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.

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.

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.

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

AIM: To analyze the strabismus surgery situation of adolescents and children in Yunnan province.METHODS: A retrospective analysis was conducted on medical records data of 3 068 adolescents and children who received strabismus surgery at Affiliated Hospital of Yunnan University from January 2017 to December 2021. The analysis included gender, constituent ratio of age, distribution of strabismus types and combination with other ocular diseases, etc.RESULTS: Among the included patients, 52.12% were males, and 47.88% were females. Preschool patients(1 to 6 years old)accounted for 32.89%, primary pupils(7 to 12 years old)accounted for 45.89% and high school students(13 to 18 years old)accounted for 21.22%. Exotropia accounted for 63.17% of the total strabismus, of which intermittent exotropia was the most common type. Esotropia accounted for 19.69%, and concomitant esotropia was the most common type. The special type of strabismus accounted for 17.14%, and A-V syndrome and dissociative vertical deviation(DVD)were the most common types. Strabismus combined with ametropia accounted for 61.02% and amblyopia accounted for 10.89%. A few patients also combined with other eye diseases.CONCLUSION: In Yunnan province, intermittent exotropia was the most common type of strabismus among adolescents and children. Some patients combined with other ocular diseases.

Objective: To investigate the risk factors for the development of deep infiltration in early colorectal tumors (ECT) and to construct a prediction model to predict the development of deep infiltration in patients with ECT. Methods: The clinicopathological data of ECT patients who underwent endoscopic treatment or surgical treatment at the Cancer Hospital, Chinese Academy of Medical Sciences from August 2010 to December 2020 were retrospectively analyzed. The independent risk factors were analyzed by multifactorial regression analysis, and the prediction models were constructed and validated by nomogram. Results: Among the 717 ECT patients, 590 patients were divided in the within superficial infiltration 1 (SM1) group (infiltration depth within SM1) and 127 patients in the exceeding SM1 group (infiltration depth more than SM1). There were no statistically significant differences in gender, age, and lesion location between the two groups (P>0.05). The statistically significant differences were observed in tumor morphological staging, preoperative endoscopic assessment performance, vascular tumor emboli and nerve infiltration, and degree of tumor differentiation (P<0.05). Multivariate regression analysis showed that only erosion or rupture (OR=4.028, 95% CI: 1.468, 11.050, P=0.007), localized depression (OR=3.105, 95% CI: 1.584, 6.088, P=0.001), infiltrative JNET staging (OR=5.622, 95% CI: 3.029, 10.434, P<0.001), and infiltrative Pit pattern (OR=2.722, 95% CI: 1.347, 5.702, P=0.006) were independent risk factors for the development of deep submucosal infiltration in ECT. Nomogram was constructed with the included independent risk factors, and the nomogram was well distinguished and calibrated in predicting the occurrence of deep submucosal infiltration in ECT, with a C-index and area under the curve of 0.920 (95% CI: 0.811, 0.929). Conclusion: The nomogram prediction model constructed based on only erosion or rupture, local depression, infiltrative JNET typing, and infiltrative Pit pattern has a good predictive efficacy in the occurrence of deep submucosal infiltration in ECT.
Humans ; Retrospective Studies ; Colorectal Neoplasms/pathology* ; Nomograms ; Neoplasm Staging ; Risk Factors

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

Background: The widespread use of biological agents in recent years can improve the nutritional status of partial patients with Crohn's disease (CD) and change the course of the disease. Aims: To investigate the correlation between the nutritional risk and clinical and endoscopic features in CD patients treated with biological agents. Methods: Sixty⁃eight CD patients treated with biological agents from June 2021 to June 2022 at the First Affiliated Hospital of Anhui Medical University were enrolled. Nutritional risk screening was conducted by nutritional risk screening 2002 (NRS2002), and its correlation with clinical and endoscopic features was analyzed. Results: In 68 CD patients treated with biological agents, incidence of nutritional risk was 66.2%. There was statistically significant difference in incidence of nutritional risk in patients with different disease behaviors, SES⁃CD score and postoperative Rutgeerts score (all P<0.05). The incidence of nutritional risk was not correlated with age, lesion location, perianal lesion, CDAI score, and the interval between CD diagnosis and the use of biological agents (all P>0.05). Conclusions: The incidence of nutritional risk is high in CD patients treated with biological agents, and is correlated with CD disease behavior, SES ⁃ CD score, and postoperative Rutgeerts score.