The China birth cohort study (CBCS) is a prospective longitudinal, mega-cohort study and the first national-based birth cohort study, aiming to establish a birth cohort covering representative geographical areas of the whole of China to investigate risk factors for birth defects and develop strategies for their reduction. Pregnant women who are of Chinese nationality, are 6–13⁺⁶ weeks of gestation, plan to attend the routine antenatal examination and deliver in the study site, and give their informed, written consent are eligible to participate in this study. All participants are followed-up through an in-person interview at 20–23⁺⁶ weeks and again at 28–33⁺⁶ weeks of gestation, and at delivery, respectively. CBCS has been divided into three phases from 20th November 2017 to 31st December 2021, and the first two phases have now been completed on 29th February 2020, enrolling 120 377 eligible pregnant women during this period. During the same period a total of 40 837 participants had been followed up to the end of pregnancy. Study recruitment will continue until December 2021 to achieve the target of 500 000 participants. Meanwhile, biological samples including peripheral blood, amniocytes, cord blood, placenta, or umbilical cord tissue have been collected from participants according to various conditions. The incidence of birth defects in this group is 2.5% and congenital heart disease is the most common type of birth defect seen so far. A website is in the advanced stages of planning, to allow seamless data transfer and facilitate collaboration with groups around the world.

Tumor-associated macrophages (TAMs) play a pivotal role in immune suppression, tumor progression, and metastasis within the tumor microenvironment (TME) of ovarian cancer. While TAMs are known to promote T-cell dysfunction, the precise molecular mechanisms governing this process remain poorly understood. Here, we performed an integrated analysis of six high-grade serous ovarian cancer (HGSOC) single-cell sequencing datasets to investigate the molecular and functional diversity of TAMs in HGSOC. We identified an SPP1⁺ TAM subpopulation enriched in HGSOC and strongly associated with poor prognosis. These macrophages promoted T-cell exhaustion via the SPP1-CD44 axis, which emerged as the principal mediator of immune suppression. Functional assays demonstrated that SPP1 secreted by TAMs drove T-cell exhaustion, weakening anti-tumor immunity. Blocking either SPP1 or CD44 effectively reversed T-cell exhaustion, restored CD8⁺ T-cell functionality, and suppressed tumor growth in vivo. Furthermore, molecular docking and dynamics simulations identified nilotinib as a potential SPP1 inhibitor, exhibiting strong binding affinity and stability. In vitro assays confirmed that nilotinib reduced PD-1 expression in Jurkat cells induced by M2-type macrophages, underscoring its therapeutic potential in reversing T-cell exhaustion in ovarian cancer. The research demonstrates that SPP1⁺ TAMs drive immune suppression and T-cell exhaustion in ovarian cancer via the SPP1-CD44 axis, highlighting this pathway as a promising therapeutic target for reprogramming the immune microenvironment and improving patient outcomes.

Objective: There is a high burden of both diabetes (DM) and tuberculosis (TB) in China. We evaluated the association between DM and the pattern of disease, 2‐month sputum smear conversion and treatment outcomes of patients with TB in Guangzhou, China.Method: All patients registered with TB from September 2011 to June 2012 were screened for DM and assessed for treatment outcomes in relation to presence or absence of DM and quality of DM control using patient registers, treatment cards and electronic record systems.Results: There were 1589 patients with TB of whom 189 (12%) had DM. Among those with DM, there was a significantly higher proportion of men, persons aged 35 years and older and persons with smear‐positive pulmonary tuberculosis (PTB) (P < 0.01). In patients with DM and new smear‐positive PTB, there was a higher proportion who had positive sputum smears at 2 months (21.7% vs. 5.6%, RR 3.85, 95%CI 2.24–6.63), who were lost‐to‐follow‐up (5.2% vs. 1.7%, RR 3.23, 95%CI 1.08–9.63) and who failed treatment (10.3% vs. 2.3%, RR 4.46, 95%CI 1.96–10.18) compared with patients who had no DM. There was no significant association between these adverse outcomes and DM control as measured by 2 and 6‐month fasting blood glucose.Conclusion: Diabetes mellitus in new smear‐positive patients with PTB was associated with failure to sputum smear convert at 2 months and adverse treatment outcomes of loss‐to‐follow‐up and failure. Further research is needed to understand the reasons for these findings and to determine whether the current length of treatment of 6 months is adequate.

Drug response to PD-1/PD-L1 blockade: based on biomarkers Qi Chen, Tianhe Li, Wentao Yue Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, People’s Republic of China In recent years, immunotherapies targeting programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) have provided great hopes for patients with cancer. A successful anti-PD-1/PD-L1 therapy includes not only the elimination of immunosuppressive tumor cells but also the rejuvenation of exhausted T cells. Nevertheless, the efficacy of therapy is still low, so that biomarker-driven therapy has attracted more and more attention to identify patients who are likely to benefit from therapy and to reduce unnecessary disease progression. While many studies have focused on characteristics of tumor biopsies, biomarkers linked to T cell exhaustion and rejuvenation have just become new hot spots in drug response studies. However, no biomarker is perfect in drug response prediction currently, so there is an urgent need for other biomarkers to compensate for the deficiency. In this review, we summarize some approved and candidate biomarkers predictive of drug response before and during PD-1/PD-L1 blockade, including those characterizing responsive or suppressive tumor cells and those evaluating the T cell rejuvenation. Overall, we set up a comprehensive network of biomarkers of tumor characteristics and T cell rejuvenation, predicting drug response before and during anti-PD-1/PD-L1 therapies. Keywords: PD-1, PD-L1, biomarker, network, tumor, T cell rejuvenation