Objective To investigate the clinical characteristics,treatment and prognosis of tuberculosis in patients with autoimmune diseases after tumor necrosis factor-αinhibitors.Methods Clinical data of 33 patients with TB after biologics(tumor necrosis factor-α inhibitors)treated in Guangzhou Chest Hospital from January 2019 to March 2023 were collected,including 25 males and 8 females,with a median age of 32 years.The clinical symptoms,laboratory results,imaging and tracheoscopic features,pathological features,treatment and outcome were analyzed retrospectively.Results The common clinical manifestations were cough(26/33),sputum(23/33)and fever(17/33).The most common cases were pulmonary tuberculosis(32/33),bronchial tuberculosis(15/33),mediastinum and hilar lymph node tuberculosis(11/33).Bilateral lung spread of tuberculosis(21/33),intrapulmonary spread of tuberculosis(bronchus,mediastinal hilar lymph nodes,pleura)(19/33),extrapulmonary tuberculosis(18/33),pulmonary tuberculosis with intrapulmonary or extrapulmonary tuberculosis(26/33).Blood CD4+T lymphocyte test was normal(23/33),and blood IGRA test was positive(27/33).Pulmonary imaging miliary nodules(8/33).The histopathology of the lymph nodes showed atypical granulomatous nodules.The duration of anti-tuberculosis treatment is 8-32 months.1 case of death.Conclusion Patients with autoimmune diseases complicated with tuberculosis after the application of tumor necrosis fact-α inhibitor are more likely to have double lung lesions,which are easy to spread to lung tissues and multiple organs of the body,and have decreased immune function.Most of them need to extend the treatment course,and the prognosis is generally good after comprehensive treatment.

Objective:To investigate the incidence and risk factors of ultrafiltration failure (UFF) in patients undergoing continuous ambulatory peritoneal dialysis (CAPD).Methods:The clinical data of 65 patients undergoing CAPD at the Hubei Provincial Corps Hospital of Chinese People's Armed Police Forces and the General Hospital of Central Theater Command from January 2016 to December 2021 were retrospectively analyzed. The clinical data included patient history, smoking history, duration of peritoneal dialysis, incidence of peritonitis, levels of hemoglobin, albumin, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol, and triglyceride. Univariate and multivariate regression analyses were conducted to investigate the correlation between UFF and various indicators in patients undergoing CAPD.Results:Among the 65 patients undergoing CAPD, the incidence of UFF was 35.4% (23/65). There were significant differences in duration of peritoneal dialysis, history of peritonitis, history of type 2 diabetes mellitus, serum albumin, low-density lipoprotein cholesterol, and triglyceride between patients with UFF and those without UFF ( t = -5.05, χ2 = 11.51, 6.83, t = 5.91, -3.28, -2.83, all P < 0.05). Multivariate regression analysis showed that albumin was negatively correlated with UFF ( r = -1.06, P < 0.05), while duration of peritoneal dialysis, level of low-density lipoprotein cholesterol, and peritonitis were positively correlated with UFF ( r = 0.43, 2.20, 1.67, all P < 0.05). Conclusion:Peritoneal dialysis duration, peritonitis, and low-density lipoprotein cholesterol are risk factors for UFF in patients undergoing CAPD, while albumin is a protective factor against UFF in these patients.

Objective To investigate the clinical efficacy of mitral valve repair technique in the treatment of rheumatic mitral valve lesions. Methods The clinical data of patients diagnosed with rheumatic mitral valve lesions and undergoing mitral valve repair under extracorporeal circulation in our department from 2021 to 2022 were retrospectively analyzed. Results A total of 100 patients were collected, including 78 females and 22 males with an average age of 52 years. There were no secondary open heart or death in the whole group. Extracorporeal circulation time was 136.3±33.1 min, aortic cross-clamping time was 107.6±27.5 min, ventilator use time was 12.9±5.9 h, ICU stay was 2.6±1.4 d, and vasoactive medication use was 823.4±584.4 mg. Before and after the surgery, there were statistical differences in the left ventricular end diastolic diameter, left atrial end systolic diameter, effective mitral valve orifice area, shortening rate of left ventricular short axis, mitral E-peak blood flow velocity, mean mitral transvalvular pressure difference, mitral pressure half-time, and cardiac function graded by New York Heart Association (P＜0.05). While there was no statistical difference in left ventricular ejection fraction or left ventricular end-diastolic volume (P>0.05). Conclusion Overall repair of rheumatic mitral valve lesions can significantly improve the cardiac function and hemodynamics of the patients, and is a good choice for patients with rheumatic mitral valve lesions.

Objective:To investigate the correlation between hearing loss and microvascular complications in diabetes.Methods:This cross-sectional study conducted the data from 572 patients with diabetes hospitalized in the Endocrinology Department of the General Hospital of Southern Theater Command from September 2022 to July 2023. All participants underwent electrical audiometry and acoustic immittance in the ENY department. Based on the audiometric results, participants were categorized into normal hearing group and hearing loss group. Additionally, 572 non-diabetic patients from the outpatient department were enrolled as the non-diabetic group. The general information and laboratory results were collected and compared using t test, rank sum test or χ2 test. Binary logistic regression analysis was used to evaluate the association of diabetic hearing loss with diabetic kidney disease(DKD), diabetic retinopathy (DR), and diabetic peripheral neuropathy (DPN). Results:Among 572 patients with diabetes, 429 suffered from hearing loss and 143 were normal. χ2 test showed significant differences in combined DKD and DPN between two groups, but not in DR. Multivariate binary logistic regression analysis identified DKD and DPN as risk factors for hearing loss, but no correlation was found with DR. Conclusion:Diabetic patients with DKD or DPN should be monitored for potential hearing loss. Early screening and treatment are crucial to prevent severe hearing impairment.

Objective:To investigate the expression of p21-activated kinase 2 (PAK2) in laryngeal squamous cell carcinoma and its relationship with the clinicopathological characteristics and chemosensitivity of patients.Methods:Transcriptome sequencing (RNA-seq) data for laryngeal squamous cell carcinoma were downloaded from the Cancer Genome Atlas (TCGA) database, and 123 patients were included in the study (12 cases had cancer tissues and normal tissues data, and the remaining 111 only had cancer tissues data). Differential expression of PAK2 in cancer and para-cancer tissues was analyzed by using R software, and the potential function of PAK2 in laryngeal squamous cell carcinoma was investigated by using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database signaling pathway enrichment. A total of 34 patients with primary laryngeal squamous cell carcinoma tissues and corresponding para-carcinoma 34 tissue specimens who underwent surgical resection were retrospectively selected from Chaoyang Central Hospital between April 2016 and June 2021, and 20 cases of normal laryngeal mucosa tissues were selected as the controls. Immunohistochemistry was used to detect the expression of PAK2 in various tissues, and its correlation with clinicopathological factors was analyzed. A total of 35 supraglottic primary laryngeal squamous cell carcinoma patients were retrospectively collected before induction chemotherapy during the same period, including 20 patients sensitive to chemotherapy and 15 patients resistant to chemotherapy. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the relative expression level of PAK2 mRNA in cancer tissues.Results:Analysis of TCGA database data showed that PAK2 expression was increased in cancer tissues compared with that in para-cancer tissues ( P = 0.012); KEGG database signaling pathways showed that the high expression of PAK2 in laryngeal squamous cell carcinoma was related to signal transduction pathways, cell cycle, and cancer. Immunohistochemistry showed that the proportion of PAK2 positive in 34 cases of laryngeal squamous cell carcinoma tissues was higher than that in adjacent tissues and normal tissues [58.82% (20/34) vs. 0.03% (1/34), 0 (0/20), all P < 0.001]. There were statistically significant differences in the proportion of PAK2 positive patients stratified with different degrees of differentiation [high differentiation vs. low or middle differentiation: 33.33% (6/18)vs. 87.50% (14/16)], lymph node metastasis [presence vs. absence: 90.91% (10/11) vs. 43.48% (10/23)], TNM staging [stage Ⅲ-Ⅳ vs. stage Ⅰ-Ⅱ: 82.35% (14/17) vs. 35.29% (6/17)] (all P < 0.05), and PAK2 positive patients were not associated with clinical type, tumor size, smoking history, drinking history, and age (all P > 0.05). qRT-PCR showed that the relative expression level of PAK2 mRNA in the chemotherapy-resistant group was higher than that in the chemotherapy-sensitive group (3.89±0.12 vs. 0.78±0.23, P < 0.001). Conclusions:The expression level of PAK2 in laryngeal squamous cell carcinoma tissues is increased, and the high expression of PAK2 is closely related to the malignant clinical characteristics of patients with laryngeal squamous cell carcinoma. The high expression of PAK2 may indicate the insensitivity to traditional chemotherapy regimens, and PAK2 may be a potential gene that targets and regulates the chemosensitivity of laryngeal squamous cell carcinoma.

Objective:To explore the efficacy and safety of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and human granulocyte colony-stimulating factor (G-CSF) for the prevention of post-chemotherapy infections in pediatric hematologic neoplasms.Methods:A total of 134 children hospitalized for chemotherapy in 6 tertiary hospitals from July 2016 to June 2018 were collected, including 60 cases in Children's Hospital of Fudan University, 38 cases in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 29 cases in Children's Hospital Affiliated to Soochow University, 4 cases in the Affiliated Hospital of Qingdao University, 2 cases in Northwestern Women and Children's Hospital, and 1 case in Shandong Provincial Qianfoshan Hospital. The children were divided into GM-CSF group (38 cases), G-CSF group (45 cases) and GM-CSF+G-CSF group (51 cases) by using random number table method. The incidence of infections, the recovery time of absolute neutrophil counting (ANC), the decrease of blood platelet count (Plt) and the incidence of adverse reactions were compared among the three groups.Results:In all children, a total of 64 cases (47.8%) had infections during the myelosuppression phase after chemotherapy, of which 18 cases (47.4%) in GM-CSF group, 20 cases (44.4%) in G-CSF group, and 26 cases (51.0%) in GM-CSF+G-CSF group. The incidence of respiratory infection in G-CSF group was higher than that in GM-CSF group and GM-CSF+ G-CSF group [22.2% (10/45) vs. 2.6% (1/38), 4.0% (2/51), χ2 = 12.00, P = 0.002]. The median time to recovery of ANC > 1.5×10 9/L was 10.5 d (8 d, 15 d) in all children, 12 d (10 d, 16 d) in GM-CSF group, 9 d (8 d, 12 d) in G-CSF group, and 10 d (8 d, 16 d) in GM-CSF+G-CSF group. In all children, a total of 101 cases (75.4%) had Plt<50×10 9/L during the myelosuppression phase, and 79 cases (59.0%) had Plt <20×10 9/L. The differences in the incidence of Plt <50×10 9/L and <20×10 9/L among the three groups were not statistically significant (both P > 0.05). In all children, the adverse reactions occurred in 24 cases (17.9%), including 20 cases (14.9%) of fever, 2 cases (1.5%) of sore throat, 1 case (0.7%) of nausea, and 1 case (0.7%) of diarrhea; no adverse reactions of grade 2 or above occurred. The difference in the incidence of adverse reactions among the three groups was not statistically significant ( P>0.05). Conclusions:The efficacy of GM-CSF and G-CSF for the prevention of infections in pediatric hematologic neoplasms during the myelosuppression phase after chemotherapy is roughly equivalent, and combination of both has a good tolerance. The incidence of respiratory infection using GM-CSF alone or GM-CSF+G-CSF is low, which might benefit from the effect of GM-CSF on lung infections.

Objective:To introduce a modified stent technique of nasal septal extension graft (SEG) with auricle cartilage, and to explore its effect on rhinoplasty.Methods:For 116 patients that underwent rhinoplasty, the cartilage of bilateral auricula was sutured with shell alignment and the dovetail was modified to prepare SEG stent; PTFE or silicone prosthesis was used for nasal dorsal graft. The patients were follow up for 6-18 months after surgery. A number of indicators including length of nose, tip projection, nasal tip and nasolabial angle morphology were used to assess surgical outcomes.Results:The 116 patients obtained satisfactory appearance immediately after operation. Length of nasal extension was 3-6 mm, tip projection was extended by 2-5 mm. Following up for 6-18 months showed stable effect (0.5-1.5 mm retraction) and satisfactory nose tip and nasolabial angle. The skin color was normal. No deformity occured in the ear cartilage donor area existed with no obvious scar.Conclusions:The modified SEG stent of auricle cartilage has good support and stability. It has a good effect on the slight and moderate extension of the short nose. In addition, the elevation of the nasal tip and the severe short nose of the first rhinoplasty and secondary rhinoplasty with mild contracture are also improved.

Objective:To investigate the clinical characteristics, drug resistance and serotypes of children′s invasive pneumococcal disease(IPD) in Shenzhen.Methods:Clinical data and drug sensitivity results of IPD children enrolled in Shenzhen Children′s Hospital, from January 2012 to December 2018, were analyzed retrospectively, and serotypes of the retained strains were identified by capsule swelling method or polymerase chain reaction(PCR) method.Results:One hundred and forty-one cases were enrolled, majority of them were less than 2 years old (86 cases, 61.0%). A total of 99 cases(70.2%) had onset in autumn and winter.The clinical manifestation included single bloodstream infection(62 cases, 45.4%), purulent meningitis(30 cases, 21.3%), pneumonia with bacteremia(28 cases, 19.9%), bone and joint infection(12 cases, 8.5%), purulent pleurisy (4 cases, 2.8%), peritonitis (3 cases, 2.1%), and infective endocarditis (2 cases, 1.4%). Underlying diseases were found in 33 cases(23.4%), co-infection in 14 cases (9.9%), complications in 39 cases (27.7%). After active treatment, 5 cases (3.5%) who were all under 2 years old died, and all of the isolates had multi-drug resistance.Four cases (2.8%) were discharged without recovery, and the rest cases were improved.The incidence of Penicillin insensitive Streptococcus pneumoniae (PNSP) with underlying diseases (30.7% vs.15.4%, χ2=3.956), meningitis(32.0% vs.9.2%, χ2=10.722) and multiple drug resistance (86.7% vs.63.1%, χ2=10.538)were higher than those of Penicillin sensitive Streptococcus pneumo- niae(PSSP)(all P<0.05). The serotypes of 97 invasive Streptococcus pneumoniae strains were identified.Types of 14 and 19F (21 strains for each type, 21.6%) were the most common, followed by type 19A (15 strains, 15.5%), type 6B and 23F (13 strains for each type, 13.4%), and type 3 (3 strains, 3.1%). The serotype coverage of 13-valent pneumococcal conjugate vaccine (PCV13) was 92.8% (90/97 strains). Conclusions:Children under 2 years old are prone to IPD and death.The IPD distribution varies in different seasons, and single bloodstream infection is the most common clinical manifestation; PNSP is more likely to occur in children with underlying diseases and meningitis, and the multi-drug resistance of pathogenic strains may be related to poor prognosis.PCV13 can cover most IPD serotypes.

The primary cilium is a microtubule-based sensory organelle. The molecular mechanism that regulates ciliary dynamics remains elusive. Here, we report an unexpected finding that MLN4924, a small molecule inhibitor of NEDD8-activating enzyme (NAE), blocks primary ciliary formation by inhibiting synthesis/assembly and promoting disassembly. This is mainly mediated by MLN4924-induced phosphorylation of AKT1 at Ser473 under serum-starved, ciliary-promoting conditions. Indeed, pharmaceutical inhibition (by MK2206) or genetic depletion (via siRNA) of AKT1 rescues MLN4924 effect, indicating its causal role. Interestingly, pAKT1-Ser activity regulates both ciliary synthesis/assembly and disassembly in a MLN4924 dependent manner, whereas pAKT-Thr determines the ciliary length in MLN4924-independent but VHL-dependent manner. Finally, MLN4924 inhibits mouse hair regrowth, a process requires ciliogenesis. Collectively, our study demonstrates an unexpected role of a neddylation inhibitor in regulation of ciliogenesis via AKT1, and provides a proof-of-concept for potential utility of MLN4924 in the treatment of human diseases associated with abnormal ciliogenesis.