Objective To explore factors associated with early postoperative hormonal remission in patients with prolactinoma and to develop prediction models based on clinical and radiological features. Methods Data from 107 patients with prolactinoma who underwent transsphenoidal surgery at The First People’s Hospital of Huai’an, Nanjing Medical University between January 2020 and December 2024 was collected, included general clinical characteristics, preoperative laboratory indicators, and imaging features. Based on whether early postoperative prolactin (PRL) levels normalized, patients were divided into a remission group (n=76) and a non-remission group (n=31). Univariate logistic regression was used for preliminary evaluation of candidate variables, followed by LASSO regression for feature selection. Multiple machine learning models were constructed, including logistic regression, random forest, support vector machine, K-nearest neighbors, naive Bayes, decision tree, neural network, and gradient boosting decision tree (GBDT). All models were trained and evaluated using ten-fold cross-validation, with comprehensive assessment of model performance based on the area under the ROC curve (AUC), accuracy, sensitivity, specificity, precision, and F1 score. Results The maximum diameter of tumors in the non remission group was larger than that in the remission group (P=0.019), and the incidence of tumor stroke and preoperative PRL levels were significantly higher than those in the remission group (P＜0.001). Univariate analysis showed that sex, maximum tumor diameter, tumor stroke, and preoperative PRL levels were influencing factors for early postoperative hormone response in patients with prolactinoma (P＜0.05). The comparison results of machine learning models show that the neural network model performs the best (AUC=0.921) and has good clinical application value, followed by the GBDT model (AUC=0.893) and the support vector machine model (AUC=0.884). Other models also show certain predictive ability. Conclusions Sex, preoperative PRL levels, maximum tumor diameter, Hounsfield unit value, and tumor stroke are important factors affecting early hormone response after prolactinoma surgery. The machine learning model constructed based on the above variables has good predictive performance, and performs the best and has good clinical application value.

Mitochondrial DNA (mtDNA) acts as a bridge between tissue damage and immune activation, triggering innate and adaptive immune responses through multiple signaling pathways. This review introduces the biological characteristics of mtDNA and its release mechanism in solid organ transplantation-related injuries, discusses the immune responses it mediates, and further explores its relationship with graft damage and rejection in different types of solid organ transplantation. By deeply understanding the biological functions of mtDNA, new ideas are expected to be provided for promoting marginal organ repair, optimizing graft monitoring methods, and developing targeted intervention strategies for transplant-related immune responses.

Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Objective To investigate the characteristics of peripheral blood in the treatment of aplastic anemia(AA)with Bushen Shengxue Method and Yiqi Yangxue Method combined with Western medicine.Methods Totally 492 AA patients who were treated in 19 centers including Xiyuan Hospital China Academy of Chinese Medical Sciences from September 2018 to March 2021 were selected,and were randomized into three groups:161 cases in the Bushen Shengxue group,164 cases in the Yiqi Yangxue group,and 167 cases in the control group.All three groups were orally administered cyclosporine and androgens.Bushen Shengxue group was given Bushen Shengxue Granules,Yiqi Yangxue group was given Yiqi Yangxue Granules,and the control group was given placebo(half dosage of Bushen Shengxue granules).The general data,overall efficacy,and peripheral blood at the 1st month,the 4th month,and 6th month after treatment were analyzed.Results The total effective rate of Bushen Shengxue group was 98.8％(159/161),which was significantly higher than that of Yiqi Yangxue group(79.9％)and the control group(61.7％),with statistical significance(P＜0.001);The total effective rate of Yiqi Yangxue group was significantly higher than that of the control group(P＜0.001).Compared with before treatment,the hemoglobin(HGB)levels of all three groups of patients significantly increased after treatment(P＜0.001,P＜0.01),and the platelet levels of Bushen Shengxue group and the control group significantly increased after treatment(P＜0.001);after treatment,the HGB levels in the three groups were ranked from high to low as the Bushen Shengxue group,Yiqi Yangxue group and the control group(P＜0.01).25％of patients had HGB levels exceeding 20％of baseline values,Bushen Shengxue group took 1 month,while Yiqi Yangxue group and control group took 4 months;25％of patients had an increase in HGB levels exceeding 50％of the baseline value,Bushen Shengxue group took 6 months,while Yiqi Yangxue group and control group took more than 6 months.At 6 months,the number of patients with HGB elevation exceeding 20％and 50％of baseline values in Bushen Shengxue group was higher than that in Yiqi Yangxue group and the control group(P＜0.05,P＜0.001).25％of patients had white blood cell elevation exceeding 50％of the baseline value,Bushen Shengxue group took 4 months,Yiqi Yangxue group took 6 months,and the control group took more than 6 months.25％of patients showed an increase in platelet levels exceeding 100％of the baseline value,Bushen Shengxue group took 4 months,while Yiqi Yangxue group and control group took 6 months;at 6 months,the number of patients in Bushen Shengxue group and Yiqi Yangxue group with platelet elevation exceeding 20％of the baseline value was significantly higher than that in the control group(P＜0.01,P＜0.05).Conclusion Bushen Shengxue method combined with Western medicine intreating AA is better than the method of Yiqi Yangxue method combined with Western medicine.In terms of improving HGB,it is reflected in shortening the recovery time and increasing the number of beneficiaries,and the dosage can affect the recovery time and the number of beneficiaries at the same time;in terms of improving white blood cell and platelet,it is reflected in shortening the recovery time,and the dosage can affect the recovery time.

OBJECTIVE To compare the ability of ultra-high-resolution CT(U-HRCT)and multi-slice spiral CT(MSCT)to display key vocal transmission structures in the middle ear.METHODS Subjects with normal middle ear structures who underwent 0.1 mm layer thickness U-HRCT and 0.625 mm layer thickness MSCT scans at the same time in Beijing Friendship Hospital affiliated to Capital Medical University from December 2019 to August 2024 were retrospectively enrolled.Two experienced head and neck radiologists reconstruct standard transsectional,coronal images based on the thinnest layer thickness.According to the 5-point method,16 key sound transmission structures of the middle ear,including malleus,incus and stapes,as well as joints,ligaments and tendons,were evaluated for image quality scoring.The standard deviation(SD)value,signal noise ratio(SNR),and contrast noise ratio(CNR)of bone in the malleus region and intratympanic gas were measured and calculated on the two examination images.RESULTS Thirty patients(47 sides)with normal middle ear structure were included,including 18 males and 12 females.The two physicians compared the results of U-HRCT in showing malleus head,malleus neck,malleus handle,incus body,long process,and short process,5 points accounted for 100%,and the 5-point scores of incudomalleolar joint space,incudostapedial joint space,stapes footplate and annular ligament were 100%,98.29%,75.83%and 77.83%,respectively,which were significantly higher than those of MSCT(P<0.001).In addition,U-HRCT showed higher scores for lenticular process,stapes head,anterior arch of stapes,posterior arch of stapes,annular ligament,stapes muscle,and tendo musculi tensoris tympani than MSCT(P<0.001),and the lenticular process showed a 100%display rate.There was no significant difference in the SNR between the two groups(P>0.05),but the SD value of the malleus in U-HRCT was 161.6±36.4,which was significantly lower than that in MSCT(297.8±128.1),and the difference was statistically significant(P<0.001).CONCLUSION U-HRCT can clearly visualize the key sound transmission structures of the middle ear,and its visualization ability is significantly better than that of MSCT.

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

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Cyclin-dependent kinase 9 (CDK9) is a member of the transcription CDK subfamily and plays a role in transcriptional regulation. Selective CDK9 degraders possess potent clinical advantages over reversible CDK9 inhibitors. Herein, we report the first ATG101-recruiting selective CDK9 degrader, AZ-9, based on the hydrophobic tag kinesin degradation technology. AZ-9 showed significant degradation effects and selectivity toward other homologous cell cycle CDKs in vitro and in vivo, which could also affect downstream related phenotypes. Mechanism research revealed that AZ-9 recruits ATG101 to initiate the autophagy-lysosome pathway, and forms autophagosomes through the recruitment of LC3, which then fuses with lysosomes to degrade CDK9 and the partner protein Cyclin T1. These dates validated the existence of non-proteasomal degradation pathway of hydrophobic driven protein degradation strategy for the first time, which might provide research ideas for chemical induction intervention on other types of pathogenic proteins.

OBJECTIVES: To investigate the effect of curcumin on lipid metabolism in non-small cell lung cancer (NSCLC) and its molecular mechanism. METHODS: The inhibitory effect of curcumin (0-70 μmol/L) on proliferation of A549 and H1299 cells was assessed using MTT assay, and 20 and 40 μmol/L curcumin was used in the subsequent experiments. The effect of curcumin on lipid metabolism was evaluated using cellular uptake assay, wound healing assay, triglyceride (TG)/free fatty acid (NEFA) measurements, and Oil Red O staining. Western blotting was performed to detect the expressions of PGC-1α, PPAR-α, and HIF-1α in curcumin-treated cells. Network pharmacology was used to predict the metabolic pathways, and the results were validated by Western blotting. In a nude mouse model bearing A549 cell xenograft, the effects of curcumin (20 mg/kg) on tumor growth and lipid metabolism were assessed by measuring tumor weight and observing the changes in intracellular lipid droplets. RESULTS: Curcumin concentration-dependently inhibited the proliferation of A549 and H1299 cells and significantly reduced TG and NEFA levels and intracellular lipid droplets. Western blotting revealed that curcumin significantly upregulated PGC-1α and PPAR‑α expressions in the cells. KEGG pathway enrichment analysis predicted significant involvement of the HIF-1 signaling pathway in curcumin-treated NSCLC, suggesting a potential interaction between HIF-1α and PPAR‑α. Western blotting confirmed that curcumin downregulated the expression of HIF-1α. In the tumor-bearing mice, curcumin treatment caused significant reduction of the tumor weight and the number of lipid droplets in the tumor cells. CONCLUSIONS Curcumin inhibits NSCLC cell proliferation and lipid metabolism by downregulating the HIF-1α pathway.
Curcumin/pharmacology* ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Animals ; Lipid Metabolism/drug effects* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Mice, Nude ; Down-Regulation ; Mice ; Cell Proliferation/drug effects* ; Cell Line, Tumor ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; PPAR alpha/metabolism* ; Signal Transduction/drug effects* ; A549 Cells