Ginkgo biloba, an ancient relict plant, holds a lengthy medicinal tradition in China. The leaves and seeds of this remarkable species contain flavonoids, a class of active compounds that offer a multitude of pharmacological advantages. The understanding of the synthesis process of these flavonoids can be deepened substantially by elucidating their biosynthetic pathway and metabolic regulation mechanisms. This can thereby provide a foundation for achieving precise regulation of flavonoid biosynthesis, which is of great significance for improving the production efficiency and quality of flavonoids in G. biloba. This review comprehensively summarizes research advancements in metabolomics, genomics, and transcriptomics of flavonoids in G. biloba, aiming to establish a thorough academic framework. It examines key enzymes in the biosynthetic pathway of flavonoids in G. biloba and their functions, highlighting their crucial roles in flavonoid production. Additionally, it outlines transcriptional regulation mechanisms associated with flavonoid in G. biloba biosynthesis, focusing on transcription factors responsive to environmental cues and their regulatory networks that modulate flavonoid gene expression. These insights offer a theoretical foundation for precise control of G. biloba flavonoid production. By amalgamating these diverse research findings, this review aims to establish a robust theoretical groundwork for future studies on biosynthesis and efficient utilization of flavonoids in G. biloba.
Ginkgo biloba/chemistry* ; Flavonoids/biosynthesis* ; Gene Expression Regulation, Plant ; Plant Proteins/genetics* ; Biosynthetic Pathways

Objective:To analyze the current adoption of palliative care by patients with unresectable metastatic colorectal cancer (mCRC) in China.Methods:From 1 March 2023 to 30 June 2023, a questionnaire survey was conducted by random sampling. An exclusive research platform for the Blue Book on Clinical Diagnosis and Treatment of Metastatic Colorectal Cancer. An online questionnaire was sent to medical oncologists (including chief physicians, associate chief physicians, attending physicians and residents) in general hospitals and oncology hospitals in four major regions of East, Central, South and Northeast China. The questionnaire contained 28 questions requesting basic information about doctors, the number of patients with mCRC, the status of treatment from first to fourth line and beyond, points concerning treatment of pain in patients with mCRC, and expectations for the future. A medical team was responsible for the quality control of data collected, whereas statisticians performed the data cleaning and sorting and statistical analysis.Results:A total of 300 clinical questionnaires were collected, including 217 (72%) from doctors in general hospitals and 83 (28%) from doctors in oncology hospitals. Senior physicians (including associate chief physicians and chief physicians) accounted for 65% of the respondents, attending physicians 30%, and residents 5%. Within 3 months (average for each month), 46.4±26.6% patients were diagnosed with recurrent or unresectable mCRC by each physician, 51.6±26.8% of the patients being in cancer hospitals and 44.4±26.3% in general hospitals. One hundred percent of patients receiving first-line treatment received palliative care, as did 80.3% of those receiving second-line treatment, 58.2% of those receiving third-line treatment, and 35.1% of those receiving ≥fourth-line treatment. The primary factor governing selection of first-line treatment was guideline recommendations, whereas comorbidities and the patients' physical status dictated second line to fourth line treatment. Standard first-line treatment was administered to 93.8% of eligible patients, standard second-line treatment to 94.3%; and standard third-line treatment to 73.5%. First-line therapy included targeted therapy in 63.6% of patients and immunotherapy in 2.8%; second-line therapy included targeted therapy in 63.0% of patients and immunotherapy in 2.0%; third-line therapy included targeted therapy in 59.2% of patients and immunotherapy in 2.2%; and fourth-line therapy included targeted therapy in 48.7% of patients and immunotherapy in 3.1%. First-line treatment lasted an average of 9.6 months, second-line treatment 6.7 months, third-line treatment 4.9 months, and fourth-line treatment 3.7 months. More than 70% of the patients maintained a good quality of life after receiving first and second-line treatment and more than 60% of them had ECOG performance scores of 0–1. After receiving third- and fourth-line treatment, 50%–60% of patients maintained a good quality of life and 40%–50% of them maintained ECOG performance scores of 0–1. The survey also revealed that the main deficiencies in treatment were limited effectiveness of third-line treatment, insufficient availability and opportunity for clinical research, popularity of new drugs or new drug combination strategies, and limited channels for participation in multidisciplinary diagnosis and treatment. Clinicians reported looking forward to participating in more clinical research on new drugs, hearing about the experience of experts in the field, and discovery of new targets and new drugs that increased the options for posterior line treatment of colorectal cancer.Conclusions:This report objectively summarizes the current situation, treatment difficulties, and expectations of frontline physicians concerning management of mCRC, thus providing a basis for decision-making and future direction for the diagnosis and research on treatment of mCRC.

Objective:To analyze the current adoption of palliative care by patients with unresectable metastatic colorectal cancer (mCRC) in China.Methods:From 1 March 2023 to 30 June 2023, a questionnaire survey was conducted by random sampling. An exclusive research platform for the Blue Book on Clinical Diagnosis and Treatment of Metastatic Colorectal Cancer. An online questionnaire was sent to medical oncologists (including chief physicians, associate chief physicians, attending physicians and residents) in general hospitals and oncology hospitals in four major regions of East, Central, South and Northeast China. The questionnaire contained 28 questions requesting basic information about doctors, the number of patients with mCRC, the status of treatment from first to fourth line and beyond, points concerning treatment of pain in patients with mCRC, and expectations for the future. A medical team was responsible for the quality control of data collected, whereas statisticians performed the data cleaning and sorting and statistical analysis.Results:A total of 300 clinical questionnaires were collected, including 217 (72%) from doctors in general hospitals and 83 (28%) from doctors in oncology hospitals. Senior physicians (including associate chief physicians and chief physicians) accounted for 65% of the respondents, attending physicians 30%, and residents 5%. Within 3 months (average for each month), 46.4±26.6% patients were diagnosed with recurrent or unresectable mCRC by each physician, 51.6±26.8% of the patients being in cancer hospitals and 44.4±26.3% in general hospitals. One hundred percent of patients receiving first-line treatment received palliative care, as did 80.3% of those receiving second-line treatment, 58.2% of those receiving third-line treatment, and 35.1% of those receiving ≥fourth-line treatment. The primary factor governing selection of first-line treatment was guideline recommendations, whereas comorbidities and the patients' physical status dictated second line to fourth line treatment. Standard first-line treatment was administered to 93.8% of eligible patients, standard second-line treatment to 94.3%; and standard third-line treatment to 73.5%. First-line therapy included targeted therapy in 63.6% of patients and immunotherapy in 2.8%; second-line therapy included targeted therapy in 63.0% of patients and immunotherapy in 2.0%; third-line therapy included targeted therapy in 59.2% of patients and immunotherapy in 2.2%; and fourth-line therapy included targeted therapy in 48.7% of patients and immunotherapy in 3.1%. First-line treatment lasted an average of 9.6 months, second-line treatment 6.7 months, third-line treatment 4.9 months, and fourth-line treatment 3.7 months. More than 70% of the patients maintained a good quality of life after receiving first and second-line treatment and more than 60% of them had ECOG performance scores of 0–1. After receiving third- and fourth-line treatment, 50%–60% of patients maintained a good quality of life and 40%–50% of them maintained ECOG performance scores of 0–1. The survey also revealed that the main deficiencies in treatment were limited effectiveness of third-line treatment, insufficient availability and opportunity for clinical research, popularity of new drugs or new drug combination strategies, and limited channels for participation in multidisciplinary diagnosis and treatment. Clinicians reported looking forward to participating in more clinical research on new drugs, hearing about the experience of experts in the field, and discovery of new targets and new drugs that increased the options for posterior line treatment of colorectal cancer.Conclusions:This report objectively summarizes the current situation, treatment difficulties, and expectations of frontline physicians concerning management of mCRC, thus providing a basis for decision-making and future direction for the diagnosis and research on treatment of mCRC.

Objective:To explore the clinical application and triage management value of using blood circulating cell-free DNA (cfDNA) (cysteine dioxygenase type 1 gene, CDO1, and Homeobox protein A9 gene, HOXA9) hypermethylation level to detect and diagnose ovarian cancer.Methods:A case-control study was conducted on patients who went for surgery at Chengdu Womens and Childrens Central Hospital from November 2022 to October 2023. Blood samples were collected before surgery for evaluation of cancer antigen 125 (CA125), human epididymis protein 4 (HE4), risk of ovarian malignancy algorithm (ROMA) score, and DNA methylation testing. The basic clinical information, biomarkers, and transvaginal ultrasound (TVS) information were collected simultaneously. Information from a total of 151 patients was collected, including 122 cases with benign pathology and 29 ovarian cancer cases. The pathologic diagnosis of ovarian tissue was defined as the gold standard. The multivariate logistic regression analysis was used to identify high-risk factors for ovarian cancer. The clinical efficacy of DNA methylation detection for ovarian cancer was analyzed using the area under curve (AUC).Results:The results showed that the age, menopausal status, CA125 and HE4 detection, ROMA score, positivity rate of CDO1 gene and HOXA9 gene single or combined testing in ovarian cancer patients were higher than those in the benign group and showed significant differences ( P<0.05). Among these detection protocols, the AUC of CDO1 and HOXA9 dual gene methylation testing for ovarian cancer was the highest at 0.936 (95% CI, 0.878-0.994), with 89.7% (95% CI 73.6%-96.4%) sensitivity and 97.5% (95% CI 93.0%-99.2%) specificity, respectively. The positive detection rate of CDO1 and HOXA9 dual gene methylation in early ovarian cancer FOGO I-II stage is 12/14 higher than other tests. Conclusion:Blood cfDNA methylation detection, a simple, non-invasive, and highly sensitive detection method, is superior to the current ovarian cancer testing in the risk assessment and early detection.

Objective To analyze the characteristics of time in range(TIR)and its relationship with oxidative stress(OS)and insulin resistance status(HOMA-IR)in patients with type 2 diabetes mellitus(T2DM)and sleep apnea-hypopnea syndrome(OSAHS).Methods According to apnea-hypopnea index(AHI),165 T2DM in patients were divided into simple T2DM group(AHI<5 times/h,n=43),T2DM combine OSAHS mild group(OSAHS-G,5≤AHI<15 times/h,n=51),T2DM combined OSAHS moderate group(OSAHS-M,15≤AHI≤30 times/h,n=40)and T2DM combine OSAHS severe group(OSAHS-S,AHI>30 times/h,n=31).TIR was calculated by dynamic blood glucose monitoring.Superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and other indexes were detected and analyzed.Results Compared with simple T2DM group,the levels of HOMA-IR,8-iso-PGF2a and Ox-LDL were higher in T2DM combined OSAHS-G,OSAHS-M or OSAHS-S group,while the levels of TIR,SOD and GSH-Px were lower(P<0.05).Pearson correlation analysis showed that TIR was positively correlated with the levels of SOD and GSH-Px(P<0.05 or P<0.01),and negatively correlated with the levels of 8-iso-PGF2a,Ox-LDL,HbA1c,HOMA-IR and the severity of OSAHS(P<0.01).Logistic regression analysis showed that TIR,SOD and GSH-Px were protective factors for severe OSAHS in T2DM patients,while 8-iso-PGE2a and Ox-LDL were the risk factors for severe OSAHS.Conclusions The glucose level fluctuates greatly in patients with T2DM and OSAHS.Insulin resistance and oxidative stress are factors that affect the normalization of TIR.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To investigate the application effect of the compound flap transfer in tubularized incised plate (TIP) urethroplasty.Methods:Children with hypospadias who received TIP in the Department of Pediatric Urology, the Affiliated Xuzhou Children’s Hospital of Xuzhou Medical University from January 2018 to March 2022 were prospectively divided into compound flap transfer group (group A) and traditional TIP group (group B) by random number method. Group A was treated with TIP modified by compound flap transfer, and group B was treated with traditional TIP covered with fascia.The improvement of the compound flap transfer for TIP operation is mainly reflected in the multi-layer cover of the new urethra and the free skin embedded in the incision of the penile head. According to the intention-to-treat (ITT) principle, the final full analysis set (FAS) includes both group A and group B. Some patients were excluded from the analysis of the primary endpoint events due to reasons such as loss to follow-up or treatment group switch. Additionally, the final per-protocol set (PPS) consisting of group A and group B, which adheres to the study protocol, is subjected to statistical analysis.Independent sample t-test or Wilcoxon rank sum test was used for average age, the width of the penile head, degree of chordee, length of neourethra, and operative time. The classification of hypospadias, proportion of dorsal tunica albuginea plication, and incidence of postoperative complications were compared using the Chi-square test or Fisher’s exact test, P < 0.05 was considered statistically significant. Results:According to ITT principles, 50 children were included in FAS group A, ranging in age from 8 months to 15 years and 2 months, with an average age of 4 years. Group B included 50 children, ranging in age from 10 months to 14 years and 9 months, with an average age of 4 years and 1 month. Thirty-seven children in PPS group A were included, ranging in age from 1 year 2 months to 12 years 1 month, with an average age of 4 years. Group B consisted of 41 children, ranging in age from 1 year 2 months to 11 years 9 months, with an average age of 4 years 2 months. Statistical analysis showed that no matter FAS set or PPS, there were no statistically significant differences in the mean age, hypospadias type, average penile head width, average penile subcurvature number, number of dorsal tunica albuginea plication, and the average length of plastic neourethra between group A and group B ( P > 0.05). The average operative time of group A was higher than that of group B. The difference was statistically significant ( P < 0.05). The postoperative follow-up was 3 to 48 months, with an average follow-up of 2 years and 3 months. The complication rate of group A was lower than that of group B [10.81% (4/37) vs 29.27% (12/41)], and the difference was statistically significant ( P< 0.05). Urethral fistula occurred in 3 cases (8.11%), respectively and 6 cases (14.63%) in the two groups, the difference was not statistically significant ( P>0.05); urethral stricture occurred in 1 case (2.70%) and 5 cases (12.20%) respectively, the difference was not statistically significant ( P>0.05), There were 0 case and 1 case (2.44%) of urethral orifice descending or urethral dehiscence respectively, and the difference was not statistically significant ( P> 0.05). Conclusion:TIP with an improved compound flap transfer can reduce the overall postoperative complication rate and is worthy of promotion.

Objective:To investigate the application effect of the compound flap transfer in tubularized incised plate (TIP) urethroplasty.Methods:Children with hypospadias who received TIP in the Department of Pediatric Urology, the Affiliated Xuzhou Children’s Hospital of Xuzhou Medical University from January 2018 to March 2022 were prospectively divided into compound flap transfer group (group A) and traditional TIP group (group B) by random number method. Group A was treated with TIP modified by compound flap transfer, and group B was treated with traditional TIP covered with fascia.The improvement of the compound flap transfer for TIP operation is mainly reflected in the multi-layer cover of the new urethra and the free skin embedded in the incision of the penile head. According to the intention-to-treat (ITT) principle, the final full analysis set (FAS) includes both group A and group B. Some patients were excluded from the analysis of the primary endpoint events due to reasons such as loss to follow-up or treatment group switch. Additionally, the final per-protocol set (PPS) consisting of group A and group B, which adheres to the study protocol, is subjected to statistical analysis.Independent sample t-test or Wilcoxon rank sum test was used for average age, the width of the penile head, degree of chordee, length of neourethra, and operative time. The classification of hypospadias, proportion of dorsal tunica albuginea plication, and incidence of postoperative complications were compared using the Chi-square test or Fisher’s exact test, P < 0.05 was considered statistically significant. Results:According to ITT principles, 50 children were included in FAS group A, ranging in age from 8 months to 15 years and 2 months, with an average age of 4 years. Group B included 50 children, ranging in age from 10 months to 14 years and 9 months, with an average age of 4 years and 1 month. Thirty-seven children in PPS group A were included, ranging in age from 1 year 2 months to 12 years 1 month, with an average age of 4 years. Group B consisted of 41 children, ranging in age from 1 year 2 months to 11 years 9 months, with an average age of 4 years 2 months. Statistical analysis showed that no matter FAS set or PPS, there were no statistically significant differences in the mean age, hypospadias type, average penile head width, average penile subcurvature number, number of dorsal tunica albuginea plication, and the average length of plastic neourethra between group A and group B ( P > 0.05). The average operative time of group A was higher than that of group B. The difference was statistically significant ( P < 0.05). The postoperative follow-up was 3 to 48 months, with an average follow-up of 2 years and 3 months. The complication rate of group A was lower than that of group B [10.81% (4/37) vs 29.27% (12/41)], and the difference was statistically significant ( P< 0.05). Urethral fistula occurred in 3 cases (8.11%), respectively and 6 cases (14.63%) in the two groups, the difference was not statistically significant ( P>0.05); urethral stricture occurred in 1 case (2.70%) and 5 cases (12.20%) respectively, the difference was not statistically significant ( P>0.05), There were 0 case and 1 case (2.44%) of urethral orifice descending or urethral dehiscence respectively, and the difference was not statistically significant ( P> 0.05). Conclusion:TIP with an improved compound flap transfer can reduce the overall postoperative complication rate and is worthy of promotion.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*