The 2 arylpropionic acid derivatives, or "profens", are an important group of nonsteroidal antiinflammatory drugs (NSAIDs). Widely used members of this group include ibuprofen, naproxen, flurbiprofen, and etodolac. Most of these drugs were marketed as racemates, however the individual enantiomers differ in their pharmacological activity, mechanism and toxicity. This drug class is widely focused because of its various biologic properties that affect their clinical use. This review will demonstrate enantioselective pharmacodynamics and pharmacokinetics of "profens".

T lymphocyte immune dysfunction plays an important role in the occurrence and development of chronic obstructive pulmonary disease (COPD), but the specific mechanism is not fully understood. Programmed cell death 1 (PD-1) negatively regulates the activation and effector function of T lymphocytes by binding to its ligand PD-L1, thus participating in the maintenance of immune tolerance. Recent studies have found that blocking the PD-1/PD-L1 signaling pathway can improve T-cell depletion and enhance the ability of anti-infection in COPD patients. Therefore, understanding the regulatory effects of PD-1 on T lymphocytes is of great significance to studying the pathogenesis and clinical treatment of COPD. This article briefly reviewed the research progress in PD-1 in terms of structure, function, T cell regulation and relationship with COPD.

Objective To analyze the clinical data and TUBB4A mutation of hypomyelination with atrophy of the basal ganglia and cerebellum (HABC)in a family,thus to provide accurate genetic counseling and prenatal diagno-sis for this family with HABC,and also to provide clinical experience for the diagnosis of HABC in China.Methods The clinical data of the proband and her family members were collected at the Department of Pediatrics,Peking Univer-sity First Hospital,December 201 4,including medical history,physical signs,and brain MRI,biochemical tests and metabolic disease screening.The associated gene of hereditary leukoencephalopathy was screened for the proband and her family members were screened by targeting -high -throughput sequencing technology,and then the genetic varia-tions were verified by Sanger sequencing.With those detection methods,the gene mutation was confirmed,and then ge-netic features were analyzed.Results Clinical features were as follows:nystagmus as the first symptom,and motor and mental retardation,dystonia and ataxia followed.Brain MRI indicated hypomyelination of white matter and atrophy of the basal ganglia and cerebellum.The clinical diagnosis of HABC was established based on the clinical features and brain MRI features above.Genetics features showed that one novel TUBB4A c.974G >T heterozygous missense muta-tion was found from the proband,which caused an amino acid change from the Trp into Leu (p.Trp325Leu).Both of her parents with normal phenotype were of wild -type in this site.Conclusions The proband from this family was diagnosed clinically based on her clinical data.One novel TUBB4Ac.974G > T (p.Trp325Leu)was founded in this study.Therefore,the spectrum of TUBB4A mutation will be expanded.In addition,this study elucidated clinical and genetic characteristics in this family with HABC,which may lay a solid foundation for the accurate genetic counseling and prenatal diagnosis.This study reported the first case of HABC caused by TUBB4A mutation in China.

OBJECTIVETo investigate the anti-damage effect of iminoethyl-lysine on noise-induced cochlea damage in guinea pig.

METHODS40 healthy red eye guinea pigs were randomly divided into 4 groups: Group A, normal control group; Group B, noise group; Group C, noise and drug group; Group D, iminoethyl-lysine group. Guinea pigs of both group B and group C were exposed to 115 dB white noise for 6 hours/day for 6 days. Group C and Group D were treated with iminoethyl-lysine(10 mg/kg) intraperitoneally, while Group B were treated with the same volume of physiological saline. ABR hearing threshold was measured in all animals before and after experiment. The expression of inducible nitric oxide synthase(NOS II) in the cochlea was examined by the method of immunohistochemistry. Also the cochlea of four groups were examined with scanning electronic microscope. ABR hearing threshold, expression of NOS II and structure of cochlea of four groups were compared with each other.

RESULTSThere was no significant difference in ABR hearing threshold among four groups before the experiment(P > 0.05). There was no significant ABR hearing threshold shift in Group A and Group D after the experiment(P > 0.05), and there was significant ABR hearing threshold shift in Group B and Group C(P < 0.05). After the experiment, the ABR hearing threshold of group B(60.23 +/- 11.23) dB, was higher than that of Group C(38.46 +/- 7.24) dB, P < 0.05. The expression of NOS II was negative in the cochlea of Group A and Group D, but was stronger in Group B than that in Group C. The damage of outer hair cells of cochlea of Group B was more severe than that of Group C.

CONCLUSIONSThe expression of NOS II in the guinea pig's cochlea damaged by noise is positive. Iminoethyl-lysine could inhibit the activity of NOS II and has the anti-damage effect on noise-induced cochlea damage. It is indicated that nitric oxide plays an important role in the pathogenesis of noise-induced hearing loss.

Animals ; Auditory Threshold ; Cochlea ; pathology ; Evoked Potentials, Auditory, Brain Stem ; Guinea Pigs ; Immunohistochemistry ; Lysine ; analogs & derivatives ; pharmacology ; Microscopy, Electron, Scanning ; Nitric Oxide ; physiology ; Nitric Oxide Synthase Type II ; analysis ; Noise ; adverse effects

Objective: To explore the phenotypic and genotypic characteristics in Chinese children with classic pantothenate kinase-associated neurodegeneration (PKAN). Method: The clinical, radiographic and genetic data of all PKAN patients diagnosed at pediatric department of Peking University First Hospital from November 2006 to December 2016 were retrospectively collected and analyzed. Result: Twenty patients with classic PKAN were included in the study. The median age at onset was 3.5 years (ranging from 1.0 to 10.0 years), and the most common initial symptom was gait disturbance (16 cases). At the last evaluation, the clinical features were limbs dystonia (20 cases), dysarthria (16 cases), dysphagia (11 cases), pyramidal sign (7 cases), mental regression (3 cases) and pigmentary retinopathy (5 cases). For those classic PKAN patients, the median time from onset of disease to loss of independent ambulation was 6.9 years (ranging from 2.0 to 12.0 years). Imaging data showed, except "eye of tiger" in MRI (19 cases), globus pallidus calcification in CT was also found in four patients. In gene testing, 26 different mutations in PANK2 gene were identified, and 16 of 26 were novel mutations. Moreover, c. 1502T>C (p.Ile501Asn) was the most common mutation (4 cases). Conclusion Dystonia is the major neurologic feature of classic PKAN. Disease progression is rapid, with loss of independent ambulation within 10 years after onset. Except "eye of tiger" in MRI, globus pallidus calcification in CT may be another imaging feature of PKAN.Sixteen novel mutations of PANK2 gene were identified in the study.

Objective:To analyze the correlation between body mass index (BMI) and lung function in patients with bronchial asthma (asthma).Methods:This study was a retrospective study. A total of 828 patients with asthma were included from March 2013 to November 2022 in the first affiliated Hospital of Guangxi Medical University, including 292 males and 536 females, aged 21-82 years, with a median age of 47 years. According to BMI, these asthma patients were divided into high BMI group (BMI≥24 kg/m 2), normal BMI group (18.5 kg/m 2≤BMI<24 kg/m 2) and low BMI group (BMI<18.5 kg/m 2). Forced vital capacity (FVC), forced expiratory volume in first second (FEV 1), FEV 1/FVC, maximum mid-expiratory flow (MMEF), forced expiratory flow at 25%, 50% and 75% of FVC (FEF 25%, FEF 50%, FEF 75%), peak expiratory flow (PEF), absolute increases in measured values of FVC and FEV 1 and percentage increases in FVC%pred (“%pred” represents the percentage of related indicators to expected value) and FEV 1%pred after inhalation of bronchodilator (salbutamol) were measured by pulmonary function meter. The correlation between BMI and the above indexes was analyzed. Results:In the high BMI group, FEV 1%pred, MMEF, FEF 25%, FEF 50% and FEF 75% were significantly lower than those in the normal BMI group and the low BMI group (all P<0.05), FVC% pred was significantly lower than those in the normal BMI group( P<0.05), and the percentage increase of FEV 1%pred was significantly lower than those in low BMI group ( P<0.05). FVC% pred in the normal BMI group was significantly higher than that in the low BMI group ( P<0.05). In male patients, BMI was negatively correlated with the absolute increase of FEV 1 ( r=-0.148, P<0.05); In female patients, BMI was negatively correlated with FEV 1%, FEV 1/FVC, MMEF, FEF 25%, FEF 50%, FEF 75% and the percentage increase of FEV 1%pred ( r=-0.124, -0.127, -0.165, -0.138, -0.156, -0.162, -0.106, all P<0.05). Conclusion:There is a significant correlation between BMI and lung function in patients with asthma, and the lung function in patients with high BMI is relatively worse; and in female patients, the effect of BMI on lung function is more significant; the increase of BMI can lead to the decrease of lung function and airway reversibility, suggesting that attention should be paid to the management of BMI in asthma management.

Objective:To explore the application of the mandarin Chinese version of the Leicester cough questionnaire (LCQ-MC) in the chronic disease management of adult patients with severe asthma.Methods:Thirty patients with severe asthma without a smoking history who received treatment and chronic disease management in the First Affiliated Hospital of Guangxi Medical University from December 2018 to December 2020 and met the inclusion criteria were selected as the research subjects. Their clinical symptoms, LCQ-MC, asthma control test (ACT), mini asthma quality of life questionnaire (MiniAQLQ), visual analogue scale (VAS) and lung function test were recorded. The reliability of LCQ-MC and its correlation with ACT, MiniAQLQ, VAS and lung function were analyzed.Results:Among the 30 patients, there were 14 males and 16 females, with an average age of (50.5±10.5) years old and a medical history of (38.3±15.5) years. The main manifestations were cough which was observed in 29 cases (96.7%), wheezing in 25 cases (83.3%), nasal symptoms in 14 cases (46.7%) and chest tightness in 11 cases (36.7%). All lung functions were consistent with the diagnosis of asthma. The total score of LCQ-MC was (16.1±4.2), in which the physiological, psychological and social dimensions were (5.0±1.2), (5.6±1.6), (5.5±1.7), respectively; and ACT (18.9+5.5), MiniAQLQ (4.9±1.4), VAS (33.5±32.4). The Cronbach′s α for the questionnaire was more than 0.70, and the results were positively correlated with ACT and MiniAQLQ ( r=0.553, 0.593, P=0.002, 0.001), negatively correlated with VAS ( r=-0.762, P<0.001). The correlations between LCQ-MC and these scores were consistent with the results after 6 months. Conclusion:Cough is an important symptom of severe asthma, and LCQ-MC can be effectively used for evaluation and chronic disease management of adult patients with severe asthma.

Objective:To improve the understanding of primary pulmonary lymphoepithelioma-like carcinoma (PPLELC).Methods:A retrospective case series study was conducted. The clinical data of 31 patients with PPLELC who were admitted to the First Affiliated Hospital of Guangxi Medical University from January 2012 to June 2023 were retrospectively analyzed, and their clinical features were summarized. The correlations of organ metastasis, tumor stage, serum tumor markers, lactate dehydrogenase, and albumin with survival time were analyzed.Results:Among the 31 patients, 13 (41.9%) were male and 18 (58.1%) were female, aged (50±9) years old, with no smoking history in 24 cases (77.4%). The common clinical manifestations were cough(24 cases, 77.4%) and sputum (19 cases, 61.3%), and 7 patients (22.6%) were detected by physical examination; 24 cases (77.4%) had elevated levels of serum tumor markers, and the rest of the 7 cases (22.6%) had normal levels of various tumor markers. All of the patients had a single lesion, with a predominance of the right middle lung (8 cases, 25.8%), and 23 cases (74.2%) had lymph node metastasis. Immunohistochemical detection showed that the positive rate of CK was 67.7% (21/31), and the positive rates of squamous cell carcinoma markers CK5/6, p63 and p40 were 90.3% (28/31), 80.6% (25/31) and 77.4% (24/31), respectively. The positive rate of EBER in situ hybridization detection was 85.2% (23/27). Genetic testing showed 6 cases had epidermal growth factor receptor (EGFR) mutation. The median survival time [ M ( Q1, Q3)] of the groups without lymph node metastasis and with lymph node metastasis was 33.0 months (7.3 months, 9.3 months) and 19.0 months (7.0 months, 27.0 months), and the difference was statistically significant ( P < 0.001). The median survival time of patients with stage Ⅰ-Ⅱ and with stage Ⅲ-Ⅳ was 20.0 months (12.5 months, 42.0 months) and 18.5 months (6.5 months, 38.5 months), and the difference was statistically significant ( P = 0.002). One stage Ⅰ A patient was treated with surgery alone and survived at 92 months of follow-up. Ten cases were treated with immunotherapy and had a good outcome. Conclusions:PPLELC is prevalent in non-smokers, the lesions are mostly in the right middle lung, and it is easily misdiagnosed as squamous cell carcinoma. The positive EBER in situ hybridization detection can help the diagnosis; lymph node metastasis is common. Tumor stage, lymph node metastasis and CYFRA21-1 level may be correlated with the survival of patients. The patients can benefit from immunotherapy, and anti-angiogenic therapy combined with chemotherapy is an optional treatment regimen.