Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

CRISPR/Cas9-based therapeutics face significant challenges in penetrating the dense microenvironment of solid tumors, resulting in insufficient gene editing and compromised treatment efficacy. Current nanostrategies, which mainly focus on the paracellular pathway attempted to improve gene editing performance, whereas their efficiency remains uneven in the heterogenous extracellular matrix. Here, the nanoCRISPR system is prepared with self-cascading mechanisms for gene editing-mediated robust apoptosis and transcellular penetration. NanoCRISPR unlocks its self-cascade capability within the matrix metallopeptidase 2-enriched tumor microenvironment, initiating the transcellular penetration. By facilitating cellular uptake, nanoCRISPR triggers robust apoptosis in edited malignancies, promoting further transcellular penetration and amplifying gene editing in neighboring tumor cells. Benefiting from self-cascade between robust apoptosis and transcellular penetration, nanoCRISPR demonstrates continuous gene transfection/tumor killing performance (transfection/apoptosis efficiency: 1st round: 85%/84.2%; 2nd round: 48%/27%) and homogeneous penetration. In xenograft tumor-bearing mice, nanoCRISPR treatment achieves remarkable anti-tumor efficacy (∼83%) and significant survival benefits with minimal toxicity. This strategy presents a promising paradigm emphasizing transcellular penetration to enhance the effectiveness of CRISPR-based antitumor therapeutics.

Alzheimer′s disease(AD), as a common cognitive impairment disorder in the elderly, has imposed a significant burden on the global public health system.The latest international diagnostic criteria emphasize defining AD from a biological perspective and viewing it as a continuous pathological and physiological change process.This article, guided by the principle of ′early diagnosis-precision intervention′, systematically elaborates on the current research status of AD regarding diagnostic criteria, biomarkers, new drug development, and the establishment of China-specific AD cohorts.It also provides an in-depth outlook on the future research directions and clinical application prospects of AD.

Alzheimer′s disease(AD), as a common cognitive impairment disorder in the elderly, has imposed a significant burden on the global public health system.The latest international diagnostic criteria emphasize defining AD from a biological perspective and viewing it as a continuous pathological and physiological change process.This article, guided by the principle of ′early diagnosis-precision intervention′, systematically elaborates on the current research status of AD regarding diagnostic criteria, biomarkers, new drug development, and the establishment of China-specific AD cohorts.It also provides an in-depth outlook on the future research directions and clinical application prospects of AD.

Objective:To investigate the clinical manifestations, genotype characteristics and treatment of cytochrome P450 oxidoreductase deficiency (PORD) patients with 46,XX karyotype in China.Methods:The clinical data of twelve patients with 46, XX karyotype who were admitted to Peking Union Medical College Hospital from January 2021 to March 2024 and finally diagnosed as PORD by whole exome sequencing were retrospectively analyzed. The clinical manifestations, hormone characteristics and genetic etiology of the disease were summarized.Results:A total of 12 women were diagnosed with PORD, including one young girl with ambiguous genitalia and skeletal malformations at an early stage, and eleven adolescence and adult patients with menstrual disorders and (or) ovarian cysts. Five patients presented with male genitals. Ten patients presented with varying degrees of skeletal deformity. Eleven patients with abnormal menstruation and (or) ovarian cysts presented with unilateral or bilateral multilocular ovarian enlargement, and the larger patient′s ovarian size reached 12.0 cm×7.7 cm. The ovarian cysts disappeared after 3-6 months of combined oral contraceptives (COC) treatment, and the patients were followed up regularly after drug withdrawal and no recurrences were observed during the follow-up period of 1-2 years. Progesterone levels were elevated in all patients. All patients carried biallelic mutations of POR gene. The most common mutation was c.1370G>A in exon 11, which occurred in 11/12 patients. Two novel nonsense mutations, c.1684dupG and c.2040dupC were identified.Conclusions:PORD is one of the causes of unexplained menstrual disorders and ovarian cysts in post-pubertal women. PORD should be considered in patients with genital abnormalities and skeletal malformations. COC could effectively inhibit recurrent ovarian cysts in PORD women, routine ovarian cystectomy should be avoided to protect ovarian fertility. c.1370G>A might be the most common type of POR gene mutation in China.

Objective:To investigate the clinical manifestations, genotype characteristics and treatment of cytochrome P450 oxidoreductase deficiency (PORD) patients with 46,XX karyotype in China.Methods:The clinical data of twelve patients with 46, XX karyotype who were admitted to Peking Union Medical College Hospital from January 2021 to March 2024 and finally diagnosed as PORD by whole exome sequencing were retrospectively analyzed. The clinical manifestations, hormone characteristics and genetic etiology of the disease were summarized.Results:A total of 12 women were diagnosed with PORD, including one young girl with ambiguous genitalia and skeletal malformations at an early stage, and eleven adolescence and adult patients with menstrual disorders and (or) ovarian cysts. Five patients presented with male genitals. Ten patients presented with varying degrees of skeletal deformity. Eleven patients with abnormal menstruation and (or) ovarian cysts presented with unilateral or bilateral multilocular ovarian enlargement, and the larger patient′s ovarian size reached 12.0 cm×7.7 cm. The ovarian cysts disappeared after 3-6 months of combined oral contraceptives (COC) treatment, and the patients were followed up regularly after drug withdrawal and no recurrences were observed during the follow-up period of 1-2 years. Progesterone levels were elevated in all patients. All patients carried biallelic mutations of POR gene. The most common mutation was c.1370G>A in exon 11, which occurred in 11/12 patients. Two novel nonsense mutations, c.1684dupG and c.2040dupC were identified.Conclusions:PORD is one of the causes of unexplained menstrual disorders and ovarian cysts in post-pubertal women. PORD should be considered in patients with genital abnormalities and skeletal malformations. COC could effectively inhibit recurrent ovarian cysts in PORD women, routine ovarian cystectomy should be avoided to protect ovarian fertility. c.1370G>A might be the most common type of POR gene mutation in China.

Neoadjuvant chemotherapy has become an indispensable weapon against high-risk resectable cancers, which benefits from tumor downstaging. However, the utility of chemotherapeutics alone as a neoadjuvant agent is incapable of generating durable therapeutic benefits to prevent postsurgical tumor metastasis and recurrence. Herein, a tactical nanomissile (TALE), equipped with a guidance system (PD-L1 monoclonal antibody), ammunition (mitoxantrone, Mit), and projectile bodies (tertiary amines modified azobenzene derivatives), is designed as a neoadjuvant chemo-immunotherapy setting, which aims at targeting tumor cells, and fast-releasing Mit owing to the intracellular azoreductase, thereby inducing immunogenic tumor cells death, and forming an in situ tumor vaccine containing damage-associated molecular patterns and multiple tumor antigen epitopes to mobilize the immune system. The formed in situ tumor vaccine can recruit and activate antigen-presenting cells, and ultimately increase the infiltration of CD8⁺ T cells while reversing the immunosuppression microenvironment. Moreover, this approach provokes a robust systemic immune response and immunological memory, as evidenced by preventing 83.3% of mice from postsurgical metastasis or recurrence in the B16-F10 tumor mouse model. Collectively, our results highlight the potential of TALE as a neoadjuvant chemo-immunotherapy paradigm that can not only debulk tumors but generate a long-term immunosurveillance to maximize the durable benefits of neoadjuvant chemotherapy.

Objective To establish the chemical synthesis of the active ingredient rosavin of Rhodiola rosea. Methods β-D-pentaacetylglucose, 1-hydroxy-2,3,4-triacetylarabinose and cinnamyl alcohol were used as starting materials. The target compound was prepared by 1-position selective of β-D-pentaacetylglucose deacetylation, glycosylation reaction, glucose 6-OH selective protection and deprotection and other 8-step reactions. Results The target product, rosavage, was successfully obtained with high yield. The structure was confirmed by ESI-MS, ¹H-NMR and ¹³C-NMR. The protection of 6-OH with high selectivity and high yield of tert-butyldiphenyl chlorosilane played a vital role in the synthesis process,. Conclusion The synthetic route has the advantages of simple operation, high yield, and good safety.

OBJECTIVE: To analyze the current status of diagnosis and management of acute appendicitis (AA) in China. METHODS: Questionnaire survey was used to retrospectively collect data of hospitalized patients with AA from 43 medical centers nationwide in 2017 (Sort by number of cases provided: Jinling Hospital of Medical School of Nanjing University, The First Affiliated Hospital of Xinjiang Medical University, Lu'an People's Hospital, Tengzhou Central People's Hospital, Dalian Central Hospital, The Affiliated Hospital of Xuzhou Medical University, Dongying People's Hospital, Jinjiang Hospital of Traditional Chinese Medicine, Huangshan Shoukang Hospital, Xuyi People's Hospital, Nanjing Jiangbei People's Hospital, Lanzhou 940th Hospital of PLA, Heze Municipal Hospital, The First College of Clinical Medical Science of China Three Gorges University, Affiliated Jiujiang Hospital of Nanchang University, The Second People's Hospital of Hefei, Affiliated Central Hospital of Shandong Zaozhuang Mining Group, The Third People's Hospital of Kunshan City, Xuzhou First People's Hospital, The 81st Group Army Hospital of PLA, Linyi Central Hospital, The General Hospital of Huainan Eastern Hospital Group, The 908th Hospital of PLA, Liyang People's Hospital, The 901th Hospital of Joint Logistic Support Force, The Third Affiliated Hospital of Chongqing Medical University, The Fourth Hospital of Jilin University, Harbin Acheng District People's Hospital, The First Affiliated Hospital of Zhengzhou University, Nanjing Luhe People's Hospital, Taixing Municipal People's Hospital, Baotou Central Hospital, The Affiliated Hospital of Nantong University, Linyi People's Hospital, The 72st Group Army Hospital of PLA, Zaozhuang Municipal Hospital, People's Hospital of Dayu County, Taixing City Hospital of Traditional Chinese Medicine, Suzhou Municipal Hospital, Beijing Guang'anmen Hospital, Langxi County Hospital of Traditional Chinese Medicine, Nanyang Central Hospital, The Affiliated People's Hospital of Inner Mongolia Medical University).The diagnosis and management of AA were analyzed through unified summary. Different centers collected and summarized their data in 2017 and sent back the questionnaires for summary. RESULTS: A total of 8 766 AA patients were enrolled from 43 medical centers, including 4 711 males (53.7%) with median age of 39 years and 958 (10.9%) patients over 65 years old. Of 8 776 patients, 5 677 cases (64.6%) received one or more imaging examinations, and the other 3 099 (35.4%) did not receive any imaging examination. A total of 1 858 (21.2%) cases received medical treatment, mainly a combination of nitroimidazoles (1 107 cases, 59.8%) doublet regimen, followed by a single-agent regimen of non-nitroimidazoles (451 cases, 24.4%), a nitroimidazole-free doublet regimen (134 cases, 7.2%), a triple regimen of combined nitroimidazoles (116 cases, 6.3%), nitroimidazole alone (39 cases, 2.1%) and nitroimidazole-free triple regimen (3 cases, 0.2%). Of the 6 908 patients (78.8%) who underwent surgery, 4 319 (62.5%) underwent laparoscopic appendectomy and 2589 (37.5%) underwent open surgery. Ratio of laparotomy was higher in those patients under 16 years old (392 cases) or over 65 years old (258 cases) [15.1%(392/2 589) and 10.0%(258/2 589), respectively, compared with 8.5%(367/4 316) and 8.0%(347/4 316) in the same age group for laparoscopic surgery, χ²=91.415, P<0.001; χ²=15.915,P<0.001]. Patients with complicated appendicitis had higher ratio of undergoing open surgery as compared to those undergoing laparoscopic surgery [26.7%(692/2 589) vs. 15.6%(672/4 316), χ²=125.726, P<0.001].The cure rates of laparoscopic and open surgery were 100.0% and 99.8%(2 585/2 589) respectively without significant difference (P=0.206). Postoperative complication rates were 4.5%(121/2 589) and 4.7%(196/4 316) respectively, and the difference was not statistically significant (χ²=0.065, P=0.799). The incidence of surgical site infection was lower (0.6% vs. 1.7%, χ²=17.315, P<0.001), and hospital stay was shorter [6(4-7) days vs. 6(5-8) days, U=4 384 348.0, P<0.001] in the laparoscopic surgery group, while hospitalization cost was higher (median 12 527 yuan vs. 9 342 yuan, U=2 586 809.0, P<0.001). CONCLUSIONS The diagnosis of acute appendicitis is still clinically based, supplemented by imaging examination. Appendectomy is still the most effective treatment at present. Laparoscopic appendectomy has become the main treatment strategy, but anti-infective drugs are also very effective.
Acute Disease ; Adolescent ; Adult ; Aged ; Anti-Bacterial Agents ; therapeutic use ; Appendectomy ; Appendicitis ; diagnosis ; therapy ; China ; Female ; Health Care Surveys ; Humans ; Laparoscopy ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult

BACKGROUND: There is no report on the treatment of suppurative discitis with posterior microendoscopic discectomy, antibiotic artificial bone implantation and one-stage percutaneous pedicle screw fixation. OBJECTIVE: To evaluate the clinical effectiveness of posterior microendoscopic debridement, antibiotic artificial bone implantation and one-stage percutaneous pedicle screw fixation for pyogenic spondylodiscitis. METHODS: Thirty-one patients with suppurative discitis admitted at the Department of Spinal Surgery, the First Affiliated Hospital of Guangzhou Medical University from January 2014 to December 2017, including 17 males and 14 females, aged 28-78 years, were included. All the patients underwent posterior microendoscopic lesion clearance and antibiotic artificial bone grafting and one-stage percutaneous pedicle screw fixation. The erythrocyte sedimentation rate and C-reactive protein levels were detected at postoperative follow-up. The Visual Analog Scale and the Japanese Orthopaedic Association scores were used for detection. RESULTS AND CONCLUSION: (1) All the surgical operations of the 31 patients were successfully completed and all patients had immediate relief of low back pain and lower extremity radiation pain. They were able to move ground wearing a waistband at 1-4 days postoperatively. (2) Thirty-one patients were followed up for 9-18 months. All patients had a significant decrease in C-reactive protein and erythrocyte sedimentation rate at 1 week after surgery, and C-reactive protein and erythrocyte sedimentation rate were in the normal range at 1, 3, and 6 months postoperatively. (3) The Visual Analog Scale scores of all patients at 1 week of follow-up were significantly lower than those before surgery (P < 0.05) , and the Japanese Orthopaedic Association scores were significantly higher than those before surgery (P < 0.05) . (4) In the follow-up examination of CT and MRI, there was no recurrence, pseudoarticular formation or internal fixation loosening. (5) These results suggest that posterior microendoscopic discectomy, antibiotic artificial bone implantation combined with one-stage percutaneous pedicle screw fixation for treating suppurative discitis can result in little trauma, few bleeding and rapid pain relief, and patients can move to the ground early. The operation method has a good clinical effect.