Humans ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis ; Biomarkers, Tumor/genetics* ; Mutation/genetics* ; Colorectal Neoplasms/genetics* ; Proto-Oncogene Proteins B-raf/metabolism*

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

Purpose To investigate the clinicopathologic,immunophenotypic features,genetic alterations and prognosis of melanotic Xp11 neoplasms/melanotic TFE3-rearrangement neo-plasms.Methods Five cases were selected from the Depart-ment of Pathology,Union Hospital,Huazhong University of Sci-ence and Technology from November 2018 to July 2023.The clinicopathologic,immunohistochemical,FISH assays,next-generation sequencing(NGS)and follow-up details were collect-ed.Results There were 1 male and 4 females,with their ages ranging from 16 to 59 years(mean 28.2 years).The maximum diameters of the masses were 3-6 cm(average 4.7 cm).The tumors located in right kidneys(3 cases),tubal interstitium(1 case)and pelvis(1 case).Microscopically,most tumors shared similar morphology such as nested,acinar structures sep-arated by a delicate vascular network.Epithelioid tumor cells presented with clear to granular eosinophilic cytoplasm.Lym-phocytic infiltration was seen in the background;melanin depo-sition was noted in the cases;neoplastic necrosis was detected in 4 cases.Mitotic activity was low with 5 cases showing＜3/10 HPF.Intravascular tumor thrombus was detected in 2 cases,no lymphovascular and nerve invasions were detected in other 3 ca-ses.Immunohistochemically,all 5 cases expressed TFE3 dif-fusely,and expressed HMB45,Melan A to varying degrees,CK(AE1/AE3),CK7,EMA,PAX8,TFEB,S-100,SOX10,SMA,desmin were all non-reactive in the 5 cases.The Ki67-la-beling index was＜20％.TFE3 separation signal in 4 cases were detected by FISH,1 case was interpreted as negative due to atypical signal which was confirmed by next-generation se-quencing(NGS)assay as RBM10-TFE3.Clinical follow-up was available for five patients for 2-60 months,in which four pa-tients were alive with no evidence of disease after initial resec-tion,and one patient with thoracic spine metastasis was currently in stable condition.Conclusion Melanotic Xp1 1 neoplasms/melanotic TFE3-rearrangement neoplasms has unique morpholog-ic,immunophenotypic and genetic characteristics.It might be reclassified into a distinctive malignant mesenchymal tumor enti-ty.

OBJECTIVE: To compare the therapeutic effect between Hunyuan moxibustion and oral western medication on diarrhea-predominant irritable bowel syndrome（IBS-D）of spleen and kidney yang deficiency. METHODS: Sixty patients with IBS-D of spleen and kidney yang deficiency were randomly divided into a Hunyuan moxibustion group and a western medication group, 30 cases each group. The Hunyuan moxibustion group was treated with Hunyuan moxibustion at Guanyuan（CV 4），40 min each time, once a day; in the western medication group，loperamide hydrochloride capsules (2 mg each time, 3 times a day) and bacillus licheniformis live capsules (0.5 g each time, 3 times a day) were given orally.Both groups were treated for 20 days. The scores of irritable bowel syndrome（IBS）symptom severity scale（IBS-SSS）, IBS quality of life scale (IBS-QOL) and TCM symptom grading quantitative were observed before and after treatment, and the clinical efficacy and safety were evaluated in the two groups. RESULTS: After treatment，each item scores and total scores of IBS-SSS in the two groups were lower than those before treatment（P<0.05）, and the total scores of IBS-QOL were higher than those before treatment (P<0.05)；each item score and total score of IBS-SSS in the Hunyuan moxibustion group were lower than those in the western medication group (P<0.05), and the total score of IBS-QOL in the Hunyuan moxibustion group was higher than that in the western medication group (P<0.05).After treatment, each item score and total score of TCM symptom grading quantitative in the Hunyuan moxibustion group were lower than those before treatment (P<0.05), the abdominal pain, diarrhea, lack of appetite scores and total score in the western medication group were lower than those before treatment (P<0.05)；and the abdominal pain, soreness and weakness of waist and knees, fear to cold and cold limbs scores and total score in the Hunyuan moxibustion group were lower than those in the western medication group (P<0.05).The total effective rate was 90.0%（27/30）in the Hunyuan moxibustion group, which was higher than 73.3%（22/30）in the western medication group (P<0.05). No adverse reactions occurred in both groups during treatment. CONCLUSION Hunyuan moxibustion can effectively improve the symptom severity and quality of life in patients with IBS-D of spleen and kidney yang deficiency, especially in improving the symptoms of abdominal pain, soreness and weakness of waist and knees, fear to cold and cold limbs.Its therapeutic effect is superior to western medication.
Humans ; Spleen ; Irritable Bowel Syndrome/therapy* ; Quality of Life ; Capsules ; Moxibustion ; Yang Deficiency/therapy* ; Kidney ; Abdominal Pain/therapy* ; Diarrhea/therapy*

BACKGROUND: The prognostic benefit of complete revascularization in elderly patients (aged over 75 years) with multi-vessel disease and acute coronary syndrome (ACS) is currently unclear. This study aimed to determine the long-term prognostic impact of complete revascularization in this population. METHODS: We conducted this study using data obtained from the BleeMACS (Bleeding complications in a Multicenter registry of patients discharged after an Acute Coronary Syndrome) registry, which was carried out from 2003 to 2014. The objective was to categorize older patients diagnosed with ACS into two groups: those who underwent complete revascularization and those who did not. Propensity score matching and the Kaplan-Meier analysis were employed to examine differences in one-year clinical outcomes. The primary endpoint was major adverse cardiovascular event (MACE), which encompassed a combination of all-cause mortality and myocardial infarction. RESULTS: Out of 1263 patients evaluated, 445 patients (35.2%) received complete revascularization. Patients who underwent complete revascularization had a higher prevalence of hypertension and prior percutaneous coronary intervention compared to those who did not. During the one-year follow-up period, complete revascularization was associated with a significantly decreased risk of MACE [13.7% vs. 20.5%, hazard ratio (HR) = 0.63, 95% CI: 0.45-0.88, P = 0.007] and a lower risk of myocardial infarction (5.9% vs. 9.9%, HR = 0.55, 95% CI: 0.33-0.92, P = 0.02). However, it was not linked to a lower risk of all-cause death (9.5% vs. 13.5%, HR = 0.68, 95% CI: 0.45-1.02, P = 0.06). Similar results were observed in the subgroup analysis. CONCLUSIONS Long-term clinical improvements were observed in ACS patients aged over 75 years with multi-vessel disease who achieved complete revascularization. Therefore, adhering to guidelines for complete revascularization should be recommended for elderly patients.

The modernization and development of traditional Chinese medicine has led to higher standards for the quality of traditional Chinese medicine products. The extraction process is a crucial component of traditional Chinese medicine production, and it directly impacts the final quality of the product. However, the currently relied upon methods for quality assurance of the extraction process, such as simple wet chemical analysis, have several limitations, including time consumption and labor intensity, and do not offer precise control of the extraction process. As a result, there is significant value in incorporating near-infrared spectroscopy (NIRS) in the production process of traditional Chinese medicine to improve the quality control of the final products. In this study, we focused on the extraction process of Xiao'er Xiaoji Zhike oral liquid (XXZOL), using near-infrared spectra collected by both a Fourier transform near-infrared spectrometer and a portable near-infrared spectrometer. We used the concentration of synephrine, a quality control index component specified by the pharmacopoeia, to achieve rapid and accurate detection in the extraction process. Moreover, we developed a model transfer method to facilitate the transfer of models between the two types of near-infrared spectrometers (analytical grade and portable), thus resolving the low resolution, poor performance, and insufficient prediction accuracy issues of portable instruments. Our findings enable the rapid screening and quality analysis of XXZOL onsite, which is significant for quality monitoring during the traditional Chinese medicine production process.

Humans ; Mesothelioma/pathology* ; Mesothelioma, Malignant ; Pleural Neoplasms/diagnosis* ; Pleural Effusion, Malignant ; Pleural Effusion/pathology*

Fingerprints of 18 batches of substance benchmark of Shentong Zhuyu Decoction(SZD) were established by UPLC under the following conditions: Waters Sun Fire C_(18) column(3.0 mm×150 mm, 3.5 μm), column temperature of 35 ℃, gradient elution with mobile phase of acetonitrile(A)-0.1% phosphoric acid aqueous solution(B) at the flow rate of 0.4 mL·min~(-1), and detection by wavelength switching. A total of 16 common peaks were identified. The similarities among the fingerprints were calculated by Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 Edition) and the result showed they were in the range of 0.911-0.988. Based on the 16 common peaks, cluster analysis(CA), principal component analysis(PCA), and partial least square discriminant analysis(PLS-DA) all categorized the 18 batches of samples into two groups(S1, S2, S5-S8, S14, and S17 in one group, and S1, S2, S5-S8, S14, and S17 in another), and 11 most influential components were screened. Five known components with great difference among samples(hydroxysafflor yellow A, ferulic acid, benzoic acid, ecdysone, and ammonium glycyrrhizinate) were determined. The combination of multi-component content determination and fingerprints can reflect the overall cha-racteristics of the primary standards of SZD, which is simple, feasible, reproducible, and stable. This study can serve as a reference for the quality control of the primary standards of SZD.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/standards* ; Quality Control

Objective: To investigate the clinicopathological features and HER2 expression of metaplastic squamous cell carcinoma (MSCC) of the breast. Methods: A total of 47 MSCC cases diagnosed in the Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China from January 2010 to December 2021 were reviewed. The clinical information (including the follow-up data of HER2 positive patients) and pathological features were collected and analyzed. Results: All of the patients were female. Among the 47 cases, 25 were pure squamous cell carcinoma (PSCC) and 22 were mixed metaplastic carcinoma with squamous cell component (MMSC). The median age of the patients was 54 years (range, 29-84 years). The maximum diameter of the mass ranged from 0.8 to 10.0 cm, with a mean value of 3.3 cm, 85.7% (24/28) of the cases were smaller than 5 cm, and only 4 cases were larger than or equal to 5 cm. 89.5% of the MMSC presented with a solid mass. Cystic changes were more commonly found in the PSCC group (50%, P<0.05) than the MMSC group. 36.7% (11/30) of the patients had lymph node metastasis at the time of diagnosis. The squamous cell carcinoma component in all cases showed diffuse or patchy expression of p63, p40 and CK5/6. 55.3% (26/47) of the cases showed triple-negative phenotype. Among the 7 HER2-positive patients, 6 were MMSC group, which had a significantly higher rate of HER2-positivity than that in the PSCC group (1 case). In 1 MMSC case, immunohistochemistry showed HER2 2+in the invasive ductal carcinoma component and HER2 negativity (0) in the squamous cell carcinoma component, but HER2 FISH was negative in invasive ductal carcinoma and positive in squamous cell carcinoma component. Six HER2-positive MSCC patients received anti-HER2-targeted therapy, including two patients who received neoadjuvant chemotherapy combined with anti-HER2-targeted therapy before surgery. One patient achieved pathological complete remission, while the other achieved partial remission (the residual tumors were squamous cell carcinoma components). After 9-26 months of follow-up, four patients had no disease progression, two patients developed pulmonary metastases, and one patient showed local recurrence. Conclusions: MSCC is a group of heterogeneous diseases. PSCC and MMSC may be two different entities. Most of the MSCC are triple-negative and HER2 positivity is more commonly seen in MMSC with invasive ductal carcinoma component. Some HER2-positive MSCC patients can achieve complete remission or long-term progression-free survival after receiving anti-HER2 targeted therapy, but the squamous cell carcinoma component may be less sensitive to targeted therapy than the invasive ductal carcinoma component.
Carcinoma, Ductal ; Carcinoma, Squamous Cell/pathology* ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Receptor, ErbB-2/metabolism*

Humans ; RNA-Binding Protein EWS/genetics* ; Histiocytoma, Malignant Fibrous/pathology* ; Oncogene Proteins, Fusion/genetics* ; Biomarkers, Tumor ; Cyclic AMP Response Element-Binding Protein/genetics*