Fibrosis is an important pathoIogicaI change in a variety of diseases and with compIicated causes. Fibrosis diseases in different organs have different causes,but the common manifestations of fibrobIast are proIiferation and coIIagen deposition that couId eventuaIIy Iead to normaI tissue damage and Ioss of function. Fibrosis in such important organs as the heart or Iung couId be Iife-threatening. There are different reguIating factors and drugs to fibrosis. Chinese medicine treatment is stiII the main method cIinicaIIy for Iiver fibrosis. Because there is no effective cure for puImonary fibrosis,treatment focuses on anti-infIammation by aIIeviating Iesion and improving kidney function. Despite the tremendous progress in fibrosis treatment,there is stiII a Iack of targeted drugs that couId cure a specific disease in a specific area. With the deveIopment of gene technoIogy,gene therapy wiII become an important treatment for this disease. This paper introduces anti-myocardiaI fibrosis drugs according to the mechanism.

Objective To summarize clinical experiences for the management of upper cervical fracture associated with mild to moderate craniocerebral injury in order to improve the outcome of patients with craniocervical injury.Methods Twenty-two cases (13 males and 9 females) of non-nerve damage treated surgically from June 2008 to June 2012 were enrolled.Mean age was 41 years (range,23-68 years).Mechanisms of injury were traffic accidents in 12 cases,high falls in 7 cases and violence or others in 3 cases.Dens fractures were noted in 7 cases,Jefferson fractures in 5 cases and axial vertebral arch fractures in 4 cases,and combined atlas and axis fractures in 6 cases.Admission Glasgow Coma Score (GCS) was 12-14 points in 10 cases and 9-11 points in 12 cases.All cases suffered some degree of brain damage including brain contusion and laceration,and epidural,subdural or intracerebral hematoma.Three cases of cervical fractures were misdiagnosed in the early stage.Twelve cases required emergent craniotomy due to the primary craniocerebral injury and had elective upper cervical spine surgery until the medical condition was stabilized.Another 10 cases underwent conservation treatment of craniocerebral injury and had cervical spine surgery within 1 week due to the severe dislocation of the upper cervical spine.Operation time,blood loss,hospital stay,hospitalization cost and perioperative complications were analyzed.Outcome was evaluated with Glasgow Outcome Scale (GOS) at discharge.Fracture union,bone fusion and cervical stability were assayed with X-rays and CT films.Results All were followed up for a mean period of 18 months (range,12-36 months).Among the 12 cases of primary craniocerebral injury,operation time was (115 ± 22) min,blood loss was (280 ± 72) ml,hospitalization period was (23 ±7)d and overall cost was 88,000 yuan;one case sustained wound infection cured two weeks after debridement and dressing and two cases sustained pulmonary infection cured after antibiotic treatment;discharge GOS was grade Ⅳ in 2 cases and grade Ⅴ in 10 cases.Among the 10 cases of primary cervical injury,operation time was (125 ± 38) min,blood loss was (330 ± 90) ml,hospitalization period was (17 ± 6)d and overall cost was 61,000 yuan;no perioperative complications occurred;discharge GOS was grade Ⅳ in 1 case and grade Ⅴ in 9 cases.Pain radiating to occipital region,limited neck mobility and other clinical symptoms were alleviated at discharge.X-rays verified good healing of the bone and no malposition of the screws.Conclusion For cervical fracture associated with craniocerebral injury,cervical examination and protection are important.Once medical condition becomes stable,early surgery can be performed for upper cervical fracture.

Objective To study the expression of Snail in laryngeal carcinoma and to explore its relationship with invasion and metastasis in subgroup laryngeal carcinoma cells. Method The expression of Snail protein was examined by immunohistochemistry staining in the tissue of laryngeal carcinoma. The statistical evaluation was performed to detect the correlation between the Snail protein expression and clinical features. In different subgroups of laryngeal carcinoma cells (CD 44+CD 133+cells, CD 44 and CD 133-cells), the expression of Snail and adhesion molecules E-cadherin were detected by RT-PCR,Western blot test and immunochemical staining which were studied in the correlation with invasion and metastasis. Results The result of immunohistochemical staining revealed that Snail was moderately or highly expressed in the tissue of laryngeal carcinoma significantly and higher than those in adjacent non-cancerous tissues(P<0.01). Expression of Snail was highly correlated with lymph node metastasis, tumor differentiation and clinical classification(P<0.05).However, it was not related to the age , gender and clinical type. RT-PCR and Western blot test results confirmed that the expression level of Snail was significantly higher in CD 44+CD 133+laryngeal cancer cells than in CD 44-and CD 133-laryngeal cancer cells, otherwise the expression level of E-cadherin in CD 44+CD 133+laryngeal cancer cells was significantly lower than in the CD 44-and CD 133-laryngeal cancer cells. Cell immunohistochemical staining confirmed the expression of Snail and E-cadherin were negatively correlated in CD 44+CD 133+laryngeal cancer cells. Conclusion Over expression of Snail in laryngeal carcinoma is closely related to the development of laryngeal cancer and lymph node metastasis. The expression of Snail in the CD 44+CD 133+laryngeal cancer cell subgroup is negatively correlated with adhesion molecules E-cadherin, which is a close correlation with invasion and metastasis of laryngeal cancer cells.

Objective:To investigate the expression of activator of basal transcription 1 (ABT1) protein in gastric cancer tissue and its relationships with the clinical parameters and prognosis of gastric cancer patients, and to clarify the role of ABT1in the occurrence and development of gastric cancer.Methods:A total of 100cases of cancer tissue of the gastric cancer patients and 80pairs of adjacent tissue were selected.The expressions of ABT1in cancer tissue and adjacent tissue were detected by immunohistochemistry and the proportion of stained cells and the degree of staining in the immunohistochemistry results were analyzed using semi-quantitative analysis.The relationships between the semi-quantitative analysis results and the clinical parameters of gastric cancer patients were statistically analyzed.Kaplan-Meier method was used to analyze the correlation between the ABT1 protein expression level and the survival of gastric cancer patients.Results:ABT1-positive staining was observed in the nucleus and cytoplasm of gastric cancer tissue and adjacent gastric tissue.The expression level of ABT1in gastric cancer tissue was lower than that in adjacent tissue (P=0.021) .The ABT1protein expression level in gastric cancer tissue was significantly negatively correlated with the pathological grade (r=-0.224, P=0.026) .The Kaplan-Meier analysis results of the survival curve showed that the high expression of ABT1was associated with good prognosis in the gastric cancer patients (HR=1.483, P＜0.01) .The survival rate of gastric cancer patients with high ABT1expression was significantly higher than that of the patients with low ABT1expression (HR=2.411, P=0.0272) .Conclusion:The expression of ABT1in gastric cancer tissue is lower, indicating that ABT1can be used one of the markers of good prognosis of gastric cancer.

Objective:The clinical features, laboratory indices, and imaging data of patients with Pneumocystis jirovecii pneumonia (PJP) were described and analyzed, aiming to provide helpful information for the diagnosis and treatment of PJP. Methods:A retrospective study were conducted with data from 154 PJP patients who visited China-Japan Friendship Hospital from May 2017 to August 2020. Their clinical characteristics, laboratory and imaging data, and clinical outcomes were collected for analysis. The patients were further divided into the death group (51 cases) and the survival group(103 cases). The differences between the groups were compared by using t-test, nonparametric test, and chi-square test. Results:Of the 154 PJP patients, there were 89 males and 65 females, with a mean age of (53.7±14.8) years. Among them, 85.7% (132/154) were on immunosuppressive/glucocorticoids agents within the past month. Besides, 27.9% (43/154) and 33.1% (51/154) had kidney diseases and connective tissue diseases, respectively. The major clinical manifestations in these patients involved fever 82.9% (126/154), cough 59.7% (92/154), and dyspnea 52.6% (81/154). For the laboratory data, the lactate dehydrogenase (LDH) was 561.0 (434.3, 749.0) IU/L and the value increased in 91.3% (95/104) of the patients. The CD4+T-cell lymphocytes in 88.0% (95/108) and 57.4% (62/108) of patients were lower than 400/μl and 200/μl, respectively. Furthermore, (1, 3)-β-D glucan (BG) increased in 74.4% (67/90) of PJP patients (≥100.0 ng/L). For the imaging results, chest computed tomography (CT) showed diffuse ground-glass shadows/grid shadows in 90% (117/130) patients. Compared with the survival group, higher LDH [690.5 (528.8, 932.3) IU/L vs 502.5 (381.8, 657.0) IU/L, Z=-3.375, P=0.001], white blood cell count (WBC) [9.8 (5.8, 12.6) ×10 9/L vs 7.3 (5.0, 10.1) ×10 9/L, Z=-2.392, P=0.017], and age [(69.8±14.5) years vs (50.6±14.0) years, t=-3.756, P=0.001] were found in the death group. Lower lymphocyte ratio [5.3 (3.2, 9.3) % vs 9.6 (5.6, 17.2) %, Z=?3.262, P=0.001] and oxygen partial pressure (PaO 2) levels [(73.2±20.5) mmHg vs (64.8±17.7) mmHg (1 mmHg=0.133 kPa), t=2.345, P=0.021] were also observed in the death group. Furthermore, in the death group, the bacterial and fungal infection rate was higher than the rates in the survival group [55.1% (27/51) vs 21.5% (22/103), χ 2=15.372, P=0.001]. Conclusions:Long-term use of immunosuppressive agents or glucocorticoids predispose to PJP. CD4+T-lymphocytes, LDH, and BG might be used as important auxiliary examinations for PJP patients. Age, LDH, WBC, lymphocyte ratio, PaO 2 and possible combinations with bacterial or fungal infections are more closely related to the prognostic of PJP patients.

Objective:To explore the expression of KAP1 (KRAB-associated protein 1, KAP1) in Malignant pleural mesothelioma (MPM) based on the cancer genome atlas (TCGA) and clinical trials. And elucidate the correlation between the expression of KAP1 and the clinical pathological parameters of patients with MPM and its prognosis.Methods:In April 2022, Based on the second generation KAP1mRNA sequencing data and clinicopathological data of MPM patients downloaded from TCGA database, the correlation between KAP1mRNA expression and clinical parameters was analyzed, and the correlation between KAP1 protein expression and clinicopathological parameters and its prognostic value were analyzed based on Chuxiong data set cohort clinical samples. The expression of KAP1 mRNA in MPM samples and matched normal tumor adjacent tissues was detected by qRT-PCR, and the expression of KAP1 protein in MPM and normal pleural tissues was detected by immunohistochemistry and Westernblotting. To construct a Kaplan-Meier model to explore the effect of KAP1 expression on the prognosis of MPM patients, and to analyze the prognostic factors of MPM patients by Cox regression.Results:qRT-PCR and Western blotting detection showed that the expression levels of KAP1 gene in four different MPM cells (NCI-H28, NCI-H2052, NCI-H2452, and MTSO-211H) were significantly higher than those in normal pleural mesothelial cells Met-5A. qRT-PCR, Western blotting and IHC results demonstrated that the mRNA and protein expression levels of KAP1 in MPM tissues was significantly higher than that in matching normal mesothelial tissues, and the expression level of KAP1 protein was correlated with TP 53 protein expression levels and serum CEA levels ( P<0.05) . The mRNA expression level was significantly correlated with the prognosis, The overall survival time of mesothelioma patients with high KAP1mRNA expression was significantly shorter (HR=3.7, Logrank P<0.001) . Tumor type, age and the mRNA expression were related to the prognosis of MPM patients ( P<0.05) . Multivariate analysis showed that tumor type and KAP1 mRNA expression level were independent prognostic factors of MPM patients ( P<0.05) . Conclusion:In this study, TCGA database and Chuxiong cohort experiment samples were used to collect the relevant information of KAP1 expression in malignant melanoma tissues. It was confirmed that KAP1 is highly expressed in MPM tissues. The mRNA expression level and pathological type are correlated with the prognosis of patients.

Objective:To investigate the efficacy and safety of oral testosterone therapy in individuals diagnosed with androgen insensitivity syndrome (AIS).Methods:A self-controlled study design was utilized, focusing on individuals with AIS who were genetically diagnosed at the Department of Endocrinology, Genetics, and Metabolism of Beijing Children′s Hospital between 2009 and 2021. These patients underwent treatment involving the administration of testosterone. The primary observed indexes include the measurement of penis length, which should meet the minimal surgical standard (penis length≥2.5 cm) or greater than or equal to -2.5 s (lower limit of normal). Secondary observed indexes include penile length standard deviation score (PL-SDS), an increase in penis longitude (ΔPL), medication dosage, the course of therapy, and safety indicators, among others. There were 4 courses of treatment. After each course, patients were evaluated to determine whether termination of treatment was appropriate. Patients who exhibited inadequate post-treatment penile length growth were advised to continue with further treatment. The statistical methodology included t-test, and a Wilcoxon rank sum test to describe efficacy and safety. The patients were followed up until 2023. Results:The study comprised a total of 51 individuals with AIS, comprising 33 males and 18 females (gender of registered permanent residence). Among these patients, 10 were diagnosed with complete androgen insensitivity syndrome (CAIS) and 41 were diagnosed with partial androgen insensitive syndrome (PAIS). There were 2 children with CAIS were diagnosed by doctors and prescribed testosterone undecanoate, but the children did not really take medicine.The penile length of CAIS patients could not be measured (penile length<0.5 cm) before and after treatment. For PAIS patients, baseline penile length and PL-SDS were (2.3±0.6) cm and -3.7±1.3, respectively. The measurements for penile length and PL-SDS after each treatment course were recorded as follows: (2.7±0.8), (2.8±0.6), (2.6±0.4), (2.6±0.4) cm and -2.8±1.6, 2.5±1.6, 2.9±1.2, -3.2±0.9, respectively. Both penile length and PL-SDS interventions showed statistically significant gains when compared to the baseline performance of the 4 courses ( t=4.05、3.56、2.55、2.23 and 3.88、3.50、2.50、2.19, all P<0.05). Before treatment, 13 PAIS patients (32%) reached 2.5 cm and seven (17%) reached greater than or equal to -2.5 s. Following the initial, subsequent, third, and fourth therapeutic interventions, 18 cases (44%), 24 cases (59%), 25 cases (61%), and 26 cases (63%) reached 2.5 cm, respectively. Additionally, A total of 12 cases (29%), 15 cases (37%), 20 cases (49%), and 21 cases (51%), respectively, were found to reach greater than or equal to -2.5 s. The study involved the longitudinal monitoring of patients with the highest recorded age being 13.7 years. The weight, height, body mass index, bone age/age, cholesterol, hemoglobin and so on were all within the normal range and the difference were not statistically significant (all P>0.05). All 49 patients were no abnormalities in blood electrolyte, liver and kidney function and thyroid function and no changes in precocious puberty, pubic hair growth, aggressive behavior, vulvar skin darkening, diarrhea or other conditions. Conclusions:Testosterone undecanote in children with CAIS was no effective. The initial course of treatment for patients with PAIS demonstrates observable enhancements in penile length and PL-SDS. For patients with inadequate penile length growth, continued treatment in subsequent courses (such as the second, third, and fourth courses) is recommended toenhance outcomes gradually. Testosterone undecanoate was safe and effective for the majority of individuals with PAIS patients, with few adverse effects and good treatment tolerance.

Objective:To explore the expression of KAP1 (KRAB-associated protein 1, KAP1) in Malignant pleural mesothelioma (MPM) based on the cancer genome atlas (TCGA) and clinical trials. And elucidate the correlation between the expression of KAP1 and the clinical pathological parameters of patients with MPM and its prognosis.Methods:In April 2022, Based on the second generation KAP1mRNA sequencing data and clinicopathological data of MPM patients downloaded from TCGA database, the correlation between KAP1mRNA expression and clinical parameters was analyzed, and the correlation between KAP1 protein expression and clinicopathological parameters and its prognostic value were analyzed based on Chuxiong data set cohort clinical samples. The expression of KAP1 mRNA in MPM samples and matched normal tumor adjacent tissues was detected by qRT-PCR, and the expression of KAP1 protein in MPM and normal pleural tissues was detected by immunohistochemistry and Westernblotting. To construct a Kaplan-Meier model to explore the effect of KAP1 expression on the prognosis of MPM patients, and to analyze the prognostic factors of MPM patients by Cox regression.Results:qRT-PCR and Western blotting detection showed that the expression levels of KAP1 gene in four different MPM cells (NCI-H28, NCI-H2052, NCI-H2452, and MTSO-211H) were significantly higher than those in normal pleural mesothelial cells Met-5A. qRT-PCR, Western blotting and IHC results demonstrated that the mRNA and protein expression levels of KAP1 in MPM tissues was significantly higher than that in matching normal mesothelial tissues, and the expression level of KAP1 protein was correlated with TP 53 protein expression levels and serum CEA levels ( P<0.05) . The mRNA expression level was significantly correlated with the prognosis, The overall survival time of mesothelioma patients with high KAP1mRNA expression was significantly shorter (HR=3.7, Logrank P<0.001) . Tumor type, age and the mRNA expression were related to the prognosis of MPM patients ( P<0.05) . Multivariate analysis showed that tumor type and KAP1 mRNA expression level were independent prognostic factors of MPM patients ( P<0.05) . Conclusion:In this study, TCGA database and Chuxiong cohort experiment samples were used to collect the relevant information of KAP1 expression in malignant melanoma tissues. It was confirmed that KAP1 is highly expressed in MPM tissues. The mRNA expression level and pathological type are correlated with the prognosis of patients.

Objective To explore whether voluntary wheel running affects liver oxidative stress by regulating the Nrf2/HO-1 pathway,thereby alleviating HFFC diet-related lipid deposition in the liver.Methods Eight-week-old C57BL/6J mice were randomly divided into a normal diet group(NC group,n=10)and high-fat,fructose,and cholesterol diet group(HFFC group,n=20)after 1 week of adaptive feeding.Ten weeks of feeding later,mice in the HFFC group were divided into a quiet group(HFFC group,n=10)and HFFC combined with exercise group(HFFC+EX group,n=10).HFFC+EX group mice were caged with voluntary running wheels for free movement,and the number of running wheels was recorded every day for 8 weeks.After the last treatment,the mice were sacrificed by fasting for 12 hours at an interval of 24 hours,and the blood and liver were collected for analysis.Results(1)Body weight,liver weight,and liver index of mice fed the HFFC diet were significantly higher than those of the NC group,which significantly decreased after exercise(P＜0.05).(2)Compared with the NC group,HDL-C and LDL-C in the HFFC group were significantly increased,and the LDL-C level was significantly decreased after 8 weeks of exercise(P＜0.05).(3)The liver fat droplet area and liver TG content in the HFFC group were significantly higher than those in the NC group,whereas those in HFFC+EX group were significantly decreased(P＜0.05).(4)Compared with the NC group,the content of oxidase MDA in the HFFC group were significantly increased,and nuclear translocation and gene expression of Nrf2 were significantly decreased.After exercise,the activities of SOD and T-AOC were significantly increased,and the nuclear translocation and gene expression of Nrf2 and expression levels of HO-1 and SOD-1 were significantly increased(P＜0.05).(5)The number of apoptotic hepatocytes and CHOP expression in the HFFC diet group were significantly higher than those in the NC group,whereas the number of apoptotic hepatocytes,and CHOP and Bax/Bcl-2 expression in the exercise group were significantly lower than those in the NC group(P＜0.05).Conclusions Voluntary wheel can alleviate HFFC diet induced liver lipid deposition by regulating the Nrf2/HO-1 pathway,thereby alleviating oxidative stress and reducing apoptosis in liver cells.

Although chromosomal mosaic embryos detected by trophectoderm(TE)biopsy offer healthy embryos available for transfer,high-resolution postnatal karyotyping and chromosome testing of the transferred embryos are insufficient.Here,we applied single-cell multi-omics sequenc-ing for seven infants with blastula chromosomal mosaicism detected by TE biopsy.The chromo-some ploidy was examined by single-cell genome analysis,with the cellular identity being identified by single-cell transcriptome analysis.A total of 1616 peripheral leukocytes from seven infants with embryonic chromosomal mosaicism and three control ones with euploid TE biopsy were analyzed.A small number of blood cells showed copy number alterations(CNAs)on seem-ingly random locations at a frequency of 0％-2.5％per infant.However,none of the cells showed CNAs that were the same as those of the corresponding TE biopsies.The blastula chromosomal mosaicism may be fully self-corrected,probably through the selective loss of the aneuploid cells dur-ing development,and the transferred embryos can be born as euploid infants without mosaic CNAs corresponding to the TE biopsies.The results provide a new reference for the evaluations of trans-ferring chromosomal mosaic embryos in certain situations.