Rheumatoid arthritis （RA） is a common chronic systemic autoimmune disease with synovitis as the main manifestation， which often causes joint swelling and pain or even deformity. It is considered to be an incurable lifelong disease. Although the current Western medicine treatment can alleviate the progression of the disease， it has the clinical limitations of liver injury， cardiovascular complications， and other adverse reactions， along with easy recurrence. Traditional Chinese medicine （TCM） has a long history and has the advantages of individualized treatment and fewer adverse reactions. It can effectively relieve the symptoms of joint swelling and pain in RA patients and slow down the progression of bone destruction， which has attracted wide concern in the medical community. Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling pathway is an important intracellular pathway involved in cell proliferation， differentiation， apoptosis， immune regulation， and other biological behaviors， and plays an important role in the pathophysiological process of RA. In recent years， many studies have confirmed that TCM monomers and compounds can inhibit inflammation and angiogenesis by regulating the JAK/STAT signaling pathway， induce apoptosis and inhibit proliferation of fibroblast-like synoviocytes （FLS）， regulate immune response， and thus exert an effect in the treatment of RA. However， there is still a lack of comprehensive and systematic induction and overview. Therefore， by searching the relevant literature in China National Knowledge Infrastructure （CNKI） and PubMed databases from 2009 to 2024， this study described the mechanism of the JAK/STAT signaling pathway in the occurrence and development of RA and summarized the research progress of TCM monomers and compounds in regulating the JAK/STAT signaling pathway in RA intervention. The study aims to provide new ideas and strategies for the clinical treatment of RA with TCM and the research and development of new drugs.

Objective:To analyze and confirm the ambiguous results of HLA-DRB1 genotyping in one case.Methods:HLA genotyping was performed on a sample of hematopoietic stem cell donor using Illumina MiSeq-based next-generation sequencing(NGS).The ambiguous results of HLA-DRB1 locus were further analyzed and confirmed through PacBio SMRT third-generation sequencing.Results:The Illumina MiSeq-based NGS typing results suggested the presence of a new HLA-DRB1*11 allele(DRB1*11:NEW,12:01)in the specimen,with a mismatch of G＞A located in the 40th residue of exon 1 compared with the nearest allele DRB1*11:01:01:03.However,due to the long sequence of intron 1,this observed mutation site was so far away from the near heterozygous sites that no reads could cover this gap.Therefore,it was impossible to determine which consensus the mutation site was located in,and the NGS-based genotyping results were obtained from the random allocation by the software,which was ambiguous and unreliable.In order to confirm the results,the long-read third generation sequencing technology based on PacBio was applied to genotype the DRB1 locus.The results showed that the DRB1 typing was HLA-DRB1*11:01,12:10.E1-40A was actually located in the allele HLA-DRB1*12:XX,which was exactly matched with HLA-DRB1*12:10.Conclusion:For some new alleles suggested by NGS,especially the ambiguous ones that are far away from other heterozygous sites,it is necessary to analyze and confirm them by other methods such as the third-generation long-read sequencing technology to obtain reliable results.

Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.

Objective:To analyze the factors associated with long-term survival after radical resection of hepatitis B virus(HBV)-associated hepatocellular carcinoma(HCC),and to construct random forest and Cox regression models,to evaluate the two models.Methods:A total of 368 patients with HBV-infected HCC who underwent radical resection were selected retrospectively.These patients were categorized as having a good prognosis(n=266)or a poor prognosis(n=102)based on their survival and mortality status.Univariate and Cox regression analysis were used to identify fac-tors that predict poor prognosis in HCC patients after surgery,and Cox regression and random forest prediction models were constructed and evaluated.Results:There were significant differences in smoking history,Child-Pugh classifica-tion,cirrhosis,microvascular invasion,TNM staging,tumor capsule integrity,platelet-to-lymphocyte ratio(PLR),regular antiviral therapy,HBV-DNA load,alpha-fetoprotein(AFP),neutrophil-to-lymphocyte ratio(NLR),systemic immune in-flammatory index(SII),and albumin-to-globulin ratio(AGR)between the two groups(P<0.05);Cox regression showed that cirrhosis,microvascular invasion,regular antiviral treatment,HBV-DNA load,NLR,PLR,SII,and AGR were related factors that negatively affected the prognosis of patients with HBV-infected HCC after surgery(P<0.05),with an AUC of 0.870 for predicting prognosis;the importance ranking obtained by the random forest model was HBV-DNA load,cirrho-sis,regular antiviral therapy,microvascular invasion,NLR,PLR,AGR,and SII,with an AUC of 0.926 for predicting prog-nosis;the AUC predicted by the random forest model was greater than that predicted by the Cox regression model(Z=2.411,P=0.016).Conclusion:HBV-DNA load,cirrhosis,regular antiviral therapy,microvascular invasion,NLR,PLR,AGR,and SII are factors that affect the poor prognosis of patients with HBV-related HCC after surgery.The random for-est prediction model constructed based on these factors has high predictive value and is superior to the Cox regression prediction model.

Objective:To analyze the factors associated with long-term survival after radical resection of hepatitis B virus(HBV)-associated hepatocellular carcinoma(HCC),and to construct random forest and Cox regression models,to evaluate the two models.Methods:A total of 368 patients with HBV-infected HCC who underwent radical resection were selected retrospectively.These patients were categorized as having a good prognosis(n=266)or a poor prognosis(n=102)based on their survival and mortality status.Univariate and Cox regression analysis were used to identify fac-tors that predict poor prognosis in HCC patients after surgery,and Cox regression and random forest prediction models were constructed and evaluated.Results:There were significant differences in smoking history,Child-Pugh classifica-tion,cirrhosis,microvascular invasion,TNM staging,tumor capsule integrity,platelet-to-lymphocyte ratio(PLR),regular antiviral therapy,HBV-DNA load,alpha-fetoprotein(AFP),neutrophil-to-lymphocyte ratio(NLR),systemic immune in-flammatory index(SII),and albumin-to-globulin ratio(AGR)between the two groups(P<0.05);Cox regression showed that cirrhosis,microvascular invasion,regular antiviral treatment,HBV-DNA load,NLR,PLR,SII,and AGR were related factors that negatively affected the prognosis of patients with HBV-infected HCC after surgery(P<0.05),with an AUC of 0.870 for predicting prognosis;the importance ranking obtained by the random forest model was HBV-DNA load,cirrho-sis,regular antiviral therapy,microvascular invasion,NLR,PLR,AGR,and SII,with an AUC of 0.926 for predicting prog-nosis;the AUC predicted by the random forest model was greater than that predicted by the Cox regression model(Z=2.411,P=0.016).Conclusion:HBV-DNA load,cirrhosis,regular antiviral therapy,microvascular invasion,NLR,PLR,AGR,and SII are factors that affect the poor prognosis of patients with HBV-related HCC after surgery.The random for-est prediction model constructed based on these factors has high predictive value and is superior to the Cox regression prediction model.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Objective To explore the value of thyroid nodule fine needle aspiration cytology(FNAC)combined with B-Raf proto-oncogene,serine/threonine kinase(BRAF)gene detection in the differential diagnosis of benign and malignant thyroid tumors.Methods According to the results of pathological examination,198 patients with thyroid nodules were divided into the benign lesion group(n=107)and the malignant lesion group(n=91).All patients underwent ultrasound-guided FNAC,and expression of BRAF gene was detected by real-time fluorescence quantitative polymerase chain reaction.The value of FNAC,BRAF gene detection and combined detection in the differential diagnosis of benign and malignant thyroid tumors was analyzed by Kappa consistency test and receiver operating characteristic(ROC)curves.Results The nodules were mostly under envelope in the malignant lesion group,while in the benign lesion group,which were mostly located within glands(P＜0.05).FNAC results showed that 62 cases with type II Bethesda,26 cases with type III Bethesda,29 cases with type IV Bethesda,14 cases with type V Bethesda and 67 cases with type VI Bethesda.There were significant differences in diagnostic positive rates between FNAC,BRAF gene detection,combined detection and pathological examination(P＜0.05).The area under ROC curve(AUC)of FNAC combined with BRAF gene detection for differentiating benign and malignant thyroid tumors was 0.871(95%CI:0.816-0.914),sensitivity was 90.11%,specificity was 84.11%and Kappa value was 0.737.The AUC of FNAC diagnosis was 0.833(95%CI:0.774-0.882),sensitivity was 76.92%,specificity was 89.72%and Kappa value was 0.672.The AUC of BRAF gene detection was 0.829(95%CI:0.770-0.879),sensitivity was 78.02%,specificity was 87.85%and Kappa value was 0.663.Conclusion FNAC combined with BRAF gene detection can improve differential diagnosis efficiency for benign and malignant thyroid lesions,especially enhancing the diagnostic sensitivity.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Objective To explore the value of thyroid nodule fine needle aspiration cytology(FNAC)combined with B-Raf proto-oncogene,serine/threonine kinase(BRAF)gene detection in the differential diagnosis of benign and malignant thyroid tumors.Methods According to the results of pathological examination,198 patients with thyroid nodules were divided into the benign lesion group(n=107)and the malignant lesion group(n=91).All patients underwent ultrasound-guided FNAC,and expression of BRAF gene was detected by real-time fluorescence quantitative polymerase chain reaction.The value of FNAC,BRAF gene detection and combined detection in the differential diagnosis of benign and malignant thyroid tumors was analyzed by Kappa consistency test and receiver operating characteristic(ROC)curves.Results The nodules were mostly under envelope in the malignant lesion group,while in the benign lesion group,which were mostly located within glands(P＜0.05).FNAC results showed that 62 cases with type II Bethesda,26 cases with type III Bethesda,29 cases with type IV Bethesda,14 cases with type V Bethesda and 67 cases with type VI Bethesda.There were significant differences in diagnostic positive rates between FNAC,BRAF gene detection,combined detection and pathological examination(P＜0.05).The area under ROC curve(AUC)of FNAC combined with BRAF gene detection for differentiating benign and malignant thyroid tumors was 0.871(95%CI:0.816-0.914),sensitivity was 90.11%,specificity was 84.11%and Kappa value was 0.737.The AUC of FNAC diagnosis was 0.833(95%CI:0.774-0.882),sensitivity was 76.92%,specificity was 89.72%and Kappa value was 0.672.The AUC of BRAF gene detection was 0.829(95%CI:0.770-0.879),sensitivity was 78.02%,specificity was 87.85%and Kappa value was 0.663.Conclusion FNAC combined with BRAF gene detection can improve differential diagnosis efficiency for benign and malignant thyroid lesions,especially enhancing the diagnostic sensitivity.

Objective To study the expression levels of karyopherin β1(KPNB1) and Mer receptor tyrosine kinase (MERTK) in non-small cell lung cancer (NSCLC) tissues and their correlation with clinical pathological features,as well as the prognosis of progression-free survival. Methods A total of 118 NSCLC patients who visited Ordnance Industry 521 Hospital from February 2018 to February 2020 were selected. Immunohistochemical methods were used to detect the expression of KPNB1 and MERTK in NSCLC cancer and paracancer tissue. Kaplan-Meier survival curve analysis was conducted to assess the impact of KPNB1 and MERTK on the progression-free survival prognosis of NSCLC patients. COX regression analysis was performed to identify factors affecting the prognosis of progression-free survival in NSCLC patients. Results The positive rates of KPNB1 (61.02％) and MERTK (62.71％) in cancer tissues were higher than those in adjacent tissues (8.48％,6.78％),and the differences were statistically significant (x2=69.945,81.408,all P<0.001). There was a significant positive correlation between KPNB1 and MERTK expression in the organization (r=0.744,P<0.001). The positive rates of KPNB1(84.21％,82.50％),MERTK (84.21％,85.00％)in NSCLC tissues with lymph node metastasis and TNM stage ⅢA were higher than those without lymph node metastasis(50.00％,52.50％) and TNM stage Ⅰ～Ⅱ(50.00％,51.28％),and the differences were statistically significant (x2=11.078～12.855,all P<0.001). The 3-year progression-free survival rates of KPNB1and MERTK positive and negative groups were 26.39％ (19/72) and 56.52％ (26/46),27.03％ (20/74) and 56.82％ (25/44),respectively,with statistically significant differences (Log Rankx2=0.980,8.463,P=0.001,0.004) . KPNB1 positive,MERTK positive,lymph node metastasis and TNM stage ⅢA were risk factors for progression free survival prognosis in NSCLC patients (waldx2=7.810～10.906,all P<0.001). Conclusion The expression of KPNB1 and MERTK is elevated in NSCLC,both of which are related to TNM staging and lymph node metastasis. They are new biomarkers for evaluating the progression-free survival prognosis of NSCLC.