Background Intrauterine growth restriction (IUGR) is closely associated with placental dysfunction. However, the effects of preconception co-exposure to β-cypermethrin (β-CYP) and emamectin benzoate (EMB) on fetal growth and placental function remain unclear. Objective To investigate the effects of prenatal exposure to β-CYP and EMB on embryonic development in female rats and to elucidate the mechanisms by which these substances cause IUGR from the perspectives of placental structure, progesterone synthesis, and mitochondrial autophagy. Methods Forty-eight specific pathogen-free (SPF) adult female Sprague-Dawley (SD) rats were randomly assigned to a control group, a β-CYP group, an EMB group, and a co-exposure group (n=12 per group). A whole-body dynamic inhalation exposure system was used to simulate greenhouse exposure. Rats in the control group were exposed to clean air, whereas those in the exposure groups were exposed to β-CYP (55 mg·m⁻³), EMB (7.8 mg·m⁻³), or their combination for 2 h per day for 90 consecutive days. After exposure, ovarian and serum estradiol (E₂) levels were determined in six rats from each group, while the remaining six rats were mated. Of the mated rats, three per group were sacrificed on gestational day 18, and the other remaining three were allowed to deliver naturally. Pregnancy outcomes and fetal development were evaluated. Placental morphology, progesterone (Prog) levels, progesterone synthesis-related factors, oxidative stress, mitochondrial function, and mitophagy-related indicators were subsequently assessed. Results Compared with the control group, fetal body weight on gestational day 18 and neonatal body weight were significantly decreased, whereas the incidence of IUGR was significantly increased in the β-CYP, EMB, and co-exposure groups (P<0.05). The EMB and co-exposure groups exhibited an increased proportion of the placental junctional zone thickness to total placental thickness and a reduced proportion of the labyrinth zone (P<0.05). Ovarian E₂ and placental Prog levels were decreased in all three exposure groups. In addition, the placental expression of cytochrome P450 family 11 subfamily A member1(CYP11A1)、3β-hydroxysteroid dehydrogenase type 1(HSD3B1)、progesterone receptor(PgR) was downregulated, catalase (CAT) activity and adenosine triphosphate (ATP) content were reduced, and lactate dehydrogenase (LDH) activity was increased in all exposure groups (P < 0.05). Furthermore, the expression of translocase of outer mitochondrial membrane 2 was decreased, whereas the expression levels of microtubule-associated protein 1 light chain 3 (LC3), PTEN-induced kinase 1 (PINK1), parkin RBR E3 ubiquitin-protein ligase (Parkin), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) were increased in all exposure groups (P<0.05). Conclusion Prenatal exposure to β-CYP and EMB can cause structural damage to the rat placenta, affect the expression of markers related to progesterone synthesis, and is accompanied by oxidative stress, mitochondrial dysfunction, and alterations in PINK1/Parkin-mediated mitochondrial autophagy, ultimately affecting the intrauterine growth and development of the fetus.

Adolescent idiopathic scoliosis(AIS)is a complex three-dimensional deformity involving coronal,sagittal,and axial planes,with a prevalence that should not be overlooked.With advancements in technology and in-depth research,an increasing number of hospitals and physicians are exploring standardized diagnostic and treatment approaches for AIS.Comprehensive and in-depth understanding is required for AIS,including its etiology,screening and diagnosis,classification,assessment and examination,treatment options,exploration of current focus,and evaluation of quality of life.Such understanding ensures that the diagnostic and treatment are scientific,standardized,and timely.Based on the principles of evidence-based medicine,a consensus on the diagnosis and treatment of AIS is reached after multiple discussions among spinal surgery experts,aiming to provide reference and guidance for clinical practice.

Objective:To explore the clinical and pathological features and survival outcomes of patients with early-onset intrahepatic cholangiocarcinoma (EOICC).Methods:This is a multicenter, retrospective cohort study. Data of 1 160 intrahepatic cholangiocarcinoma patients undergoing radical resection in 14 tertiary Grade A hospitals in China from January 2010 to November 2021 were retrospectively collected. The cohort included 632 males and 528 females, aged( M (IQR)) 61 (14) years (range: 22 to 93 years). ICC aged ≤50 years at the time of diagnosis was defined as EOICC and >50 years as late-onset intrahepatic cholangiocarcinoma (LOICC). Of these, there were 247 cases in the EOICC group and 913 cases in the LOICC. The clinical and pathological characteristics of both groups were analyzed and compared using the independent sample t-test, Mann-Whitney U test or Kaplan-Meier method. Univariate and multivariate Cox regression models for patient outcomes were constructed and forest graphed. Results:Compared with the patients in the LOICC group, patients in the EOICC group had lower carcinoembryonic antigen levels (2.5(4.0) μg/L vs. 3.1(5.2)μg/L, U=124 899, P=0.009) and CA19-9 level (63.4(524.7)U/ml vs. 77.9(611.3)U/ml, U=120 320, P=0.013), higher levels of ALT (29(35)U/L vs. 24(26)U/L, U=101 214, P=0.013), a lower score of the Eastern US Cooperative Oncology Group (0 score patients: 54.7% vs. 44.1%, χ2=12.472, P=0.014), higher TNM stage ( χ2=11.807, P=0.038), and proportion of lymph node dissection (62.3% vs. 54.1%, χ2=5.355, P=0.021). Patients in the two groups in sex, first diagnosis symptoms, intrahepatic bile duct stone history, nail protein, albumin, total bilirubin, transaminase, liver function Child-Pugh grade, T stage, stage, N stage, preoperative laparoscopic exploration proportion, tumor diameter, vascular invasion proportion, differentiation, margin, intraoperative bleeding, postoperative complications, postoperative hospital days were no statistical significance (all P>0.05). Patients in the EOICC group had better outcomes than the LOICC group (median survival time: 29.7 months vs. 25.0 months, 3-year overall survival: 45.1% vs. 37.8%, P=0.027). Conclusion:EOICC patients are better than LOICC patients in carcinoembryonic antigen, CA19-9, ALT, physical strength status and TNM stage, and the long-term prognosis is also better than LOICC patients.

Epitope vaccine is a novel strategy for vaccine development in recent years,exhibiting ad-vantages such as safety,and the ability to induce specific humoral and cellular immune responses a-gainst pathogens.Among them,the identification and delivery of epitopes are crucial in the design of multi-epitope vaccines.Compared to traditional methods of antigenic epitope identification,vari-ous new techniques such as bioinformatics,ELIspot,and intracellular cytokine staining have been developed.Since the direct immunization of multi-epitope peptides results in low protective effica-cy,efficient delivery systems are urgently needed.The antigenic epitopes commonly used delivery systems include viral vectors,and non-virus vectors such as nanoparticles,etc.Additionally,to en-hance the immunization efficacy of vaccines,antigenic epitopes are usually modified,including mul-tiple epitopes in tandem and epitope targeting modification and other strategies.This review sum-marizes the methods for accurate identification of antigenic epitopes with well immunogenicity as well as effective delivery strategies for antigenic epitopes,providing new insight into the develop-ment of novel multi-epitope vaccines.

Epitope vaccine is a novel strategy for vaccine development in recent years,exhibiting ad-vantages such as safety,and the ability to induce specific humoral and cellular immune responses a-gainst pathogens.Among them,the identification and delivery of epitopes are crucial in the design of multi-epitope vaccines.Compared to traditional methods of antigenic epitope identification,vari-ous new techniques such as bioinformatics,ELIspot,and intracellular cytokine staining have been developed.Since the direct immunization of multi-epitope peptides results in low protective effica-cy,efficient delivery systems are urgently needed.The antigenic epitopes commonly used delivery systems include viral vectors,and non-virus vectors such as nanoparticles,etc.Additionally,to en-hance the immunization efficacy of vaccines,antigenic epitopes are usually modified,including mul-tiple epitopes in tandem and epitope targeting modification and other strategies.This review sum-marizes the methods for accurate identification of antigenic epitopes with well immunogenicity as well as effective delivery strategies for antigenic epitopes,providing new insight into the develop-ment of novel multi-epitope vaccines.

Objective:To explore the clinical and pathological features and survival outcomes of patients with early-onset intrahepatic cholangiocarcinoma (EOICC).Methods:This is a multicenter, retrospective cohort study. Data of 1 160 intrahepatic cholangiocarcinoma patients undergoing radical resection in 14 tertiary Grade A hospitals in China from January 2010 to November 2021 were retrospectively collected. The cohort included 632 males and 528 females, aged( M (IQR)) 61 (14) years (range: 22 to 93 years). ICC aged ≤50 years at the time of diagnosis was defined as EOICC and >50 years as late-onset intrahepatic cholangiocarcinoma (LOICC). Of these, there were 247 cases in the EOICC group and 913 cases in the LOICC. The clinical and pathological characteristics of both groups were analyzed and compared using the independent sample t-test, Mann-Whitney U test or Kaplan-Meier method. Univariate and multivariate Cox regression models for patient outcomes were constructed and forest graphed. Results:Compared with the patients in the LOICC group, patients in the EOICC group had lower carcinoembryonic antigen levels (2.5(4.0) μg/L vs. 3.1(5.2)μg/L, U=124 899, P=0.009) and CA19-9 level (63.4(524.7)U/ml vs. 77.9(611.3)U/ml, U=120 320, P=0.013), higher levels of ALT (29(35)U/L vs. 24(26)U/L, U=101 214, P=0.013), a lower score of the Eastern US Cooperative Oncology Group (0 score patients: 54.7% vs. 44.1%, χ2=12.472, P=0.014), higher TNM stage ( χ2=11.807, P=0.038), and proportion of lymph node dissection (62.3% vs. 54.1%, χ2=5.355, P=0.021). Patients in the two groups in sex, first diagnosis symptoms, intrahepatic bile duct stone history, nail protein, albumin, total bilirubin, transaminase, liver function Child-Pugh grade, T stage, stage, N stage, preoperative laparoscopic exploration proportion, tumor diameter, vascular invasion proportion, differentiation, margin, intraoperative bleeding, postoperative complications, postoperative hospital days were no statistical significance (all P>0.05). Patients in the EOICC group had better outcomes than the LOICC group (median survival time: 29.7 months vs. 25.0 months, 3-year overall survival: 45.1% vs. 37.8%, P=0.027). Conclusion:EOICC patients are better than LOICC patients in carcinoembryonic antigen, CA19-9, ALT, physical strength status and TNM stage, and the long-term prognosis is also better than LOICC patients.

Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.

Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.

OBJECTIVE: To establish the dynamic treatment strategy of Chinese medicine (CM) for metastatic colorectal cancer (mCRC) by machine learning algorithm, in order to provide a reference for the selection of CM treatment strategies for mCRC. METHODS: From the outpatient cases of mCRC in the Department of Oncology at Xiyuan Hospital, China Academy of Chinese Medical Sciences, 197 cases that met the inclusion criteria were screened. According to different CM intervention strategies, the patients were divided into 3 groups: CM treatment alone, equal emphasis on Chinese and Western medicine treatment (CM combined with local treatment of tumors, oral chemotherapy, or targeted drugs), and CM assisted Western medicine treatment (CM combined with intravenous regimen of Western medicine). The survival time of patients undergoing CM intervention was taken as the final evaluation index. Factors affecting the choice of CM intervention scheme were screened as decision variables. The dynamic CM intervention and treatment strategy for mCRC was explored based on the cost-sensitive classification learning algorithm for survival (CSCLSurv). Patients' survival was estimated using the Kaplan-Meier method, and the survival time of patients who received the model-recommended treatment plan were compared with those who received actual treatment plan. RESULTS: Using the survival time of patients undergoing CM intervention as the evaluation index, a dynamic CM intervention therapy strategy for mCRC was established based on CSCLSurv. Different CM intervention strategies for mCRC can be selected according to dynamic decision variables, such as gender, age, Eastern Cooperative Oncology Group score, tumor site, metastatic site, genotyping, and the stage of Western medicine treatment at the patient's first visit. The median survival time of patients who received the model-recommended treatment plan was 35 months, while those who receive the actual treatment plan was 26.0 months (P=0.06). CONCLUSIONS The dynamic treatment strategy of CM, based on CSCLSurv for mCRC, plays a certain role in providing clinical hints in CM. It can be further improved in future prospective studies with larger sample sizes.
Humans ; Colorectal Neoplasms/therapy* ; Machine Learning ; Female ; Male ; Middle Aged ; Neoplasm Metastasis ; Algorithms ; Medicine, Chinese Traditional/methods* ; Aged ; Adult ; Kaplan-Meier Estimate

Objective To investigate the current situation of skin tests for β-lactams in 155 hospitals in Beijing.Methods The questionnaires were sent to medical institutions in Beijing to statistically described the current situation of β-lactams skin test,and the relevant influencing factors were analyzed by Fisher exact test,and Chi-square test.Results A total of 3 097 questionnaires were received from 155 medical institutions,of which 3 057 were valid questionnaires(effective rate is 98.71％).In this study,122 hospitals conducted skin test before using intravenous penicillins,accounting for 99.19％of 123 hospitals with intravenous penicillins.Hospitals with infectious disease pharmacists conducted more skin tests before using intravenous penicillins(98.59％vs 88.46％,P＜0.001),and some hospitals didn't conduct skin tests before using oral penicillins.Seventy hospitals(45.16％)had not yet cancelled skin tests for cephalosporins,more hospitals with infectious disease pharmacists cancelled routine skin test(59.74％vs 50.00％,P＜0.05),and more tertiary hospitals cancelled cephalosporin skin test(80.65％vs 51.40％,29.41％,all P＜0.01).After the promulgation of the"Guiding Principle for Skin Test of β-lactams(2021 edition)",more primary hospitals have developed or updated the rules or regulation for skin test of β-lactams according to the Guiding Principle,compared with secondary hospitals(72.22％vs 41.18％,P＜0.05).Hospitals with infectious disease pharmacists developed or updated the rules or regulation for skin test of β-lactams in their hospitals(78.57％vs 60.00％,P＜0.05).Infectious disease pharmacists had promoting effect on the publicity of the rules or regulation of skin test in the hospital(92.65％vs 80.46％,P＜0.05).Conclusion Many hospitals in Beijing have not cancelled cephalosporins skin test,and the current situation of cancelling cephalosporins skin test in tertiary hospitals is better than that in primary and secondary hospitals.