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.

The breakage pattern of unit particles during the production of oral solid dosage forms (OSD) is closely related to the quality of intermediate or final products. To accurately characterize the particles and study the evolution law of particle breakage, the Bonding model of the discrete element method (DEM) was used to investigate the breakage patterns of model parameters, particle shape and process conditions (loading mode and loading rate) on the dynamic breakage, force-time curve, breakage rate, maximum breakage size ratio and fracture strength of particles. The results showed that the particle breakage force was positively correlated with normal strength and bonded disk scale, negatively correlated with normal stiffness per unit area and tangential stiffness per unit area, and weakly correlated with tangential strength. The particle breakage rate was negatively correlated with the aspect ratio of the particles, and the maximum breakage size ratio was positively correlated with the aspect ratio of the particles; among the three loading modes, the breakage rate of compression breakage model was the largest, the breakage rate of shear breakage model was the second largest, and the breakage rate of wear breakage model was the smallest; the maximum breakage size ratio was positively correlated with the loading rate, the loading mode and the loading rate had no mutual influence on particle breakage rate, but had mutual influence on the maximum breakage size ratio. The research results will provide a theoretical basis for the shift of OSD from batch manufacturing to advanced manufacturing.

Objective To study the clinical characteristics of children with anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV).Methods A retrospective analysis was conducted on the clinical data of 25 children diagnosed with AAV at the Second Xiangya Hospital of Central South University from January 2010 to June 2022.Results Among the AAV children,there were 5 males and 20 females,with a median age of onset of 11.0 years.Involvement of the urinary system was seen in 18 cases(72%);respiratory system involvement in 10 cases(40%);skin involvement in 6 cases(24%);eye,ear,and nose involvement in 5 cases(20%);joint involvement in 4 cases(16%);digestive system involvement in 2 cases(8%).Eleven cases underwent kidney biopsy,with 5 cases(46%)showing focal type,2 cases(18%)showing crescentic type,2 cases(18%)showing mixed type,and 2 cases(18%)showing sclerotic type.Immune complex deposits were present in 5 cases(45%).Seven cases reached chronic kidney disease(CKD)stage Ⅴ,with 2 cases resulting in death.Two cases underwent kidney transplantation.At the end of the follow-up period,2 cases were at CKD stage Ⅱ,and 1 case was at CKD stage Ⅲ.Of the 16 cases of microscopic polyangiitis(MPA)group,13(81%)involved the urinary system.Of the 9 cases of granulomatosis with polyangiitis(GPA),6 cases(66%)had sinusitis.Serum creatinine and uric acid levels were higher in the MPA group than in the GPA group(P<0.05),while red blood cell count and glomerular filtration rate were lower in the MPA group(P<0.05).Conclusions AAV is more common in school-age female children,with MPA being the most common clinical subtype.The onset of AAV in children is mainly characterized by renal involvement,followed by respiratory system involvement.The renal pathology often presents as focal type with possible immune complex deposits.Children with MPA often have renal involvement,while those with GPA commonly have sinusitis.The prognosis of children with AAV is poor,often accompanied by renal insufficiency.

Abstract: Objective　To analyze the surveillance of Mycobacterium tuberculosis/HIV (TB/HIV) co-infection in Liaoning Province from 2016 to 2021, providing a scientific basis for formulating future prevention and control measures applicable to the province-wide co-infection. Methods　A descriptive analysis was conducted on patient registration, two-way screening, and treatment information from the annual report of patients with TB/HIV co-infection in Liaoning Province from 2016 to 2021. Results From 2016 to 2021, 222 cases of TB/HIV co-infection were registered in Liaoning Province, accounting for 0.16% (222/136 709) of TB patients and 1.42% (222/15 584) of HIV/AIDS patients. In HIV/AIDS, the symptom screening rate was 96.01%, showing a downward trend (χ2trend=982.28, P<0.05). The TB detection rate was 0.47%, also showing a downward trend (χ2trend=36.56, P<0.05), while the chest radiograph or sputum detection rate was 94.61%, showing an overall upward trend (χ2trend=96.5, P<0.05). Among TB patients, 65 188 were tested for HIV antibodies, with a detection rate of 47.68%, which showed an overall upward trend (χ2trend=3 326.38, P<0.05). There were 39 HIV-positive cases detected, with the positive detection rate in TB patients decreasing from 0.12% to 0.07%. From 2016 to 2021, the majority of co-infected patients were male and ≥15 years old, with 496 cases (92.36%) of males and 41 cases (7.64%) of females. Among the 537 patients with co-infection, 47 cases (8.75%) received anti-tuberculosis therapy alone, 72 cases (13.41%) received anti-HIV therapy alone, and 408 cases (75.98%) received combined therapy, with an overall downward trend (χ2trend=9.54, P<0.05). Conclusions Focus should be placed on the male population and those aged ≥15 years, with future efforts aimed at enhancing two-way screening work among TB and HIV/AIDS patients and improving the rate of combined treatment.

OBJECTIVE: To evaluate the effectiveness and safety of Chinese medicine (CM) in the treatment of coronavirus disease 2019 (COVID-19) in China. METHODS: A multi-center retrospective cohort study was carried out, with cumulative CM treatment period of ⩾3 days during hospitalization as exposure. Data came from consecutive inpatients from December 19, 2019 to May 16, 2020 in 4 medical centers in Wuhan, China. After data extraction, verification and cleaning, confounding factors were adjusted by inverse probability of treatment weighting (IPTW), and the Cox proportional hazards regression model was used for statistical analysis. RESULTS: A total of 2,272 COVID-19 patients were included. There were 1,684 patients in the CM group and 588 patients in the control group. Compared with the control group, the hazard ratio (HR) for the deterioration rate in the CM group was 0.52 [95% confidence interval (CI): 0.41 to 0.64, P<0.001]. The results were consistent across patients of varying severity at admission, and the robustness of the results were confirmed by 3 sensitivity analyses. In addition, the HR for all-cause mortality in the CM group was 0.29 (95% CI: 0.19 to 0.44, P<0.001). Regarding of safety, the proportion of patients with abnormal liver function or renal function in the CM group was smaller. CONCLUSION This real-world study indicates that the combination of a full-course CM therapy on the basic conventional treatment, may safely reduce the deterioration rate and all-cause mortality of COVID-19 patients. This result can provide the new evidence to support the current treatment of COVID-19. Additional prospective clinical trial is needed to evaluate the efficacy and safety of specific CM interventions. (Registration No. ChiCTR2200062917).
Humans ; Retrospective Studies ; Male ; Female ; Middle Aged ; COVID-19/epidemiology* ; COVID-19 Drug Treatment ; Aged ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/adverse effects* ; SARS-CoV-2 ; Treatment Outcome ; China/epidemiology* ; Adult

With the increasing rate of overweight and obesity in children worldwide, adiposity rebound(AR)closely related to obesity has become the spotlight, and early AR phase has a broad impact on pubertal development in girls, but the specific mechanism of action isn't very clear.This paper is review of the prevalence of early AR at home and abroad, and its influencing factors, the impact of AR on the adolescent development of girls and related mechanisms, to identify high-risk individuals with early AR, early AR to identify early adolescent development, and take early intervention measures to promote children's health.
Female ; Adolescent ; Child ; Humans ; Adiposity ; Pediatric Obesity/epidemiology* ; Adolescent Development ; Body Mass Index ; Overweight/epidemiology*

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

OBJECTIVE To clarify the core content of traditional Chinese medicine （TCM） policy in the provinces of China， so as to provide reference for optimizing the structure of the policy system of traditional Chinese medicine in China and assisting the inheritance and innovation of TCM industry in various regions. METHODS The websites of directly affiliated organs in 31 provinces， excluding Hong Kong， Macao and Taiwan， were retrieved to collect the TCM policies released from 2000 to 2021. The importance of keywords in the TCM policies of each province was measured based on term frequency-inverse documentation frequency （TF-IDF） keyword extraction method， and the similarities and differences were analyzed among TCM policies. RESULTS & CONCLUSIONS A total of 99 documents related to TCM policies of various provinces were obtained in this study， most of which were released after 2016. The theme of national TCM policy covered four aspects： building TCM talent team， perfecting TCM service system， strengthening TCM resource management and promoting TCM industry innovation. The TF-IDF values of “medical institutions”“traditional Chinese medicine”“medical treatment” were higher than other keywords in each province， indicating that the provinces paid more attention to the construction of TCM service system and the management of TCM resources than other aspects. Anhui and Jiangsu， Beijing and Henan， Hubei and Jilin， Hubei and Tianjin， and Hubei and Yunnan had the more degree of similarity in TCM policies， which all contained 16 of the same keywords. Therefore， the above regions should be encouraged to strengthen exchanges and cooperation and realize mutual promotion and joint development. Among all the keywords whose importance ratio was greater than 0.2，“ Tibetan medicine” was unique to Qinghai and Tibet，“ disease type” was unique to Guangdong， and the TF-IDF value of “supervision and management” in Beijing was higher， indicating that the emphasis of TCM policy formulation in different provinces was various. Meanwhile， the top 10 keywords of TF- IDF value in all provinces did not have words related to financial input， and the TF-IDF values of “informatization” in most provinces did not rank at the top. It is suggested to increase financial input or encourage social financing， and add “Internet+new business” in the field of TCM.