[Research progress on induced hepatic stellate cell ferroptosis in prevention and treatment of liver fibrosis].

Liver fibrosis is a key pathological stage in the progression of chronic liver disease. If the disease is mistreated, it can further deteriorate into liver failure, which seriously affects the quality of life of patients and brings heavy medical costs. Hepatic stellate cell(HSC) activation triggers extracellular matrix(ECM) deposition, which plays an important driving role in liver fibrosis, and ferroptosis is an effective strategy to clear or reverse the activation of HSCs into a deactivated phenotype. Therefore, inhibiting the activation and proliferation of HSCs by regulating ferroptosis is the key to the treatment of this disease, so as to derive the prospect of inducing ferroptosis of HSCs(including RNA-binding proteins, non-coding RNA, chemicals, and active components of traditional Chinese medicine) to intervene in liver fibrosis. On this basis, this paper started from the activation of HSCs to induce ECM deposition and focused on summarizing the mechanism of inducing HSC ferroptosis in delaying the progression of liver fibrosis, so as to continuously enrich the clinical practice of liver fibrosis and provide a reference for subsequent basic research.

China stroke surveillance report 2021.

Since 2015, stroke has become the leading cause of death and disability in China, posing a significant threat to the health of its citizens as a major chronic non-communicable disease. According to the China Stroke High-risk Population Screening and Intervention Program, an estimated 17.8 million [95% confidence interval (CI) 17.6-18.0 million] adults in China had experienced a stroke in 2020, with 3.4 million (95% CI 3.3-3.5 million) experiencing their first-ever stroke and another 2.3 million (95% CI 2.2-2.4 million) dying as a result. Additionally, approximately 12.5% (95% CI 12.4-12.5%) of stroke survivors were left disabled, as defined by a modified Rankin Scale score greater than 1, equating to 2.2 million (95% CI 2.1-2.2 million) stroke-related disabilities in 2020. As the population ages and the prevalence of risk factors like diabetes, hypertension, and hyperlipidemia continues to rise and remains poorly controlled, the burden of stroke in China is also increasing. A large national epidemiological survey initiated by the China Hypertension League in 2017 showed that the prevalence of hypertension was 24.7%; the awareness, treatment, and control rates in hypertensive patients were: 60.1%, 42.5%, and 25.4%, respectively. A nationally representative sample of the Chinese mainland population showed that the weighted prevalence of total diabetes diagnosed by the American Diabetes Association criteria was 12.8%, suggesting there are 120 million adults with diabetes in China, and the awareness, treatment, and control rates in diabetic patients were: 43.3%, 49.0%, and 49.4%, respectively. The "Sixth National Health Service Statistical Survey Report in 2018" showed that the proportion of the obese population in China was 37.4%, an increase of 7.2 points from 2013. Data from 1599 hospitals in the Hospital Quality Monitoring System and Bigdata Observatory Platform for Stroke of China (BOSC) showed that a total of 3,418,432 stroke cases [mean age ± standard error (SE) was (65.700 ± 0.006) years, and 59.1% were male] were admitted during 2020. Of those, over 80% (81.9%) were ischemic stroke (IS), 14.9% were intracerebral hemorrhage (ICH) strokes, and 3.1% were subarachnoid hemorrhage (SAH) strokes. The mean ± SE of hospitalization expenditures was Chinese Yuan (CNY) (16,975.6 ± 16.3), ranging from (13,310.1 ± 12.8) in IS to (81,369.8 ± 260.7) in SAH, and out-of-pocket expenses were (5788.9 ± 8.6), ranging from (4449.0 ± 6.6) in IS to (30,778.2 ± 156.8) in SAH. It was estimated that the medical cost of hospitalization for stroke in 2020 was CNY 58.0 billion, of which the patient pays approximately CNY 19.8 billion. In-hospital death/discharge against medical advice rate was 9.2% (95% CI 9.2-9.2%), ranging from 6.4% (95% CI 6.4-6.5%) for IS to 21.8% for ICH (95% CI 21.8-21.9%). From 2019 to 2020, the information about 188,648 patients with acute IS receiving intravenous thrombolytic therapy (IVT), 49,845 patients receiving mechanical thrombectomy (MT), and 14,087 patients receiving bridging (IVT + MT) were collected through BOSC. The incidence of intracranial hemorrhage during treatment was 3.2% (95% CI 3.2-3.3%), 7.7% (95% CI 7.5-8.0%), and 12.9% (95% CI 12.3-13.4%), respectively. And in-hospital death/discharge against medical advice rate was 8.9% (95% CI 8.8-9.0%), 16.5% (95% CI 16.2-16.9%), and 16.8% (95% CI 16.2-17.4%), respectively. A prospective nationwide hospital-based study was conducted at 231 stroke base hospitals (Level III) from 31 provinces in China through BOSC from January 2019 to December 2020 and 136,282 stroke patients were included and finished 12-month follow-up. Of those, over 86.9% were IS, 10.8% were ICH strokes, and 2.3% were SAH strokes. The disability rate [% (95% CI)] in survivors of stroke at 3-month and 12-month was 14.8% (95% CI 14.6-15.0%) and 14.0% (95% CI 13.8-14.2%), respectively. The mortality rate [% (95% CI)] of stroke at 3-month and 12-month was 4.2% (95% CI 4.1-4.3%) and 8.5% (95% CI 8.4-8.6%), respectively. The recurrence rate [% (95% CI)] of stroke at 3-month and 12-month was 3.6% (95% CI 3.5-3.7%) and 5.6% (95% CI 5.4-5.7%), respectively. The Healthy China 2030 Stroke Action Plan was launched as part of this review, and the above data provide valuable guidelines for future stroke prevention and treatment efforts in China.

Age and geographic disparities in acute ischaemic stroke prehospital delays in China: a cross-sectional study using national stroke registry data.

Background: Stroke has been the leading cause of death in China for decades. The extremely low intravenous thrombolysis rate is largely due to the prehospital delays that make patients ineligible for the time-sensitive therapy. Limited studies evaluated prehospital delays across China. We investigated prehospital delays in the stroke population across China and the associated age, rurality, and geographic disparities. Methods: A cross-sectional study design was employed using the Bigdata Observatory platform for Stroke of China in 2020, the nationwide, prospective, multicentre registry of patients with acute ischaemic stroke (AIS). Mixed-effect regression models were used to account for the clustered data. Findings: The sample contained 78,389 AIS patients. The median onset-to-door (OTD) time was 24 h, with only 11.79% (95% confidence interval [CI]: 11.56-12.02%) patients arriving at hospitals within 3 h. About 12.43% (95% CI: 12.11-12.74%) of patients 65 years or older arrived at hospitals within 3 h, which was significantly higher than the young and middle-aged patients (11.03%; 95% CI: 10.71-11.36%). After controlling for potential confounders, young and middle-aged patients were less likely to present to hospitals within 3 h (adjusted odds ratio: 0.95; 95% CI: 0.90-0.99) compared to patients 65 years or older. The 3-h hospital arrival rate was the highest in Beijing (18.40%, 95% CI: 16.01-20.79%), which was almost 5 times higher than that in Gansu (3.45%, 95% CI: 2.69-4.20%). The arrival rate in urban areas was almost 2 times higher than that in rural areas (13.35% versus. 7.66%). Interpretation: We found that the low rates of timely arrival at hospitals after a stroke is more salient in the younger population, rural settings, or those residing in less developed geographic regions. This study calls for more tailored interventions focusing on younger people, rural areas, and less developed geographic regions. Funding: The National Natural Science Foundation of China; CIHR, Grant/Award Number: 81973157, PI: JZ. Natural Science Foundation of Shanghai; CIHR, Grant/Award Number: 17dz2308400, PI: JZ. Funding from the University of Pennsylvania; Grant/Award Number: CREF-030, PI: RL.

Metformin use is associated with low risk of case fatality and disability rates in first-ever stroke patients with type 2 diabetes.

Background: To assess the effectiveness of metformin treatment on long-term outcomes in first-ever stroke patients with type 2 diabetes mellitus (T2DM) in China. Methods: From August to September 2019, all patients with first-ever stroke and T2DM from 232 hospitals in China Mainland were included. The enrolled patients were divided into two groups: the metformin treatment (MT) and the no-metformin treatment (No-MT) groups. All discharged patients would receive a telephone follow-up at 12-month after admission. Results: In total, 7587 first-ever stroke patients with T2DM [age: median (IQR) = 66 (57-73) years; 57.35% male] were recruited. Out of those 7587 included patients, 3593 (47.36%) received MT. The in-hospital case fatality rate was lower in the MT group than the No-MT group [MT group versus No-MT group: 1.09% versus 2.30%; absolute difference = -1.75% (95% CI = -2.15 to -1.17%); OR = 0.63 (95% CI = 0.47 to 0.84)]. The 12-month case fatality rate was lower in the MT group than the No-MT group [4.72% versus 8.05%; absolute difference = -4.05% (95% CI = -5.58 to -2.41); OR = 0.69 (95% CI = 0.50 to 0.88)]. The 12-month disability rate was also lower in the MT group than the No-MT group [14.74% versus 19.41%; absolute difference = -5.70% (95% CI = -7.25 to -3.22); OR = 0.83 (95% CI = 0.70 to 0.95)]. Furthermore, the recurrence rate did not differ significantly between the MT and No-MT groups (p = 0.29). Conclusion: The study reveals that metformin use in stroke patients with T2DM results in a less severe stroke and lower fatality and disability rates.

Rates of intravenous thrombolysis and endovascular therapy for acute ischaemic stroke in China between 2019 and 2020.

BACKGROUND: In recent years, a series of initiatives have been launched to promote intravenous thrombolysis (IVT) and endovascular therapy (EVT) for acute ischaemic stroke (AIS) in China. We aimed to update the rates of IVT and EVT in China between 2019 and 2020 and to evaluate the current IVT and EVT according to hospital grades. METHODS: Cross-sectional data on patients receiving IVT/EVT were derived from the Bigdata Observatory platform for Stroke of China (BOSC). The monthly number of discharged patients with a principal diagnosis of AIS was derived from the first pages of medical records of each hospital. The rates and information of IVT and EVT were analysed according to hospital grades. FINDINGS: During this period, 938 tertiary hospitals and 786 secondary hospitals from 31 provinces continuously reported data to the BOSC. The overall IVT rate for AIS was 5·64%, and the EVT rate was 1·45%. The IVT rate in secondary hospitals was higher than that in tertiary hospitals (6·39% vs. 5·39%, P < 0·001), whereas the EVT rate in secondary hospitals was much lower than that in tertiary hospitals (0·29% vs. 1·84%, P < 0·001). Significant differences in demographic and clinical characteristics of patients receiving IVT/EVT were also shown between tertiary and secondary hospitals. INTERPRETATION: The rates of IVT and EVT for AIS have greatly increased in China, but there is still a large gap compared with developed countries. Hospital inhomogeneity in IVT and EVT suggests the importance of developing a region-specific network for stroke treatment. FUNDING: None.

Thrombolytic DNT and fatality and disability rates in acute ischemic stroke: a study from Bigdata Observatory Platform for Stroke of China.

OBJECTIVE: To evaluate whether shorter door-to-needle times (DNT) with intravenous tissue plasminogen activator (tPA) for acute ischemic stroke are associated with improved 1-year outcomes in Chinese patients. METHODS: From August to September 2019, all first-ever ischemic stroke patients who were treated with intravenous tPA within 4.5 h of the time they were last known to be well from 232 hospitals in China were included. Patients were divided into four groups according to DNT time (≤ 45 min; 45-60 min; 60-90 min; > 90 min). All discharged patients would receive a telephone follow-up at 12-month after admission. Death and disability events were recorded. RESULTS: Finally, 2370 patients were analyzed. The median age was 65 years, 66.6% were male, and 2.4% were of ethnic minorities. In the 1-year follow-up, 211 patients died (8.9%; 95%CI: 7.8-10.0%). The patients (53.1%) had DNT times of longer than 45 min, compared with those treated within 45 min, did not have significantly higher 1-year mortality (8.9% vs 8.9% [absolute difference, 0.03% {95% CI, - 0.05% to - 0.10%}, odd ratio {OR}, 1.00 {95% CI, 0.75 to 1.33}]). In addition, 385 patients (16.2%; 14.8-17.3%) out of those survivors had disability events. The patients had DNT times of longer than 45 min, compared with those treated within 45 min, did not have significantly higher 1-year disability rate (18.9% vs 16.7% [absolute difference, 1.9% {95% CI, 1.1% to 3.0%}, odd ratio {OR}, 1.22 {95% CI, 0.89 to 1.43}]). CONCLUSIONS: The results did not show that shorter DNT for tPA administration was significantly associated with better 1-year outcomes.

Case-fatality, disability and recurrence rates after first-ever stroke: A study from bigdata observatory platform for stroke of China.

BACKGROUND: There is currently a lack of data on stroke hospitalizations and long-term outcomes in China. Therefore, we investigated 12-month stroke fatality, disability, and recurrence rates after the first-ever stroke. METHODS: This was a prospective nationwide hospital-based cohort study. From August to September 2019, all patients with first-ever stroke (ischemic stroke [IS], intracerebral hemorrhage [ICH], and subarachnoid hemorrhage [SAH]) and with symptom onset within 14 days from 232 hospitals were included. Case fatality, disability, and recurrence rates for one year were estimated. RESULTS: In total, 36250 first-ever stroke patients from 194 hospitals were recruited (median age was 65(IQR, 56-73) years and 61.4 % were male). The rate of intravenous thrombolysis and endovascular treatment for IS were 9.5 % and 4.4 %, respectively. In-hospital death rate was 1.9 % (95 %CI: 1.7 %-2.0 %) for stroke inpatients, ranging from 0.9 % (0.8 %-1.1 %) for IS to 5.1 % (4.6 %-5.6 %) for ICH. The 12-month fatality rate was 8.6 % (95 %CI: 8.3 %-8.9 %) for discharged stroke patients, ranging from 6.0 % (5.7 %-6.3 %) for IS to 17.7 % (16.7 %-18.7 %) for ICH. The 12-month disability rate was 16.6 % (95 %CI: 16.2 %-17.0 %) for stroke survivors, ranging from 11.1 % (9.3 %-12.8 %) for SAH to 29.2 % (27.9 %-30.4 %) for ICH. The stroke recurrence rate was 5.7 % (5.5 %-6.0 %) for stroke survivors, ranging from 2.5 % (1.7 %-3.3 %) for SAH to 6.4 % (6.0 %-6.7 %) for IS. CONCLUSION: Our results support the hypothesis that the prognosis of Chinese stroke patients appears to have improved and is not very bad.

Stroke prevention and control system in China: CSPPC-Stroke Program.

In China, stroke is a major cause of mortality, and long-term physical and cognitive impairment. To meet this challenge, the Ministry of Health China Stroke Prevention Project Committee (CSPPC) was established in April 2011. This committee actively promotes stroke prevention and control in China. With government financial support of 838.4 million CNY, 8.352 million people from 536 screening points in 31 provinces have received stroke screening and follow-up over the last seven years (2012-2018). In 2016, the CSPPC issued a plan to establish stroke centers. To shorten the pre-hospital period, the CSPPC established a stroke center network, stroke map, and stroke "Green Channel" to create three 1-h gold rescue circles, abbreviated as "1-1-1" (onset to call time <1 h; pre-hospital transfer time < 1 h, and door-to-needle time < 1 h). From 2017 to 2018, the median door-to-needle time dropped by 4.0% (95% confidence interval (CI), 1.4-9.4) from 50 min to 48 min, and the median onset-to-needle time dropped by 2.8% (95% CI, 0.4-5.2) from 180 min to 175 min. As of 31 December 2018, the CSPPC has established 380 stroke centers in mainland China. From 1 November 2018, the CSPPC has monitored the quality of stroke care in stroke center hospitals through the China Stroke Data Center Data Reporting Platform. The CSPPC Stroke program has led to a significant improvement in stroke care. This program needs to be further promoted nationwide.

Stroke Center Care and Outcome: Results from the CSPPC Stroke Program.

The aim of this study was to assess the association between admission to stroke centers for acute ischemic stroke and complications and mortality during hospitalization in a Chinese population by means of an observational study using data from the China Stroke Center Data-Sharing Platform. We compared in-hospital complications and mortality for patients admitted with acute ischemic stroke (N = 13,236) between November 1, 2018 and December 31, 2018 at stroke center (SH) and non-stroke center (CH) hospitals using distance to hospitals as an instrumental variable to adjust for potential prehospital selection bias. The results showed that complication rates during hospitalization among ischemic stroke patients who received thrombolytic therapy (n = 11,203) were lower in the SH group than in the CH group: 11.1% vs 15.7% (absolute difference, - 5.11% [95% CI, - 6.05 to - 3.99%], odds ratio [OR] 0.85 [95% CI, 0.74 to 0.92]). The incidence of intracranial hemorrhage was reduced from 4.2 to 3.2%: SH group vs CH group, 3.2% vs 4.2% (absolute difference, - 1.24% [95% CI, - 1.65 to - 0.82%], OR 0.83 [95% CI, 0.69 to 0.0.98]). Furthermore, the total mortality rate in the SH group was also lower than in the CH group: SH group vs CH group, 2.2% vs 3.0% (absolute difference, - 0.92% [95% CI, - 1.48 to - 0.53%], OR 0.85 [95% CI, 0.73 to 0.96]). The data showed that admission to SH hospitals was associated with a lower risk of treatment complications and death for patients with an acute ischemic stroke receiving thrombolytic therapy.

Resveratrol and genistein inhibition of rat isolated gastrointestinal contractions and related mechanisms.

AIM: To investigate the effects and underlying mechanisms of resveratrol and genistein on contractile responses of rat gastrointestinal smooth muscle. METHODS: Isolated strips of gastrointestinal smooth muscle from Spraque-Dawley rats were suspended in organ baths containing Kreb's solution, and the contractility of smooth muscles was measured before and after incubation with resveratrol and genistein, and the related mechanisms were studied by co-incubation with various inhibitors. RESULTS: Resveratrol and genistein dose-dependently decreased the resting tension, and also reduced the mean contractile amplitude of gastrointestinal smooth muscle. Estrogen receptor blockades (ICI 182780 and tamoxifen) failed to alter the inhibitory effects induced by resveratrol and genistein. However, their effects were attenuated by inhibitions of α-adrenergic receptor (phentolamine), nitric oxide synthase (levorotatory-NG-nitroarginine), ATP-sensitive potassium channels (glibenclamide), and cyclic adenosine monophosphate (SQ22536). In high K(+)/Ca(2+)-free Kreb's solution containing 0.01 mmol/L egtazic acid, resveratrol and genistein reduced the contractile responses of CaCl2, and shifted its cumulative concentration-response curves rightward. CONCLUSION: Resveratrol and genistein relax gastrointestinal smooth muscle via α-adrenergic receptors, nitric oxide and cyclic adenosine monophosphate pathways, ATP-sensitive potassium channels, and inhibition of L-type Ca(2+) channels.

Optical properties of Ag nanoparticle-polymer composite film based on two-dimensional Au nanoparticle array film.

The nanocomposite polyvinyl pyrrolidone (PVP) films containing Ag nanoparticles and Rhodamine 6G are prepared on the two-dimensional distinctive continuous ultrathin gold nanofilms. We investigate the optical properties and the fluorescence properties of silver nanoparticles-PVP polymer composite films influenced by Ag nanoparticles and Au nanoparticles. Absorption spectral analysis suggests that the prominently light absorption in Ag nanowire/PVP and Ag nanowire/PVP/Au film arises from the localized surface plasmon resonance of Ag nanowire and Au nanofilm. The enhanced fluorescence is observed in the presence of Ag nanowire and Au nanofilm, which is attributed to the excitation of surface plasmon polariton resonance of Ag nanowire and Au nanofilm. The gold nanofilm is proven to be very effective fluorescence resonance energy transfer donors. The fabricated novel structure, gold ultrathin continuous nanofilm, possesses high surface plasmon resonance properties and prominent fluorescence enhancement effect. Therefore, the ultrathin continuous gold nanofilm is an active substrate on nanoparticle-enhanced fluorescence.

Effects of estrogen and phytoestrogens on endometrial leakage in ovariectomized rats and the related mechanisms.

Phytoestrogens, a group of plant-derived non-steroidal compounds that can behave as estrogens by binding to estrogen receptors, have drawn great attention for their potentially beneficial effects on human health. However, there are few studies investigating the potential side effects of phytoestrogens on the reproductive system. The present study was to elucidate the effects of 17ß-estradiol (E2), progesterone (P4), and phytoestrogens genistein (Gen), resveratrol (Res), and phloretin (Phl) on eosinophilic infiltration of the ovariectomized rat uterus and endometrial vascular permeability, and to analyze the underlying mechanisms. The ovariectomized rats received daily subcutaneous injections of E2, E2+P4, P4, Gen, Res, Phl, or an equivalent volume of vehicle for 21 days, and sham-operated animals (Sham rats) were used as the controls. Hematoxylin-eosin staining revealed a marked increase in uterine eosinophilic infiltrations in ovariectomized rats treated with E2, E2+P4 or P4, which was associated with increased expression of vascular endothelial growth factor (VEGF), nuclear factor-κB (NF-κB), and tumor necrosis factor-α (TNF-α) proteins as determined by immunohistochemical and Western blot analysis. However, all three phytoestrogens had no markedly effect on the uterine eosinophilic infiltration and the expressions of VEGF, NF-κB, and TNF-α in the uterus of ovariectomized rats. Our data demonstrate that E2 alone or in combination with P4 increases uterine eosinophilic infiltration which is related with vascular hyperpermeability caused by VEGF, NF-κB and TNF-α, whereas phytoestrogens Gen, Res, and Phl, have no such an effect.

Two-dimensional ultrathin gold film composed of steadily linked dense nanoparticle with surface plasmon resonance.

BACKGROUND: Noble metallic nanoparticles have prominent optical local-field enhancement and light trapping properties in the visible light region resulting from surface plasmon resonances. RESULTS: We investigate the optical spectral properties and the surface-enhanced Raman spectroscopy of two-dimensional distinctive continuous ultrathin gold nanofilms. Experimental results show that the one- or two-layer nanofilm obviously increases absorbance in PEDOT:PSS and P3HT:PCBM layers and the gold nanofilm acquires high Raman-enhancing capability. CONCLUSIONS: The fabricated novel structure of the continuous ultrathin gold nanofilms possesses high surface plasmon resonance properties and boasts a high surface-enhanced Raman scattering (SERS) enhancement factor, which can be a robust and cost-efficient SERS substrate. Interestingly, owing to the distinctive morphology and high light transmittance, the peculiar nanofilm can be used in multilayer photovoltaic devices to trap light without affecting the physical thickness of solar photovoltaic absorber layers and yielding new options for solar cell design.

Fabrication and spectroscopic investigation of branched silver nanowires and nanomeshworks.

Wide wavelength ranges of light localization and scattering characteristics can be attributed to shape-dependent longitude surface plasmon resonance in complicated nanostructures. We have studied this phenomenon by spectroscopic measurement and a three-dimensional numerical simulation, for the first time, on the high-density branched silver nanowires and nanomeshworks at room temperature. These nanostructures were fabricated with simple light-induced colloidal method. In the range from the visible to the near-infrared wavelengths, light has been found effectively trapped in those trapping sites which were randomly distributed at the corners, the branches, and the junctions of the nanostructures in those nanostructures in three dimensions. The broadened bandwidth electromagnetic field enhancement property makes these branched nanostructures useful in optical processing and photovoltaic applications.

Toward sustainable and comprehensive control of schistosomiasis in China: lessons from Sichuan.

Triggered by a fascinating publication in the New England Journal of Medicine detailing China's new multi-pronged strategy to control and eventually interrupt the transmission of Schistosoma japonicum, this PLoS Neglected Tropical Diseases Debate critically examines the generalizability and financial costs of the studies presented from the marshlands of the lake region. Edmund Seto from the University of California and colleagues emphasize that the epidemiology and control of schistosomiasis varies according to the social-ecological context. They conjecture that the successful intervention packages piloted in the lake region is not fully fit for the hilly and mountainous environments in Sichuan and Yunnan provinces, and hence call for more flexible, setting-specific, and less expensive control strategies. In response, Xiao-Nong Zhou from the National Institute of Parasitic Diseases at the Chinese Center of Disease Control and Prevention and colleagues explain the steps from designing pilot studies to the articulation and implementation of a new national control strategy through a careful process of scaling-up and adaptations. Finally, the two opponents converge. The need for integrated, intersectoral, and setting-specific control measures is stressed, supported by rigorous surveillance and continuous research. Experiences and lessons from China are important for shaping the schistosomiasis elimination agenda.