Background and Purpose:Previous studies have investigated the prognostic significance of skeletal muscle and adipose tissue composition and distribution in colorectal cancer patients,yet most have not differentiated between rectal and colon cancer patient cohorts.This study aimed to explore the relationship between body composition and long-term prognosis,and to develop a postoperative predictive model.Methods:Clinical data of rectal cancer patients who underwent surgical treatment at Qingdao University Affiliated Hospital from January 2018 to December 2021 were retrospectively collected.Inclusion criteria:①Age＞18 years;② Preoperative colonoscopy and pathological diagnosis of colorectal cancer;③ Complete surgical resection;④Abdominal computed tomography(CT)scan 1 month before surgery.Exclusion criteria:① Clinical data is missing;② Multiple metastases of tumors;③ Tumor T stage 0 or carcinoma in situ;④ Severe artifacts lead to poor quality CT imaging,making it difficult to distinguish between fat and muscle;⑤ Inability to obtain follow-up results.This study has been approved by the Medical Ethics Committee of the Affiliated Hospital of Qingdao University(approval number:QYFYWZLL30313),and informed consent has been waived in the ethical approval process.The skeletal muscle index(SMI)and subcutaneous adipose tissue index(SATI)were calculated by dividing the areas of skeletal muscle and subcutaneous fat observed on CT scans by the square of the patient's height.Univariate and multivariate COX regression analyses were conducted to identify risk factors influencing recurrence-free survival(RFS)and overall survival(OS)in rectal cancer patients.Based on the results of the multivariate analysis,a nomogram prediction model was developed,its predictive power and accuracy were assessed using the receiver operating characteristic(ROC)curve,calibration plots and decision curve analysis(DCA),and internal validation was conducted.Results:A total of 696 patients were included in this study,with 96(13.8%)patients experiencing postoperative recurrence and 89(12.8%)patients dying.Multivariate COX regression analysis showed that SMI,SATI,tumor T stage and N stage were independent factors affecting the postoperative RFS and OS of patients.Nomogram prediction models for RFS and OS in rectal cancer patients were constructed based on the above independent predictors.The area under ROC curve(AUC)for 3-,4-and 5-year RFS was 0.862,0.846 and 0.824,respectively;the AUC for 3-,4-and 5-year OS was 0.886,0.898 and 0.875,respectively.The models were evaluated using calibration curves and decision curves,and internal validation was performed,which showed that the prediction accuracy of the models was good.Conclusion:CT body composition is an independent predictor of RFS and OS in rectal cancer patients,and the nomogram model developed based on these factors demonstrates good predictive value for patient prognosis.

Objective:To investigate the effects of chronic persistent hypoxia on hepatic function, histological morphology, and ultrastructure in aged mice, and to evaluate the protective role of pyrroloquinoline quinone(PQQ).Methods:Thirty-two 2-month-old (young group)and thirty-two 18-month-old(aged group)male C57BL6/J mice were each randomly divided into four groups (n=8 per group): normoxia+ normal saline (NS)group, normoxia+ PQQ group, hypoxia+ NS group, and hypoxia+ PQQ group.The normoxia+ NS and normoxia+ PQQ groups were housed under normoxic conditions[fraction of inspired oxygen(FiO 2)=21%], while the hypoxia+ NS and hypoxia+ PQQ groups were continuously exposed to a hypoxic environment[FiO 2=(10±0.5)%]simulated by a custom-made hypoxic chamber, maintaining a constant oxygen concentration for 24 hours per day.The normoxia+ NS and hypoxia+ NS groups received daily intragastric administration of NS, whereas the normoxia+ PQQ and hypoxia+ PQQ groups received daily intragastric administration of PQQ disodium salt(8 mg·kg -1·d -1).After 8 weeks of continuous intervention, blood samples were collected to measure red blood cell count, hemoglobin levels, and liver function-related biochemical indicators.Lung tissues were processed for HE staining, and liver tissues were processed for both HE staining and electron microscopy.The histological and ultrastructural features of each group were observed under light and electron microscopy, respectively, and the differences between the groups were compared and analyzed. Results:Compared with the normoxia+ NS groups, both young and aged hypoxia+ NS groups exhibited significant pulmonary arteriole narrowing( P<0.001), with markedly elevated red blood cell count and hemoglobin levels (all P<0.001), which were not alleviated by PQQ.Compared with the young normoxia+ NS group, the young hypoxia+ NS group showed significantly higher alanine aminotransferase (ALT)and lactate dehydrogenase (LDH)levels( Z=2.72, 2.53, P=0.007, 0.011), whereas the young hypoxia+ PQQ group exhibited LDH levels similar to those of the young normoxia+ NS group.The aged hypoxia+ NS group exhibited significant ALT elevation( t=2.66, P=0.013)compared with the aged normoxia+ NS group.Light microscopy revealed hepatocyte ballooning degeneration, mild fatty accumulation, and focal necrosis around central veins in the young hypoxia+ NS group, while the young hypoxia+ PQQ group exhibited no significant pathological damage but displayed numerous deeply stained binucleated hepatocytes.The aged normoxia+ NS group demonstrated hepatocyte ballooning degeneration and inflammatory cell infiltration around central veins, whereas the aged normoxia+ PQQ group exhibited no obvious pathological damage with scattered deeply stained binucleated hepatocytes.The aged hypoxia+ NS group exhibited significant necrosis following physiological oxygen concentration gradient distribution, while the aged hypoxia+ PQQ group displayed no obvious pathological damage with scattered deeply stained binucleated hepatocytes.Electron microscopy revealed that the aged normoxia+ NS group had reduced mitochondrial electron density ( P<0.001)and less developed rough endoplasmic reticulum compared with the young normoxia+ NS group.The young hypoxia+ NS group exhibited a smaller mitochondrial area( P<0.001), decreased mitochondrial matrix electron density( P<0.001), blurred or absent mitochondrial cristae, inactive rough endoplasmic reticulum, and increased accumulation of glycogen and lipid droplets compared with the young normoxia+ NS group, while the young hypoxia+ PQQ group maintained mitochondrial matrix electron density comparable to the young normoxia+ NS group.The aged hypoxia+ NS group exhibited larger mitochondrial area( P=0.001), decreased mitochondrial matrix electron density( P<0.001), blurred or absent mitochondrial cristae, mitochondrial edema, increased lysosomes, and elevated cytoplasmic electron density compared with the aged normoxia+ NS group.The aged hypoxia+ PQQ group exhibited reduced mitochondrial area( P<0.001)and restored mitochondrial matrix electron density to levels comparable with the aged normoxia+ NS group.The aged normoxia+ PQQ group demonstrated increased mitochondrial matrix electron density compared with the aged normoxia+ NS group( P<0.001). Conclusions:Chronic persistent hypoxia induces hepatic functional, histological and ultrastructural damage in mice, with more pronounced effects in aged animals.PQQ provides a certain degree of protection against these injuries.

Dental caries,a chronic disease characterized by tooth decay,occupies the second position in terms of disease burden and is primarily caused by cariogenic bacteria,especially Streptococcus mutans,because of its acidogenic,aciduric,and biofilm-forming capabilities.Developing novel targeted anti-virulence agents is always a focal point in caries control to overcome the limitations of conventional anti-virulence agents.The current study represents an up-to-date review of in silico approaches of drug design against dental caries,which have emerged more and more powerful complementary to biochemical attempts.Firstly,we categorize the in silico approaches into computer-aided drug design(CADD)and AI-assisted drug design(AIDD)and highlight the specific methods and models they contain respectively.Subsequently,we detail the design of anti-virulence drugs targeting single or multiple cariogenic virulence targets of S.mutans,such as glucosyltransferases(Gtfs),antigen Ⅰ/Ⅱ(AgⅠ/Ⅱ),sortase A(SrtA),the VicRK signal transduction system and superoxide dismutases(SODs).Finally,we outline the current opportunities and challenges encountered in this field to aid future endeavors and applications of CADD and AIDD in anti-virulence drug design.

Dental caries, a chronic disease characterized by tooth decay, occupies the second position in terms of disease burden and is primarily caused by cariogenic bacteria, especially Streptococcus mutans, because of its acidogenic, aciduric, and biofilm-forming capabilities. Developing novel targeted anti-virulence agents is always a focal point in caries control to overcome the limitations of conventional anti-virulence agents. The current study represents an up-to-date review of in silico approaches of drug design against dental caries, which have emerged more and more powerful complementary to biochemical attempts. Firstly, we categorize the in silico approaches into computer-aided drug design (CADD) and AI-assisted drug design (AIDD) and highlight the specific methods and models they contain respectively. Subsequently, we detail the design of anti-virulence drugs targeting single or multiple cariogenic virulence targets of S. mutans, such as glucosyltransferases (Gtfs), antigen I/II (AgI/II), sortase A (SrtA), the VicRK signal transduction system and superoxide dismutases (SODs). Finally, we outline the current opportunities and challenges encountered in this field to aid future endeavors and applications of CADD and AIDD in anti-virulence drug design.

Objective:To investigate the effects of chronic persistent hypoxia on hepatic function, histological morphology, and ultrastructure in aged mice, and to evaluate the protective role of pyrroloquinoline quinone(PQQ).Methods:Thirty-two 2-month-old (young group)and thirty-two 18-month-old(aged group)male C57BL6/J mice were each randomly divided into four groups (n=8 per group): normoxia+ normal saline (NS)group, normoxia+ PQQ group, hypoxia+ NS group, and hypoxia+ PQQ group.The normoxia+ NS and normoxia+ PQQ groups were housed under normoxic conditions[fraction of inspired oxygen(FiO 2)=21%], while the hypoxia+ NS and hypoxia+ PQQ groups were continuously exposed to a hypoxic environment[FiO 2=(10±0.5)%]simulated by a custom-made hypoxic chamber, maintaining a constant oxygen concentration for 24 hours per day.The normoxia+ NS and hypoxia+ NS groups received daily intragastric administration of NS, whereas the normoxia+ PQQ and hypoxia+ PQQ groups received daily intragastric administration of PQQ disodium salt(8 mg·kg -1·d -1).After 8 weeks of continuous intervention, blood samples were collected to measure red blood cell count, hemoglobin levels, and liver function-related biochemical indicators.Lung tissues were processed for HE staining, and liver tissues were processed for both HE staining and electron microscopy.The histological and ultrastructural features of each group were observed under light and electron microscopy, respectively, and the differences between the groups were compared and analyzed. Results:Compared with the normoxia+ NS groups, both young and aged hypoxia+ NS groups exhibited significant pulmonary arteriole narrowing( P<0.001), with markedly elevated red blood cell count and hemoglobin levels (all P<0.001), which were not alleviated by PQQ.Compared with the young normoxia+ NS group, the young hypoxia+ NS group showed significantly higher alanine aminotransferase (ALT)and lactate dehydrogenase (LDH)levels( Z=2.72, 2.53, P=0.007, 0.011), whereas the young hypoxia+ PQQ group exhibited LDH levels similar to those of the young normoxia+ NS group.The aged hypoxia+ NS group exhibited significant ALT elevation( t=2.66, P=0.013)compared with the aged normoxia+ NS group.Light microscopy revealed hepatocyte ballooning degeneration, mild fatty accumulation, and focal necrosis around central veins in the young hypoxia+ NS group, while the young hypoxia+ PQQ group exhibited no significant pathological damage but displayed numerous deeply stained binucleated hepatocytes.The aged normoxia+ NS group demonstrated hepatocyte ballooning degeneration and inflammatory cell infiltration around central veins, whereas the aged normoxia+ PQQ group exhibited no obvious pathological damage with scattered deeply stained binucleated hepatocytes.The aged hypoxia+ NS group exhibited significant necrosis following physiological oxygen concentration gradient distribution, while the aged hypoxia+ PQQ group displayed no obvious pathological damage with scattered deeply stained binucleated hepatocytes.Electron microscopy revealed that the aged normoxia+ NS group had reduced mitochondrial electron density ( P<0.001)and less developed rough endoplasmic reticulum compared with the young normoxia+ NS group.The young hypoxia+ NS group exhibited a smaller mitochondrial area( P<0.001), decreased mitochondrial matrix electron density( P<0.001), blurred or absent mitochondrial cristae, inactive rough endoplasmic reticulum, and increased accumulation of glycogen and lipid droplets compared with the young normoxia+ NS group, while the young hypoxia+ PQQ group maintained mitochondrial matrix electron density comparable to the young normoxia+ NS group.The aged hypoxia+ NS group exhibited larger mitochondrial area( P=0.001), decreased mitochondrial matrix electron density( P<0.001), blurred or absent mitochondrial cristae, mitochondrial edema, increased lysosomes, and elevated cytoplasmic electron density compared with the aged normoxia+ NS group.The aged hypoxia+ PQQ group exhibited reduced mitochondrial area( P<0.001)and restored mitochondrial matrix electron density to levels comparable with the aged normoxia+ NS group.The aged normoxia+ PQQ group demonstrated increased mitochondrial matrix electron density compared with the aged normoxia+ NS group( P<0.001). Conclusions:Chronic persistent hypoxia induces hepatic functional, histological and ultrastructural damage in mice, with more pronounced effects in aged animals.PQQ provides a certain degree of protection against these injuries.

Objective:To explore the spousal correlations of total cholesterol(TC),total triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C),and to investigate the reasons behind these spousal correlations.Methods:Participants and data were from the baseline survey of family-based cohort studies in Fangshan,Beijing and Tulou,Fujian.The ori-gin of spousal correlations were explored from perspectives of convergence,assortative mating,social ho-mogamy.Pearson's correlation and generalized linear models(GLM)were used to estimate the spousal correlation.Convergence was assessed by Pearson's correlation between the phenotypic differences be-tween couples and the duration of marriage,with GLM used for further validation.Pearson's correlation of genetic risk scores(GRS)and couple-specific Mendelian randomization(MR)were calculated to assess the genetic correlation and possible causal relationships between spouses.Two-independent-sample t-tests were used to compare GRS consistency across subgroups divided by education attainment,couple-specific MR and Q statistics used to test assortative mating in subgroups and intergroup differences.Results:In the study,342 couples(287 couples from Fangshan and 55 couples from Fujian)were included,with the average age of(64.91±8.76)years.Spousal correlations of TC,TG,HDL-C,and LDL-C showed statistically significant associations both before and after adjusting for covariates,with effect sizes of 0.229(95％CI:0.125-0.327),0.257(95％CI:0.155-0.354),0.179(95％CI:0.074-0.280),and 0.181(95％CI:0.076-0.282).For convergence,for each additional year of marriage,ΔTC increased by 0.016 mmol/L(95％CI:0.001-0.033 mmol/L),and ΔLDL-C increased by 0.017 mmol/L(95％CI:0.002-0.031 mmol/L).For assortative mating,GRS correlations and results of couple specific MR didn't show any statistical significance.For social homogamy,no differences in GRS or assortative mating were found between subgroups stratified by education attainment.Conclusion:The blood lipid in participants exhibit spousal phenotypic correlations,however,no effects of convergence,assortative mating or social homogamy were observed.More independent studies with larger sample sizes are warranted to further validate these findings in the future.

OBJECTIVE To analyze the homology and drug resistance characteristics of clinical carbapenem-resistant Klebsiella pneumoniae(CRKP)isolates from the children and adults in Kunming area so as to provide guidance for prevention and control of CRKP strains.METHODS Totally 41 strains of clinical CRKP isolates were collected from the children in 4 hospitals of Kunming area in 2023,and 54 strains were collected from the adults.The ho-mology of the strains was analyzed by means of repetitive extragenic palindromic-polymerase chain reaction(REP-PCR);the phenotypes of carbapenemases and the genes in the strains were detected.RESULTS The 95 strains of CRKP were divided into 30 genotypes.There was clustering of genotypes in some strains.The type A enzyme was most common among the strains from the adults(47 strains,87.04％),while the type A enzyme(18 strains,43.90％)and the type B enzyme(23 strains,56.10％)were both detected in the strains from the children.A-mong the strains producing type A enzyme,the strains carrying with KPC gene were both dominant among the strains isolated from the adults(44 strains,81.48％)and the strains isolated from the children(18 strains,43.90％).Among the strains producing type B enzyme,the strains carrying with NDM gene were dominant a-mong the strains from the children(22 strains,53.66％).CONCLUSIONS There is colonization and inter-hospital transmission of CRKP strains in the hospitals of Kunming area.It is necessary for the clinical departments of the children's hospitals to strengthen the active screening of the transferring children and carefully carry out the cleaning and disinfection of nosocomial environment so as to reduce the probability of the CRKP infection among the children.Mean-while,the clinicians of the pediatrics department should comprehensively take all the factors into accounts such as the type of enzyme,formulate the appropriate medication regimens and raise the cure rate of the children with CRKP infection.

Background and Purpose:Previous studies have investigated the prognostic significance of skeletal muscle and adipose tissue composition and distribution in colorectal cancer patients,yet most have not differentiated between rectal and colon cancer patient cohorts.This study aimed to explore the relationship between body composition and long-term prognosis,and to develop a postoperative predictive model.Methods:Clinical data of rectal cancer patients who underwent surgical treatment at Qingdao University Affiliated Hospital from January 2018 to December 2021 were retrospectively collected.Inclusion criteria:①Age＞18 years;② Preoperative colonoscopy and pathological diagnosis of colorectal cancer;③ Complete surgical resection;④Abdominal computed tomography(CT)scan 1 month before surgery.Exclusion criteria:① Clinical data is missing;② Multiple metastases of tumors;③ Tumor T stage 0 or carcinoma in situ;④ Severe artifacts lead to poor quality CT imaging,making it difficult to distinguish between fat and muscle;⑤ Inability to obtain follow-up results.This study has been approved by the Medical Ethics Committee of the Affiliated Hospital of Qingdao University(approval number:QYFYWZLL30313),and informed consent has been waived in the ethical approval process.The skeletal muscle index(SMI)and subcutaneous adipose tissue index(SATI)were calculated by dividing the areas of skeletal muscle and subcutaneous fat observed on CT scans by the square of the patient's height.Univariate and multivariate COX regression analyses were conducted to identify risk factors influencing recurrence-free survival(RFS)and overall survival(OS)in rectal cancer patients.Based on the results of the multivariate analysis,a nomogram prediction model was developed,its predictive power and accuracy were assessed using the receiver operating characteristic(ROC)curve,calibration plots and decision curve analysis(DCA),and internal validation was conducted.Results:A total of 696 patients were included in this study,with 96(13.8%)patients experiencing postoperative recurrence and 89(12.8%)patients dying.Multivariate COX regression analysis showed that SMI,SATI,tumor T stage and N stage were independent factors affecting the postoperative RFS and OS of patients.Nomogram prediction models for RFS and OS in rectal cancer patients were constructed based on the above independent predictors.The area under ROC curve(AUC)for 3-,4-and 5-year RFS was 0.862,0.846 and 0.824,respectively;the AUC for 3-,4-and 5-year OS was 0.886,0.898 and 0.875,respectively.The models were evaluated using calibration curves and decision curves,and internal validation was performed,which showed that the prediction accuracy of the models was good.Conclusion:CT body composition is an independent predictor of RFS and OS in rectal cancer patients,and the nomogram model developed based on these factors demonstrates good predictive value for patient prognosis.

Objective To analyze the expression and detection significance of community acquired respiratory distress syndrome(CARDS)toxin in bronchoalveolar lavage fluid(BALF)in children with severe Mycoplasma pneumoniae pneumonia(SMPP).Methods The BALF samples of children diagnosed with Mycoplasma pneumoniae pneumonia(MPP)were collected from the Department of Pulmonology,Children's Hospital Affiliated to Capital Institute of Pediatrics from August 2021 to April 2022,the relative expression of CARDS toxins was determined by quantitative realtime polymerase chain reaction(qPCR).The patients were divided into SMPP group and non-SMPP group(control group).The relative expression of CARDS toxin and other clinical indicators were compared between the two groups.The risk factors of SMPP were analyzed.The predictive value of the indicators was analyzed using receiver operating characteristic(ROC)curves.Results ①The relative expression level of CARDS toxin(Z=-6.151),D-dimer(Z=-5.102)and lactate dehydrogenase(LDH)(Z=-6.337)in SMPP group were significantly higher than those in control group(P<0.001).The white blood cell(Z=-2.155),neutrophil ratio(t=2.988)and C-reactive protein(CRP)(Z=-3.360)were higher than those in control group(P<0.05).②The relative expression of CARDS toxin was positively correlated with serum LDH(r=0.258,P<0.05).③Binary Logistic regression analysis showed that fever time(OR=1.271,95% CI:1.079-1.497),LDH(OR=1.011,95% CI:1.005-1.017)and CARDS toxin(OR=6.210,95% CI:2.646-14.577)were risk factors for SMPP.Conclusion CARDS toxin was closely related to MPP disease,and was significantly increased in SMPP group.CARDS toxin was one of the independent risk factors for SMPP and positively correlated with serum LDH level.It can be used as a good indicator to evaluate the condition,combined with fever time and LDH has clinical significance.

Objective:To explore the spousal correlations of total cholesterol(TC),total triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C),and to investigate the reasons behind these spousal correlations.Methods:Participants and data were from the baseline survey of family-based cohort studies in Fangshan,Beijing and Tulou,Fujian.The ori-gin of spousal correlations were explored from perspectives of convergence,assortative mating,social ho-mogamy.Pearson's correlation and generalized linear models(GLM)were used to estimate the spousal correlation.Convergence was assessed by Pearson's correlation between the phenotypic differences be-tween couples and the duration of marriage,with GLM used for further validation.Pearson's correlation of genetic risk scores(GRS)and couple-specific Mendelian randomization(MR)were calculated to assess the genetic correlation and possible causal relationships between spouses.Two-independent-sample t-tests were used to compare GRS consistency across subgroups divided by education attainment,couple-specific MR and Q statistics used to test assortative mating in subgroups and intergroup differences.Results:In the study,342 couples(287 couples from Fangshan and 55 couples from Fujian)were included,with the average age of(64.91±8.76)years.Spousal correlations of TC,TG,HDL-C,and LDL-C showed statistically significant associations both before and after adjusting for covariates,with effect sizes of 0.229(95％CI:0.125-0.327),0.257(95％CI:0.155-0.354),0.179(95％CI:0.074-0.280),and 0.181(95％CI:0.076-0.282).For convergence,for each additional year of marriage,ΔTC increased by 0.016 mmol/L(95％CI:0.001-0.033 mmol/L),and ΔLDL-C increased by 0.017 mmol/L(95％CI:0.002-0.031 mmol/L).For assortative mating,GRS correlations and results of couple specific MR didn't show any statistical significance.For social homogamy,no differences in GRS or assortative mating were found between subgroups stratified by education attainment.Conclusion:The blood lipid in participants exhibit spousal phenotypic correlations,however,no effects of convergence,assortative mating or social homogamy were observed.More independent studies with larger sample sizes are warranted to further validate these findings in the future.