Rheumatoid arthritis belongs to arthralgia in the theory of traditional Chinese medicine, with cold dampness obstruction pattern (CDO) and damp heat obstruction pattern (DHO) as the main pattern types. Fine therapeutic effects have been obtained in clinical practice following the differentiation of CDO and DHO. However, suitable animal models are not available currently. For adapting to the clinical diagnosis, as well as carrying out basic research of integrated Chinese and Western medicine and preclinical study on new Chinese medicine in a better way, the “Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold Dampness Obstruction Pattern and Damp Heat Obstruction Pattern” (referred to as “Guidelines”) were compiled by our research group in cooperation with renowned experts in clinical, pharmaceutical, zoological, and methodological research fields. According to the theory of disease and syndrome integration, experts standardized the establishment methods for animal models of rheumatoid arthritis with CDO and DHO. The Guidelines were compiled via the nominal group method according to the principle of evidence coming in main place, consensus as the auxiliary, and experience as the references. Contents such as animal species, arthritis induction methods, external stimulation conditions, and assessment indicators were specified in the Guidelines based on the comprehensive evaluation of pathogenesis homology, behavioral phenotypic consistency, and drug therapy predictability between animal models and human diseases. The Guidelines will be applicable to the research on syndromes in rheumatoid arthritis, elucidation of acting mechanism, and development of new medicine, and provide reference for standardizing other types of animal models with the integration of disease and syndrome, to promote the modernization of Chinese medicine research.

OBJECTIVES: This study aims to explore the association between single nucleotide polymorphisms (SNPs) loci near the haplotype region hg19 chr9:100560865-100660865 of the forkhead box E1 (FOXE1) gene and the occurrence of non-syndromic cleft lip with or without cleft palate (NSCL/P) in western Han Chinese population. METHODS: In the first stage, our study recruited 159 NSCL/P patients and performed targeted region sequencing to screen SNPs loci near the haplotype region of the FOXE1 gene associated with NSCL/P. In the second stage, we selected 21 common SNPs and re-enrolled 1 000 non-syndromic cleft lip only (NSCLO) patients, 1 000 non-syndromic cleft palate only (NSCPO) patients, and 1 000 normal controls to verify the association. PLINK software was used to perform Hardy-Weinberg equilibrium (HWE) test. Association analysis for common variants, gene burden analysis for rare mutations, and function prediction of SNPs with non-synonymous mutations were performed using Mutation Taster and other software programs. RESULTS: In the first stage, 126 variants, including 76 single nucleotide variants and 50 insertion-deletions were identified. All the included SNPs confirmed to HWE, and the results of gene burden analysis and prediction of functional harmfulness for rare variants were not statistically significant. Association analysis showed that rs13292899 of the FOXE1 gene was significantly associated with NSCL/P (P=1.85E-27) and was also correlated with NSCLO (P=6.41E-23) and non-syndromic cleft lip with cleft palate (NSCLP) (P=2.36E-15) subtypes. In the validation phase, rs79268293 (P=0.013, P=0.022), rs10983951 (P=0.009 2, P=0.007 6), rs117227387 (P=0.009 2, P=0.007 6), rs3758250 (P=0.009 2, P=0.007 6), and rs116899397 (P=0.009 2, P=0.007 6) were significantly associated with NSCLO and NSCPO; rs13292899 (P=0.008 5), rs74606599 (P=0.008 3), rs143226042 (P=0.008 3), and rs117236550 (P=0.01) were associated with the occurrence of NSCLO; and rs12343182 (P=0.008 7), rs10119760 (P=0.012), rs10113907 (P=0.012), and rs13299924 (P=0.012) were associated with the occurrence of NSCPO. CONCLUSIONS This study found a new susceptible SNP rs13292899 of the FOXE1 gene that is closely associated with NSCL/P and NSCLO subtype and 13 other SNPs associated with NSCLO or NSCPO.
Female ; Humans ; Male ; China ; Cleft Lip/genetics* ; Cleft Palate/genetics* ; Forkhead Transcription Factors/genetics* ; Haplotypes ; Polymorphism, Single Nucleotide ; East Asian People/genetics*

Objective:To investigate the impact of the number of cesarean deliveries on adverse maternal and neonatal outcomes.Methods:A retrospective analysis was conducted on 11 904 singleton pregnant women who underwent cesarean delivery at the Third Affiliated Hospital of Guangzhou Medical University from January 1st, 2019 to December 31st, 2023. The women were grouped according to the number of cesarean deliveries: those undergoing their first cesarean delivery (1CD group, 7 231 cases), those undergoing their second cesarean delivery (2CD group, 3 749 cases), those undergoing their third cesarean delivery (3CD group, 841 cases), and those undergoing their fourth or more cesarean deliveries (4CD group, 83 cases). Differences in clinical characteristics, related surgical procedures, and adverse maternal and neonatal outcomes among the groups were compared. Binary logistic regression analysis was used to assess the impact of the number of cesarean deliveries on related surgical procedures and adverse maternal and neonatal outcomes.Results:(1) During the 5-year period, the total number of women undergoing cesarean delivery in our hospital showed a slight downward trend, while the proportion of women undergoing three or more cesarean deliveries increased. (2) Compared with women undergoing their first cesarean delivery, women in each repeat cesarean delivery group were older, had higher proportions of advanced maternal age and pre-pregnancy body mass index, and had more pregnancies, deliveries, and induced abortions; the incidence of placenta previa, placental implantation, antepartum hemorrhage, gestational hyperglycemia, and failed trial of labor requiring conversion to surgery was higher, while the incidence of premature rupture of membranes was lower; the proportions of ureteral stent placement, adhesiolysis of the pelvic and abdominal cavities, uterine rupture, uterine reconstruction, uterine artery ligation, hysterectomy, postpartum hemorrhage, and postoperative intestinal obstruction were higher, and the amount of postpartum hemorrhage was greater; the gestational age at delivery of neonates was earlier, but the rates of preterm birth at 28-31 +6 and 32-33 +6 weeks of gestation were lower; the differences were statistically significant ( P<0.05) for all comparisons. (3) The number of cesarean deliveries was not an independent risk factor for the dose-dependent occurrence of placenta previa (a OR=0.99, 95% CI: 0.98-1.01; P=0.261). In women without placenta previa, the number of cesarean deliveries was not a risk factor for placental implantation (a OR=1.12, 95% CI: 0.90-1.39; P=0.320). However, in women with placenta previa, the number of cesarean deliveries was a risk factor for placental implantation (a OR=4.01, 95% CI: 3.08-5.22; P<0.001). In the overall population, the number of cesarean deliveries was a risk factor for ureteral stent placement, adhesiolysis of the pelvic and abdominal cavities, bladder rupture repair, uterine rupture, uterine reconstruction, uterine artery ligation, hysterectomy, postpartum hemorrhage, and preterm birth (all P<0.05). However, the number of cesarean deliveries was not a risk factor for postoperative intestinal obstruction, admission to the intensive care unit, neonatal asphyxia, admission to the neonatal intensive care unit, or neonatal death (all P<0.05). Conclusions:The number of cesarean deliveries could lead to adverse maternal and neonatal outcomes, but the relationship is not simply dose-dependent. It is speculated that the occurrence of severe adverse maternal and neonatal outcomes is more closely related to maternal complications and comorbidities, as well as whether multidisciplinary comprehensive management was received.

Rheumatoid arthritis belongs to arthralgia syndrome in the theory of traditional Chinese medicine， and cold-dampness obstruction syndrome and dampness-heat obstruction syndrome are core syndromes and main syndrome differentiation types of this disease. Fine therapeutic effects have been obtained in the long-term clinical practice of many famous traditional Chinese medicine practitioners following the syndrome differentiation and treatment based on the guiding principles of cold and heat. To adapt to the clinical diagnosis practice of combining disease differentiation and syndrome differentiation， and to better carry out basic research on integrated Chinese and Western medicine and preclinical study on new traditional Chinese medicines， Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold-Dampness Obstruction Syndrome and Dampness-Heat Obstruction Syndrome （hereinafter referred to as the Guidelines） were compiled by our research group， in cooperation with the renowned experts in research fields including traditional Chinese medicine， clinical medicine， zoology and evidence-based medicine， which provide a meaningful reference for scientific research， teaching and clinical applications. The compilation process of the Guidelines was guided by the theory of disease and syndrome integration and the principles of "evidence takes the main place， consensus plays an auxiliary role， and experience serves as the reference". Based on the comprehensive evaluation of pathogenesis homology， behavioral phenotypic consistency， and drug treatment predictability compared between animal models and human diseases， by the nominal group method， "recommendations" were formed for recommendations supported by evidence， and "consensus recommendations" were formed for recommendations not supported by evidence. Guidelines were formed involving content such as animal types， arthritis modeling methods， external stimulation conditions， and modeling assessment indicators during the establishment of the animal models of rheumatoid arthritis with cold-dampness obstruction syndrome and dampness-heat obstruction syndrome. The Guidelines are applicable for the disease and syndrome research on rheumatoid arthritis， investigation of therapeutic mechanisms， and development of new traditional Chinese medicine. The Guidelines also provide a reference for the establishment of guidelines on other types of diseases and syndromes combined with animal models to further promote the modernization of traditional Chinese medicine research and its integration with international academic development.

The Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold-dampness Obstruction Syndrome and Dampness-heat Obstruction Syndrome （hereinafter referred to as the Guidelines） （No. T/CACM1567-2024） was published by Chinese Association of Chinese Medicine on January 11， 2024. To assist researchers and medical workers in understanding and applying the Guidelines more accurately， and also to provide reference and assistance for the establishment of guidelines on other types of diseases and syndromes combined with animal models， this paper made a declaration of the workflow， technological links， development references， promotion of its application and after-effect evaluation of the Guidelines that has been made according to the requirements of "Draft Group Standard of the Standardization Office of the Chinese Association of Traditional Chinese Medicine".

Objective:To explore the operioperative and long-term outcomes of inflatable mediastinoscopic resection of esophageal carcinoma (IVMTE) and minimally invasive Mckeown resection of esophageal carcinoma (MIME) in early esophageal cancer.Methods:This is a retrospective cohort study. A retrospectively analysis was conducted on 176 patients with cT1N0M0 esophageal cancer who underwent IVMTE or MIME at the Department of Thoracic Surgery, Anhui Provincial Hospital Affiliated with Anhui Medical University from April 2017 to April 2019. There were 128 males and 48 females, aged (66.4±7.7) years (range: 45 to 87 years). General data, perioperative outcomes, pathological data of the tumors, and complications were recorded. Independent sample t-test, χ2 test, or Wilcoxon rank-sum test was used to compare the data between the two groups. Propensity score matching was performed with gender, age, tumor location, differentiation degree, pT stage, pN stage, American Society of Anesthesiologists (ASA) classification, smoking history, and alcohol history were considered as covariates. The IVMTE group and MIME group were matched in a 1∶2 ratio using nearest neighbor match method with a caliper value of 0.02. Kaplan-Meier method was used to plot survival curves, with Log-rank test for univariate survival analysis. The Cox proportional hazards model was applied to analyze prognostic factors for overall survival, and subgroup stratification analysis was performed for pT stage. Results:After matching, the MIME group consisted of 54 cases, and the IVMTE group consisted of 27 cases. There were no statistically significant differences between the two groups in terms of gender, age, smoking history, alcohol history, ASA classification, tumor location, and other factors. The IVMTE group had shorter surgery time ( M(IQR), 220 (45) minutes vs. 245 (56) minutes, Z=2.950, P=0.003) and less intraoperative blood loss (100 (50) ml vs. 125 (100) ml, Z=2.193, P=0.028) compared to the MIME group. There were no differences between the two groups in the number and quantity of lymph node stations dissected, and the IVMTE group was not at a disadvantage in terms of the number of lymph nodes dissected around the recurrent laryngeal nerve (all P>0.05). The 1-, 3-, and 5-year overall survival (OS) rates and recurrence-free survival (RFS) rates were not significantly different between the two groups (all P>0.05). Subgroup analysis showed no significant difference in OS and RFS rates between the pT1 and pT2 subgroups (all P>0.05). Multivariate Cox regression analysis suggested that ASA classification ( HR=2.516, 95% CI: 1.126 to 5.624, P=0.025), pN stage ( HR=2.485, 95% CI: 0.984 to 6.274, P=0.046), and whether adjuvant therapy was given postoperatively ( HR=2.915, 95% CI: 1.304 to 6.515, P=0.009) were independent risk factors affecting 5-year OS rate. For 5-year RFS, pT stage ( HR=0.403, 95% CI: 0.194 to 0.838, P=0.011), pN stage ( HR=5.219, 95% CI: 2.401 to 11.346, P<0.01), and whether adjuvant therapy was given postoperatively ( HR=5.644, 95% CI: 2.691 to 11.838, P<0.01) were independent risk factors, while the surgical approach was not an independent risk factor affecting patient prognosis. Conclusion:The short-term and long-term effect of IVMTE in the treatment of early esophageal cancer is good, and it can achieve effects comparable to MIME.

Objectives:To summarize the characteristics of Fabry′s disease with cardiac involvement.Methods:This was a single-center, cross-sectional, retrospective study. Patients with Fabry disease who were admitted to Zhongda Hospital Affiliated to Southeast University from January 2022 to March 2023 were included. Clinical data, laboratory results, electrocardiogram, echocardiography and cardiac magnetic resonance findings of enrolled patients were collected. Clinical presentations and imaging features of patients with Fabry′s disease with cardiac involvement were summarized and analyzed.Results:A total of 17 patients from 8 families were included, with 9 males and diagnosis age of (44.35±13.72) years. Cardiac involvement and other organ involvement were presented in all patients and the heart was the most vulnerable organ (17/17). 24 h electrocardiogram showed frequent sinus arrhythmia in 3 patients. Echocardiography showed reduced left ventricular ejection fraction in 1 patient, myocardial hypertrophy in 13 patients, and left ventricular wall thickness ≥13 mm in 10 patients. Mitral regurgitation was observed in 11 patients and tricuspid regurgitation in 12 patients. Two patients underwent two-dimensional speckle tracking echocardiography, both revealing reduced regional longitudinal strain of the left ventricle, primarily in the basal segments. Cardiac magnetic resonance showed reduced left ventricular ejection fraction in 2 patients, myocardial hypertrophy in 16 patients, and left ventricular wall thickness≥13 mm in 14 patients. T1 value was reduced in 16 patients, with late gadolinium enhancement observed in 9 patients and “pseudo-normalization” of T1 values in 1 patient. The most susceptible target organ besides the heart was the kidneys (14/17), followed by the central nervous system (9/17). Additional findings inclucling cutaneous angiokeratoma in 4 patients, peripheral neuropathy with burning pain and hypohidrosis or hyperhidrosis in 6 patients, and corneal vortex opacities in 2 patients.Conclusion:The main manifestations of cardiac involvement in Fabry′s disease are decreased cardiac function, left ventricular hypertrophy and myocardial fibrosis. Advanced imaging techniques such as two-dimensional speckle tracking, T1 Mapping, and late gadolinium enhancement are useful in detecting myocardial pathological changes of Fabry′s disease.

Objective:To investigate the impact of the number of cesarean deliveries on adverse maternal and neonatal outcomes.Methods:A retrospective analysis was conducted on 11 904 singleton pregnant women who underwent cesarean delivery at the Third Affiliated Hospital of Guangzhou Medical University from January 1st, 2019 to December 31st, 2023. The women were grouped according to the number of cesarean deliveries: those undergoing their first cesarean delivery (1CD group, 7 231 cases), those undergoing their second cesarean delivery (2CD group, 3 749 cases), those undergoing their third cesarean delivery (3CD group, 841 cases), and those undergoing their fourth or more cesarean deliveries (4CD group, 83 cases). Differences in clinical characteristics, related surgical procedures, and adverse maternal and neonatal outcomes among the groups were compared. Binary logistic regression analysis was used to assess the impact of the number of cesarean deliveries on related surgical procedures and adverse maternal and neonatal outcomes.Results:(1) During the 5-year period, the total number of women undergoing cesarean delivery in our hospital showed a slight downward trend, while the proportion of women undergoing three or more cesarean deliveries increased. (2) Compared with women undergoing their first cesarean delivery, women in each repeat cesarean delivery group were older, had higher proportions of advanced maternal age and pre-pregnancy body mass index, and had more pregnancies, deliveries, and induced abortions; the incidence of placenta previa, placental implantation, antepartum hemorrhage, gestational hyperglycemia, and failed trial of labor requiring conversion to surgery was higher, while the incidence of premature rupture of membranes was lower; the proportions of ureteral stent placement, adhesiolysis of the pelvic and abdominal cavities, uterine rupture, uterine reconstruction, uterine artery ligation, hysterectomy, postpartum hemorrhage, and postoperative intestinal obstruction were higher, and the amount of postpartum hemorrhage was greater; the gestational age at delivery of neonates was earlier, but the rates of preterm birth at 28-31 +6 and 32-33 +6 weeks of gestation were lower; the differences were statistically significant ( P<0.05) for all comparisons. (3) The number of cesarean deliveries was not an independent risk factor for the dose-dependent occurrence of placenta previa (a OR=0.99, 95% CI: 0.98-1.01; P=0.261). In women without placenta previa, the number of cesarean deliveries was not a risk factor for placental implantation (a OR=1.12, 95% CI: 0.90-1.39; P=0.320). However, in women with placenta previa, the number of cesarean deliveries was a risk factor for placental implantation (a OR=4.01, 95% CI: 3.08-5.22; P<0.001). In the overall population, the number of cesarean deliveries was a risk factor for ureteral stent placement, adhesiolysis of the pelvic and abdominal cavities, bladder rupture repair, uterine rupture, uterine reconstruction, uterine artery ligation, hysterectomy, postpartum hemorrhage, and preterm birth (all P<0.05). However, the number of cesarean deliveries was not a risk factor for postoperative intestinal obstruction, admission to the intensive care unit, neonatal asphyxia, admission to the neonatal intensive care unit, or neonatal death (all P<0.05). Conclusions:The number of cesarean deliveries could lead to adverse maternal and neonatal outcomes, but the relationship is not simply dose-dependent. It is speculated that the occurrence of severe adverse maternal and neonatal outcomes is more closely related to maternal complications and comorbidities, as well as whether multidisciplinary comprehensive management was received.

Objective Study on the relationship between detection of 10 driver gene mutations in non-small cell lung cancer tis-sues and clinical pathological characteristics,as well as the diagnostic value of multi gene combined models.Methods Selected 79 patients diagnosed with NSCLC in Zhongshan People's Hospital from December 2022 to April 2023 as the research objects,collected tissue samples,used PCR technology for mutation detection,obtain the detection rate of each driver gene,and explore gene mutations and NSCLC patients correlation of clinicopathological characteristics.Logistic regression method was used to es-tablish a multi-gene joint model of joint predictors and evaluate its diagnostic value.Results Among the 79 cases,the total muta-tion rate of the ten driving genes was 81.01%(64/79),Among them the mutation rate of EGFR was 54.43%(43/79),the mutation frequency of KRAS was 13.92%(11/79),the mutation rate of HER2 was 3.80%(3/79),the fusion frequency of ALK was 2.53%(2/79),the fusion frequency of ROS1 was 2.53%(2/79),the mutation rate of MET was 2.53%(2/79),the mutation rate of NRAS was 1.27%(1/79),and no mutations were detected in RET,BRAF and PIK3CA.The mutation frequency of EGFR in fe-male patients was higher than that in males(χ2=20.512,P<0.001),ALK fusion was also more common in females(χ2=192.080,P<0.001),while KRAS was the opposite.The mutation frequency in male patients was higher than that in females(χ2=4.545,P<0.05).EGFR mutations were more common in individuals＜60 years old(χ2=33.907,P<0.001),while KRAS mutations had a higher individuals in patients≥60 years old than in those＜60 years old(χ2=8.909,P<0.001).The positive mutation of EGFR was more common in stage IV patients(χ2=15.429,P<0.001).ROS1 fusion is more common in stage III b patients(χ2=4.000,P<0.05),EGFR mutation had a significantly higher mutation rate in non-smoking patients than in smoking patients(χ2=50.651,P<0.001),and ALK fusion had a higher mutation rate in smoking patients than in non-smoking patients(χ2=4.000,P<0.05).Con-structed a Logistic regression model to evaluate the diagnostic value of driver gene joint detection,and constructed a Logistic re-gression model to predict the occurrence of NSCLC in patients.The model expression was:logit(P)=-0.190+0.168 EGFR muta-tion(X1)+0.516 KRAS mutation(X2)+0.331 ALK fusion(X3)+0.403 ROS1 fusion(X4)+0.429 NRAS mutation(X5)+0.515 HER2 mutation(X6)+0.405 MET mutation(X7).The ROC curve results show that the diagnostic value of the joint prediction model for NSCLC was higher than that of a single indicator.Conclusion There is a correlation between driver gene mutation status and pathological characteristics,and the co-mutation information provided by multi-gene joint detection can make a more accurate diagnosis of NSCLC.

Objective Study on the relationship between detection of 10 driver gene mutations in non-small cell lung cancer tis-sues and clinical pathological characteristics,as well as the diagnostic value of multi gene combined models.Methods Selected 79 patients diagnosed with NSCLC in Zhongshan People's Hospital from December 2022 to April 2023 as the research objects,collected tissue samples,used PCR technology for mutation detection,obtain the detection rate of each driver gene,and explore gene mutations and NSCLC patients correlation of clinicopathological characteristics.Logistic regression method was used to es-tablish a multi-gene joint model of joint predictors and evaluate its diagnostic value.Results Among the 79 cases,the total muta-tion rate of the ten driving genes was 81.01%(64/79),Among them the mutation rate of EGFR was 54.43%(43/79),the mutation frequency of KRAS was 13.92%(11/79),the mutation rate of HER2 was 3.80%(3/79),the fusion frequency of ALK was 2.53%(2/79),the fusion frequency of ROS1 was 2.53%(2/79),the mutation rate of MET was 2.53%(2/79),the mutation rate of NRAS was 1.27%(1/79),and no mutations were detected in RET,BRAF and PIK3CA.The mutation frequency of EGFR in fe-male patients was higher than that in males(χ2=20.512,P<0.001),ALK fusion was also more common in females(χ2=192.080,P<0.001),while KRAS was the opposite.The mutation frequency in male patients was higher than that in females(χ2=4.545,P<0.05).EGFR mutations were more common in individuals＜60 years old(χ2=33.907,P<0.001),while KRAS mutations had a higher individuals in patients≥60 years old than in those＜60 years old(χ2=8.909,P<0.001).The positive mutation of EGFR was more common in stage IV patients(χ2=15.429,P<0.001).ROS1 fusion is more common in stage III b patients(χ2=4.000,P<0.05),EGFR mutation had a significantly higher mutation rate in non-smoking patients than in smoking patients(χ2=50.651,P<0.001),and ALK fusion had a higher mutation rate in smoking patients than in non-smoking patients(χ2=4.000,P<0.05).Con-structed a Logistic regression model to evaluate the diagnostic value of driver gene joint detection,and constructed a Logistic re-gression model to predict the occurrence of NSCLC in patients.The model expression was:logit(P)=-0.190+0.168 EGFR muta-tion(X1)+0.516 KRAS mutation(X2)+0.331 ALK fusion(X3)+0.403 ROS1 fusion(X4)+0.429 NRAS mutation(X5)+0.515 HER2 mutation(X6)+0.405 MET mutation(X7).The ROC curve results show that the diagnostic value of the joint prediction model for NSCLC was higher than that of a single indicator.Conclusion There is a correlation between driver gene mutation status and pathological characteristics,and the co-mutation information provided by multi-gene joint detection can make a more accurate diagnosis of NSCLC.