive moxibustion successively. The incidences were all reduced obviously as compared with those before treatment. (3) After the 1st treatment, the active acceptance rate of heat-sensitive moxibustion was 100% (42/42) in the patients, higher than 11.9% (5/42) before treatment. CONCLUSION: Adjuvant treatment with heat-sensitive moxibustion effectively relieves the symptoms of COVID-19 such as chest oppression, poor appetite and lassitude, and alleviates the negative emotions, such as tension and anxiety. This therapy improves the therapeutic effect of COVID-19 and deserves to be promoted in clinical practice.

[Systematic review on the treatment of functional constipation with electroacupuncture and gastro-kinetic drugs].

OBJECTIVE: To compare the therapeutic effect and safety in treatment of functional constipation between electroacupuncture (EA) and gastro-kinetic drugs. METHODS: Using "functional constipation"， "prucalopride"， "mosapridecitrate"， "electro-acupuncture" and "randomized controlled trial"， both in Chinese and English, as search terms, the articles of randomized controlled trial (RCT) regarding to the comparison of therapeutic effect on functional constipation in the patients between EA and gastro-kinetic drugs were retrieved from CMB, Wanfang, VIP, CNKI, OpenGrey, CINAHL, Cochrane Library, JBI, PubMed, WOS and Ovid databases. The retrieval time was from the establishment date to June 2018. The two researchers screened articles, extracted data and assessed literature quality in reference to Cochrane Handbook. Using RevMan 5.3 software, the meta-analysis was conducted. RESULTS: A total of 11 articles were included finally, with 744 patients involved. It was found after meta-analysis that in EA group, the weekly spontaneous defecation frequency, constipation related quality of life in patients, depression relief and incidence of adverse reaction were all better than those in gastro-kinetic medication group. The therapeutic effect of the improvements in stool character and defecation difficulty in EA group were better or similar to that in gastro-kinetic medication group. CONCLUSION: Regarding the therapeutic effect and safety in treatment of functional constipation, the results of electroacupuncture are superior or similar to gastro-kinetic medication, presenting a satisfactory therapeutic prospect.

[Clinical observation of heat-sensitive moxibustion treatment for coronavirus disease 2019].

OBJECTIVE: To observe clinical effect of heat-sensitive moxibustion on coronavirus disease 2019 (COVID-19) and to discusses the effective moxibustion treatment program. METHODS: A total of 42 patients with COVID-19 (general type) were treated with heat-sensitive moxibustion at the acupoint area of Shenque (CV 8) and Tianshu (ST 25). The treatment was conducted under the standards of heat-sensitive moxibustion manipulation, which were "locating acupoint by feeling, moxibustion by differentiate sensation, dosage varies individually, ending after sufficient dosage". The incidence of deqi after first heat-sensitive moxibustion, the reduction of negative emotions, the improvement of chest distress and impaired appetite, and the active acceptance rate of moxibustion before and after treatment were observed. RESULTS: ① The deqi rate of heat-sensitive moxibustion for 20 min、40 min、1 h were respectively 52.4% (22/42), 90.5% (38/42), 100.0% (42/42). ② The incidences of feeling relaxed and comfortable immediately after the first, second, and third heat-sensitive moxibustion were 61.9% (26/42), 73.8% (31/42), and 92.9% (39/42), which were higher than 42.9% (18/42) before heat-sensitive moxibustion treatment (P<0.05). ③ The incidences of chest distress after the first, second, and third heat-sensitive moxibustion were 23.8% (10/42), 16.7% (7/42), and 9.5% (4/42), which were lower than 50.0% (21/42) before heat-sensitive moxibustion treatment (P<0.05); the incidences of impaired appetite after the first, second, and third heat-sensitive moxibustion were 26.2% (11/42), 19.0% (8/42), 9.5% (4/42), which were lower than 57.1% (24/42) before heat-sensitive moxibustion treatment (P<0.05). ④ After the first treatment, the active acceptance rate of patients for heat-sensitive moxibustion was 100.0% (42/42), which was higher than 11.9% (5/42) before heat-sensitive moxibustion (P<0.05). CONCLUSION: The heat-sensitive moxibustion can effectively reduce the negative emotions and improve the symptoms of chest distress and impaired appetite with COVID-19. It is generally accepted by patients, and worthy of popularization and application in clinical treatment.

Targeting Hidden Pathogens: Cell-Penetrating Enzybiotics Eradicate Intracellular Drug-Resistant Staphylococcus aureus.

Staphylococcus aureus is a major concern in human health care, mostly due to the increasing prevalence of antibiotic resistance. Intracellular localization of S. aureus plays a key role in recurrent infections by protecting the pathogens from antibiotics and immune responses. Peptidoglycan hydrolases (PGHs) are highly specific bactericidal enzymes active against both drug-sensitive and -resistant bacteria. However, PGHs able to effectively target intracellular S. aureus are not yet available. To overcome this limitation, we first screened 322 recombineered PGHs for staphylolytic activity under conditions found inside eukaryotic intracellular compartments. The most active constructs were modified by fusion to different cell-penetrating peptides (CPPs), resulting in increased uptake and enhanced intracellular killing (reduction by up to 4.5 log units) of various S. aureus strains (including methicillin-resistant S. aureus [MRSA]) in different tissue culture infection models. The combined application of synergistic PGH-CPP constructs further enhanced their intracellular efficacy. Finally, synergistically active PGH-CPP cocktails reduced the total S. aureus by more than 2.2 log units in a murine abscess model after peripheral injection. Significantly more intracellular bacteria were killed by the PGH-CPPs than by the PGHs alone. Collectively, our findings show that CPP-fused PGHs are effective novel protein therapeutics against both intracellular and drug-resistant S. aureusIMPORTANCE The increasing prevalence of antibiotic-resistant bacteria is one of the most urgent problems of our time. Staphylococcus aureus is an important human pathogen that has acquired several mechanisms to evade antibiotic treatment. In addition, S. aureus is able to invade and persist within human cells, hiding from the immune response and antibiotic therapies. For these reasons, novel antibacterial strategies against these pathogens are needed. Here, we developed lytic enzymes which are able to effectively target drug-resistant and intracellular S. aureus Fusion of these so-called enzybiotics to cell-penetrating peptides enhanced their uptake and intracellular bactericidal activity in cell culture and in an abscess mouse model. Our results suggest that cell-penetrating enzybiotics are a promising new class of therapeutics against staphylococcal infections.