[摘 要] 目的：构建负载STING激动剂DMXAA的锰卟啉金属有机框架纳米颗粒（DPM），探讨其对三阴性乳腺癌（TNBC）细胞4T1及其小鼠移植瘤的治疗效果。方法：通过物理吸附法制备 DPM 纳米颗粒，利用透射电镜、扫描电镜及纳米粒度电位仪表征其形貌与理化性质。常规培养4T1细胞，细胞实验分为对照组、超声辐照组（US组）、DPM治疗组（DPM组）和DPM治疗联合超声辐照组（DPM + US组），用CCK-8法检测细胞活性，免疫荧光法检测高迁移率族蛋白B1（HMGB1）和钙网蛋白（CRT）的表达，WB法检测STING通路相关蛋白的表达。构建4T1细胞移植瘤小鼠模型，分为四组，处理同细胞实验，测量肿瘤体积，免疫荧光法检测移植瘤组织中Ki-67、HMGB1、CRT和缺氧诱导因子-1ɑ（HIF-1ɑ）蛋白的表达，TUNEL法检测细胞凋亡，流式细胞术检测免疫细胞活化情况，对主要器官进行H-E染色，以评估纳米材料的体内安全性。结果：DPM呈梭形，平均粒径（268 ± 3.302）nm，电位（33.1 ± 0.87）mV。细胞实验中，DPM联合超声辐照可明显抑制4T1细胞的增殖（P < 0.001），提高4T1细胞中ROS水平（P < 0.001），诱导4T1细胞CRT表达上调（P < 0.001），HMGB1从细胞核中移至细胞质，激活STING信号通路[p-STING、p-TBK1、p-IRF3蛋白表达均显著增加（均P < 0.001）]。体内实验中，DPM联合超声辐照可显著抑制4T1细胞移植瘤生长（P < 0.001）并促进免疫细胞表型转化（P < 0.001），抑制移植瘤组织中Ki-67、HIF-1α蛋白表达（均P < 0.01），谷胱甘肽（GSH）产生（P < 0.01），促进CRT、HMGB1蛋白表达、ROS产生（P < 0.001），对主要器官结构无明显影响。结论： DPM联合超声辐照可通过激活STING通路显著抑制4T1细胞及其移植瘤的生长，诱导抗肿瘤免疫应答，且对主要器官无明显毒性。

AIM: To compare the control effect of spherical and toric orthokeratology on low-to-moderate myopia with astigmatism(-1.00--1.50 DC)in adolescents.METHODS: The clinical data of 119 cases(119 eyes)of low-to-moderate myopia with astigmatism(-1.00--1.50 DC)adolescents who were treated and fitted with orthokeratology in the ophthalmology department of Sichuan Provincial People's Hospital from June 2021 to January 2022 were retrospectively analyzed. They were divided into spherical group, with 65 cases(65 eyes), and toric group, with 54 cases(54 eyes)according to the type of orthokeratology. The changes of uncorrected visual acuity(UCVA), axial length and corneal astigmatism before and after wearing lenses were recorded to evaluate the therapeutic effect.RESULTS: The UCVA of both the groups significantly improved at 1 and 2 a after wearing lenses(all P<0.01); corneal astigmatism decreased, but there was no significant difference(all P>0.05); the axial length was longer than that before wearing lenses(P<0.01). There were no statistical significant differences in the UCVA and corneal astigmatism between the spherical group and the toric group(Fintergroup=0.829,Pintergroup=0.364; Fintergroup=0.997,Pintergroup=0.320); and there were no statistical significant differences in the axial length growth between the spherical group and the toric group after wearing lenses for 1 a(0.18±0.11 mm vs 0.17±0.14 mm), and 2 a(0.17±0.10 mm vs 0.16±0.10 mm; all P>0.05).CONCLUSION: Both orthokeratology lenses can improve the UCVA, reduce corneal astigmatism, and delay axial length growth of adolescents with low-to-moderate myopia with astigmatism(-1.00--1.50 DC), and there are no significant differences in the control effect of spherical design orthokeratology and the toric design orthokeratology on myopia.

OBJECTIVE: To evaluate the effect and safety of Chinese medicine (CM) Fuzheng Huazhuo Decoction (FHD) in treating patients with coronavirus disease 2019 (COVID-19) who persistently tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This retrospective cohort study was conducted at Shanghai New International Expo Center shelter hospital in China between April 1 and May 30, 2022. Patients diagnosed as COVID-19 with persistently positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test results for ⩾8 days after diagnosis were enrolled. Patients in the control group received conventional Western medicine (WM) treatment, while those in the FHD group received conventional WM plus FHD for at least 3 days. The primary outcome was viral clearance time. Secondary outcomes included negative conversion rate within 14 days, length of hospital stay, cycle threshold (Ct) values of the open reading frame 1ab (ORF1ab) and nucleocapsid protein (N) genes, and incidence of new-onset symptoms during hospitalization. Adverse events (AEs) that occurred during the study period were recorded. RESULTS: A total of 1,765 eligible patients were enrolled in this study (546 in the FHD group and 1,219 in the control group). Compared with the control group, patients receiving FHD treatment showed shorter viral clearance time for nucleic acids [hazard ratio (HR): 1.500, 95% confidence interval (CI): 1.353-1.664, P<0.001] and hospital stays (HR: 1.371, 95% CI: 1.238-1.519, P<0.001), and a higher negative conversion rate within 14 days (96.2% vs. 82.6%, P<0.001). The incidence of new-onset symptoms was 59.5% in the FHD group, similar to 57.8% in the control group (P>0.05). The Ct values of ORF1ab and N genes increased more rapidly over time in the FHD group than those in the control group post-randomization (ORF1ab gene: β =0.436±0.053, P<0.001; N gene: β =0.415 ±0.053, P<0.001). The incidence of AEs in the FHD group was lower than that in the control group (24.2% vs. 35.4%, P<0.001). No serious AEs were observed. CONCLUSION FHD was effective and safe for patients with persistently positive SARS-CoV-2 PCR tests. (Registration No. ChiCTR2200063956).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Retrospective Studies ; Male ; Female ; Middle Aged ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects* ; COVID-19/virology* ; Adult ; Aged ; Treatment Outcome

Previous studies have identified two group-level processes, neural representations of interracial between-group difference and intraracial within-group similarity, that contribute to the racial categorization of faces. What remains unclear is how the brain tracks race-related information that varies across different faces as an individual-level neural process involved in race perception. In three studies, we recorded functional MRI signals when Chinese adults performed different tasks on morphed faces in which proportions of pixels contributing to perceived racial identity (Asian vs White) and expression (pain vs neutral) varied independently. We found that, during a pain expression judgment task, tracking other-race and same-race-related information in perceived faces recruited the ventral occipitotemporal cortices and medial prefrontal/anterior temporal cortices, respectively. However, neural tracking of race-related information tended to be weakened during explicit race judgments on perceived faces. During a donation task, the medial prefrontal activity also tracked race-related information that distinguished between two perceived faces for altruistic decision-making and encoded the Euclidean distance between the two faces that predicted decision-making speeds. Our findings revealed task-dependent neural mechanisms underlying the tracking of race-related information during face perception and altruistic decision-making.
Adult ; Female ; Humans ; Male ; Young Adult ; Brain/diagnostic imaging* ; Brain Mapping ; Decision Making/physiology* ; Facial Recognition/physiology* ; Judgment/physiology* ; Magnetic Resonance Imaging ; Photic Stimulation ; Racial Groups ; Social Perception ; East Asian People

Osteosarcoma is a kind of mesenchymal tissue tumor, which is highly invasive and metastatic. Pro-angiogenic factors and vascular endothelial cells play key roles in the angiogenesis and metastasis of osteosarcoma, and the interaction between vascular endothelial cells and osteosarcoma cells can affect the growth and metastasis of osteosarcoma. Anti-vascular therapeutics agents for osteosarcoma, including monoclonal antibodies, tyrosine kinase inhibitors and traditional Chinese medicines, can inhibit the progression of osteosarcoma. An in-depth study of the correlation between osteosarcoma and angiogenesis can provide new ideas for the study of vascularization of osteosarcoma and anti-vascular treatment of osteosarcoma.

Objective To investigate the therapeutic efficacy of modified Buyang Huanwu Decoction in the treatment of type 2 diabetes mellitus(T2DM)patients with peripheral neuropathy of qi deficiency and blood stasis type,and to observe its effects on serum fibroblast growth factor 21(FGF21),25-hydroxyvitamin D[25(OH)D],endothelin 1(ET-1)levels and hypercoagulable state of the patients.Methods A total of 124 T2DM patients with peripheral neuropathy of qi deficiency and blood stasis type who admitted to Haikou Hospital of Traditional Chinese Medicine from December 2019 to December 2022 were randomly divided into a control group and an observation group,with 62 cases in each group according to the random number table method.The control group was treated with conventional western medicine,and the observation group was treated with modified Buyang Huanwu Decoction on the basis of treatment for the control group.The course of treatment for the two groups covered 12 weeks.The changes of traditional Chinese medicine(TCM)syndrome scores,blood glucose indicators,hemorheology indicators,nerve conduction velocity(NCV)and levels of serum FGF21,25(OH)D,ET-1,interleukin 6(IL-6)in the two groups before and after treatment were observed.After treatment,the therapeutic efficacy of the two groups was evaluated.Results(1)After 12 weeks of treatment,the total effective rate of the observation group was 96.77%(60/62)and that of the control group was 83.87%(52/62),and the intergroup comparison(tested by chi-square test)showed that the therapeutic efficacy of the observation group was significantly superior to that of the control group(P<0.05).(2)After treatment,the total TCM syndrome scores and the scores of TCM symptoms such as limb pain,hypoesthesia,excessive eating with frequent hunger,and limb numbness in the two groups were decreased when compared with those before treatment(P<0.05),and the decrease in the observation group was significantly superior to that in the control group(P<0.05).(3)After treatment,the levels of hemorheology indicators such as hematocrit,whole blood viscosity at high-shear rate,and plasma viscosity in the two groups of patients were decreased when compared with those before treatment(P<0.05),and the decrease in the observation group was significantly superior to that in the control group(P<0.05).(4)After treatment,the motor conduction velocity of the common peroneal nerve and the median nerve in the two groups of patients was increased when compared with that before treatment(P<0.05),and the increase in the observation group was significantly superior to that in the control group(P<0.05).(5)After treatment,the serum levels of blood glucose indicators such as fasting blood glucose(FBG)and glycosylated hemoglobin(HbA1C)in the two groups of patients were decreased when compared with those before treatment(P<0.05),and the decrease in the observation group was significantly superior to that in the control group(P<0.05).(6)After treatment,the serum FGF21,ET-1,and IL-6 levels in the two groups were decreased(P<0.05),and serum 25(OH)D level was increased(P<0.05),and the decrease of serum FGF21,ET-1,and IL-6 levels as well as the increase of serum 25(OH)D level in the observation group was significantly superior to that in the control group(P<0.05).Conclusion For T2DM patients with peripheral neuropathy of qi deficiency and blood stasis type,the combination of modified Buyang Huanwu Decoction with conventional treatment in western medicine is helpful for reducing the inflammatory response,alleviating the damage of vascular endothelial function,regulating the levels of blood glucose,improving the neurologic function,and enhancing the clinical efficacy.

Background::Pulmonary arterial hypertension (PAH) is characterized by excessive proliferation of small pulmonary arterial vascular smooth muscle cells (PASMCs), endothelial dysfunction, and extracellular matrix remodeling. G protein-coupled receptor kinase 2 (GRK2) plays an important role in the maintenance of vascular tone and blood flow. However, the role of GRK2 in the pathogenesis of PAH is unknown.Methods::GRK2 levels were detected in lung tissues from healthy people and PAH patients. C57BL/6 mice, vascular smooth muscle cell-specific Grk2-knockout mice ( Grk2?SM22), and littermate controls ( Grk2flox/flox) were grouped into control and hypoxia mice ( n = 8). Pulmonary hypertension (PH) was induced by exposure to chronic hypoxia (10%) combined with injection of the SU5416 (cHx/SU). The expression levels of GRK2 and Yes-associated protein (YAP) in pulmonary arteries and PASMCs were detected by Western blotting and immunofluorescence staining. The mRNA expression levels of Grk2 and Yes-associated protein ( YAP) in PASMCs were quantified with real-time polymerase chain reaction (RT-PCR). Wound-healing assay, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, and 5-Ethynyl-2′-deoxyuridine (EdU) staining were performed to evaluate the proliferation and migration of PASMCs. Meanwhile, the interaction among proteins was detected by immunoprecipitation assays. Results::The expression levels of GRK2 were upregulated in the pulmonary arteries of patients with PAH and the lungs of PH mice. Moreover, cHx/SU-induced PH was attenuated in Grk2?SM22 mice compared with littermate controls. The amelioration of PH in Grk2?SM22 mice was accompanied by reduced pulmonary vascular remodeling. In vitro study further confirmed that GRK2 knock-down significantly altered hypoxia-induced PASMCs proliferation and migration, whereas this effect was severely intensified by overexpression of GRK2. We also identified that GRK2 promoted YAP expression and nuclear translocation in PASMCs, resulting in excessive PASMCs proliferation and migration. Furthermore, GRK2 is stabilized by inhibiting phosphorylating GRK2 on Tyr86 and subsequently activating ubiquitylation under hypoxic conditions. Conclusion::Our findings suggest that GRK2 plays a critical role in the pathogenesis of PAH, via regulating YAP expression and nuclear translocation. Therefore, GRK2 serves as a novel therapeutic target for PAH treatment.

Objective To investigate the effect of iTBS stimulation on walking function in patients with stroke.Methods Fifty patients with post-stroke walking dysfunction who met the inclusion criteria were selected for 3-week rehabilitation treatment,and were randomly divided into iTBS group(n=25)and sham group(n=25).The iTBS group was treated with conventional rehabilitation therapy combined with iTBS stimulation of contral-esional cerebellum,and the sham group was treated with conventional rehabilitation therapy plus iTBS stimulation of contralesional cerebellum.Relevant indicators were analyzed before treatment and at 21 days of treatment.Lower limb motor function scores of the two groups were compared before and after treatment.Fugl-Meyer motor function lower limb activity score,Berg Balance Scale score,Brunnstrom stage(lower limb),hamstring/quadriceps(H/Q)on the affected side,Modified Barthel index(MBI),gait analysis parameters,and TMS-MEP were used to evaluate the effectiveness of cerebellar iTBS in the rehabilitation of walking dysfunction after stroke.Results After 21 days of treatment,the improvements of Brunnstrom stage,Holden grade,Berg score,FMA score,6-minute walking dis-tance,NIHSS score and MBI score in iTBS group were significantly better than those in sham group(P<0.05).Af-ter treatment,the H/Q in iTBS group was significantly higher thanbefore(P<0.05),but there was no significant difference between the two groups(P>0.05).Stride speed,stride frequency,stride width,single support phase on the affected side and GDI score in iTBS group were significantly improved compared with sham group(P<0.05),and there was no significant difference in stride length between the two groups after treatment(P>0.05).The amplitude of MEP in the affected cerebral cortex of iTBS group was lower after treatment than before(P<0.05).Conclusion Contralesional cerebellar iTBS combined with routine rehabilitation could improve lower limb walk-ing function and daily living ability of stroke patients.

Objective To investigate the expression level and diagnostic value of microRNA-373(miR-373)in gastric cancer.Methods A total of 80 patients with gastric cancer admitted to the Gastric Cancer Diagnosis and Treatment Center of Dongguan Third Clinical College of Guangdong Medical University from February 2021 to February 2023 were selected as the gastric cancer group.80 patients with benign gastric diseases who underwent gastroscopy in Dongguan Third Clinical College of Guangdong Medical University during the same period and did not have tumors by pathological examination were selected as the benign gastric disease group,and 80 healthy subjects who underwent the physical examination during the same period were selected as the control group.Serum samples were collected from the subjects,and the expression level of miR-373 was detec-ted by real-time quantitative polymerase chain reaction(qRT-PCR),and its correlation with clinicopathologi-cal features was analyzed.Serum carbohydrate antigen 199(CA199)and carcinoembryonic antigen(CEA)were detected by automatic chemiluminescence immunoassay.The diagnostic efficacy of miR-373,CA199 and CEA for gastric cancer was evaluated by receiver operating characteristic(ROC)curve.Results The expres-sion levels of serum miR-373,CA199 and CEA in gastric cancer group were higher than those in benign gastric disease group and control group,and the differences were statistically significant(P＜0.05).The expression level of miR-373 was closely related to tumor maximum diameter,lymph node metastasis and TNM stage in patients with gastric cancer(P＜0.05).ROC curve analysis showed that the area under the curve of miR-373,CA199 and CEA in the diagnosis of gastric cancer was(95i％CI:0.819-0.926),0.874(95％CI:0.813-0.921)and 0.836(95％CI:0.769-0.889),respectively.The diagnostic efficacy of miR-373 was better than that of traditional tumor markers CA199 and CEA.Conclusion miR-373 is highly expressed in gastric cancer tissues,and the expression level of miR-373 is related to the clinicopathological features of gastric cancer,which has high application value in the early diagnosis of gastric cancer.

By sorting out the differences and connections between family doctor teams and specialized disease teams, role competency and mutual collaboration, and introducing the learning health system (LHS) mechanism, a comprehensive operating system for community general practice learning organizations based on LHS was constructed, focusing on five single disease types. The system includes a combination of general and specialized medicine that links three levels of medical institutions, thereby opening up the business cooperation process between professionals in different institutions, and establishing a sustainable collaboration mechanism. This allows medical institutions at three levels to continuously tap the potential of their disciplines, achieve their own ability growth and feel higher work value, and also bring better health solutions to residents, guided by the common goal of "health centered, patient centered".