Objective:To investigate the clinical features, imaging characteristics, surgical strategies, and therapeutic outcomes of otitis media complicated with inflammatory response of local meninges.Methods:A retrospective analysis was conducted on the clinical data of 8 patients with chronic suppurative otitis media complicated with inflammatory response of local meninges, treated by the Department of Otolaryngology, Head and Neck Surgery, PLA General Hospital from 2019 to 2023. Appropriate surgical strategies were selected based on the patient′s clinical manifestations, imaging characteristics, extent of lesions, and facial nerve function. Follow-up was performed postoperatively to assess the therapeutic outcomes.Results:Among the eight patients, there were six males and two females, with an average age of (55.9±12.6) years old. The primary clinical manifestations included otorrhea, hearing loss, facial paralysis, earache, headache, and fever. All patients had a history of chronic suppurative otitis media and tympanic membrane perforation, with varying degrees and types of hearing loss. Seven patients presented with peripheral facial palsy preoperatively, with the House-Brackmann (H-B) grading scale as follows: 4 cases (4/7) in grade Ⅳ, 1 case (1/7) in grade Ⅴ, and 2 cases (2/7) in grade Ⅵ. The mean duration of otorrhea and/or hearing loss was (24.68±12.18) years, while, the average duration of severe headache, aggravated otorrhea and facial paralysis was (2.73±3.92) months. Preoperative high-resolution CT scan of the temporal bone revealed soft tissue shadow in the middle ear and mastoid process, with partial defects in the mastoid cortex. Cranial MRI T1WI showed high signal in the meninges on the affected side, with contrast-enhanced MRI indicating localized meningeal thickening. Four patients (4/8) had diabetes mellitus, and 2 patients (2/8) had a history of middle ear/mastoid surgery. All patients underwent surgical treatment, including thorough removal of lesions, adequate drainage, and facial nerve decompression. Tympanoplasty and hearing reconstruction were performed when conditions permitted. Specifically, 5 patients underwent intact canal wall radical mastoidectomy with facial nerve decompression and tympanoplasty, 2 patients underwent canal wall down mastoidectomy with facial nerve exploration decompression, and 1 patient underwent modified radical mastoidectomy. Postoperatively, patients experienced significant relief and gradual disappearance of ear and head pain. The postoperative H-B grading scale of facial nerve function was as follows: 4 cases in grade Ⅰ (4/8, including 1 case without preoperatively facial palsy), 2 cases (2/8) in grade Ⅱ, and 2 cases (2/8) in grade Ⅲ. Postoperative cranial MRI showed a significant reduction in localized meningeal thickening on the affected side.Conclusions:Patients with long-term chronic suppurative otitis media and/or cholesteatoma who suddenly presented with headache, fever, aggravated otorrhea, and facial paralysis should be suspected of having inflammatory response of local meninges. High-resolution CT of temporal bone and cranial MRI provide crucial diagnostic information. Early surgical exploration and thorough lesion removal are effective treatment methods.

Objective To investigate whether ginsenoside Rh1(G-Rh1)can alleviate liver fibrosis induced by a choline-deficient,L-amino acid-defined,high-fat diet(CDAHFD)and to explore its underlying mechanisms.Methods Male C57BL/6J mice were randomly divided into 6 groups(n=8 in each group),including a standard diet group(or the control group),a high-fat diet group(or the CDAHFD group),a silymarin group(given silymarin at 5 mg/kg),a low-dose G-Rh1 group(given G-Rh1at 5 mg/kg),a medium-dose G-Rh1 group(given G-Rh1at 10 mg/kg),and a high-dose G-Rh1 group(given G-Rh1 at 20 mg/kg).The control group was given a standard feed,while the other groups were fed CDAHFD for 7 weeks to establish the mouse model of liver fibrosis.Starting from the first week,the mice in the treatment groups were administered the corresponding drugs by intragastric gavage once daily for 7 weeks in succession.After the administration of the final drug treatment,the body mass and organ mass of the mice in different groups were measured,and the organ index was obtained according.Liver tissues were examined using HE staining,Sirius red staining,and immunohistochemistry(IHC)staining.Western blot was performed to measure α-smooth muscle actin(α-SMA)and transforming growth factor-β1(TGF-β1),two liver fibrosis-related proteins,and fibroblast growth factor 12(FGF-12),a pathway-related protein.The serum biochemical indicators,including aspartate transferase(AST),alanine aminotransferase(ALT),total bilirubin(TBIL),and direct bilirubin(DBIL),were measured.Additionally,RAW246.7 cells were randomly divided into 5 groups,including a control group,a lipopolysaccharide(LPS)group,and 3 G-Rh1 treatment groups.The control group had only RAW246.7 cells in the culture medium.The other groups were given LPS(500 ng/mL),and the 3 treatment groups received G-Rh1 at 10,20,and 40 μmol/L in addition.The supernatants from the 5 groups of RAW246.7 cells were collected and cocultured with HSC-T6 cells for 24 hours to observe and compare the effects of G-Rh1 and LPS on the expression of fibrosis-related proteins,including α-SMA,Col1a1,etc,in HSC-T6 cells and on the expression of fibrotic signaling pathway-related proteins,including fibroblast growth factor 12(FGF-12)and signal transducer and activator of transcription 3(STAT3)/phosphorylated STAT3(p-STAT3),in RAW264.7 cells.Flow cytometry was conducted to analyze the phenotypes of RAW246.7 cells,and ELISA was performed to measure fibrosis-related factors,including monocyte chemoattractant protein-1(MCP-1)and transforming growth factor-β(TGF-β).Results Compared with the control mice,the mice in the CDAHFD group exhibited obvious liver fibrosis.Compared with CDAHFD mice,mice in the G-Rh1 treatment groups all showed alleviation of liver fibrosis of was alleviated to some extent in a dose-dependent manner,and the improvement effect was superior to that of silymarin,a reference drug.G-Rh1 also alleviated CDAHFD-induced body mass loss(P＜0.01),reduced the liver index(P＜0.01),and significantly decreased the serum levels of AST,ALT,DBIL,and TBIL(P＜0.0001).Significant differences in the protein expression ofα-SMA,TGF-β1,and FGF-12 in the liver were observed(P＜0.01).Compared with the LPS group,the LPS+G-Rh,groups exhibited significant differences in the expression of FGF-12 and p-STAT3/STAT3 in RAW246.7 cells,and α-SMA and Col1a1 in HSC-T6 cells(P＜0.001).In the LPS+G-Rh,groups(the 20 μmol/L and 40 μmol/L treatment groups),the conversion ratio of Ly6C-low expressing RAW246.7 cells into Ly6C-high expressing RAW246.7 cells decreased significantly(P＜0.0001),while the secretion of fibrosis-related factors MCP-1 and TGF-β decreased(P＜0.0001),which was consistent with the trend of the activation levels of HSC-T6 cells.Conclusions G-Rh1 can prevent and improve CDAHFD-induced liver fibrosis in mice,potentially through mechanisms involving the reduction of RAW264.7 phenotype transformation mediated by FGF-12 overexpression.

Objective:To explore the efficacy and adverse reactions of CAG regimen combined with venetoclax,chidamide,and azacitidine in the treatment of elderly patients with acute myeloid leukemia(AML).Methods:15 elderly AML patients aged ≥ 60 years old who were admitted to the Hematology Department of our hospital from May 2022 to October 2023 were treated with the CAG regimen combined with venetoclax,chidamide and azacitidine,and the efficacy,treatment-related adverse events,overall survival(OS)and event-free survival(EFS)were analyzed.Results:After one course of treatment,11 out of 15 patients achieved complete response(CR),3 patients achieved CR with incomplete hematologic recovery(CRi),and 1 patient died due to prior infection before efficacy evaluation,and the overall response rate(ORR)was 93.3％(14/15).The median follow-up time was 131(19-275)days,with median OS and EFS both remaining unreached.Next-generation sequencing(NGS)analysis showed that among the 15 patients,13 were detected with gene mutations,and there were 7 genes with mutation frequencies of more than 10％,including ASXL1(4 cases),RUNX1(4 cases),BCOR(3 cases),DNMT3A(3 cases),STAG2(2 cases),IDH1/2(2 cases),and TET(2 cases).Among the 13 patients with detectable mutations,12 patients achieved composite response(CR+CRi).The average recovery time of white blood cell count was 14.6 days after chemotherapy,and the average recovery time of platelets was 7.7 days after chemotherapy.The main adverse event was myelosuppression,with 10 patients accompanied by infection.Except for 1 patient who died due to septic shock during chemotherapy,no patients experienced serious complications such as heart,liver,or kidney damage during the treatment process.Conclusion:The CACAG+V regimen,which combines the CAG regimen with venetoclax,chidamide,and azacitidine,can be applied in the treatment of elderly AML patients,demonstrating good safety and induction remission rate.

Objective:To investigate the clinical features, imaging characteristics, surgical strategies, and therapeutic outcomes of otitis media complicated with inflammatory response of local meninges.Methods:A retrospective analysis was conducted on the clinical data of 8 patients with chronic suppurative otitis media complicated with inflammatory response of local meninges, treated by the Department of Otolaryngology, Head and Neck Surgery, PLA General Hospital from 2019 to 2023. Appropriate surgical strategies were selected based on the patient′s clinical manifestations, imaging characteristics, extent of lesions, and facial nerve function. Follow-up was performed postoperatively to assess the therapeutic outcomes.Results:Among the eight patients, there were six males and two females, with an average age of (55.9±12.6) years old. The primary clinical manifestations included otorrhea, hearing loss, facial paralysis, earache, headache, and fever. All patients had a history of chronic suppurative otitis media and tympanic membrane perforation, with varying degrees and types of hearing loss. Seven patients presented with peripheral facial palsy preoperatively, with the House-Brackmann (H-B) grading scale as follows: 4 cases (4/7) in grade Ⅳ, 1 case (1/7) in grade Ⅴ, and 2 cases (2/7) in grade Ⅵ. The mean duration of otorrhea and/or hearing loss was (24.68±12.18) years, while, the average duration of severe headache, aggravated otorrhea and facial paralysis was (2.73±3.92) months. Preoperative high-resolution CT scan of the temporal bone revealed soft tissue shadow in the middle ear and mastoid process, with partial defects in the mastoid cortex. Cranial MRI T1WI showed high signal in the meninges on the affected side, with contrast-enhanced MRI indicating localized meningeal thickening. Four patients (4/8) had diabetes mellitus, and 2 patients (2/8) had a history of middle ear/mastoid surgery. All patients underwent surgical treatment, including thorough removal of lesions, adequate drainage, and facial nerve decompression. Tympanoplasty and hearing reconstruction were performed when conditions permitted. Specifically, 5 patients underwent intact canal wall radical mastoidectomy with facial nerve decompression and tympanoplasty, 2 patients underwent canal wall down mastoidectomy with facial nerve exploration decompression, and 1 patient underwent modified radical mastoidectomy. Postoperatively, patients experienced significant relief and gradual disappearance of ear and head pain. The postoperative H-B grading scale of facial nerve function was as follows: 4 cases in grade Ⅰ (4/8, including 1 case without preoperatively facial palsy), 2 cases (2/8) in grade Ⅱ, and 2 cases (2/8) in grade Ⅲ. Postoperative cranial MRI showed a significant reduction in localized meningeal thickening on the affected side.Conclusions:Patients with long-term chronic suppurative otitis media and/or cholesteatoma who suddenly presented with headache, fever, aggravated otorrhea, and facial paralysis should be suspected of having inflammatory response of local meninges. High-resolution CT of temporal bone and cranial MRI provide crucial diagnostic information. Early surgical exploration and thorough lesion removal are effective treatment methods.

Objective:To investigate the efficacy and safety of Venetoclax combined with CACAG regimen in treatment of patients with refractory/relapse acute myeloid leukemia(R/R AML).Methods:The study was a singlecenter prospective clinical trial.The enrolled patients met the criteria for R/R AML.Treatment included Azacidine(75mg/m2,d1-7),Ara-C(75-100 mg/m2,q12h,d1-5),Aclacinomycin(20 mg d1,d3,d5),Chidamide(30 mg d1,d4),Venetoclax(100 mg d1,200 mg d2,400 mg d3-d14,in combination with Triazole Drug,reduced to 100 mg/d),and granulocyte colony-stimulating factor(300 μg/d until neutrophil recovery).The primary endpoint of observation was overall response rate after 1 course of treatment.Results:A total of 19 patients were enrolled from January 2022 to April 2023.After 1 course of treatmen,the overall response rate was 81.3％(13/16),the CR rate was 68.8％(11/16),and the PR was 12.5％(2/16).Among the 11 patients who got CR/CRi,8 cases achieved CRm(minimal residual disease negative CR)and 3 cases did not.As of March 27,2023,the median follow-up time was 111(19-406)days.The six-month overall survival and progression-free survival rates were both 55.7％,the 1-year overall survival and progression-free survival rates were 46.4％and 47.7％,respectively.In addition,compared with the non-CRm group,CRm patients had a better PFS(377 days vsi11 days,P=0.046).Treatment-related adverse events were mainly 3-4 degrees of bone marrow suppression,complicated by various degrees of infection(n=12),hypokalemia(n=12)and hypocalcemia(n=10)and elevated liver enzymes(n=8),of which 3/4 degrees accounted for 47.4％(9/19).Conclusion:The Venetoclax combined with CACAG regimen is an effective salvage therapy for patients with R/R AML,with high remission rate and safety profile.

Objective:To investigate the clinical characteristics,coexisting gene mutations and prognosis of acute myeloid leukemia(AML)patients with GATA2 gene mutation.Methods:The clinical data of 370 newly diagnosed AML patients treated in our hospital from January 2008 to January 2021 was analyzed retrospectively,the next-generation sequencing technology was used to detect the mutated genes in those patients.The clinical characteristics of AML patients with GATA2 mutations,the co-mutated genes of GATA2 mutations,and the effect of GATA2 mutation on prognosis were analyzed.Results:A total of 23 patients(6.2％)with GATA2 mutation was detected in 370 AML patients.Compared with GATA2 non-mutation group,patients in GATA2 mutation group were mostly normal karyotypes(P=0.037)and in low-risk cytogenetic stratification(P=0.028).The incidence of CEBPAdm and NRAS in GATA2 mutation group was significantly higher than that in GATA2 non-mutation group(P=0.010,P=0.009).There were no statistically significant differences between the two groups in terms of sex,age,white blood cell count(WBC),platelet count,hemoglobin,bone marrow(BM)blast,induction chemotherapy regimen and CR rate(P＞0.05).Among the 23 patients with GATA2 mutation,the most common co-mutated genes were CEBPAdm,NRAS(both 39.1％),NPM1,FLT3,TET2,WT1(all 17.4％),ASXL1 and IDH1(both 13.0％).Survival analysis showed that there was no statistical difference in 5-year overall survival(OS)and leukemia-free survival(LFS)rates between patients with and without GATA2 mutations in whole cohort(n=370)(P=0.306,P=0.308).Among 306 patients without CEBPAdm,the 5-year OS and LFS rates in GATA2 mutation group showed an increasing trend compared with GATA2 non-mutation group,but the difference was not statistically significant(P=0.092,P=0.056).Among 64 patients with CEBPAdm,there was no statistically significant difference in 5-year OS rate between the GATA2 mutation group and the GATA2 non-mutation group(P=0.104),but the 5-year LFS rate of the GATA2 mutation group was significantly decreased(P=0.047).Among the 23 patients with GATA2 mutation,16 cases received the"3+7"induction regimen,of which 12 cases received allogeneic hematopoietic stem cell transplantation(allo-HSCT);7 cases received the"DCAG"induction regimen,of which 3 cases received allo-HSCT.The CR rate was not statistically different between the"3+7"regimen group and the"DCAG"regimen group(P=1.000).The 5-year OS rate and LFS rate in the transplantation group were significantly higher than the chemotherapy group(P=0.021,P=0.020).Conclusion:GATA2 mutation is more common in AML patients with normal karyotype and low-risk cytogenetic stratification,and it is significantly associated with CEBPAdm and NRAS co-mutations.The prognostic significance of GATA2 is influenced by CEBPAdm.The choice of"3+7"or"DCAG"induction regimen in patients with GATA2 mutation does not affect their CR rate,while the choice of allo-HSCT can significantly improved the prognosis compared with chemotherapy only.

Objective To investigate the effects of Simo decoction on duodenal microinflammation and NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate-specific proteinase-1(Caspase-1)/gasdermin D(GSDMD)signaling pathway in rats with functional dyspepsia(FD).Methods The FD model was established by multifactorial method.SD rats were randomly divided into normal group,model group(FD model),positive control group(gavage administration of 0.305 mg·kg-1 mosapride injection)and experimental-H,-M,-L groups(gavage administration of 5.62,2.81,1.40 g·kg-1 Simo decoction).Small intestinal advancement rate and gastric emptying rate was determined;the levels of interleukin(IL)-1 β and IL-18 in serum were determined by enzyme linked immunosorbent assay(ELISA);the protein expression of NLRP3 and GSDMD in duodenal tissue was detected by Western blotting.Results The gastric emptying rates of normal,model,positive control and experimental-H,-M,-Lgroupswere(58.34±5.72)％,(29.16±8.37)％,(48.77±6.10)％,(48.35±6.04)％,(48.20±3.49)％and(39.24±4.20)％;the small intestinal propulsion rates were(82.01±7.55)％,(41.95±9.53)％,(64.61±10.18)％,(75.04±9.76)％,(60.58±7.13)％and(45.89±7.40)％;serum IL-1 β expression were(12.86±0.88),(43.73±4.60),(18.84±0.86),(24.61±1.57),(19.14±0.77)and(29.04±0.72)pg·mL-1;IL-18 expressions were(95.00±3.74),(170.60±8.78),(108.50±3.05),(118.90±3.45),(99.90±8.70)and(141.00±3.71)pg·mL-1;the relative expression levels of NLRP3 proteins were 0.32±0.02,0.84±0.05,0.42±0.03,0.48±0.02,0.61±0.04 and 0.62±0.05;the relative expression levels of GSDMD proteins were 0.34±0.05,0.93±0.06,0.35±0.03,0.52±0.02,0.53±0.06 and 0.55±0.05,respectively.Compared with the normal group,the above indexes in the model group have statistical significance;compared with the model group,the above indexes in the experimental-H group and the positive control group also have statistical significance(P＜0.01 or P＜0.05).Conclusion Simo decoction can effectively improve the general condition and duodenal microinflammation in FD rats,and the mechanism may be related to the inhibition of duodenal NLRP3/Caspase-1/GSDMD signaling pathway.

Objective: To investigate the incidence and risk factors of systemic allergic reactions induced by subcutaneous immunotherapy (SCIT) in patients undergoing SCIT injections in Peking Union Medical College Hospital (PUMCH). Methods: This is a single center retrospective cohort study. Using the outpatient information system of PUMCH, the demographic information and injection-related reaction data of patients undergoing SCIT injection in Allergy Department of PUMCH from December 2018 to December 2022 were retrospectively analyzed to count the incidence and risk factors of systemic allergic reactions caused by SCIT. Mann-Whitney nonparametric test or chi-square test was used for single-factor analysis, and multiple logistic regression was used for multiple-factor analysis. Results: A total of 2 897 patients received 18 070 SCIT injections in Allergy Department during the four years, and 40 systemic allergic reactions occurred, with the overall incidence rate of 0.22%. The incidence of systemic allergic reaction was 0.37% when using imported dust mite preparation and 0.15% when using domestic multi-component allergen preparation. The risk factors significantly related with SCIT-induced systemic allergic reactions in patients using imported dust mite preparation were age less than 18 years old (OR=3.186,95%CI: 1.255-8.085), highest injection concentration (OR value could not be calculated because all patients with systemic reactions were injected with highest concentration), and large local reaction in previous injection (OR=22.264,95%CI: 8.205-60.411). The risk factors for SCIT-induced systemic allergic reactions in patients using domestic allergen preparation were 5 or more types of allergens (OR=3.455,95%CI: 1.147-10.402), highest injection concentration (OR=3.794,95%CI: 1.226-11.740) and large local reaction in previous injection (OR=63.577,95%CI: 22.248-181.683). However, SCIT injection in pollen allergic patients during the pollen season did not show a correlation with systemic allergic reaction. Conclusion: The incidence of SCIT-induced systemic allergic reactions was low in the Chinese patient population of this study. Patients with one or more risk factors, such as multiple allergen injection, highest injection concentration, large local reaction in previous injection, should be given high attention and vigilance against systemic allergic reactions.
Humans ; Allergens ; Asian People ; Desensitization, Immunologic/adverse effects* ; Hypersensitivity/epidemiology* ; Retrospective Studies

Objective: To investigate the incidence and risk factors of systemic allergic reactions induced by subcutaneous immunotherapy (SCIT) in patients undergoing SCIT injections in Peking Union Medical College Hospital (PUMCH). Methods: This is a single center retrospective cohort study. Using the outpatient information system of PUMCH, the demographic information and injection-related reaction data of patients undergoing SCIT injection in Allergy Department of PUMCH from December 2018 to December 2022 were retrospectively analyzed to count the incidence and risk factors of systemic allergic reactions caused by SCIT. Mann-Whitney nonparametric test or chi-square test was used for single-factor analysis, and multiple logistic regression was used for multiple-factor analysis. Results: A total of 2 897 patients received 18 070 SCIT injections in Allergy Department during the four years, and 40 systemic allergic reactions occurred, with the overall incidence rate of 0.22%. The incidence of systemic allergic reaction was 0.37% when using imported dust mite preparation and 0.15% when using domestic multi-component allergen preparation. The risk factors significantly related with SCIT-induced systemic allergic reactions in patients using imported dust mite preparation were age less than 18 years old (OR=3.186,95%CI: 1.255-8.085), highest injection concentration (OR value could not be calculated because all patients with systemic reactions were injected with highest concentration), and large local reaction in previous injection (OR=22.264,95%CI: 8.205-60.411). The risk factors for SCIT-induced systemic allergic reactions in patients using domestic allergen preparation were 5 or more types of allergens (OR=3.455,95%CI: 1.147-10.402), highest injection concentration (OR=3.794,95%CI: 1.226-11.740) and large local reaction in previous injection (OR=63.577,95%CI: 22.248-181.683). However, SCIT injection in pollen allergic patients during the pollen season did not show a correlation with systemic allergic reaction. Conclusion: The incidence of SCIT-induced systemic allergic reactions was low in the Chinese patient population of this study. Patients with one or more risk factors, such as multiple allergen injection, highest injection concentration, large local reaction in previous injection, should be given high attention and vigilance against systemic allergic reactions.
Humans ; Allergens ; Asian People ; Desensitization, Immunologic/adverse effects* ; Hypersensitivity/epidemiology* ; Retrospective Studies

Senescence is an inevitable natural life process that involves structural and functional degeneration of tissues and organs. Recently, the process of skin aging has attracted much attention. Determining a means to delay or even reverse skin aging has become a research hotspot in medical cosmetology and anti-aging. Dysfunction in the epidermis and fibroblasts and changes in the composition and content of the extracellular matrix are common pathophysiological manifestations of skin aging. Reactive oxygen species and matrix metalloproteinases play essential roles in this process. Stem cells are pluripotent cells that possess self-replication abilities and can differentiate into multiple functional cells under certain conditions. These cells also possess a strong ability to facilitate tissue repair and regeneration. Stem cell transplantation has the potential for application in anti-aging therapy. Increasing studies have demonstrated that stem cells perform functions through paracrine processes, particularly those involving exosomes. Exosomes are nano-vesicular substances secreted by stem cells that participate in cell-to-cell communication by transporting their contents into target cells. In this chapter, the biological characteristics of exosomes were reviewed, including their effects on extracellular matrix formation, epidermal cell function, fibroblast function and antioxidation. Exosomes derived from stem cells may provide a new means to reverse skin aging.