Objective:To evaluate the clinical efficacy, safety and treatment persistence of upadacitinib in Crohn's disease (CD) patients.Methods:The single-center retrospective cohort study was conducted. The patients with moderate-to-severe active CD initiating upadacitinib therapy from November 2023 to November 2024 in Nanjing Drum Tower Hospital were collected through searching the electronic medical records and paper-based patient databases. The primary outcome was the clinical remission rate at week 12. Secondary outcomes included the clinical response rate at week 12; clinical response and remission rates at weeks 4, 24 and 48; biomarker (fecal calprotectin or C-reactive protein) remission rates at all time points; as well as endoscopic remission and response rates, treatment persistence and safety evaluation.Results:A total of 44 CD patients were included, comprising 24 males (54.5%) and 20 females (45.5%). The median age was 33 (25, 40) years. The baseline Crohn's disease activity index (CDAI) score was 260.5 (225.9, 550.0) points. Patients had previously received a median of 2 (1, 2) biologic treatments. All 44 patients completed the 12-week induction therapy. With a median follow-up of 30.00 (16.25, 46.25) weeks, the clinical remission rate was 50.0% (22/44) at week 12. The clinical remission rate, clinical response rate, and biomarker remission rate were 52.3% (23/44), 88.6% (39/44) and 72.7% (32/44) respectively at week 4, and the clinical response rate and biomarker remission rate were 88.6% (39/44) and 77.2% (34/44) respectively at week 12. The clinical remission rates, clinical response rates and biomarker remission rates evolved to 43.3% (13/30), 86.7% (26/30) and 80.0% (24/30) at week 24, and further to 44.4% (4/9), 77.8% (7/9) and 77.8% (7/9) at week 48. During the follow-up period, 13 CD patients completing endoscopic evaluation, endoscopic remission and response rates were 30.8% and 23.1% respectively. CD-related surgery rate was 4.5% (2/44). Safety analysis demonstrated that the overall adverse events rate was 56.8% (25/44) including 7 patients with serious adverse events. A total of 8 patients discontinued treatment, among which 3 were due to primary loss of response, 1 due to secondary loss of response, 2 due to drug-related adverse events alone, and 2 due to concurrent primary loss of response and adverse events. The Kaplan-Meier curve for treatment persistence showed that among 39 CD patients who achieved clinical response at week 12, the continued treatment rates were 90.3% at week 12 and 85.3% at week 24 of follow-up. Two patients (5.6%) received dose escalation of upadacitinib, both of whom achieved clinical remission.Conclusion:Real-world research data demonstrate that upadacitinib exhibits significant clinical efficacy and a favorable safety profile in the treatment of moderate-to-severe active CD patients with prior biologic exposure, and no new unexpected adverse events are identified.

Objective:To investigate the variations and co-alteration of KRAS and HER-family genes in the patients with ampullary carcinoma.Methods:A total of 37 formalin-fixed paraffin-embedded primary ampullary carcinoma specimens, which were collected at Peking Union Medical College Hospital from April 2019 to October 2024 were analyzed for KRAS and HER-family gene mutations using next-generation sequencing (NGS). Immunohistochemistry (IHC) was performed for HER2 protein expression in HER2 mutation cases and fluorescence in situ hybridization (FISH) for further gene status in HER2 IHC 2+cases.Results:In our cohort (22 males, 15 females; 31-82 years old), KRAS gene mutations were detected in 51.4% (19/37) of cases, with G12D being the most frequent abnormality (7/19), followed by G12V (5/19) and Q61R (3/19). Other variants of KRAS gene included G12C, A146T, N116H, and Q61H (each 1/19). In this cohort, 27.0% (10/37) of cases harbored HER-family gene alterations with most frequently in HER2 (6/10) and HER3 genes (missense mutations mainly). Notably, 3 cases (8.1%, 3/37) with coexistence of KRAS and HER-family genes mutations were recognized in our series, including KRAS p.G12D/HER2 p.V842I/HER2 p.V777L (c.2329 G>T)/HER3 p.Asp581Asn, KRAS p.Q61R/HER4 p.D1018H and KRAS p.G12C/HER2 p.R678Q. Additionally, a mutation of HER3 p.V104L (c.310 G>C) was identified in our population. Moreover, 4 novel mutations including HER3 p.V296E, HER3 p.V920L (c.2758 G>T), HER3 p.Asp581Asn, and HER4 p.D1018H were detected. In 6 tumors with HER2 gene changes (16.2%, 6/37), 5 variants with the high proportion of HER2 p.S310Y (3/6) were revealed. A tumor (HER2 IHC 2+) with HER2 p.S310Y presented HER2 gene amplification confirmed by NGS and FISH, and another one (also HER2 IHC 2+) with HER2 p.L755S possessed HER2 gene amplification determined by FISH assay.Conclusion:In ampullary carcinoma, co-alteration of KRAS and HER-family genes is observed, and HER2 gene mutations account for more than half of HER-family gene abnormities, which may be accompanied by gene amplification.

Objective:To evaluate the clinical efficacy, safety and treatment persistence of upadacitinib in Crohn's disease (CD) patients.Methods:The single-center retrospective cohort study was conducted. The patients with moderate-to-severe active CD initiating upadacitinib therapy from November 2023 to November 2024 in Nanjing Drum Tower Hospital were collected through searching the electronic medical records and paper-based patient databases. The primary outcome was the clinical remission rate at week 12. Secondary outcomes included the clinical response rate at week 12; clinical response and remission rates at weeks 4, 24 and 48; biomarker (fecal calprotectin or C-reactive protein) remission rates at all time points; as well as endoscopic remission and response rates, treatment persistence and safety evaluation.Results:A total of 44 CD patients were included, comprising 24 males (54.5%) and 20 females (45.5%). The median age was 33 (25, 40) years. The baseline Crohn's disease activity index (CDAI) score was 260.5 (225.9, 550.0) points. Patients had previously received a median of 2 (1, 2) biologic treatments. All 44 patients completed the 12-week induction therapy. With a median follow-up of 30.00 (16.25, 46.25) weeks, the clinical remission rate was 50.0% (22/44) at week 12. The clinical remission rate, clinical response rate, and biomarker remission rate were 52.3% (23/44), 88.6% (39/44) and 72.7% (32/44) respectively at week 4, and the clinical response rate and biomarker remission rate were 88.6% (39/44) and 77.2% (34/44) respectively at week 12. The clinical remission rates, clinical response rates and biomarker remission rates evolved to 43.3% (13/30), 86.7% (26/30) and 80.0% (24/30) at week 24, and further to 44.4% (4/9), 77.8% (7/9) and 77.8% (7/9) at week 48. During the follow-up period, 13 CD patients completing endoscopic evaluation, endoscopic remission and response rates were 30.8% and 23.1% respectively. CD-related surgery rate was 4.5% (2/44). Safety analysis demonstrated that the overall adverse events rate was 56.8% (25/44) including 7 patients with serious adverse events. A total of 8 patients discontinued treatment, among which 3 were due to primary loss of response, 1 due to secondary loss of response, 2 due to drug-related adverse events alone, and 2 due to concurrent primary loss of response and adverse events. The Kaplan-Meier curve for treatment persistence showed that among 39 CD patients who achieved clinical response at week 12, the continued treatment rates were 90.3% at week 12 and 85.3% at week 24 of follow-up. Two patients (5.6%) received dose escalation of upadacitinib, both of whom achieved clinical remission.Conclusion:Real-world research data demonstrate that upadacitinib exhibits significant clinical efficacy and a favorable safety profile in the treatment of moderate-to-severe active CD patients with prior biologic exposure, and no new unexpected adverse events are identified.

Objective:To investigate the variations and co-alteration of KRAS and HER-family genes in the patients with ampullary carcinoma.Methods:A total of 37 formalin-fixed paraffin-embedded primary ampullary carcinoma specimens, which were collected at Peking Union Medical College Hospital from April 2019 to October 2024 were analyzed for KRAS and HER-family gene mutations using next-generation sequencing (NGS). Immunohistochemistry (IHC) was performed for HER2 protein expression in HER2 mutation cases and fluorescence in situ hybridization (FISH) for further gene status in HER2 IHC 2+cases.Results:In our cohort (22 males, 15 females; 31-82 years old), KRAS gene mutations were detected in 51.4% (19/37) of cases, with G12D being the most frequent abnormality (7/19), followed by G12V (5/19) and Q61R (3/19). Other variants of KRAS gene included G12C, A146T, N116H, and Q61H (each 1/19). In this cohort, 27.0% (10/37) of cases harbored HER-family gene alterations with most frequently in HER2 (6/10) and HER3 genes (missense mutations mainly). Notably, 3 cases (8.1%, 3/37) with coexistence of KRAS and HER-family genes mutations were recognized in our series, including KRAS p.G12D/HER2 p.V842I/HER2 p.V777L (c.2329 G>T)/HER3 p.Asp581Asn, KRAS p.Q61R/HER4 p.D1018H and KRAS p.G12C/HER2 p.R678Q. Additionally, a mutation of HER3 p.V104L (c.310 G>C) was identified in our population. Moreover, 4 novel mutations including HER3 p.V296E, HER3 p.V920L (c.2758 G>T), HER3 p.Asp581Asn, and HER4 p.D1018H were detected. In 6 tumors with HER2 gene changes (16.2%, 6/37), 5 variants with the high proportion of HER2 p.S310Y (3/6) were revealed. A tumor (HER2 IHC 2+) with HER2 p.S310Y presented HER2 gene amplification confirmed by NGS and FISH, and another one (also HER2 IHC 2+) with HER2 p.L755S possessed HER2 gene amplification determined by FISH assay.Conclusion:In ampullary carcinoma, co-alteration of KRAS and HER-family genes is observed, and HER2 gene mutations account for more than half of HER-family gene abnormities, which may be accompanied by gene amplification.

Objective To explore the efficacy and safety of low-dose tirofiban in stent-assisted coil embolization(SAC)for ruptured intracranial aneurysms.Methods From April 2011 to September 2020,335 patients of ruptured intracranial aneurysms with subarachnoid hemorrhage(SAH)admitted in the First People's Hospital of Changzhou were retrospectively analyzed.All cases underwent stent-assisted coil embolization within 24-48 h and antiplatelet medications.The patients were divided into dual antibody group(89 cases)and tirofiban group(246 cases).Baseline and clinical data of all patients were collected for comparison between groups,including age,sex,hypertension,diabetes mellitus,Hunt-Hess grade at admission,modified Fisher scale score at admission,aneurysm diameter(＞5 mm,≤5 mm),aneurysm location(anterior circulation,posterior circulation),postoperative acute hydrocephalus or intraventricular hemorrhage,postoperative complete embolization rate of ruptured aneurysm.All patients with ruptured intracranial aneurysm with SAH were confirmed by emergency cerebral CT scan after admission.The Raymond grading criteria were used to evaluate the embolization effect after operation:grade Ⅰ refers to no development(complete embolization),grade Ⅱ refers to only aneurysm neck development(incomplete embolization),and grade Ⅲ refers to aneurysm body development,in which Raymond grading Ⅰ orⅡ indicates effective embolization.Tirofiban group:4.2 μg/kg tirofiban was intravenously injected after the coil was placed in the aneurysm lumen and the stent was released,followed by maintenance dose 0.07 μg/(kg·min)for 6-8 h,and aspirin 100 mg and clopidogrel 75 mg were given as sequential dual antiplatelet therapy 2 hours before the tirofiban infusion was stopped.Dual antiplatelet group:a loading dose of aspirin 300 mg and clopidogrel 300 mg was given at least 2 hours before stent implantation,and then transferred to aspirin 100 mg and clopidogrel 75 mg given on the second day after operation.All patients received aspirin(100mg/d)for 6 months and clopidogrel(75 mg/d)for 3 months after operation.The efficacy indicators,safety indicators,adverse events and other complications of the two groups were collected and compared.The efficacy indicators were the incidence of thrombotic events during operation and within 72 hours after operation.The safety indicators were the incidence of intraoperative and early postoperative intracranial hemorrhage(within 48 hours after operation),the incidence of late postoperative intracranial hemorrhage(over 48 hours after operation),and the incidence of intracranial hemorrhage related to external ventricular drainage(symptomatic and asymptomatic).The adverse event was the occurrence of drug-related thrombocytopenia.Other complications were delayed ischemic events.The modified Rankin scale(mRS)score was used to evaluate the clinical prognosis of patients at 180 days after operation.mRS score ≤2 was defined as good prognosis,mRS score＞2 was defined as poor prognosis,of which 6 was defined as death.Results(1)There were no significant differences in baseline and clinical data between the tirofiban group and the dual antibody group(all P＞0.05).(2)There was no significant difference in the proportion of patients with good outcome(75.2％[185/246]vs.74.2％[66/89],P=0.845)and death(10.2％[25/246]vs.12.4％[11/89],P=0.566)at 180 days after operation between the tirofiban group and the dual antiplatelet group.(3)There was no significant difference in the incidence of intraoperative(0.8％[2/246]vs.4.5％[4/89],P=0.075)and postoperative thrombotic events(11.0％[27/246]vs.13.5％[12/89],P=0.527)between the tirofiban group and the dual antiplatelet group.(4)Results about safety comparison between this two antiplatelet regimens showed that the incidence of early postoperative intracranial hemorrhage were lower in the tirofiban group than that in the dual antiplatelet group(2.8％[7/246]vs.10.1％[9/89],P=0.014).There were no significant differences in the symptomatic external ventricular drainage related intracranial hemorrhage(0 vs.2/15,P=0.050),incidences of intraoperative intracranial hemorrhage(1.6％vs.3.4％,P=0.580),late postoperative intracranial hemorrhage(3.3％vs.4.5％,P=0.836),and drug-related thrombocytopenia(0.4％vs.1.1％,P=0.461)between the two groups.Conclusion Low-dose tirofiban infusion in SAC for ruptured aneurysms may prevent perioperative thromboembolic events without high risk of intracranial hemorrhage.

In accordance with the theory of'treating the skin diseases with the skin',skin-related Chinese medicinals are usually used for the treatment of skin diseases,which reflects the thinking mode of holistic syndrome differentiation and classification according to the manifestations in traditional Chinese medicine.With ying-yang theory as the principle of differentiation and treatment of diseases and based on the core pathogenesis of'yin-yang imbalance causing the manifestations of the skin'for the skin diseases,Chinese medical master XU AN Guo-Wei has used skin-related Chinese medicinals in the treatment of skin diseases and has given full play to their unique advantage by following the theory of'treating the skin diseases with the skin'and'balanced regulation of yin and yang'.In the clinical practice,allergic skin diseases were usually treated with Cicadae Periostracum plus Dictamni Cortex for dispelling wind and relieving itching,hypopigmentation related skin diseases were usually treated with Sojae Semen Nigrum skin plus Dictamni Cortex for dispelling wind and tonifying kidney,autoimmune skin diseases were usually treated with Moutan Cortex plus Lycii Cortex for nourishing yin,clearing heat and activating blood,and skin diseases associated with abnormal sebum secretion were usually treated with Mori Cortex plus Lycii Cortex for purging lung and nourishing kidney.Skin-related Chinese medicinals have the actions of expelling wind and promoting eruption of papules,tonifying kidney and nourishing yin.The medication method of'treating the skin diseases with the skin'will provide reference for the treatment of skin diseases.

AIM:This study aims to investigate the utility of the Christie-Atkinson-Munch-Peterson(CAMP)test in identifying Streptococcus agalactiae and to assess the sensitivity of positive CAMP test results for this identification.We also identified and analyzed Streptococcus agalactiae isolates that exhibited negative CAMP test results and conducted a preliminary study on the possible mechanisms behind these occurrences.METHODS:Streptococcus agalactiae isolates were collected from the University Town Branch of Guangdong Provincial Hospital of Traditional Chinese Medicine be-tween January 2018 and January 2023.Isolates identified as Streptococcus agalactiae using an automated rapid microbial mass spectrometry detection system underwent the CAMP test.CAMP-negative strains were screened,and the presence of the cfb gene was assessed.We also conducted a statistical analysis of the clinical sources of the samples and the drug sensi-tivity test results for Streptococcus agalactiae.RESULTS:Among 112 Streptococcus agalactiae strains,two CAMP-nega-tive strains were identified,which were confirmed as Streptococcus agalactiae through 16S rDNA sequencing and showed negative detection of the cfb gene.The clinical sample sources for the 112 strains were as follows:midstream urine(34.82%),semen(34.82%),cervical swab(8.04%),secretion(4.46%),urethral swab(4.46%),venous blood(3.57%),pus(3.57%),sputum(1.79%),wound swab(1.79%),and unknown sources(1.79%).All Streptococcus agalactiae strains in our laboratory were found to be 100%sensitive to penicillin,linezolid,ampicillin,and vancomycin,while the resistance rate to levofloxacin was 24.44%.CONCLUSION:The positive results of the CAMP test demonstrate its potential for identifying Streptococcus agalactiae.The negative CAMP test results observed in the two strains could be at-tributed to the deletion of the cfb gene.The majority of Streptococcus agalactiae detected in clinical laboratory work were sourced from midstream urine and semen,indicating a potential association with urinary tract infections.However,the correlation with male reproductive diseases remains uncertain.

Objective:To compare the safety of radial artery puncture in elderly patients aged 75 years and older who are undergoing neurointerventional procedures.Methods:A single-center retrospective study was conducted, involving 350 elderly patients aged 75 years and older who received neurointerventional treatment at Beijing Tiantan Hospital, Capital Medical University, from June to December 2022.The participants were divided into two groups based on the puncture site: femoral artery puncture and radial artery puncture.The safety indicators compared between the two groups included puncture failure, changes in puncture site, general puncture complications(such as subcutaneous bleeding, puncture site hematoma, and vasospasm), severe puncture complications(including distal limb ischemia and pseudoaneurysm), and lower limb venous thrombosis.Multivariate Logistic regression analysis was conducted to evaluate the impact of different puncture methods on the occurrence of complications.Results:Among the 350 patients, 280 underwent femoral artery puncture, while 70 underwent radial artery puncture.There were no statistically significant differences in baseline characteristics between the two groups(all P>0.05).The proportions of patients using antiplatelet drugs prior to surgery, puncture failure rates, rates of change in puncture sites, and the incidence of severe complications-including distal limb ischemia and pseudoaneurysm-were not significantly different between the two groups( χ2=2.051, 0.075, 0.588, 3.175; P=0.152, 0.784, 0.443, 0.075).In the femoral artery puncture group, 20.4%(57 cases)of patients experienced general puncture complications(including subcutaneous bleeding, puncture site hematoma, and vasospasm), whereas only 8.6%(6 cases)in the radial artery puncture group experienced such complications, revealing a statistically significant difference between the two groups( χ2=5.720, P=0.022).Multivariate Logistic regression analysis indicated that, compared to femoral artery puncture, radial artery puncture was associated with a reduced risk of all complications( OR=0.272, 95% CI: 0.139-0.532, P<0.001), general puncture complications( OR=0.375, 95% CI: 0.153-0.919, P=0.032)and lower limb venous thrombosis( OR=0.219, 95% CI: 0.050-0.954, P=0.043). Conclusions:In elderly patients aged 75 years and older who are undergoing neurointerventional procedures, radial artery puncture is associated with a reduced incidence of general puncture complications and lower limb venous thrombosis when compared to femoral artery puncture, indicating a superior safety profile.

AIM:This study aims to investigate the utility of the Christie-Atkinson-Munch-Peterson(CAMP)test in identifying Streptococcus agalactiae and to assess the sensitivity of positive CAMP test results for this identification.We also identified and analyzed Streptococcus agalactiae isolates that exhibited negative CAMP test results and conducted a preliminary study on the possible mechanisms behind these occurrences.METHODS:Streptococcus agalactiae isolates were collected from the University Town Branch of Guangdong Provincial Hospital of Traditional Chinese Medicine be-tween January 2018 and January 2023.Isolates identified as Streptococcus agalactiae using an automated rapid microbial mass spectrometry detection system underwent the CAMP test.CAMP-negative strains were screened,and the presence of the cfb gene was assessed.We also conducted a statistical analysis of the clinical sources of the samples and the drug sensi-tivity test results for Streptococcus agalactiae.RESULTS:Among 112 Streptococcus agalactiae strains,two CAMP-nega-tive strains were identified,which were confirmed as Streptococcus agalactiae through 16S rDNA sequencing and showed negative detection of the cfb gene.The clinical sample sources for the 112 strains were as follows:midstream urine(34.82%),semen(34.82%),cervical swab(8.04%),secretion(4.46%),urethral swab(4.46%),venous blood(3.57%),pus(3.57%),sputum(1.79%),wound swab(1.79%),and unknown sources(1.79%).All Streptococcus agalactiae strains in our laboratory were found to be 100%sensitive to penicillin,linezolid,ampicillin,and vancomycin,while the resistance rate to levofloxacin was 24.44%.CONCLUSION:The positive results of the CAMP test demonstrate its potential for identifying Streptococcus agalactiae.The negative CAMP test results observed in the two strains could be at-tributed to the deletion of the cfb gene.The majority of Streptococcus agalactiae detected in clinical laboratory work were sourced from midstream urine and semen,indicating a potential association with urinary tract infections.However,the correlation with male reproductive diseases remains uncertain.

Objective: Differential flora and differential metabolites shared by the intestinal and respiratory tracts of rats were screened to analyze the possible role of changes in intestinal flora and metabolites in the progression of pneumoconiosis in rats. Methods: In April 2020, 18 SD rats were randomly divided into three groups (control group, coal mine dust group and silica group, 6 in each group) , rats in the coal mine dust group and silica group were perfused with 1 ml of 50 mg/ml coal mine well dust suspension and silica suspension by nontracheal exposure, respectively. While rats in the control group were perfused with an equal dose of sterilized normal saline. Twenty four weeks after dust staining, rat feces, throat swabs, and lung lavages were collected. 16SrDNA gene sequencing and UHPLC-QTOF-MS untargeted metabolomics were used to analyze the flora and metabolites in feces, throat swabs and lung lavage fluid of rats in each group, to screen for shared differential flora and shared differential metabolites in intestinal and respiratory tract, and the correlation analysis between the differential flora and metabolites was performed using Spearman's statistics. Results: Compared with the control group, a total of 9 species shared differential flora between intestinal and respiratory tract were screened at phylum level, and a total of 9 species shared differential genus between intestinal and respiratory tract were screened at genus level in the coal mine dust group, mainly Firmicutes, Actinobacteria, Streptococcus, Lactobacillus, etc. Compared with the control group, a total of 9 shared differential flora were screened at the phylum level, and a total of 5 shared differential genus were screened at the genus level in the silica group, mainly Proteobacteria, Actinobacteria, Allobactera, Mucilaginibacter, etc. Compared with the control group, a total of 7 shared differential metabolites were screened for up-regulation of Stigmatellin, Linalool oxide and Isoleucine-leucine in both intestinal and respiratory tract in the coal mine dust group. Compared with the control group , a total of 19 shared differential metabolites werescreened in the silica group, of which Diethanolamine, 1-Aminocyclopropanecarboxylic acid, Isoleucine-leucine, Sphingosine, Palmitic acid, D-sphinganine, 1, 2-dioleoyl-sn-glycero-3-phosphatidylcholine, and 1-Stearoyl-2-oleoyl-sn-glycerol 3-phosphocholine were up-regulated in both the intestinal and respiratory tract. Conclusion: There is a translocation of intestinal and respiratory flora in pneumoconiosis rats, and rats have an imbalance of lipid metabolism during the progression of pneumoconiosis.
Rats ; Animals ; Isoleucine ; Leucine ; Coal Mining ; Rats, Sprague-Dawley ; Pneumoconiosis ; Dust/analysis* ; Silicon Dioxide ; Coal