In recent years, cancer treatment methods and means are becoming more and more diversified, and single treatment methods often have limited efficacy, while the synergistic effect of immunity combined with chemotherapy can inhibit tumor growth more effectively. Based on this, we constructed a sodium alginate hydrogel composite system loaded with chemotherapeutic agents and tumor vaccines (named SA-DOX-NA) with a view to the combined use of chemotherapeutic agents and tumor vaccines. Firstly, the tumor vaccine (named NA) degradable under acidic conditions was constructed by in situ polymerization using chicken ovalbumin (OVA), acrylamide (AAM) and 2-(dimethylamino) ethyl methacrylate (DMAEMA) monomer. Then a hydrogel composite system SA-DOX-NA co-loaded with chemotherapeutic drug doxorubicin (DOX) and NA was prepared using sodium alginate as a matrix. The results showed that SA-DOX-NA had good in situ gel-forming ability and formed a mesh structure that could realize the co-loading of DOX and NA as well as the slow drug release. The electron microscopy results showed that SA-DOX-NA had good in situ gel-forming ability with good internal connectivity, and the three-dimensional mesh structure could realize the co-loading of DOX and NA as well as the slow drug release. The antitumor and immunomodulatory results showed that SA-DOX-NA both effectively inhibited the growth of tumor cells and efficiently promoted the proliferation and activation of DC2.4 dendritic cells without additional adjuvant. In summary, SA-DOX-NA exerts the dual efficacy of chemotherapy and immunotherapy for tumor treatment, and has a good application prospect in local tumor treatment.

Stroke is the main cause of death and disability among adults in China and is characterized by high incidence， disability， mortality， and recurrence rates. The combination of traditional Chinese and Western medicine has great potential in treating stroke and its sequelae. The classic traditional Chinese medicine prescription Da Chengqitang （DCQT） has a long history and proven efficacy in treating stroke. Clinically， DCQT is often used to treat stroke and its sequelae. However， the number and quality of clinical trials of DCQT in treating stroke need to be improved. Because of the insufficient basic research， the active ingredients and multi-target mechanism of action of DCQT remain unclear. Our research group has previously confirmed that DCQT can effectively reverse neurological damage， reduce iron deposition， and downregulate the levels of pro-inflammatory cytokines in the rat model of hemorrhagic stroke. The treatment mechanism is related to the nuclear factor erythroid 2-related factor 2 （Nrf2）-mediated signaling pathway and p38 mitogen-activated protein kinase （MAPK） signaling-mediated microglia activation. To clarify the pharmacodynamic basis and anti-stroke mechanism of DCQT， this article reviews the research progress in the treatment of stroke with DCQT in terms of clinical trials， pharmacodynamic material basis， safety evaluation， and mechanisms of absorbed components. This article summarizes 45 major phytochemical components of DCQT， 11 of which are currently confirmed absorbed components. Among them， emodin， rhein， chrysophanol， aloe-emodin， synephrine， hesperidin， naringin， magnolol， and honokiol can be used as quality markers （Q-markers） of DCQT. The mechanism of DCQT in treating stroke is complex， involving regulation of inflammatory responses， neuronal damage， oxidative stress， blood-brain barrier， brain-derived neurotrophic factor， and anti-platelet aggregation. This article helps to deeply understand the pharmacodynamic basis and mechanism of DCQT in treating stroke and provides a theoretical basis for the clinical application of DCQT in treating stroke and the development of stroke drugs.

[摘 要] 目的：构建程序性死亡受体1（PD-1）高表达的细菌质膜纳米囊泡（BMV）BMV-PD-1，评估其对小鼠肺癌移植瘤组织的靶向性。方法：通过质粒转化将PD-1与膜孔蛋白细胞溶素A（ClyA）融合质粒ClyA-PD-1-EGFP转入大肠杆菌BL21-Codonplus，使用激光共聚焦显微镜、SDS-PAGE和WB法检测融合蛋白ClyA-PD-1-EGFP的表达。提取质膜并采用挤出法，利用挤出器制备BMV-PD-1。采用透射电子显微镜（TEM）、纳米粒子跟踪分析（NTA）技术分别对BMV-PD-1的形态、粒径和膜电位进行检测，用WB鉴定PD-1蛋白的携带情况。采用激光共聚焦成像检测Lewis肺癌LLC细胞对BMV-PD-1的摄取。建立肺癌LLC细胞C57BL/6J小鼠皮下移植瘤模型，采用小动物活体成像系统评估BMV-PD-1的肿瘤靶向性。结果：激光共聚焦显微成像结果显示，质粒ClyA-PD-1-EGFP被转入BL21-Codonplus并成功表达蛋白。SDS-PAGE结果表明，ClyA-PD-1-EGFP在BL21-Codonplus中过表达。WB分析表明，PD-1在细菌中表达且在BMV-PD-1上呈高表达（P < 0.001）状态。NTA和TEM分析表明，BMV-PD-1是一种粒径为（145 ± 14） nm、表面呈负电性的球状囊泡。激光共聚焦成像显示，PD-1高表达能显著提升肺癌细胞对BMV-PD-1的摄取（P < 0.01），小动物活体成像也进一步证实PD-1高表达能有效提升BMV-PD-1的肿瘤靶向性（P < 0.01）。结论：本研究成功构建了PD-1高表达的细菌纳米囊泡BMV-PD-1，发现PD-1高表达可显著提高BMV-PD-1的肺癌LLC细胞移植瘤组织的靶向性，为进一步开发以BMV-PD-1为载体的肿瘤靶向药物递送系统奠定基础。

A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

Endovascular interventional therapy is currently the main treatment for acute ischemic stroke，but some patients still have not achieved neurological function independence. Analysis of the predictive value of various factors for postoperative neurological function changes can provide more reference for selecting appropriate patient groups and treatment plans.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Objective To observe the clinical efficacy and safety of rituximab injection combined with leflunomide tablets in the treatment of patients with systemic lupus erythematosus(SLE).Methods The SLE patients were divided into control and treatment groups according to cohort method.The control group received leflunomide with 50 mg·d-1 after meal in the first 3 days of treatment and was adjusted to 20 mg·d-1 thereafter.On the basis of control group,the treatment group was combined with rituximab,375 mg·m-2 was given intravenously every 2 weeks in the first 3 times of treatment,and adjusted to once every 4 weeks from the 4th dose.Two groups were treated for 24 weeks.The clinical efficacy,systemic lupus erythematosus disease activity index(SLEDAI)scores,serological indicators,24-hour urinary protein and adverse drug reactions were compared between two groups.Results The treatment and control groups were enrolled 74 cases and 72 cases,respectively.After treatment,the total effective rates of treatment and control groups were 91.89％(68 cases/74 cases)and 79.17％(57 cases/72 cases)with significant difference(P＜0.05).After treatment,the SLEDAI scores of treatment and control groups were(7.21±1.67)and(9.03±1.35)points;the levels of anti-Smith/ribonucleoprotein antibodies were(81.43±18.25)and(59.38±14.61)U·mL-1;the levels of immunoglobulin G were(12.04±2.15)and(17.28±2.64)g·L-1;the levels of interleukin-10 were(33.39±7.13)and(39.87±9.02)pg·mL-1;24-hour urinary protein quantification were(1.46±0.32)and(2.67±0.54)g·24 h-1;all the differences were statistically significant(all P＜0.05).The drug adverse reactions of two groups were liver and kidney function injury and digestive tract reactions.The total incidences of drug adverse reactions in the treatment and control groups were 13.51％and 5.56％without significant difference(P＞0.05).Conclusion Rituximab injection combined with leflunomide tablets has a definitive clinical efficacy in the treatment of SLE patients,which can significantly reduce disease activity and inflammatory reactions,improve immune function,without increasing the incidence of drug adverse reactions.

Objective To analyze the predictive value of serum levels of procalcitonin(PCT)and cytokines on the prognosis of patients with COVID-19 at admission.Methods From November 2022 to February 2023,patients diagnosed with COVID-19 who were admitted to Beijing Chest Hospital were enrolled.Chemiluminescence was used to detect serum PCT levels,and flow microsphere array was used to detect serum cytokines IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17A,IL-17F,IL-22,TNF-α,TNF-β,IFN-γ level.ICU admission,mechanical ventilation and in-hospital death were defined as poor prognosis.After excluding patients with bacterial infection,the relationship between serum PCT and cytokine levels at admission and the prognosis of COVID-19 patients was analyzed.After excluding patients with bacterial infection,the relationship between serum PCT and cytokine levels at admission and the prognosis of COVID-19 patients was analyzed.Results A total of 176 patients with complete data were included,including 134 in the PCT-normal group and 42 in the PCT-elevated group,with a median age of 71.50 years and 71.59%males.Patients in the PCT elevated-group had significantly higher rates of ICU admission(38.41%vs.13.11%,P<0.05),mechanical ventilation(76.92%vs.24.59%,P<0.001)and in-hospital mortality(38.46%vs.6.56%,P<0.001)were significantly higher than those in the PCT-normal group.Serum levels of cytokines IL-6(7.40 pg/mL vs.4.78 pg/mL,P = 0.033 4)and IL-8(10.97 pg/mL vs.5.92 pg/mL,P<0.001)were significantly higher in patients with poor prognosis than in those with good prognosis.The area under the curve for PCT,IL-6,and IL-8 to predict poor prognosis in COVID-19 patients was 0.687,0.660,and 0.746,respectively;sensitivity was 52.78%,55.17%,and 72.41%,respectively;and specificity was 81.58%,74.19%,and 74.19%,respectively,as calculated from the ROC curve.When PCT,IL-6 and IL-8 jointly predict the prognosis of COVID-19 patients,the area under the curve is 0.764,the sensitivity is 70.00%,and the specificity is 80.00%.Conclusion Serum PCT and cytokines IL-6 and IL-8 could be used as predictive markers for poor prognosis in patients with COVID-19.

Tumor is one of the major diseases that endanger people’s health. At present, the treatments used for tumor include surgery, chemotherapy, radiotherapy and so on. Nonetheless, the traditional treatments have some disadvantages, such as insufficient treatment effect, liable to cause multidrug resistance, toxicity and side effect. Further research and exploration of tumor treatment schemes are still necessary. As the energy converter of cells, mitochondria are currently considered to be one of the most important targets for the design of new drugs for tumor, cardiovascular and neurological diseases. Nano-drug delivery carriers have the characteristics of being easily modified with active targeting groups, and it can achieve accurate targeted drug delivery to cells and organelles. This paper reviews the application of mitochondrial targeted nanoparticles in tumor diagnosis and treatment from the aspects of inhibiting tumor cell proliferation, promoting tumor cell apoptosis, inhibiting tumor recurrence and metastasis, and inducing cell autophagy.

Xiaoke formula (XKF) is a classic formula for the treatment of insulin resistance (IR), but there is still unclear on bioactive equivalent combinatorial components (BECC) of XKF. In this study, based on the previous research of our team, three components, berberine, astragaloside IV and chlorogenic acid, were selected as the BECC of XKF, and their efficacy and mechanism were investigated. A high-fat diet-induced IR mouse model was used to detect blood glucose, insulin sensitivity, lipid metabolism, immune & inflammatory factors, etc., and staining of pathology sections was used to detect histopathological changes. Network pharmacology was used to predict the potential targets and signaling pathways of XKF and its BECC, and the results of the network were verified by Western blot. The animal welfare and experimental procedures followed the regulations of the Laboratory Animal Ethics Committee of Beijing MDKN Biotech Company (MDKN-2023-019). The results showed that BECC, which was composed of berberine, astragaloside IV and chlorogenic acid in the ratio of the original formula of XKF, was comparable to XKF in improving the glycemia, insulin sensitivity, histopathological damage, dyslipidemia, and immuno-inflammation in IR mice. The results of network pharmacology and Western blot suggested that the BECC of XKF and XKF might alleviate IR by promoting the activation of hepatic phosphatidylinositol 3-kinase (PI3K), phosphorylation of protein kinase B (AKT), and inhibiting the expression of glucose-6-phosphate phosphatase (G6PC) and phosphoenolpyruvate carboxykinase 1 (PCK1), the key limiting enzymes of hepatic gluconeogenesis. The above results suggest that berberine, astragaloside IV and chlorogenic acid can be used as the potential BECC of XKF to improve IR, and can regulate lipid metabolism, immuno-inflammation, and promote hepatic PI3K/AKT signaling to inhibit hepatic gluconeogenesis, regulate glucose homeostasis, and improve IR in mice.