Pharmacotranscriptomic profiles, which capture drug-induced changes in gene expression, offer vast potential for computational drug discovery and are widely used in modern medicine. However, current computational approaches neglected the associations within gene‒gene functional networks and unrevealed the systematic relationship between drug efficacy and the reversal effect. Here, we developed a new genome-scale functional module (GSFM) transformation framework to quantitatively evaluate drug efficacy for in silico drug discovery. GSFM employs four biologically interpretable quantifiers: GSFM_Up, GSFM_Down, GSFM_ssGSEA, and GSFM_TF to comprehensively evaluate the multi-dimension activities of each functional module (FM) at gene-level, pathway-level, and transcriptional regulatory network-level. Through a data transformation strategy, GSFM effectively converts noisy and potentially unreliable gene expression data into a more dependable FM active matrix, significantly outperforming other methods in terms of both robustness and accuracy. Besides, we found a positive correlation between RS_GSFM and drug efficacy, suggesting that RS_GSFM could serve as representative measure of drug efficacy. Furthermore, we identified WYE-354, perhexiline, and NTNCB as candidate therapeutic agents for the treatment of breast-invasive carcinoma, lung adenocarcinoma, and castration-resistant prostate cancer, respectively. The results from in vitro and in vivo experiments have validated that all identified compounds exhibit potent anti-tumor effects, providing proof-of-concept for our computational approach.

Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 BC. Methods Patients diagnosed with HER2-negative BC(N=999)at our institution between January 2011 and December 2015 formed our study population.Clinicopathological characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were assessed.Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low groups. Results HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszel χ2 test,P<0.001,Pearson's R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative group.There were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%. Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

Objective To develop a medical positive pressure protective suit for long-voyage aeromedical evacuation to realize protective isolation and drinking water and energy supply for medical personnel during long-voyage aeromedical evacuation of respiratory infectious disease patients.Methods The medical positive pressure protective suit had a one-piece structure,with its main part made of hydroentangled non-woven fabric,head and forebreast parts made of amorphous polyethylene terephthalate anti-fog material and wearing-and taking-off parts sealed with zipper and autohesion,which was equipped with a portable positive pressure air supply device,an airborne centralized positive pressure air supply device and a monitoring and warning device.The portable positive pressure air supply device was fixed in the back of the suit at the waist,the airborne device was made by modifying the commercially available positive pressure air supply fan,and the monitoring and warning device monitored the air supply volume of the fan,the battery power and the pressure inside the suit.Results The suit behaved well in protection,clean fresh air supply without time limitation and facilitating hydration and energy replenishment of medical personnel by forming three activity spaces.Conclusion The suit developed can continuously provide a clean and comfortable microenvironment,meeting the requirements of medical personnel for protection and hydration and energy replenishment during long-voyage aeromedical evacuation.[Chinese Medical Equipment Journal,2024,45(11):113-116]

Objective: To verify the feasibility and accuracy of the transanal multipoint full-layer puncture biopsy (TMFP) technique in determining the residual status of cancer foci after neoadjuvant therapy (nCRT) in rectal cancer. Methods: Between April 2020 and November 2022, a total of 78 patients from the Beijing Chaoyang Hospital of Capital Medical University, the Beijing Friendship Hospital of Capital Medical University, the Qilu Hospital of Shandong University, the Zhongnan Hospital of Wuhan University with advanced rectal cancer received TMFP after nCRT participated in this prospective multicenter trial. There were 53 males and 25 females, aged (M(IQR)) 61 (13) years (range: 35 to 77 years). The tumor distance from the anal verge was 5 (3) cm (range: 2 to 10 cm). The waiting time between nCRT and TMFP was 73 (26) days (range: 33 to 330 days). 13-point transanal puncture was performed with a 16 G tissue biopsy needle with the residual lesion as the center. The specimens were submitted for independent examination and the complications of the puncture were recorded. The consistency of TMFP and radical operation specimen was compared. The consistency of TMPF with clinical remission rates for the diagnosis of complete pathological remission was compared by sensitivity, specificity, negative predictive value, positive predictive value and accuracy. Statistical analysis between groups was performed using the χ² analysis, and a paired χ² test was used to compare diagnostic validity. Results: Before TMFP, clinical complete response (cCR) was evaluated in 27 cases. Thirty-six cases received in vivo puncture, the number of punctures in each patient was 13 (8) (range: 4 to 20), 24 cases of tumor residue were found in the puncture specimens. The sensitivity to judgment (100% vs. 60%, χ²=17.500, P<0.01) and accuracy (88.5% vs. 74.4%, χ²=5.125, P=0.024) of TMFP for the pathologic complete response (pCR) were significantly higher than those of cCR. Implement TMFP based on cCR judgment, the accuracy increased from 74.4% to 92.6% (χ²=4.026, P=0.045). The accuracy of the in vivo puncture was 94.4%, which was 83.3% of the in vitro puncture (χ²=1.382, P=0.240). Overall, the accuracy of TMFP improved gradually with an increasing number of cases (χ²=7.112, P=0.029). Conclusion: TMFP is safe and feasible, which improves the sensitivity and accuracy of rectal cancer pCR determination after nCRT, provides a pathological basis for cCR determination, and contributes to the safe development of the watch and wait policy.

OBJECTIVE: Traditional epidemiological studies have shown that C-reactive protein (CRP) is associated with the risk of cardiovascular diseases (CVDs). However, whether this association is causal remains unclear. Therefore, Mendelian randomization (MR) was used to explore the causal relationship of CRP with cardiovascular outcomes including ischemic stroke, atrial fibrillation, arrhythmia and congestive heart failure. METHODS: We performed two-sample MR by using summary-level data obtained from Japanese Encyclopedia of Genetic association by Riken (JENGER), and we selected four single-nucleotide polymorphisms associated with CRP level as instrumental variables. MR estimates were calculated with the inverse-variance weighted (IVW), penalized weighted median and weighted median. MR-Egger regression was used to explore pleiotropy. RESULTS: No significant causal association of genetically determined CRP level with ischemic stroke, atrial fibrillation or arrhythmia was found with all four MR methods (all Ps > 0.05). The IVW method indicated suggestive evidence of a causal association between CRP and congestive heart failure ( OR: 1.337, 95% CI: 1.005-1.780, P = 0.046), whereas the other three methods did not. No clear pleiotropy or heterogeneity were observed. CONCLUSIONS Suggestive evidence was found only in analysis of congestive heart failure; therefore, further studies are necessary. Furthermore, no causal association was found between CRP and the other three cardiovascular outcomes.
C-Reactive Protein/metabolism* ; Cardiovascular Diseases/metabolism* ; Genetic Predisposition to Disease ; Genotype ; Humans ; Japan ; Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide ; Risk Factors

COVID-19/genetics* ; Genetic Predisposition to Disease ; Humans ; Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide ; Risk Factors ; SARS-CoV-2 ; Vitamin D/blood*

Objective:To investigate the surgical treatment of the tumors at cervicothoracic junction.Methods:A retrospective analyses was performed for 63 patients with tumors at the cervicothoracic junction receiving surgery from Mar 2008 to May 2020 in the Department of Thoracic Surgery, Zhongshan Hospital, Fudan University. Clinical data about manifestation, surgical approach, resection degree and pathological types were collected. There were 43 cases of asymptomatic patients and 20 cases of patients with ≥1 clinical manifestations. Twenty two patients receiving radical resection with video-assisted thoracoscopic surgery. Anterior approach was the most popular treatment in open surgery (24 cases, 38.1%), and 8 cases of anterolateral approach(6 cases of Hemiclamshell incisions, 2 cases of trap-door incisions), 1 case of posterior approach, 2 cases of posterolateral approach and 1 case of supraclavicular combined posterolateral approach.Results:Pathological examination suggested 61 cases of radical resection and 2 cases of microscopic residual. Neurilemmoma was the most common pathological type (27 cases, 42.9%), the second common pathological type was tumor originated from fibrous tissues (6 cases, 9.5%). The 3-year overall survival rate of those 63 patients was 88.9%, while the 5-year overall survival rate was 84.1%.Conclusion:Tumors involving the cervicothoracic junction are characterized as special location, complicated anatomy and various histopathological subtypes. Individualized approach and surgery improve safety and normalization of tumors at cervicothoracic junction treatment.

Moutan Cortex is one kind of famous medicinal materials. The dry root bark of Paeonia ostii which is a genuine medicinal material produced in Tongling,Anhui province,and later was introduced to Heze,Shandong province and Bozhou,Anhui province.Dangshan county is located at the northern end of Anhui province and adjacent to Shandong province. Its medicinal seedlings were came from Heze,Shandong province. At present,there is a lack of scientific investigation on the planting area of P. ostii in north China plain. On the basis of field investigation and remote sensing technology,through the data source provided by the remote sensing image of " Resources 3"( ZY-3),combined with the biological characteristics of P. ostii,the planting area of P. ostii in Dangshan county was extracted by field investigation and supervisory classification. The supervise classification method with the highest interpretation accuracy so far,the overall accuracy was 97. 81%,Kappa coefficient 0. 96. The results showed that the remote sensing classification method based on the maximum likelihood classification could extract P. ostii plots in the study area effectively. This study provides a scientific basis for the protection and rational utilization of traditional Chinese medicine resources,the development policy of traditional Chinese medicine industry and the long-term development plan in Dangshan county,and provides technical support for the poverty alleviation of traditional Chinese medicine industry in Dangshan county. It provides scientific reference for the application of remote sensing technology to investigate the planting area of P. ostii in in north China plain.
China ; Medicine, Chinese Traditional ; Paeonia ; Remote Sensing Technology

Several studies have demonstrated an association between physical activity and telomere length; however, the association remains inconsistent. A cross-sectional study consisting of 588 participants (375 females, median age of 33.8 years) was carried out to investigate the association between telomere length and physical activity in a general population from North China. The results show that relative telomere length is not significantly different in participants in the northern Chinese population with different levels of physical activity, either in the model only adjusted for age (F = 2.127, P = 0.120) or in the model adjusted for demographics and lifestyle (F = 1.227, P = 0.294). The gender-stratified analysis also produced insignificant results. Our study confirmed a non-significant association between physical activity and telomere length in the northern Chinese population, which adds to the inconsistent association between physical activity and telomere length across different ethnic populations.
Adult ; Asian Continental Ancestry Group ; genetics ; China ; Cohort Studies ; Cross-Sectional Studies ; Exercise ; physiology ; Female ; Humans ; Male ; Middle Aged ; Telomere ; Young Adult