Objective To systematically analyze the spatiotemporal distribution characteristics and epidemiological trends of tracheal, bronchus, and lung cancer (TBL) disease burden attributed to air pollution globally and in China and the United States from 1990 to 2021, and to assess the patterns of disease burden changes from 2022 to 2031 based on predictive models, providing a scientific basis for formulating targeted TBL prevention and control strategies. Methods Based on the Global Burden of Disease (GBD) 2021 database, we analyzed the disease burden data of TBL attributed to air pollution globally and in China and the United States from 1990 to 2021. R Studio 4.3.2 software was used to analyze the corresponding trends and the Bayesian age-period-cohort (BAPC) prediction model was used to predict the status of the disease burden of TBL attributed to air pollution in the world and in China and the United States from 2022 to 2031. Results In 2021, China had the highest number of deaths and disability-adjusted life years attributed to air pollution (211 400 patients and 4.8947 million person-years), followed by the United States (6 000 patients and 124 300 person-years). The age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life years rate (ASDR) of TBL due to air pollution in the world and in China and the United States showed a decreasing trend. From 1990 to 2021, the ASMR and ASDR of TBL in China due to air pollution were much higher than those in the United States and the global average. In terms of gender, from 1990 to 2021, the disease burden of male patients with TBL attributed to air pollution was much higher than that of female patients. The BAPC prediction model showed that from 2022 to 2031, the ASMR and ASDR of TBL attributed to air pollution showed an upward trend globally, while they showed a downward trend in China and the United States. Conclusion Over the past 30 years, the air pollution-related TBL disease burden in the world and in China and the United States has continued to decline, but China's disease burden is still significantly higher than the global average. The disease burden in men far exceeds that in women, with men and the population aged ≥50 years being high-risk groups. In the future, the global disease trend may reverse and rise, while China and the United States are expected to continuously decline. However, precise prevention and control for high-risk groups remains a key challenge.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Rice (Oryza sativa L.), as a thermophilic crop, is highly susceptible to cold stress during its growth process. Chilling injury at the plumule stage and seedling stage often affects the morphological development and leads to yield reduction of rice. The exploration and utilization of cold tolerance genes are among the most direct and effective approaches to address cold stress in rice. To identify quantitative trait loci (QTLs) associated with cold tolerance at plumule and seedling stages, in this study, we measured the seedling rates and survived seedling rates of the indica rice cultivar 'HZ', the japonica cultivar 'Nekken2', and their 120 recombinant inbred lines (RILs) under cold stress. A previously constructed high-density genetic linkage map was used for the mapping of the QTLs conferring cold tolerance at the plumule and seedling stages. A total of 4 QTLs for plumule-stage cold tolerance and 9 QTLs for seedling-stage cold tolerance were detected, with the maximum limit of detection reaching 5.20. Notably, a genetically overlapping QTL for both plumule and seedling stages was identified on chromosome 8, spanning a physical interval of 24 432 953-25 295 129 bp. Candidate genes within the detected QTL intervals were screened, and quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to analyze the gene expression during the plumule and seedling stages. The results revealed that LOC_Os03g06570, LOC_Os03g07100, LOC_Os06g08280, LOC_Os08g38440, LOC_Os08g39100, and LOC_Os08g39540 exhibited significantly differential expression between the parental lines. These genes were either significantly downregulated or upregulated under cold stress. Among them, the first three gene (LOC_Os03g06570, LOC_Os03g07100, and LOC_Os06g08280) were hypothesized to be key candidates regulating the cold tolerance of rice seedlings, while the latter three genes (LOC_Os08g38440, LOC_Os08g39100, and LOC_Os08g39540) were identified as comprehensive regulators of cold tolerance during both plumule and seedling stages. These findings lay a foundation for the fine mapping and cloning of cold tolerance genes at the plumule and seedling stages, providing valuable insights for breeding cold-tolerant rice varieties.
Quantitative Trait Loci/genetics* ; Oryza/growth & development* ; Seedlings/growth & development* ; Cold Temperature ; Chromosome Mapping ; Gene Expression Regulation, Plant

Human epidermal growth factor receptor 2 (HER2) is a key therapeutic target for breast cancer. With the wide application of anti-HER2 and HER2 antibody-drug conjugates such as trastuzumab, pertuzumab, trastuzumab emtansine, and trastuzumab deruxtecan, the survival of patients with advanced HER2-positive breast cancers have been significantly improved. However, the subsequent drug-induced interstitial lung disease (DILD) has gradually become an important complication affecting the therapeutic effect and safety. However, the clinical understanding of interstitial lung disease (ILD) caused by this type of drugs is still insufficient, the management lacks unified standards, and the molecular mechanism has not been fully clarified. This study, through two clinical cases of severe DILD, explores the pathogenesis, treatment strategies, risk factors and follow-up monitoring requirements of ILD caused by HER2-targeted drugs, providing a scientific basis for optimizing the clinical diagnosis and treatment plan.

Objective:To discuss the construction of a NOD-signal regulatory protein α(SIRPA)gene knock-in mouse model based on clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein(Cas)9 technology,and to provide the reference for the establishment of more advanced humanized mouse models.Methods:Based on CRISPR/Cas9 technology,the NOD-background SIRPA gene was knocked into the BALB/c mouse fertilized eggs,and homozygous mice with stable genotypes(SIRPA-KI mice)were obtained through expansion and breeding for experiments;PCR primers were designed,and mouse genotypes were identified by nucleic acid electrophoresis.The mice were divided into C57BL/6 group,BALB/c group,and SIRPA-KI group according to their strains,and 3 mice with similar ages were randomly selected from each group for experiments.Mature bone marrow-derived macrophages were co-incubated with human CD47-Fc fusion protein,stained with Streptavidin PE/Cy7,and the mean fluorescence intensity(MFI)of PE/Cy7 was detected by flow cytometry to compare the ability of SIRPA in the mice from various groups to bind human CD47 Fc.Each mouse was intravenously injected with 2×10? carboxyfluorescein diacetate,succinimidyl ester(CFSE)-labeled human red blood cells,and the phagocytosis of human red blood cells by macrophages in various groups was detected by in vivo phagocytosis assay.One BALB/c mouse and one SIRPA-KI mouse were randomly selected to induce mature bone marrow-derived macrophages,and the phagocytosis of human red blood cells by macrophages in various groups was detected by in vitro phagocytosis assay.Results:BLAB/c SIRPANOD/NOD homozygous mice were successfully obtained.The flow cytometry results showed that compared with C57BL/6 group,the MFI of the mice in BALB/c group was significantly increased(P<0.01);compared with C57BL/6 group and BALB/c group,the MFI of the mice in SIRPA-KI group was significantly increased(P<0.01).The in vivo phagocytosis assay results showed that the macrophages in C57BL/6 group exhibited the fastest overall clearance rate of human red blood cells;at 6 h of macrophage phagocytosis,compared with SIRPA-KI group,the residual percentage of the human red blood cells in C57BL/6 group was significantly decreased(P<0.01)and was closed to 0%;compared with SIRPA-KI group,the residual percentage of the human red blood cells in BALB/c group was significantly decreased(P<0.05).The in vitro phagocytosis assay results showed that the macrophages in BALB/c group significantly phagocytosed the human red blood cells,with a high phagocytic index of 30.7%;compared with BALB/c group,the phagocytic index of the macrophages in SIRPA-KI group was significantly decreased(P<0.01).Conclusion:The study successfully constructs a mouse model with enhanced affinity for human CD47 and significantly inhibited phagocytosis of human red blood cells by knocking the NOD-background SIRPA gene into the BALB/c strain using CRISPR/Cas9 technology,providing a superior human cell xenotransplantation efficiency.

The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.

Objective:To investigate the iodine nutrition status of children aged 8 - 10 and pregnant women in Xining City, Qinghai Province.Methods:From 2019 to 2021, a stratified cluster sampling method was used to divide 7 counties (districts) under the jurisdiction of Xining City, Qinghai Province into 5 sampling areas according to east, west, south, north, and center each year. One township (town, street) was selected from each area. Forty non boarding students aged 8 to 10 from each primary school (half male and half female, age balanced) and 20 pregnant women from each township (town, street) location were selected to collect edible salt samples at home and a random urine sample to measure salt iodine and urinary iodine level. B-ultrasound was used to measure thyroid volume in children and the goiter rate was calculated.Results:A total of 6 534 samples of household edible salt were collected from children and pregnant women, with an average salt iodine concentration of 25.58 mg/kg. The coverage rate of iodized salt was 97.50% (6 371/6 534), and the qualified iodized salt consumption rate was 89.46% (5 845/6 534). A total of 4 362 urine samples were collected from children, with a median urinary iodine level of 183.10 μg/L. The difference between different years was statistically significant ( H = 20.27, P < 0.001). A total of 2 169 urine samples were collected from pregnant women, with a median urinary iodine level of 168.90 μg/L. The difference between different years was statistically significant ( H = 107.09, P < 0.001). A total of 3 336 cases of thyroid gland examination were conducted in children, including 33 cases of thyroid enlargement, with a goiter rate of 0.99%. There was a statistically significant difference between different years (χ 2 = 15.00, P < 0.001). Conclusion:From 2019 to 2021, children aged 8 to 10 and pregnant women in Xining City are at an appropriate level of iodine, and the achievements in prevention and treatment of iodine deficiency disorders still need to be continuously consolidated.

Objective:To integrate and analyze the trend of the disease burden of tracheal,bronchus,and lung cancer(TBL)attributable to secondhand smoke in China from 1990 to 2021 and to analyze future projections,aiming to provide data support for the prevention and treatment of TBL in China.Methods:Based on the global burden of disease(GBD)2021 database,TBL with ICD-10 disease classification C33,C34-C34.92 was studied.Using secondhand smoke as a risk factor,the data on TBL mortality and disability-adjusted life year(DALY)due to secondhand smoke in China from 1990 to 2021 were further age-standardized.Using Joinpoint 4.7.1 regression analysis model to calculate annual percentage change(APC)and average annual percentage change(AAPC),Hiplot software was used to plot disease burden data for different ages and genders,and R 4.3.1 software was used to construct a grey model GM(1,1)to predict the predicted value and trend of TBL disease burden attributed to secondhand smoke in China from 2022 to 2031.Results:From 1990 to 2021,the TBL mortality rate,age-standardized mortality rate,and DALY rate attributed to secondhand smoke in China increased from 1.76/100 000,2.63/100 000,and 49.43/100 000 to 4.08/100 000,2.80/100 000,and 95.57/100 000,respectively;the growth was 131.18%,6.45%,and 93.34%;the age-standardized DALY rate decreased from 65.04/100 000 to 63.32/100 000 with the reduction of 2.65%.The results of the Joinpoint regres-sion showed that the AAPC(95%CI)of mortality,age-standardized mortality rate,and DALY rate for TBL were 2.75(2.58-2.93)%,0.16(0.11-0.21)%,and 2.15(2.11-2.18)%,respectively,with an overall increasing trend;the AAPC(95%CI)of age-standardized DALY rate was-0.14(-0.40-0.12)%,with an overall fluctuating and unchanged trend and it was higher in males than in females.In both 1990 and 2021,the TBL mortality rate attributable to secondhand smoke in China gradually increased with age,and the DALY rate first increased and then slowed down with age.The main groups of the burden of disease were the elderly and males.The grey prediction model GM(1,1)showed that the age-standardized mortality rate of TBL attributable to secondhand smoke from 2022 to 2031 showed a slow increasing trend,and the predicted value in 2031 would increase to 2.95/100 000.The age-standardized DALY showed a slow decreasing trend,and the predicted value in 2031 would decrease to 63.83/100 000.Conclusions:From 1990 to 2021,the TBL mortality,age-standardized mortality,and DALY rates attributable to secondhand smoke in China increased,and the age-standardized DALY rate decreased.Men and the elderly are the main groups affected by TBL.Appropriate measures should be formulated to reduce exposure to and contact with secondhand smoke,tak-ing into account gender and age differences.Additionally,efforts should be made to strengthen secondhand smoke prevention and public health education.

Objective:To investigate the clinical effect of indocyanine green angiography (ICGA)-assisted design and harvest of expanded flaps for scar reconstruction.Methods:This study was a retrospective observational study. From April 2019 to August 2023, 19 patients with scars (8 males, 11 females; aged 3-38 years) treated at the Plastic Surgery Hospital of Peking Union Medical College and Chinese Academy of Medical Sciences met the inclusion criteria. The scars were distributed on the head, face, trunk, and extremities. In stage Ⅰ surgery, skin soft tissue expanders were implanted in suitable areas around the scars for skin soft tissue expansion. In stage Ⅱ surgery, the scar tissue was excised, resulting in wound areas ranging from 100 to 210 cm 2, and expanded flaps were designed. ICGA was used to identify target perforators and their accompanying veins, and the flap design was adjusted to ensure the inclusion of complete arterial and venous axes. The expanded flap with an area of 120 to 240 cm2 was harvested using unilateral back-cut technique and transferred to the recipient site, and the donor site wound was sutured directly. The durations of the arterial and venous phases of ICGA during flap design were recorded. The length-to-width ratios of the back-cut flaps were calculated for different regions. After stage Ⅱ surgery, the blood perfusion and survival of the flap, the wound healing at the donor site, and the occurrence of complications were observed. During follow-up, the appearance, color, and texture of the patient's flap were observed. Results:The arterial phase of ICGA lasted 10-27 (18±5) s, and the venous phase lasted 78-116 (100±10) s. The length-to-width ratios of the back-cut flaps were 1.22±0.32, 1.63±0.12, and 1.15±0.21 for the head and neck, trunk, and limb regions, respectively. After stage Ⅱ surgery, one patient had a large area of insufficient blood perfusion in the flap. By comparing ICGA images before and after flap transfer, the sutures at the oral commissure were loosened, the blood flow of the flap was restored. The blood perfusion of the flaps in other patients was good. All flaps survived completely, with well-healed donor site wounds and no complications. During 0.5-14.0 months of follow-up, all flaps of patients demonstrated excellent appearance, with color and texture matching the surrounding skin.Conclusions:As a means of superficial blood flow visualization, ICGA can not only clearly show the microvascular distribution of the expanded flap before operation, assist in optimizing the design of the flap, but also evaluate the blood perfusion of the flap after operation, reduce the occurrence of complications, and provide a full-process navigation for the harvesting of expanded flaps, thereby improving the safety of flap transfer for scar reconstruction.

BACKGROUND: The effect of the interval between previous Helicobacter pylori (H. pylori) eradication and rescue treatment on therapeutic outcomes remains unknown. The aim of this study was to investigate the association between eradication rates and treatment interval durations in H. pylori infections. METHODS: This prospective observational study was conducted from December 2021 to February 2023 at six tertiary hospitals in Shandong, China. We recruited patients who were positive for H. pylori infection and required rescue treatment. Demographic information, previous times of eradication therapy, last eradication therapy date, and history of antibiotic use data were collected. The patients were divided into four groups based on the rescue treatment interval length: Group A, ≥4 weeks and ≤3 months; Group B, >3 and ≤6 months; Group C, >6 and ≤12 months; and Group D, >12 months. The primary outcome was the eradication rate of H. pylori . Drug compliance and adverse events (AEs) were also assessed. Pearson's χ2 test or Fisher's exact test was used to compare eradication rates between groups. RESULTS: A total of 670 patients were enrolled in this study. The intention-to-treat (ITT) eradication rates were 88.3% (158/179) in Group A, 89.6% (120/134) in Group B, 89.1% (123/138) in Group C, and 87.7% (192/219) in Group D. The per-protocol (PP) eradication rates were 92.9% (156/168) in Group A, 94.5% (120/127) in Group B, 94.5% (121/128) in Group C, and 93.6% (190/203) in Group D. There was no statistically significant difference in the eradication rates between groups in either the ITT ( P = 0.949) or PP analysis ( P = 0.921). No significant differences were observed in the incidence of AEs ( P = 0.934) or drug compliance ( P = 0.849) between groups. CONCLUSION: The interval duration of rescue treatment had no significant effect on H. pylori eradication rates or the incidence of AEs. REGISTRATION ClinicalTrials.gov , NCT05173493.
Humans ; Helicobacter Infections/drug therapy* ; Helicobacter pylori/pathogenicity* ; Male ; Female ; Prospective Studies ; Middle Aged ; Anti-Bacterial Agents/adverse effects* ; Adult ; Aged ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use*