Peptide-drug conjugates (PDCs) have emerged as a promising modality in precision oncology, enabling targeted delivery of cytotoxic payloads while minimizing off-target toxicity. The integration of covalent warheads, such as those based on sulfur(VI) fluoride exchange (SuFEx) chemistry, enhances drug-target residence time and tumor accumulation. However, existing screening methods for covalent peptide (CP) libraries require post-translational warhead conjugation, limiting throughput. Here, we present an integrated mRNA display platform that incorporates covalent warheads during ribosomal synthesis, enabling efficient screening of ultra-diverse covalent macrocyclic peptide libraries (>10¹³ variants). This approach, using site-specific incorporation of N-chloroacetyl-d-phenylalanine and fluorosulfate-l-tyrosine, accelerated the discovery of irreversibly binding (K _i = 3.58 μmol/L) Nectin-4-targeting peptide CP-N1-N₃ via proximity-triggered SuFEx. The peptide was further conjugated to cytotoxic payloads, yielding the covalent PDC CP-N1-MMAE with potent cytotoxicity (IC₅₀ ≈ 43 nmol/L) against MDA-MB-468 cells. This platform establishes a new paradigm for precision covalent drug discovery.

Objective:To systematically evaluate the effect of hepatitis B virus (HBV) infection on the risk of adverse pregnancy outcomes.Methods:We searched PubMed, Embase, Web of Science, and Cochrane databases. Two researchers independently screened the literature, extracted data, and evaluated the quality. Meta-analysis and cumulative meta-analysis were performed using R4.4.1 software. Fixed/random effects models were used to analyze heterogeneous and non-heterogeneous results. Heterogeneous modifiers were identified by subgroup analysis. Funnel plots and Peters' test were used to analyze potential publication bias.Results:A total of 48 studies involving 92 836 HBsAg-positive pregnant women and 7 123 292 HBsAg-negative pregnant women were included. In terms of adverse pregnancy outcomes, HBV infection was significantly correlated with the occurrence of gestational diabetes mellitus [odds ratio ( OR)=1.34, 95% confidence interval ( CI): 1.17-1.53] and intrahepatic cholestasis ( OR=2.48, 95% CI: 1.88-3.29), with statistically significant differences. In terms of adverse neonatal outcomes, HBV infection was significantly correlated with the occurrence of neonatal asphyxia ( OR=1.49, 95% CI: 1.20-1.86) and preterm birth ( OR=1.22, 95% CI: 1.12-1.33), with statistically significant differences. In addition, the cumulative meta-analysis demonstrated that the risk of gestational diabetes mellitus and preterm birth both tended to be stable in pregnant women with HBV infection following 2009 and 2010, respectively. The supplementary questions answered for repeated studies had limited significance. Conclusion:Intrahepatic cholestasis, gestational diabetes mellitus, neonatal asphyxia, and preterm birth occurrence risk can be raised with HBV infection in pregnant women.

On March 24, 2017, a patient with Von Hippel-Lindau syndrome (VHL) characterized by bilateral adrenal pheochromocytoma and pancreatic tumors was admitted to our hospital, who underwent simultaneous pancreatic body and tail tumor resection, bilateral adrenal tumor resection and Omentum transplantation of the right adrenal gland.Intraoperative hormone therapy was used. Part of the normal adrenal tissue was preserved and embedded in the omentum, but an adrenal crisis occurred on the first day after the operation.The hormone replacement was used. Postoperative hormone replacement therapy was performed for 6 months. After 4 years of follow-up, blood pressure was normal, no cortical dysfunction, no tumor recurrence or other related lesions appeared. The preserved part of adrenal tissue during simultaneous multi-organ tumor resection for such patients can reduce long-term hormone replacement after surgery and prevent late adrenal cortex dysfunction.

OBJECTIVETo investigate the association between children's and their parents' lifestyles, household environmental exposures and risk of childhood acute leukemia (AL).

METHODSA 1:2 matched case-control study of childhood AL was conducted in Shanghai between April 2011 and January 2014. The study enrolled 66 cases aged < 15, diagnosed with AL and 132 controls matched by age, gender and residence. All of the controls had no hematological diseases or previous history of malignancy. Children who had been adopted and had congenital genetic syndromes such as Down's syndrome or a positive HIV test result were not eligible as either cases or controls. Information was obtained from standardized face-to-face interviews of their parents/guardians with detailed questions on demographic characteristics, lifestyle, and household environment. Conditional logistic regression models were used to analyze effecting factors of childhood AL, odds ratios (OR) and their 95% confidence intervals (CI) were calculated.

RESULTSAmong 198 cases, 66 cases were aged (5.0 ± 3.7) years old, and 132 controls were aged (6.0 ± 3.8) years old (t = 0.48, P = 0.523). The paternal drink frequencies of cases and controls were 57.6% (38/66), and 31.1% (41/132), respectively (χ² = 4.91, P = 0.027). And the frequencies of household insecticides usage in the last year in the two groups were 78.8% (52/66), and 65.2% (86/132) (χ² = 3.87, P = 0.049). Chemical exposure during childhood (OR = 4.76, 95% CI: 1.34-16.89), maternal exposure to chemicals (OR = 4.51, 95% CI: 1.65-12.33), household insecticides use during 0-3 years of child (OR = 2.90, 95% CI: 1.31-6.39), and renovating after their children's birth (OR = 3.12, 95% CI: 1.26-7.74) were associated with an increased risk of childhood AL and these differences between the cases and the controls have statistical significance. Besides, we found that frequent contaction with other children during 0-3 years old (OR = 0.32, 95% CI: 0.15-0.69) and ventilation during sleeping in summer (OR = 0.43, 95% CI: 0.18-0.98) were associated with a decreased risk of childhood AL.

CONCLUSIONOur results support the association between children's and their parents' lifestyles, household environmental exposures and childhood AL.

Acute Disease ; Case-Control Studies ; Child ; Child, Preschool ; China ; Environmental Exposure ; Female ; Humans ; Insecticides ; Leukemia ; epidemiology ; Life Style ; Logistic Models ; Maternal Exposure ; Neoplasms ; Odds Ratio ; Parents ; Risk Factors

Objective To investigate the association between children's and their parents' lifestyles, household environmental exposures and risk of childhood acute leukemia (AL) . Methods A 1∶2 matched case-control study of childhood AL was conducted in Shanghai between April 2011 and January 2014. The study enrolled 66 cases aged<15, diagnosed with AL and 132 controls matched by age, gender and residence. All of the controls had no hematological diseases or previous history of malignancy. Children who had been adopted and had congenital genetic syndromes such as Down's syndrome or a positive HIV test result were not eligible as either cases or controls. Information was obtained from standardized face-to-face interviews of their parents/guardians with detailed questions on demographic characteristics, lifestyle, and household environment. Conditional logistic regression models were used to analyze effecting factors of childhood AL, odds ratios (OR) and their 95%confidence intervals (CI) were calculated . Results Among 198 cases, 66 cases were aged (5.0±3.7) years old, and 132 controls were aged (6.0±3.8)years old (t=0.48, P=
0.523). The paternal drink frequencies of cases and controls were 57.6% (38/66), and 31.1% (41/132), respectively (χ2=4.91, P=0.027). And the frequencies of household insecticides usage in the last year in the two groups were 78.8% (52/66), and 65.2% (86/132) (χ2=3.87, P=0.049). Chemical exposure during childhood (OR=4.76, 95%CI:1.34-16.89), maternal exposure to chemicals (OR=4.51, 95%CI:1.65-12.33), household insecticides use during 0-3 years of child (OR=2.90, 95%CI: 1.31-6.39), and renovating after their children's birth (OR=3.12, 95%CI:1.26-7.74) were associated with an increased risk of childhood AL and these differences between the cases and the controls have statistical significance. Besides, we found that frequent contaction with other children during 0-3 years old (OR=0.32, 95%CI:0.15-0.69) and ventilation during sleeping in summer (OR=0.43, 95%CI:0.18-0.98) were associated with a decreased risk of childhood AL. Conclusion Our results support the association between children's and their parents' lifestyles, household environmental exposures and childhood AL.

Objective To investigate the association between children's and their parents' lifestyles, household environmental exposures and risk of childhood acute leukemia (AL) . Methods A 1∶2 matched case-control study of childhood AL was conducted in Shanghai between April 2011 and January 2014. The study enrolled 66 cases aged<15, diagnosed with AL and 132 controls matched by age, gender and residence. All of the controls had no hematological diseases or previous history of malignancy. Children who had been adopted and had congenital genetic syndromes such as Down's syndrome or a positive HIV test result were not eligible as either cases or controls. Information was obtained from standardized face-to-face interviews of their parents/guardians with detailed questions on demographic characteristics, lifestyle, and household environment. Conditional logistic regression models were used to analyze effecting factors of childhood AL, odds ratios (OR) and their 95%confidence intervals (CI) were calculated . Results Among 198 cases, 66 cases were aged (5.0±3.7) years old, and 132 controls were aged (6.0±3.8)years old (t=0.48, P=
0.523). The paternal drink frequencies of cases and controls were 57.6% (38/66), and 31.1% (41/132), respectively (χ2=4.91, P=0.027). And the frequencies of household insecticides usage in the last year in the two groups were 78.8% (52/66), and 65.2% (86/132) (χ2=3.87, P=0.049). Chemical exposure during childhood (OR=4.76, 95%CI:1.34-16.89), maternal exposure to chemicals (OR=4.51, 95%CI:1.65-12.33), household insecticides use during 0-3 years of child (OR=2.90, 95%CI: 1.31-6.39), and renovating after their children's birth (OR=3.12, 95%CI:1.26-7.74) were associated with an increased risk of childhood AL and these differences between the cases and the controls have statistical significance. Besides, we found that frequent contaction with other children during 0-3 years old (OR=0.32, 95%CI:0.15-0.69) and ventilation during sleeping in summer (OR=0.43, 95%CI:0.18-0.98) were associated with a decreased risk of childhood AL. Conclusion Our results support the association between children's and their parents' lifestyles, household environmental exposures and childhood AL.

Objective To improve the diagnosis and treatment of pulmonary lymphangiomyomatosis (PLAM). Methods The clinical data of 1 PLAM case in our hospital was analysed, along with a review of the related literatures.Results PLAM was a rare diffuse interstitial plumonary disease of unknown cause, which was oiraracterized by recurrent spontaneous pneumothorax shortness of breath (dyspnea) with physical activity, haemopthsis and chylothorax. Radiological appearances were extensive bilateral linear pattern, and honeycomb pattern in the end. High resolution CT scan (HRCT) showed multiple thin walled cysts distributed evenly throughout the bilateral lung fields with normal intervening lung parenchyma. Pathological characters were abnormal, pervasice multiplication of smooth muscle of cell in and around the small airway, lymphatic and small blood vessels. Immunohistochemical test showed HMB45(+).Conclusion It should be considered the probability of PLAM when women of childbearing ages have some clinical manifestations as follows, the increasing dyspnoea that can not be relieved similar to emphysema, high- resolution CT scan (HRCT) shows multiple thin walled cysts distributed evenly throughout the bilateral lung fields with normal intervening lung parenchyma, and recurrent pneumothorax or chylothorax. The optimal confirm diagnostic method is lung tissue biopsy.