Gorham-Stout disease(GSD) is a rare osteolytic disorder characterized by spontaneous and progressive osteolysis, along with abnormal angiogenesis and lymphangiogenesis, with no new bone formation. We present a case of a 15-year-old female admitted due to " recurrent right leg pain for 5 years, 11 months after undergoing right femoral fracture surgery". Through comprehensive integration of the patient's clinical phenotype, laboratory tests, imaging findings, pathological examinations, and molecular biological test results, GSD was considered highly likely. A multidisciplinary treatment approach was conducted, including a combination of zoledronic acid and sirolimus to inhibit osteolysis, along with rehabilitation training and orthopedic intervention, providing a personalized and comprehensive treatment strategy.

Objective:To preliminarily explore therapeutic effects and possible molecular mechanisms of sinomenine on atopic dermatitis (AD) -like mouse models.Methods:Thirty female BALB/c mice (6 - 8 weeks old) were randomly divided into 5 groups: blank control group, model group, positive control group, topical sinomenine group, and oral sinomenine group. Except for the blank control group, all groups were subjected to repeated topical stimulation with 2,4-dinitrochlorobenzene (DNCB) on the dorsal skin to establish an AD-like mouse model. After modeling, no special treatment was given to the blank control group, the positive control group was topically treated with 100 μg of 0.1% mometasone furoate cream twice daily on the lesions, the topical sinomenine group was topically treated with 100 μl of 10 mg/ml sinomenine solution twice daily on the lesions, and the oral sinomenine group was gavaged with sinomenine solution at a dose of 100 mg·kg -1·d -1 (100 μl per dose, twice daily) . Treatments lasted for 14 days. Twelve hours after the final treatment, the severity of skin lesions in each group was assessed. Blood samples were collected via enucleation, and serum levels of interleukin (IL) -1β, IL-6, and immunoglobulin E (IgE) were measured using enzyme-linked immunosorbent assay (ELISA) . Histopathological changes in dorsal skin lesions were observed, and immunohistochemical study was performed to detect the expression levels of p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF) -κB p65 in skin tissues, expressed as the percentage of the immunopositive area. One-way analysis of variance was used for multiple group comparisons, while Tukey′s test or the Games-Howell test was applied for post-hoc comparisons between groups. Results:Compared with the blank control group, the model group exhibited epidermal hyperkeratosis with parakeratosis, thickening of the spinous layer, spongiosis, significant inflammatory cell infiltration, and prominent angiogenesis. In contrast, the positive control group, topical sinomenine group, and oral sinomenine group showed reduced spinous layer thicknesses, decreased inflammatory cell infiltration, and less pronounced angiogenesis compared to the model group. In the blank control group, model group, positive control group, topical sinomenine group, and oral sinomenine group, the severity scores of skin lesions were 0, 8.83 ± 0.75, 4.33 ± 1.08, 2.58 ± 0.49, 2.83 ± 0.93 respectively, the serum levels of IL-1β were 52.58 ± 1.72, 168.40 ± 7.23, 57.07 ± 6.39, 85.74 ± 4.15, 100.30 ± 11.55 pg/ml respectively, IL-6 levels were 86.88 ± 4.60, 215.00 ± 5.02, 79.34 ± 4.91, 127.20 ± 1.06, 149.00 ± 6.21 pg/ml respectively, IgE levels were 2 159.00 ± 176.00, 3 493.00 ± 89.61, 2 294.00 ± 158.10, 2 550.00 ± 214.70, 2 814.00 ± 119.70 μg/ml respectively, the expression levels of p38 MAPK in skin tissues were 3.03% ± 3.38%, 12.95% ± 6.89%, 2.14% ± 1.28%, 5.28% ± 3.71%, 3.85% ± 2.26% respectively, and NF-κB p65 expression levels were 0.61% ± 0.49%, 18.92% ± 6.96%, 3.77% ± 1.90%, 5.66% ± 2.28%, 6.25% ± 3.14% respectively; the differences in all the above parameters were statistically significant among groups (all P < 0.05) . Compared with the blank control group, the model group had significantly increased skin lesion severity scores, serum IL-1β, IL-6, and IgE levels, as well as elevated expression of p38 MAPK and NF-κB p65 in skin tissues (all P < 0.01) . Compared with the model group, the positive control group, topical sinomenine group, and oral sinomenine group showed significantly reduced skin lesion severity scores, decreased serum IL-1β, IL-6, and IgE levels, and lower expression of p38 MAPK and NF-κB p65 in skin tissues (all P < 0.05) . Compared with the positive control group, the topical and oral sinomenine groups exhibited further reductions in skin lesion severity scores (both P < 0.05) . Additionally, the topical sinomenine group showed significantly lower serum levels of IL-1β and IL-6 compared with the oral sinomenine group (both P < 0.05) . Conclusion:Sinomenine solution could obviously alleviate the severity of skin lesions in AD-like mouse models, likely by down-regulating the expression of IL-1β, IL-6 and IgE, inhibiting the MAPK/NF-κB signaling pathway, and thus reducing the degree of inflammation.

Objective:To preliminarily explore therapeutic effects and possible molecular mechanisms of sinomenine on atopic dermatitis (AD) -like mouse models.Methods:Thirty female BALB/c mice (6 - 8 weeks old) were randomly divided into 5 groups: blank control group, model group, positive control group, topical sinomenine group, and oral sinomenine group. Except for the blank control group, all groups were subjected to repeated topical stimulation with 2,4-dinitrochlorobenzene (DNCB) on the dorsal skin to establish an AD-like mouse model. After modeling, no special treatment was given to the blank control group, the positive control group was topically treated with 100 μg of 0.1% mometasone furoate cream twice daily on the lesions, the topical sinomenine group was topically treated with 100 μl of 10 mg/ml sinomenine solution twice daily on the lesions, and the oral sinomenine group was gavaged with sinomenine solution at a dose of 100 mg·kg -1·d -1 (100 μl per dose, twice daily) . Treatments lasted for 14 days. Twelve hours after the final treatment, the severity of skin lesions in each group was assessed. Blood samples were collected via enucleation, and serum levels of interleukin (IL) -1β, IL-6, and immunoglobulin E (IgE) were measured using enzyme-linked immunosorbent assay (ELISA) . Histopathological changes in dorsal skin lesions were observed, and immunohistochemical study was performed to detect the expression levels of p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF) -κB p65 in skin tissues, expressed as the percentage of the immunopositive area. One-way analysis of variance was used for multiple group comparisons, while Tukey′s test or the Games-Howell test was applied for post-hoc comparisons between groups. Results:Compared with the blank control group, the model group exhibited epidermal hyperkeratosis with parakeratosis, thickening of the spinous layer, spongiosis, significant inflammatory cell infiltration, and prominent angiogenesis. In contrast, the positive control group, topical sinomenine group, and oral sinomenine group showed reduced spinous layer thicknesses, decreased inflammatory cell infiltration, and less pronounced angiogenesis compared to the model group. In the blank control group, model group, positive control group, topical sinomenine group, and oral sinomenine group, the severity scores of skin lesions were 0, 8.83 ± 0.75, 4.33 ± 1.08, 2.58 ± 0.49, 2.83 ± 0.93 respectively, the serum levels of IL-1β were 52.58 ± 1.72, 168.40 ± 7.23, 57.07 ± 6.39, 85.74 ± 4.15, 100.30 ± 11.55 pg/ml respectively, IL-6 levels were 86.88 ± 4.60, 215.00 ± 5.02, 79.34 ± 4.91, 127.20 ± 1.06, 149.00 ± 6.21 pg/ml respectively, IgE levels were 2 159.00 ± 176.00, 3 493.00 ± 89.61, 2 294.00 ± 158.10, 2 550.00 ± 214.70, 2 814.00 ± 119.70 μg/ml respectively, the expression levels of p38 MAPK in skin tissues were 3.03% ± 3.38%, 12.95% ± 6.89%, 2.14% ± 1.28%, 5.28% ± 3.71%, 3.85% ± 2.26% respectively, and NF-κB p65 expression levels were 0.61% ± 0.49%, 18.92% ± 6.96%, 3.77% ± 1.90%, 5.66% ± 2.28%, 6.25% ± 3.14% respectively; the differences in all the above parameters were statistically significant among groups (all P < 0.05) . Compared with the blank control group, the model group had significantly increased skin lesion severity scores, serum IL-1β, IL-6, and IgE levels, as well as elevated expression of p38 MAPK and NF-κB p65 in skin tissues (all P < 0.01) . Compared with the model group, the positive control group, topical sinomenine group, and oral sinomenine group showed significantly reduced skin lesion severity scores, decreased serum IL-1β, IL-6, and IgE levels, and lower expression of p38 MAPK and NF-κB p65 in skin tissues (all P < 0.05) . Compared with the positive control group, the topical and oral sinomenine groups exhibited further reductions in skin lesion severity scores (both P < 0.05) . Additionally, the topical sinomenine group showed significantly lower serum levels of IL-1β and IL-6 compared with the oral sinomenine group (both P < 0.05) . Conclusion:Sinomenine solution could obviously alleviate the severity of skin lesions in AD-like mouse models, likely by down-regulating the expression of IL-1β, IL-6 and IgE, inhibiting the MAPK/NF-κB signaling pathway, and thus reducing the degree of inflammation.

Objective:To establish a method for determintation of chlorogenic acid and linarin in Yejuhua granules by HPLC.Methods:We applied HPLC methods. The Kromasil 100-5 C18 column (250 mm×4.6 mm,5 μm) was used, the mobile phase was acetonitrile-0.4%H 3PO 4 solution (gradient elution), the flow rate was 1.0 ml/min, the dection wavelenghth was 334 nm and the column temperture was 32 ℃. Results:Chlorogenic acid and buddleoside had good linearity in the ranges of 0.30-1.50 μg ( r2=0.999 1) and 0.12-0.62 μg ( r2=0.999 8), respectively. The average recoveries were 99.70% and 96.67%, with RSD<2%, respectively. Conclusion:The method is simple, rapid, reliable, efficient, and can be used for determination of chlorogenic acid and buddleoside in Yejuhua Granules.

Molecular knowledge of human gastric corpus epithelium remains incomplete. Here, by integrated analyses using single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) techniques, we uncovered the spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium. Specifically, we identified a stem/progenitor cell population in the isthmus of human gastric corpus, where EGF and WNT signaling pathways were activated. Meanwhile, LGR4, but not LGR5, was responsible for the activation of WNT signaling pathway. Importantly, FABP5 and NME1 were identified and validated as crucial for both normal gastric stem/progenitor cells and gastric cancer cells. Finally, we explored the epigenetic regulation of critical genes for gastric corpus epithelium at chromatin state level, and identified several important cell-type-specific transcription factors. In summary, our work provides novel insights to systematically understand the cellular diversity and homeostasis of human gastric corpus epithelium in vivo.
Humans ; Epigenesis, Genetic ; Gastric Mucosa/metabolism* ; Chromatin/metabolism* ; Stem Cells ; Epithelium/metabolism* ; Fatty Acid-Binding Proteins/metabolism*

Purpose: The human epidermal growth factor receptor 2 (HER2) is an established therapeutic target for various kinds of solid tumors. HER2 amplification occurs in approximately 1% to 6% of colorectal cancer. In this study, we aimed to assess the efficacy and safety of trastuzumab in combination with chemotherapy in HER2-positive metastatic colorectal cancer (mCRC). Materials and Methods: An open-label, phase II trial (Clinicaltrials.gov: NCT03185988) was designed to evaluate the antitumor activity of trastuzumab and chemotherapy in HER2-positive digestive cancers excluding gastric cancer in 2017. Patients from this trial with HER2-positive, KRAS/BRAF wild-type, unresectable mCRC were analyzed in this manuscript. Eligible patients were treated with trastuzumab (8 mg/kg loading dose and then 6 mg/kg every 3 weeks) and irinotecan (120 mg/m2 days 1 and 8 every 3 weeks). The primary endpoint was the objective response rate. Results: Twenty-one HER2-positive mCRC patients were enrolled in this study. Seven patients (33.3%) achieved an objective res-ponse, and 11 patients (52.4%) had stable disease as their best response. The median progression-free survival (PFS) was 4.3 months (95% confidence interval, 2.7 to 5.9). Four of the 21 patients (19.0%) had grade 3 adverse events, including leukopenia, neutropenia, urinary tract infection, and diarrhea. No treatment-related death was reported. Exploratory analyses revealed that high tumor tissue HER2 copy number was associated with better therapeutic response and PFS. Alterations in the mitogen-activated protein kinase pathway, HER2 gene, phosphoinositide 3-kinase/AKT pathway, and cell cycle control genes were potential drivers of trastuzumab resistance in mCRC. Conclusion Trastuzumab combined with chemotherapy is a potentially effective and well-tolerated therapeutic regimen in mCRC with a high HER2 copy number.

Objective:To investigate the occurrence and influencing factors of perioperative complications after robotic gynecologic surgery.Methods:The clinical data and occurrence of perioperative complications in 1 000 cases robotic surgery completed in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed.Results:(1) Clinical data: the average age of the patients was (50.2±10.4) years old, and the average body mass index (BMI) was (24.4±3.6) kg/m 2. Among 1 000 cases, 811 cases of them were malignant tumors, including 405 cases of cervical cancer, 279 cases of endometrial carcinoma, 112 cases of epithelial ovarian cancer (EOC), 15 cases of vulvar cancer; 189 cases of them were benign diseases, including 43 cases of uterine prolapse, 57 cases hysterectomy of uterine leiomyoma and adenomyosis of the uterus ≥12 weeks, 84 cases myomectomy of uterine leiomyoma, and 5 cases of fallopian tubal ligation requiring anastomosis. Surgical methods: in patients with malignant tumors, cervical cancer, hysterectomy plus salpingectomy or salpingo-oophorectomy for stage Ⅰa1, and radical hysterectomy plus pelvic lymphatic dissection plus salpingectomy or salpingo-oophorectomy for stage Ⅰa2-Ⅱb. Endometrial carcinoma, performed by staging surgery. Staging surgery for EOC with early stage and cytoreductive surgery with advanced EOC. Vulvar cancer, extensive vulvar resection plus inguinal lymphadenectomy. In patients with benign diseases, uterine prolapse, hysterectomy plus salpingectomy or salpingo-oophorectomy plus sacrocolpopexy. Uterine leiomyoma or adenomyosis with uterus ≥ 12 weeks, hysterectomy plus salpingectomy or salpingo-oophorectomy. Myomectomy for patients requiring uterine preservation with uterine leiomyoma. Tubal anastomosis for patients with fallopian tubal ligation. (2) Surgical complications: intraoperative complications occurred in 25 patients (2.5%, 25/1 000), including 11 patients with vascular laceration, 11 patients with ureteral injury, 2 patients with bladder injury, and 1 patient with intestinal injury. Postoperative complications occurred in 130 patients (13.0%, 130/1 000), including 66 cases of lower limb venous thrombosis, 20 cases of lymphatic cyst, 8 cases of hydronephrosis, 9 cases of ileus, 16 cases with infection, 6 cases with genital fistula, 4 cases with trocar site herniation and 1 case with subcutaneous emphysema. The incidence of intraoperative complications was 3.1% (25/811) in malignant tumors and no case in benign diseases, the incidence rate in malignant tumors was significantly higher than that in benign diseases ( χ2=4.778, P=0.029). The incidence rate in cervical cancer (4.2%, 17/405) and EOC (3.6%, 4/112) were significantly higher than those in endometrial carcinoma (1.4%, 4/279) and vulvar cancer (0/15; P<0.05). The incidence of postoperative complications was 15.2% (123/811) in malignant tumors and 3.7% (7/189) in benign diseases. The incidence rate in malignant tumors was significantly higher than that in benign diseases ( χ2=17.807, P<0.01), but there were no significant difference among different malignant tumors ( χ2=4.318, P=0.229). (3) The correlative factors affecting the occurrence of surgical complications: patient′s age, BMI, previous pelvic or abdominal surgery history, the nature of disease (malignant or benign), operation time, and comorbidities had a significant impact on the incidence of postoperative complications ( P<0.05). Multivariate logistic regression analysis showed that the patient′s age ≥40 years old, BMI ≥25 kg/m 2, previous pelvic or abdominal surgery history, malignant tumors and comorbidities were independent influential factors of the postoperative complications ( P<0.05). Conclusions:Perioperative complications vary according to the type of the surgery. The age, BMI, previous pelvic or abdominal surgery history, malignant tumors, and comorbidities are influential factors of postoperative complications.

Objective:To understand the output of research and education of clinical key Specialties in Henan Province, to analyze the current situation and existing problems, and to provide scientific evidence and suggestions for the improvement of specialist ability.Methods:Through the questionnaire survey to collect the scientific research data of key specialties from 2015 to 2019, apply Epidata 3.0 to input the data, use SPSS 21.0 software to carry out test and Mann Whitney U test, and carry out a comparative analysis of the national and provincial clinical key specialty discipline leaders, medical talent team, academic, scientific research and education output in Henan Province. Results:Academic literacy and scientific research ability of leaders of national and provincial key clinical specialties in Henan Province are equal. However, there is still a big gap in scientific research and education ability between national and provincial key clinical specialties in Henan Province.Conclusions:The provincial key clinical specialties need to improve the ability of scientific research and education in a more holistic way, further strengthen the medical talents team, and focus on the exchange of high-level academic platform and the cultivation of research talents.

Objective:To evaluate the comprehensive strength of the specialties included in the medical service capacity improvement project of Henan provincial medical and health institutions, analyze the influencing factors, and provide scientific basis for the specialty construction.Methods:A total of 52 specialties were included in the project. According to the content of construction assessment and acceptance, the questionnaire was designed and filled in by the persons in charge of the specialties from the aspects of basic conditions, medical technical team, medical service ability, medical quality, scientific research and teaching ability. TOPSIS method was used to evaluate the comprehensive strength of specialty, and the main influencing factors were analyzed by single factor analysis, Mann-Whitney U test, correlation analysis and multiple stepwise regression analysis. Results:The research and teaching ability of the specialties had the strongest correlation with the comprehensive strength of the specialties. The scientific research and teaching ability was strongly related to the medical service ability. The number of people holding the post of academic institutes at or above provincial level, the number of industry standards or national guidelines, the number of academic conferences hosted at or above the provincial level, the number of postgraduate training, the number of papers published in SCI and core journals were the main influencing factors of scientific research and teaching ability.Conclusions:It is necessary to improve the level of scientific research and teaching in key specialty to promote the improvement of medical service ability. We should pay more attention to the construction of high-level talents, the cultivation of research-oriented talents, the application of new medical technology and original research.

It is critical to regulate the senescence-associated secretory phenotype (SASP) due to its effect on promoting malignant phenotypes and limiting the efficiency of cancer therapy. In this study, we demonstrated that marchantin M (Mar-M, a naturally occurring bisbibenzyl) suppressed pro-inflammatory SASP components which were elevated in chemotherapy-resistant cells. Mar-M treatment attenuated the pro-tumorigenic effects of SASP and enhanced survival in drug-resistant mouse models. No toxicity was detected on normal fibroblast cells or in animals following this treatment. Inactivation of transcription factor EB (TFEB) and nuclear factor-B (NF-B) by Mar-M significantly accounted for its suppression on the components of SASP. Furthermore, inhibition of SASP by Mar-M contributed to a synergistic effect during co-treatment with doxorubicin to lower toxicity and enhance antitumor efficacy. Thus, chemotherapy-driven pro-inflammatory activity, seen to contribute to drug-resistance, is an important target for Mar-M. By decreasing SASP, Mar-M may be a potential approach to overcome tumor malignancy.