The guideline and item classification approach represents a distinct historical method ology, first introduced by ZHU Xi in his Compendium of Comprehensive Mirror for Aid in Government during the Southern Song Dynasty. LOU Ying later adapted this framework to the field of traditional Chinese medicine, critically analyzing and addressing the limitations of prior academic theories. By drawing upon the rich intellectual traditions of classical texts and historical works, LOU Ying restructured and refined his ideas, ultimately establishing the "guideline and item" medical theory. This innovative framework profoundly influenced LOU Ying′s work, shaping both the compilation of medical texts and the development of novel theoretical approaches in traditional Chinese medicine. In disease differentiation and treatment, LOU Ying proposed the theory of guideline and item classification, that is, taking yin and yang as two guidelines, taking qi and blood, exterior and interior, upper and lower parts, deficiency and excess, cold and heat as ten items, and constructing a syndrome differentiation system focusing on qi and blood, focusing solely on upper and lower parts, distinguishing exterior and interior, carefully examining deficiency and excess, and distinguishing cold and heat. The guideline and item classification system integrates and harmonizes multiple syndrome differentiation method ologies, including the eight-principle pattern identification, viscera syndrome differentiation, differentiation of syndromes according to the pathogenesis of Sanjiao, and qi-blood-fluid pattern identification. As a precursor to modern method of syndrome differentiation and treatment, it possesses unique theoretical significance and considerable clinical relevance. Its applicability to diagnosing and treating various diseases, coupled with its greater operational practicality compared to other methods, highlights its value in contemporary clinical practice. This system offers a complementary and enhanced framework for syndrome differentiation and treatment, warranting further adoption and promotion in the clinical setting.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Flowering and bolting are important agronomic traits in cruciferous crops such as Brassica juncea. Timely flowering can ensure the crop organ yield and quality, as well as seed propagation. The WRKY family plays an important role in regulating plant bolting and flowering, while the function and mechanism of WRKY12 in B. juncea remain unknown. To explore its function and mechanism in bolting and flowering of B. juncea, we cloned and characterized the BjuWRKY12 gene in B. juncea and found that its expression levels were significantly higher in flowers and inflorescences than in leaves. BjuWRKY12 belonged to the Ⅱc subfamily of the WRKY family, and subcellular localization indicated that the protein was located in the nucleus. Ectopic overexpression of BjuWRKY12 in transgenic lines promoted bolting and flowering, leading to significant increases in the expression levels of flowering integrators SOC1 and FUL. Furthermore, yeast one-hybrid and dual luciferase reporter system assays confirmed that BjuWRKY12 directly bound to the promoters of BjuSOC1 and BjuFUL, undergoing protein-DNA interactions. This discovery gives new insights into the regulation network and molecular mechanisms of BjuWRKY12, laying a theoretical foundation for the breeding of high-yield and high-quality varieties of B. juncea.
Mustard Plant/metabolism* ; Flowers/growth & development* ; Plant Proteins/physiology* ; Promoter Regions, Genetic/genetics* ; Gene Expression Regulation, Plant ; Plants, Genetically Modified/genetics* ; Transcription Factors/metabolism* ; MADS Domain Proteins/metabolism*

ObjectiveTo screen out the transcriptomes related to the intervention of Wuzi Yanzongwan on the spermatogenic function of semi-castrated male mice， and to explore its potential mechanism in the intervention of the progress of low spermatogenic function. MethodBalb/c mice were randomly divided into sham-operated group， model group， testosterone propionate group（0.2 mg·kg^-1·d^-1， intramuscular injection） and Wuzi Yanzongwan group（1.56 g·kg^-1·d^-1， intragastric administration） according to body weight， with 12 mice in each group. The right testicle and epididymis were extracted from the model group and the drug administration group to construct the semi-castrated model of low spermatogenic function， while the fur and the right scrotum of the sham-operated group were only cut and immediately sterilized and sutured. At the end of the intervention， hematoxylin-eosin（HE） staining was used to observe the histopathology of testis， enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of serum testosterone（T）， luteinizing hormone（LH） and follicle stimulating hormone（FSH）. The sperm count and motility of epididymis were measured by automatic sperm detector of small animal. Transcriptomic microarray technology was used to detect the mRNA expression level of testicular tissue in each group， the transcriptome of genes related to the regulation of Wuzi Yanzongwan was screened， and three mRNAs were selected for Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） to verify the transcriptome data. Through the annotation analysis of Gene Ontology（GO） and the signaling pathway analysis of Kyoto Encyclopedia of Genes and Genomes（KEGG）， the related functions of drugs regulating transcriptome were analyzed. ResultCompared with the sham-operated group， the testicular tissue of mice in the model group showed spermatogenic injury， contraction and vacuolization of the seminiferous tubules， reduction of spermatogenic cells at all levels， widening of the interstitial space， obstruction of spermatogonial cell development and other morphological abnormalities， and serum T significantly decreased， LH significantly increased（P<0.01）， and FSH elevated but no statistically significant difference， the count and vitality of epididymal sperm significantly decreased（P<0.01）. There were 882 differentially expressed mRNAs in the testicular tissues， of which 565 were up-regulated and 317 were down-regulated. Cluster analysis showed that these differentially expressed mRNA could effectively distinguish between the sham-operated group and the model group. Compared with the model group， the damage to testicular tissue in the Wuzi Yanzongwan group was reduced， the structure of the seminiferous tubules was intact， vacuolization was reduced， and the number of spermatogenic cells at all levels was significantly increased and arranged tightly. The serum T significantly increased， LH significantly decreased（P<0.01）， and FSH decreased but the difference was not statistically significant. The count and vitality of sperm in the epididymis were significantly increased（P<0.01）. Moreover， Wuzi Yanzongwan could regulate 159 mRNA levels in the testes of semi-castrated mice， of which 32 were up-regulated and 127 were down-regulated， and the data of the transcriptome assay was verified to be reliable by Real-time PCR. GO and KEGG analysis showed that the transcriptome functions regulated by Wuzi Yanzongwan were involved in the whole cell cycle process of sperm development such as sex hormone production of interstitial cells in testis， renewal， differentiation， metabolism， apoptosis and signal transduction of spermatogenic cells， and were closely related to the biological behaviors of signaling pathways such as spermatogenic stem cell function， endoplasmic reticulum protein processing and metabolic program. ConclusionWuzi Yanzongwan can effectively improve the low spermatogenic function of semi-castrated male mice， and its mechanism may be related to the regulation of testicular transcriptional regulatory network， the synthesis of sex hormones in testicular interstitial cells， the function of spermatogenic stem cells， the whole cell cycle process of spermatogenesis， as well as the expression of endoplasmic reticulum protein processing and metabolic program related genes transcription.

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Background and purpose:BRCA1/2 plays an important role in maintaining the genome stability.Whether BRCA1/2 germline mutation could increase the tumor sensitivity to radiotherapy,thereby inducing secondary primary cancer after radiotherapy is unclear.This study aimed to investigate whether postoperative radiotherapy is a risk factor for the development of second primary cancer in triple-negative breast cancer(TNBC)patients with BRCA1/2 germline mutation.Methods:This research was based on a previously reported retrospective cohort,i.e.,the Fudan University Shanghai Cancer Center TNBC cohort.Between January 1,2007 and December 31,2014,a total of 292 female TNBC patients with BRCA1/2 mutation were enrolled.We performed logistic regression analysis in patients without BRCA1/2 germline mutation(n=261)and BRCA1/2 germline mutation patients(n=31),respectively,to assess the risk factors affecting the incidence of second primary cancer.We then performed interactive analysis on the above two analyses to evaluate the interactive effect between BRCA1/2 germline mutation and postoperative radiotherapy.P<0.05 indicates a statistically significant difference.The research was approved by Fudan University Shanghai Cancer Center TNBC Ethics Committee(050432-4-2108),and each patient provided written informed consent.Results:Logistic regression analysis in patients with BRCA1/2 germline mutations showed that postoperative radiotherapy significantly increased the risk of secondary primary disease compared to non-radiotherapy[odds ratio(OR)=2.475,95%confidence interval(CI):1.933-3.167,P<0.001].In patients without BRCA1/2 germline mutation,the effect of radiotherapy on the incidence of second primary tumor was not significant.There was a significant interaction between BRCA1/2 germline mutation and postoperative radiotherapy for the incidence of secondary primary cancer(OR=9.710,95%CI:0.320-295.250,P=0.193).Conclusion:Although statistical analysis results show that patients with BRCA1/2 germline mutations have an increased risk of developing a second primary tumor after postoperative radiotherapy compared to patients who have not received radiotherapy,there is no significant correlation between BRCA1/2 germline mutations and radiotherapy for the development of a second primary tumor.Therefore,patients with BRCA1/2 germline mutations who receive radiotherapy after surgery may not increase the risk of developing a second primary tumor.

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 clinical effect of proper management of inferior pancreaticoduodenal artery (IPDA) in laparoscopic pancreaticoduodenectomy (LPD).Methods:This is a retrospective case series study. The clinical and pathological data of 70 patients who received LPD due to pancreatic head tumors, periampullary tumors, or distal common bile duct tumors in the Pancreatic Center of the Second Clinical College of Guangzhou University of Chinese Medicine from January to December 2022 were retrospectively collected. There were 47 males(67.1%) and 23 females(32.9%),aged (59.9±12.8)years(range:13 to 87 years).The procedure of IPDA exposure was as follows:a middle approach was utilized to expose the right half of superior mesenteric artery(SMA) and its right branches between the SMA and superior mesenteric vein(SMV) in superior colonic region. In the subcolonic region,SMA trunk exposure via dissection along the jejunal artery from feet to head and identification the association between IPDA and jejunal artery were prior to IPDA root ligation and dissection. The safety and efficacy of intraoperative IPDA handling were assessed based on surgical videos. Follow-up was carried out in outpatient clinic or by telephone, and outpatient follow-up was conducted once every 1 to 3 months after surgery.Results:The percentage of total LPD was 98.6%(69/70),with all patients achieving R0 resection. Nine cases(12.9%) were involved in combined vascular resection and reconstruction,with 1 case (1.4%) requiring additional upper abdominal incision for vascular and gastrointestinal reconstruction,while the remaining eight cases (11.4%) were completed laparoscopically. The operative time was (432.7±115.4)minutes(range:282 to 727 minutes), and the blood loss was (140.0±125.7)ml(range:20 to 800 ml). Only two patients(2.9%) received fresh frozen plasma transfusion,with an average volume of 650 ml. Reliable ligation and safe handling of the IPDA were achieved in 91.4%(64/70) of cases, with 8.6%(6/70) suffering from IPDA injury-related bleeding. No one was converted to opened surgery. Pathologically,the mean tumor size was (3.3±1.6)cm (range:1 to 7 cm),and the mean number of harvested lymph nodes was 17.0±7.3(range:0 to 46). Lymph node metastasis was observed in 13 cases (18.6%). Five cases (13.2%) developed grade B pancreatic fistula,while no grade C pancreatic fistula occurred. Other complications included bile leakage in one case(1.4%),delayed gastric emptying in two cases(2.9%), lymphatic leakage in 2 cases(2.9%),intra-abdominal infection in 9 cases(12.9%),and fat liquefaction of surgical incision in 1 case(1.4%). Two cases(2.9%) experienced postoperative intra-abdominal bleeding,one due to mesangial bleeding of lesser curvature of the stomach and the other due to oozing from the hepatic arterial sheath. These bleeding events were not concerned with IPDA. The average length of postoperative hospital stay was (15.2±4.6)days(range:9 to 28 days).Conclusion:Proper intraoperative management of IPDA in LPD might reduce IPDA-related bleeding during and after surgery and improve the safety of LPD.

The concept of "Bo" （搏） originates from The Inner Canon of Yellow Emperor （《黄帝内经》）. Its original meaning mostly refers to gathering and attacking， but in pulseology it reflects the potential of conflict and was widely used in the methods of taking pulse from zang-fu organs and yin and yang. This paper conducted a literature research on the concept and connotation of "Bo" （搏）， and summarized the seven meanings of it， including contention， intersection， stop， change， attachment， pulse， and pathological pulse. At the same time， the pathomechanism of "Bo" （搏） was explained and its four characteristics are summarized， including contention to transformation， concurrent transformation， latent pathogen gathering， and changes transforming to qi； the pathomechanism and locations of "Bo" （搏） were also summarized， including zang-fu organs， channels and collaterals， five body constituents， qi level， blood level， and other aspects， involving therapeutic methods like the opening and diffusing， expressing and tonifying， regulating balance. The concept and connotation of "Bo" （搏） were systematically studied and improved to provide new perspectives and ideas for the diagnosis and treatment of many modern intractable diseases.

During the Jin dynasty,the two major academic schools of Hejian and Yishui emerged in northern China.At this time,the Song dynasty migrated southward,accompanied by the southward movement of the Han ethnic culture and economic center.The dissemination of medicine also showed a trend of spreading from the north to the south.The late Yuan dynasty was an important period for the academic dissemination of the Yishui school to the south.On the one hand,ZHU Danxi,GE Yinglei,HUA Shou,and other clinicians studied the academic works of LI Dongyuan,comprehended his academic ideas,and further disseminated them through their disciples and Confucian scholars.On the other hand,academic works such as Jisheng Bacui and Weisheng Baojian carrying the study of Yishui were published in the south,playing an essential role in disseminating Yishui's study in the south.The dissemination of Yishui's learning to the south adopted a combination of book learning and mentorship,effectively breaking down the academic barriers between the Hejian and Yishui schools.The network formed by the interaction between medical scholars and Confucian scholars was an essential medium for academic dissemination.The study of Yishui was transmitted to the south and integrated with the original spleen and stomach theory in the south,promoting the further development of traditional Chinese medicine spleen and stomach theory.