Ferroptosis has received great attention as an iron-dependent programmed cell death for efficient cancer therapy. However, with the accumulation of iron in tumor cells, the antioxidant system is activated by reducing glutathione (GSH) with glutathione peroxidase 4 (GPX4), which critically limits the ferroptosis therapeutic effect. Herein, an iron and GPX4 silencing siRNA (siGPX4) co-encapsulated ferritin nanocage (HFn@Fe/siGPX4) was developed to enhance ferroptosis by disruption of redox homeostasis and inhibition of antioxidant enzyme synergistically. The siGPX4 were loaded into the nanocages by pre-incubated with iron, which could significantly improve the loading efficiency of the gene drugs when compared with the reported gene drug loading strategy by ferritin nanocages. And more iron was overloaded into the ferritin through the diffusion method. When HFn@Fe/siGPX4 was taken up by human breast cancer cell MCF-7 in a TfR1-mediated pathway, the excess iron ions in the drug delivery system could for one thing induce ferroptosis by the production of reactive oxygen species (ROS), for another promote siGPX4 escaping from the lysosome to exert gene silencing effect more effectively. Both the in vitro and in vivo results demonstrated that HFn@Fe/siGPX4 could significantly inhibit tumor growth by synergistical ferroptosis. Thus, the developed HFn@Fe/siGPX4 afforded a combined ferroptosis strategy for ferroptosis-based antitumor as well as a novel and efficient gene drug delivery system.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Aim In this study, a mouse model of psoriasis-like lesions induced by 62. 5 mg imiquimod was used to explore the effect and mechanism of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae combination for the topical treatment of psoriasis. Methods Firstly, the topical administration of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae combination for treating psoriasis in progressive and recurrent stages was evaluated by psoriatic mouse model and HE staining. Secondly, immunohistochemistry was used to study the regulatory effects of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae combination on the pivotal pathological mechanism of psoriasis-the positive feedback loop between the abnormal proliferation of keratinocytes and skin immune microenvironment. Finally, metabolomics technology was used to explore whether Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae combination topically treat psoriasis by regulating inflammation-related metabolism and lipid metabolism pathways. Results The combination of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae alleviated psoriasis-like lesions in mice. It effectively relieved the recurrence after the cure of psoriatic lesions in mice, and the efficacy is comparable to that of benweimod. The combination of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae inhibited the proliferation of mouse epidermal keratinocytes and reduced the number of T cells in the skin. The potential molecular mechanism was that the combination of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae regulated arachidonic acid metabolism, sphin- golipid metabolism, tryptophan metabolism and phenylalanine metabolism. Conclusions The combination of Sophora Flavescens Radix and Rhizoma Smilacis Glabrae can relieve psoriasis-like lesions in mice by inhibiting the proliferation of epidermal keratinocytes and reducing the number of T cells in the skin and regulating metabolism to intervene psoriasis recurrence. This study provides a potential topical drug of psoriasis for relieving psoriasis recurrence.

Objective To explore the effect of Tongdu Tiaoshen acupuncture,a needling method for dredging governor vessel and regulating mind,on cerebral hemodynamics and oxygen free radicals in the patients with post-stroke epilepsy(PSE).Methods A total of 60 patients with PSE were randomly divided into a treatment group and a control group,with 30 cases in each group.Both groups were given basic treatment for lowering lipid level,controlling blood pressure and glucose contents,and counteracting platelet aggregation.Moreover,the control group was treated with Sodium Valproate Sustained-Release Tablets,and the treatment group was treated with Tongdu Tiaoshen acupuncture mainly on the acupoints of Baihui(GV20),Shenting(GV24),Shuigou(GV26),Fengfu(GV 16),Fengchi(GB20)based on the treatment for the control group.One month constituted a course of treatment,and the treatment for the two groups covered three courses of treatment.The number of epileptic seizures,the severity of electroencephalogram(EEG),the peak systolic velocity(Vs)and end diastolic velocity(Vd)of bilateral anterior cerebral arteries,middle cerebral arteries and posterior cerebral arteries detected by transcranial Doppler ultrasonography(TCD),and the changes in the peripheral levels of oxygen free radicals such as malondialdehyde(MDA),hydroxyl radical(OH),lipid peroxide(LPO)and superoxide dismutase(SOD)in the two groups were observed before and after treatment.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After three months of treatment,the total effective rate of the treatment group was 93.33％(28/30),and that of the control group was 73.33％(23/30).The intergroup comparison(tested by chi-square test)showed that the efficacy of the treatment group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the average monthly epileptic seizure frequency in the two groups was decreased when compared with that before treatment(P＜0.05),and the decrease in the treatment group was more significant than that in the control group(P＜0.05).(3)After treatment,the grading of EEG severity in the two groups was significantly improved when compared with that before treatment(P＜0.05),and the improvement in the treatment group was significantly superior to that in the control group(P＜0.05).(4)After treatment,the peripheral levels of oxygen free radicals of MDA,OH and LPO in the two groups were lower than those before treatment(P＜0.05),and the peripheral level of SOD was higher than that before treatment(P＜0.05).The decrease of MDA,OH and LPO levels and the increase of SOD level in the treatment group were significantly superior to those in the control group(P＜0.05 or P＜0.01).(5)After treatment,the values of cerebral hemodynamic indicators of Vs and Vd of both left and right anterior cerebral artery,middle cerebral artery and posterior cerebral artery in the two groups were higher than those before treatment(P＜0.05),and the increase in the treatment group was significantly superior to that in the control group,the differences being statistically significant(P＜0.05).(6)During the treatment,there were no fainting,sticking of needle,bleeding and rash occurring during acupuncture in the two groups,which indicated that the therapy had high safety.Conclusion Tongdu Tiaoshen acupuncture can significantly reduce the seizure frequency of PSE and improve the severity of epileptic EEG.Its therapeutic mechanism may be related with the decrease of the oxygen free radical levels and with the improvement of cerebral hemodynamics.

Background:Combined double-balloon enteroscopy(DBE)plays an important role in the diagnosis and treatment of patients with suspected small bowel bleeding(SSBB).Aims:To investigate the performance of combined DBE in patients with SSBB and their clinical features.Methods:A total of 94 patients with SSBB underwent combined DBE from June 2018 to April 2023 at the Third People's Hospital of Bengbu and the First Affiliated Hospital of Anhui Medical University were enrolled,and the clinical features were analyzed.Results:Fifty-four SSBB patients completed the combined DBE,and the combination rate was 57.4%.Ten patients(10.6%)stopped combined DBE due to discovery of bleeding lesions.Five patients(5.3%)stopped combined DBE due to intestinal stenosis.Twenty-five patients(26.5%)stopped combined DBE due to difficulty in insertion.Combined DBE rate in SSBB patients was correlated with the combination time and the number of previous DBE for endoscopists(P<0.05),but not the gender,age,bleeding manifestations,tobacco smoking and alcohol drinking,nutritional risk,abdominal operation history,perianal lesions,autoimmune diseases,preoperative anemia,preoperative albumin level,and enteroscopy approach(P>0.05).ROC curve showed that when the cut-off value of first insertion depth was 385 cm,the sensitivity and specificity for successful combined DBE in SSBB patients were 72.2%and 77.5%,respectively,and the area under ROC curve was 0.800(95%CI:0.705-0.875,P<0.001).Conclusions:The combined DBE rate in SSBB patients is correlated with the combination time and the number of previous DBE for endoscopists.80%of the SSBB patients are expected to complete the combined DBE when the first insertion depth is greater than 385 cm.

In recent years, with the policy reform of new drug review and approval, China has ushered in a surge of innovative drug development. Based on the Pharnexcloud database and the Pharmcube database, we analyzed the innovative drugs approved for marketing and entered clinical trials in China, sorted out the major research and development (R&D) institutions and enterprises, the distribution of innovative drug target types, and the primary therapeutic areas of the approved innovative drugs, and compared with the global innovative drug R&D landscape. Since 2020, China's innovative drug development has shown a rapid growth trend, with intense competition among biopharmaceutical companies, and the emergence of a number of leading biopharmaceutical enterprises. Popular targets for clinical-stage and approved drugs include protein tyrosine kinase, epidermal growth factor receptor, vascular endothelial growth factor receptor, and others. Oncological diseases are the most active domain for new drug R&D in China, followed by infectious diseases and neurological diseases. Suggestions for future development are proposed to increase policy support, enhance R&D innovation investment, optimize pipeline layout, strengthen international cooperation, and focus on innovative targets. This review provides a reference for pharmaceutical R&D enterprises, scientific researchers, and government administrators.
China ; Drug Development/trends* ; Drug Approval ; Pharmaceutical Research

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Objective:To investigate the impact of " staging" hybrid coronary artery revascularization (HCR) on the short-and long-term efficacy of patients with multiple coronary artery lesions.Methods:A retrospective case-control study was conducted. Eighty patients with multiple coronary artery lesions admitted to the Baoding Second Central Hospital from January 2017 to October 2018 were selected and divided into two groups according to different surgical methods. Forty patients were treated with " staging" HCR and were designated as the HCR group, and 40 patients were treated with off-pump coronary artery bypass grafting (OPCAB) and were designated as the OPCAB group. The perioperative related indicators and perioperative serious complications were compared between the two groups. The serum myocardial injury marker levels were detected preoperatively and 48 hours postoperatively, including heart-type fatty acid binding protein (H-FABP) and troponin I (cTnI). All subjects were followed up for at least 3 years to calculate the incidence of major adverse cardiovascular and cerebrovascular events (MACCE).Results:The bypass surgery time, mechanical ventilation time, ICU stay time, and total hospital stay time in the HCR group were all less than those in the OPCAB group (all P<0.05), and the incision length in the HCR group was shorter than that in the OPCAB group ( P<0.05). The intraoperative bleeding volume, postoperative 24-hour drainage volume, red blood cell transfusion volume, and plasma transfusion volume in the HCR group were all less than those in the OPCAB group (all P<0.05). Forty-eight hours after surgery, the serum H-FABP and cTnI levels in both groups were significantly higher than those preoperatively (all P<0.05), but the increase was more significant in the OPCAB group (all P<0.05). The perioperative serious complication rate in the HCR group was 2.50%(1/40), which was significantly lower than that in the OPCAB group [20.00%(8/40)] ( P<0.05). During the 3-year follow-up after surgery, the MACCE incidence in the HCR group was 12.50%(5/40), and that in the OPCAB group was 22.50%(9/40). There was no significant difference in the long-term MACCE incidence between the two groups ( P>0.05). Conclusions:" Staging" HCR treatment for multiple coronary artery lesions can achieve ideal surgical results. Compared with OPCAB, its short-term efficacy is more significant, and long-term efficacy is equivalent.

Abstract Allergic diseases can occur in all systems of the body, covering the whole life cycle, from children to adults and to old age, can be lifelong onset and even fatal in severe cases. Children account for the largest proportion of the victims of allergic disease, Children s allergies start from scratch, ranging from mild to severe, from less to more, from single to multiple systems and systemic performance, so the prevention and treatment of allergic diseases in children is of great importance, which can not only prevent high risk allergic conditions from developing into allergic diseases, but also further block the process of allergy. At present, there is no consensus on the management system of allergic children in kindergartens and primary schools. The "Consensus on Allergy Management and Prevention in Kindergartens and Primary Schools", which includes the organizational structure, system construction and management of allergic children, provides evidence informed recommendations for the long term comprehensive management of allergic children in kindergartens and primary schools, and provides a basis for the establishment of the prevention system for allergic children.

OBJECTIVES: To investigate the distribution characteristics of non-bacterial pathogens in community-acquired pneumonia (CAP) in children. METHODS: A total of 1 788 CAP children admitted to Shenyang Children's Hospital from December 2021 to November 2022 were selected. Multiple RT-PCR and capillary electrophoresis were used to detect 10 viral pathogens and 2 atypical pathogens, and serum antibodies of Chlamydial pneumoniae (Ch) and Mycoplasma pneumoniae (MP) were detected. The distribution characteristics of different pathogens were analyzed. RESULTS: Among the 1 788 CAP children, 1 295 children were pathogen-positive, with a positive rate of 72.43% (1 295/1 788), including a viral pathogen positive rate of 59.68% (1 067/1 788) and an atypical pathogen positive rate of 22.04% (394/1 788). The positive rates from high to low were MP, respiratory syncytial virus (RSV), influenza B virus (IVB), human metapneumovirus (HMPV), human rhinovirus (HRV), human parainfluenza virus (HPIV), influenza A virus (IVA), bocavirus (BoV), human adenovirus (HADV), Ch, and human coronavirus (HCOV). RSV and MP were the main pathogens in spring; MP had the highest positive rate in summer, followed by IVA; HMPV had the highest positive rate in autumn; IVB and RSV were the main pathogens in winter. The positive rate of MP in girls was higher than that in boys (P<0.05), and there were no significant differences in other pathogens between genders (P>0.05). The positivity rates of certain pathogens differed among age groups (P<0.05): the positivity rate of MP was highest in the >6 year-old group; the positivity rates of RSV and Ch were highest in the <1 year-old group; the positivity rates of HPIV and IVB were highest in the 1 to <3 year-old group. RSV, MP, HRV, and HMPV were the main pathogens in children with severe pneumonia, while MP was the primary pathogen in children with lobar pneumonia, and MP, IVB, HMPV, RSV, and HRV were the top 5 pathogens in acute bronchopneumonia. CONCLUSIONS MP, RSV, IVB, HMPV, and HRV are the main pathogens of CAP in children, and there are certain differences in the positive rates of respiratory pathogens among children of different ages, genders, and seasons.
Humans ; Child ; Female ; Male ; Infant ; Child, Preschool ; Pneumonia ; Respiratory Syncytial Virus, Human ; Antibodies ; Community-Acquired Infections ; Hospitalization ; Influenza B virus ; Mycoplasma pneumoniae