Chlorobenzene contaminants (CBs) pose a threat to the eco-environment, and functional strains hold considerable potential for the remediation of CB-contaminated sites. To deeply explore the application potential of functional bacteria in the in-situ bioremediation of CBs, this study focused on the biodegradation characteristics and degradation kinetics of CB and 1, 2-dichlorobenzene (1, 2-DCB) in soil by the isolated strain Serratia marcescens TF-1. Additionally, an in-situ remediation trial was conducted with this strain at a chemical industrial site. Batch serum bottle experiments showed that the degradation rate of CB at the concentrations ranging from 20 to 200 mg/L by TF-1 was 0.22-0.66 mol/(g_cell·h), following the Haldane model, with the optimal concentration at 23.12 mg/L. The results from simulated soil degradation experiments indicated that the combined use of TF-1 and sodium succinate (SS) significantly enhanced the degradation of CBs, with the maximum degradation rate of CB reaching 0.104 d^-1 and a half-life of 6.66 d. For 1, 2-DCB, the maximum degradation rate constant was 0.068 7 d^-1, with a half-life of 10.087 d. The in-situ remediation results at the chemically contaminated site demonstrated that the introduction of bacterial inoculant and SS significantly improved the removal of CBs, achieving the removal rates of 84.2%-100% after 10 d. CB, 1, 4-dichlorobenzene (1, 4-DCB), and benzo[a]pyrene were completely removed. Microbial diversity analysis revealed that the in-situ remediation facilitated the colonization of TF-1 and the enrichment of indigenous nitrogen-fixing Azoarcus, which may have played a key role in the degradation process. This study provides a theoretical basis and practical experience for the in situ bioremediation of CBs-contaminated sites.
Chlorobenzenes/isolation & purification* ; Biodegradation, Environmental ; Soil Pollutants/isolation & purification* ; Serratia marcescens/metabolism* ; Industrial Waste ; Soil Microbiology

Objective:To evaluate the effectiveness and safety of belumosudil for the treatment of chronic graft-versus-host disease (cGVHD) .Methods:We retrospectively collected data on patients with cGVHD who received belumosudil at Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from May 2023 to March 2024. The study endpoints were overall response rate (ORR), organ-specific response rates, time to response (TTR), changes in Lee Symptom Scale (LSS) scores, tapering or discontinuation of corticosteroid treatment, failure-free survival (FFS), and adverse events.Results:The study included 20 patients with cGVHD who received belumosudil, of whom 15 were men and 5 women. The median age was 34.5 (12-67) years, and three patients were under 18 years old. The median follow-up duration was 5.0 (1.4 - 9.8) months. All patients had severe cGVHD, and 18 (90.0%) showed involvement of at least four organs. The median number of prior treatment lines was 4, and 15 patients (75%) had previously received ruxolitinib. All patients received 200 mg of belumosudil once daily in combination with other cGVHD systemic therapies. The ORR was 90.0% (95% CI: 68.3%-98.8%), and all responses were partial responses. The median TTR was 1.6 (0.9 - 8.4) months. The LSS scores improved in a clinically meaningful way in 80.0% (16/20) of the patients within 3 months. The corticosteroid dose was reduced in 42.6% (6/14) of the patients. The 3-month FFS was 79.6% (95% CI: 61.4%-100.0%). Most adverse events were grade 1 or grade 2, and two patients (10.0%) experienced grade 3 or higher-grade adverse events. Conclusions:In the real-world setting, belumosudil demonstrated good effectiveness and safety in patients with cGVHD with a history of severe disease and multiorgan involvement.

Objective:To evaluate the effectiveness and safety of belumosudil for the treatment of chronic graft-versus-host disease (cGVHD) .Methods:We retrospectively collected data on patients with cGVHD who received belumosudil at Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from May 2023 to March 2024. The study endpoints were overall response rate (ORR), organ-specific response rates, time to response (TTR), changes in Lee Symptom Scale (LSS) scores, tapering or discontinuation of corticosteroid treatment, failure-free survival (FFS), and adverse events.Results:The study included 20 patients with cGVHD who received belumosudil, of whom 15 were men and 5 women. The median age was 34.5 (12-67) years, and three patients were under 18 years old. The median follow-up duration was 5.0 (1.4 - 9.8) months. All patients had severe cGVHD, and 18 (90.0%) showed involvement of at least four organs. The median number of prior treatment lines was 4, and 15 patients (75%) had previously received ruxolitinib. All patients received 200 mg of belumosudil once daily in combination with other cGVHD systemic therapies. The ORR was 90.0% (95% CI: 68.3%-98.8%), and all responses were partial responses. The median TTR was 1.6 (0.9 - 8.4) months. The LSS scores improved in a clinically meaningful way in 80.0% (16/20) of the patients within 3 months. The corticosteroid dose was reduced in 42.6% (6/14) of the patients. The 3-month FFS was 79.6% (95% CI: 61.4%-100.0%). Most adverse events were grade 1 or grade 2, and two patients (10.0%) experienced grade 3 or higher-grade adverse events. Conclusions:In the real-world setting, belumosudil demonstrated good effectiveness and safety in patients with cGVHD with a history of severe disease and multiorgan involvement.

Objective:To understand the current status and analyze the factors of demoralization of patients with chronic heart failure (CHF), providing references for targeted psychological interventions of nursing staff.Methods:Using the cross-sectional survey method, from August 2022 to January 2023, 282 CHF patients who were followed up in the Cardiovascular Department of the First Affiliated Hospital of Zhengzhou University were selected as the study subjects. They were investigated using the General Information Questionnaire, Demoralization Scale Revised Mandarin Version, Brief Illness Perception Questionnaire (BIPQ), Fear of Progression Questionnaire-Short Form (FoP-Q-SF), and the factors influencing the demoralization of CHF patients were analyzed using univariate analysis and multiple linear regression.Results:Among 282 cases, male 172 cases, female 110 cases, aged (62.29±10.05) years old. The Demoralization Scale Revised Mandarin Version′s score of CHF patients was (30.30 ± 10.37) points; the score of BIPQ was (42.18 ± 13.94) points; the score of FoP-Q-SF was (35.41 ± 7.29)points, which were at high level. The results of multiple linear regression analysis showed that patient disease duration, disease stages, New York heart association cardiac function classification, the score of BIPQ, and the score of FoP-Q-SF were factors influencing the demoralization of CHF patients ( t values were 3.08 to 12.50, all P<0.05). Conclusions:There is an urgent need to focus on the current status of the demoralization of CHF patients. It is necessary to develop a systematic and effective intervention strategy for demoralization, to take into account patient disease duration, disease stages, illness perception, and fear of progression in a comprehensive manner.

Objective:To explore the mediating role of disease progression′s fear and positive affect in the relationship between disease perception and demoralization in patients with chronic heart failure. It provided a theoretical basis for targeted interventions for healthcare workers.Methods:From October 2022 to March 2023, 320 patients with chronic heart failure in the First Affiliated Hospital of Zhengzhou University were selected as the research objects by convenience sampling. The General Information Questionnaire, Demoralization Scale Redacted Mandarin Version, Brief Illness Perception Questionnaire, Fear of Progression Questionnaire-Short Form, Positive and Negative Affect Schedule (Positive Affect Schedule) were used to conduct the questionnaire survey exploring the mediating effects of fear of disease progression and positive emotions between disease perception and disorientation by construction structural equation model.Results:There were 268 valid questionnaires. Of the 268 patients, 168 were male and 100 were female, 3.36% (9/268) were ≤40 years old, 55.22% (148/268) were 41-65 years old, and 41.42% (111/268) were >65 years old. Correlation analysis showed that disease perception was positively correlated with disease progression ′s fear, and every dimension of demoralization ( r values were 0.300-0.586, all P<0.01), and negatively correlated with positive affect ( r=-0.374, P<0.01); disease progression′s fear was negatively correlated with positive affect ( r=-0.318, P<0.01), and positively correlated with every dimension of demoralization ( r values were 0.339-0.464, all P<0.01); positive affect was negatively correlated with every dimension of demoralization ( r values were -0.430--0.334, all P<0.01). Structural equation model analysis showed that the direct effect of disease perception on demoralization was significant ( β=0.407, P<0.01), and both mediating effects of disease progression ′s fear and positive affect between disease perception and demoralization in patients with chronic heart failure were significant ( β=0.074, 0.079, both P<0.01). The chain mediating effect of disease progression ′s fear and positive effect was also significant ( β=0.019, P<0.01). Conclusions:Disease perception could directly predict the demoralization of patients with chronic heart failure and indirectly predict the demoralization of patients with chronic heart failure through the mediating effect of disease progression ′s fear, positive affect, and the chain mediating effect of disease progression ′s fear and positive affect.

ObjectiveTo evaluate the effectiveness and safety of neck seven-line method combined with periauricular acupuncture as salvage treatment for sudden hearing loss in non-acute stage. MethodsSixty-six patients with non-acute stage of sudden hearing loss with a disease duration of 15-90 days were randomly divided into 33 cases each in treatment group and control group. The treatment group was given neck seven-line method combined with acupuncture at periauricular points； the control group used sham acupuncture and sham electroacupuncture at the same points. Both groups were treated 3 times a week for 6 weeks. The pure tone average hearing threshold of impaired frequencies were examined before treatment， after treatment finish and at follow-up （week 10）， and the difference between pure tone average hearing threshold of impaired frequencies before and after treatment was calculated； calculate the proportion of patients with ≥10 dB improvement in pure tone average hearing threshold of impaired frequency after treatment and at follow-up； compare the patients' Tinnitus Evaluation Scale （TEQ） scores， Chinese Medicine Quality of Life Assessment Scale （CQ-11D） health utility values and the difference between before and after treatment， and record the occurrence of adverse events. ResultsThe pure tone average of impaired frequency in the treatment group were （50.57±18.07） dB and （47.70±17.42） dB at post-treatment and follow-up respectively， and （54.38±21.77） dB and （53.36±20.99） dB in the control group at post-treatment and follow-up. Compared with the pre-treatment period， the pure tone average hearing threshold of impaired frequency in the two groups significantly decreased （P＜0.05） at post-treatment and follow-up. The difference of pure tone average hearing threshold of impaired frequency in the treatment group after treatment and at the follow-up visit compared to that before treatment was lower than those in the control group （P＜0.05）. After treatment， 13 patients （39.39%） in the treatment group and 10 patients （30.30%） in the control group showed improvement of ≥10 dB in pure tone average hearing threshold of impaired frequency； at the follow-up visit， 18 patients （54.55%） in the treatment group and 10 patients （30.30%） in the control group showed improvement of ≥10 dB in the pure tone average hearing threshold of impaired frequency， and there was no statistical significance for comparison between groups at the time of post-treatment and follow-up （P＞0.05）. The TEQ score of the treatment group significantly lower than that before treatment （P＜0.05）； the TEQ score of the treatment group and the difference between before and after treatment significantly lower than that of the control group （P＜0.05）. The difference in CQ-11D health utility values and the difference between before and after treatment were not statistically significant between the two groups （P＞0.05）. Eight cases of acupuncture-related adverse events occurred among 66 patients， including subcutaneous haematomas after needling， severe pain during needling and needle fainting， which disappeared after symptomatic treatment and did not affect the following treatment. ConclusionNeck seven-line method combined with periauricular acupuncture could be used as salvage treatment for sudden hearing loss in non-acute stage to improve the pure tone average hearing threshold of impaired frequency， alleviate tinnitus， with safety.

Objective:To investigate the effect of 131I therapy on the clinical outcome of patients with differentiated thyroid cancer (DTC) who were evaluated as indeterminate response (IDR) after surgery and before 131I therapy. Methods:A total of 281 DTC patients (89 males, 192 females, age (38.4±10.2)years ) assessed as IDR before 131I therapy and after total or near-total thyroidectomy in the Department of Nuclear Medicine of Peking Union Medical College Hospital from April 2009 to March 2022 were retrospectively analyzed. Patients were divided into 131I therapy group ( 131I group) and just thyroid stimulating hormone (TSH) suppressive therapy group (TSH group) according to whether receiving 131I therapy, and the efficacies of two groups at the end of follow-up were compared. Subgroup analysis was conducted in different risk stratifications (low-risk, moderate-risk and high-risk), positive thyroglobulin antibody (TgAb) group (TgAb≥115 kU/L) and negative TgAb group (TgAb<115 kU/L). For patients with positive TgAb, the duration and rate for TgAb declining to negative level under the 2 regimens were compared. Independent-sample t test, Mann-Whitney U test, χ2 test and Fisher exact test were performed to compare the differences between groups. Results:Median follow-up time was 39(6-146) months. There was no statistical difference between patients in 131I group and TSH group in baseline characteristics, and the efficacies at the end of follow-up was similar between the 2 groups ( χ2=6.50, P=0.075). For low-, moderate- and high-risk stratification, there were also no statistical differences of response to 2 regimens ( P=0.221; χ2=4.21, P=0.223; χ2=3.01, P=0.274). Similar results were showed for patients with positive and negative TgAb ( n=50, n=231; χ2=4.02, P=0.242; χ2=3.14, P=0.341). For patients with positive TgAb, the duration and rate for TgAb declining to negative level were not statistically different either between 2 regimens (71.0%(22/31) vs 14/19, χ2=0.04, P=0.836; 7.0(5.0, 9.3) vs 7.0(5.0, 7.3) months, z=-0.89, P=0.375). Conclusion:For DTC patients assessed as IDR after surgery, 131I therapy may not provide more benefit than follow-up with TSH suppressive therapy.

Objective: To construct nomogram to predict the risk of bone metastasis in patients with non-small cell lung cancer(NSCLC). Methods: The clinical data of NSCLC patients diagnosed in the hospital were retrospectively analyzed, including the occurrence of bone metastasis, age, gender, pathological type, smoking status, PS score, TN stage, metastasis of other sites before bone metastasis, carcinoembryonic antigen(CEA) level, alpha fetoprotein(AFP) level, serum calcium(Ca2+), serum phosphorus(P), alkaline phosphatase(ALP) level, which were determined by univariate and multivariate logistic regression analysis. Receiver operating characteristic curve(ROC) and decision curve analysis were used, DCA was used to verify the accuracy and clinical benefit of the model, and nomogram was used to visualize the model. Results: Area under the ROC curve(AUC) showed that in the modeling group(n=138) and the validation group(n=92), the AUC value predicted by combined indicators(age, gender, pathological type, CEA, ALP)(modeling group=0.792, validation group=0.629) was higher than that predicted by single indicator. Conclusion The prediction model constructed in this study has good effect and can provide reference for clinical screening of high-risk patients with bone metastasis of NSCLC.

OBJECTIVE: To explore the pathogenesis of two fetuses from one family affected with Joubert syndrome (JS). METHODS: Whole exome sequencing was employed to screen potential mutations in both fetuses. Suspected mutations were verified by Sanger sequencing. Impact of intronic mutations on DNA transcription was validated by cDNA analysis. RESULTS: Two novel TCTN1 mutations, c.342-8A>G and c.1494+1G>A, were identified in exons 2 and 12, respectively.cDNA analysis confirmed the pathogenic nature of both mutations with interference of normal splicing resulting in production of truncated proteins. CONCLUSION The genetic etiology of the family affected with JS has been identified.Above findings have enriched the mutation spectrum of TCTN1gene and facilitated understanding of the genotype-phenotype correlation of JS.
Abnormalities, Multiple ; diagnosis ; genetics ; Cerebellum ; abnormalities ; Eye Abnormalities ; diagnosis ; genetics ; Humans ; Kidney Diseases, Cystic ; diagnosis ; genetics ; Membrane Proteins ; genetics ; Mutation ; Pedigree ; Retina ; abnormalities ; Whole Exome Sequencing

OBJECTIVE： To investigate the potential pharmacological mechanism of the seed of Draba nemorosa， and to provide reference for further development， utilization and clinical application. METHODS： Effective components and related target proteins of D. nemorosa were screened and identified by using TCMSP and STRING database. Cytoscape 3.7.0 software was used to construct a visual network of effective components and target proteins for the seed of D. nemorosa， and the network topology analysis was performed. The targeting protein-protein interaction （PPI） network was constructed and analyzed by STRING database and Cytoscape 3.7.0 software. KEGG pathway enrichment of target proteins was analyzed by DAVID bioinformatics resource database. RESULTS： A total of 9 effective components were screened from the seed of D. nemorosa， including quercetin， kaempferol， β-sitosterol， etc. Totally 174 target proteins were obtained， mainly including PTGS2， NCOA2， PGR， etc. Among them， JUN and MAPK1 were core proteins in PPI network. KEGG enrichment pathway included PI3K/Akt signaling pathway， TNF-α signaling pathway， HIF-1 signaling pathway， Toll-like receptor signaling pathway and thyroid hormone signal pathway， etc. CONCLUSIONS： Effective components from the seed of D. nemorosa such as quercetin， kaempferol and β-sitosterol may act on PTGS2， JUN and MAPK1 target proteins through PI3K-Akt signaling pathway and TNF-α signaling pathway， thus exert the effects of purging lung， relieving asthma， promoting edema and reducing edema.