Analysis of the impact of immunotherapy efficacy and safety in patients with gastric cancer and liver metastasis.

BACKGROUND: Gastric cancer (GC) is the fifth most common type of cancer and has the fourth highest death rate among all cancers. There is a lack of studies examining the impact of liver metastases on the effectiveness of immunotherapy in individuals diagnosed with GC. AIM: To investigate the influence of liver metastases on the effectiveness and safety of immunotherapy in patients with advanced GC. METHODS: This retrospective investigation collected clinical data of patients with advanced stomach cancer who had immunotherapy at our hospital from February 2021 to January 2023. The baseline attributes were compared using either the Chi-square test or the Fisher exact probability method. The chi-square test and Kaplan-Meier survival analysis were employed to assess the therapeutic efficacy and survival duration in GC patients with and without liver metastases. RESULTS: The analysis comprised 48 patients diagnosed with advanced GC, who were categorized into two groups: A liver metastasis cohort (n = 20) and a non-liver metastatic cohort (n = 28). Patients with liver metastasis exhibited a more deteriorated physical condition compared to those without liver metastasis. The objective response rates in the cohort with metastasis and the cohort without metastasis were 15.0% and 35.7% (P > 0.05), respectively. Similarly, the disease control rates in these two cohorts were 65.0% and 82.1% (P > 0.05), respectively. The median progression-free survival was 5.0 months in one group and 11.2 months in the other group, with a hazard ratio of 0.40 and a significance level (P) less than 0.05. The median overall survival was 12.0 months in one group and 19.0 months in the other group, with a significance level (P) greater than 0.05. CONCLUSION: Immunotherapy is less effective in GC patients with liver metastases compared to those without liver metastasis.

Effect of laparoscopic sleeve gastrectomy on related variables of obesity complicated with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is closely related to obesity, and weight loss can significantly improve the metabolic, endocrine and reproductive functions of obese individuals with PCOS. However, the efficacy of laparoscopic sleeve gastrectomy (LSG) for obesity with PCOS are unclear. AIM: The purpose of the study was to investigate the effect of LSG on related variables in obese patients with PCOS. METHODS: A retrospective analysis was performed on 32 obese patients with PCOS who received LSG treatment at the Third Hospital of Shanxi Medical University from 2013 to 2020. The changes in anthropometric indices, insulin, testosterone, estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH), menstrual cycle and LH/FSH ratio before and 1 mo, 3 mo, 6 mo and 12 mo after the operation were statistically analyzed. RESULTS: At 1 mo, 3 mo, 6 mo and 12 mo after surgery, the anthropometric indices, such as body weight and body mass index, of all patients were lower than those before the operation. The percentage excess weight loss (EWL%) at 1 mo, 3 mo, 6 mo and 1 year of follow-up were 25, 40, 46 and 65, respectively. The PCOS-related indices, such as insulin, testosterone, estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH) and menstrual cycle, were improved to varying degrees. During the 1-year follow-up, the average serum testosterone decreased from preoperative 0.72 ng/mL to 0.43 ng/mL (P < 0.05), average fasting insulin level (9.0 mIU/mL, preoperative 34.2 mil, LH level, 4.4 mIU/mL, preoperative 6.1 mIU/mL). The level of FSH (3.8 U/L, 4.8 U/p0.05) and the ratio of LH/FSH (0.7, 1.3/p0.05) were more relieved than those before surgery. During the postoperative follow-up, it was found that the menstrual cycle of 27 patients (nasty 27) returned to normal, and 6 patients (18%) who intended to become pregnant became pregnant within 1 year after surgery. CONCLUSION: The weight loss effect of LSG is obvious and affirmative, and the endocrine index of obese patients with PCOS is also improved to some extent, although the mechanism is not clear. Laparoscopic sleeve gastrectomy is expected to become a backup choice for patients with polycystic ovaries in the future.

Simplified Chinese version of the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire: cross-cultural adaptation, reliability, and validity for patients with cervical spondylotic myelopathy.

PURPOSE: This study aimed to validate the simplified Chinese version of the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) for Chinese patients with cervical spondylotic myelopathy (CSM). METHODS: The construct validity was conducted using confirmatory factor analysis (CFA). The convergent validity was based on factor loading, composite reliability (CR), and Pearson correlation coefficients (r). Internal consistency reliability was evaluated using Cronbach's α, test-retest reliability using intraclass correlation coefficients (ICC), and the ceiling and floor effects were also examined. RESULTS: A total of 168 native Chinese-speaking patients were enrolled. The CFA indicated that construct validity did not meet the preset criteria to be considered as good. Except for Q 4-1, the factor loading was higher than the standard of 0.5, and the CR values ranged from 0.70 to 0.85. Strong to moderate correlations were found between other scales and the simplified Chinese JOACMEQ. The scale showed good internal consistency reliability (Cronbach's α 0.639-0.821), and test-retest reliability (ICC 0.760-0.916). Moreover, the ceiling effect was displayed from Q1 to Q4. CONCLUSIONS: This study indicates that the simplified Chinese JOACMEQ is a reliable and valid measure of the functional status among Chinese patients with CSM.IMPLICATIONS FOR REHABILITATIONThe JOACMEQ was translated into the simplified Chinese and culturally adapted for Chinese-speaking patients with CSM for the first time.The simplified JOACMEQ demonstrated an excellent level of internal consistency and good test-retest reliability.The simplified Chinese JOACMEQ was reliable and valid for the measurement of the functional status among the patients with CSM.

Enantioselective Synthesis Muqubilin and Negombatoperoxides B and C/D.

Muqubilin, negombatoperoxide B, and negombatoperoxide C/D were synthesized through enantioselective routes, with the quaternary center derived from a peroxy chiral building block of known absolute configuration. The C-2/C-3 stereogenic centers were introduced by asymmetric aldol condensation, and the 1,2-dioxane ring was constructed via an intramolecular alkylation of a hydroperoxide with a mesylate. The synthetic samples showed physical and spectroscopic data consistent with those reported in the literature and thus verified the configurations of the natural products. A potentially more expeditious enantioselective entry to the 1,2-dioxane-aldol moiety (C-1 to C-6) of such cyclic peroxides was also briefly explored, where the C-2/C-3 stereogenic centers were installed through a [2+2] cycloaddition and the 1,2-dioxane ring was closed via an intramolecular alkylation coupled with an alkyl-oxygen cleavage of a ß-lactone.

Regio- and Stereoselective Addition of HO/OOH to Allylic Alcohols.

A range of allylic alcohols are shown to readily react with ethereal H2O2 in the presence of catalytic amounts of Na2MoO4-gly or MoO2(acac)2, affording the C═C trans hydroxylation-hydroperoxylation products in good yields with high regio- and stereoselectivity. Use of enantiomers of cyclic substrates resulted in corresponding enantiopure diol-tert-hydroperoxides. The possibility of further conversion of the diol-tert-hydroperoxides into triols or linear building blocks with an isolated tert-peroxy group containing a quaternary center is also exemplified.

Construction of a prognosis­associated long noncoding RNA­mRNA network for multiple myeloma based on microarray and bioinformatics analysis.

At present, the association between prognosis­associated long noncoding RNAs (lncRNAs) and mRNAs is yet to be reported in multiple myeloma (MM). The aim of the present study was to construct prognostic models with lncRNAs and mRNAs, and to map the interactions between these lncRNAs and mRNAs in MM. LncRNA and mRNA data from 559 patients with MM were acquired from the Genome Expression Omnibus (dataset GSE24080), and their prognostic values were calculated using the survival package in R. Multivariate Cox analysis was used on the top 20 most significant prognosis­associated mRNAs and lncRNAs to develop prognostic signatures. The performances of these prognostic signatures were tested using the survivalROC package in R, which allows for time­dependent receiver operator characteristic (ROC) curve estimation. Weighted correlation network analysis (WGCNA) was conducted to investigate the associations between lncRNAs and mRNAs, and a lncRNA­mRNA network was constructed using Cytoscape software. Univariate Cox regression analysis identified 39 lncRNAs and 1,445 mRNAs that were significantly associated with event­free survival of MM patients. The top 20 most significant survival­associated lncRNAs and mRNAs were selected as candidates for analyzing independent MM prognostic factors. Both signatures could be used to separate patients into two groups with distinct outcomes. The areas under the ROC curves were 0.739 for the lncRNA signature and 0.732 for the mRNA signature. In the lncRNA­mRNA network, a total of 143 mRNAs were positively or negatively associated with 23 prognosis­associated lncRNAs. NCRNA00201, LOC115110 and RP5­968J1.1 were the most dominant drivers. The present study constructed a model that predicted prognosis in MM and formed a network with the corresponding prognosis­associated mRNAs, providing a novel perspective for the clinical diagnosis and treatment of MM, and suggesting novel directions for interpreting the mechanisms underlying the development of MM.

A predicted risk score based on the expression of 16 autophagy-related genes for multiple myeloma survival.

Autophagy has an important role in the pathogenesis of plasma cell development and multiple myeloma (MM); however, the prognostic role of autophagy-related genes (ARGs) in MM remains undefined. In the present study, the expression profiles of 234 ARGs were obtained from a Gene Expression Omnibus dataset (accession GSE24080), which contains 559 samples of patients with MM analyzed with 54,675 probes. Univariate Cox regression analysis identified 55 ARGs that were significantly associated with event-free survival of MM. Furthermore, a risk score with 16 survival-associated ARGs was developed using multivariate Cox regression analysis, including ATIC, BNIP3L, CALCOCO2, DNAJB1, DNAJB9, EIF4EBP1, EVA1A, FKBP1B, FOXO1, FOXO3, GABARAP, HIF1A, NCKAP1, PRKAR1A and SUPT20H, was constructed. Using this prognostic signature, patients with MM could be separated into high- and low-risk groups with distinct clinical outcomes. The area under the curve values for the receiver operating characteristic curves were 0.740, 0.741 and 0.712 for 3, 5 and 10 years prognosis predictions, respectively. Notably, the prognostic role of this risk score could be validated with another four independent cohorts (accessions: GSE57317, GSE4581, GSE4452 and GSE4204). In conclusion, ARGs may serve vital roles in the progression of MM, and the ARGs-based prognostic model may provide novel ideas for clinical applications in MM.

Biased gene retention during diploidization in Brassica linked to three-dimensional genome organization.

The non-random three-dimensional (3D) organization of the genome in the nucleus is critical to gene regulation and genome function. Using high-throughput chromatin conformation capture, we generated chromatin interaction maps for Brassica rapa and Brassica oleracea at a high resolution and characterized the conservation and divergence of chromatin organization in these two species. Large-scale chromatin structures, including A/B compartments and topologically associating domains, are notably conserved between B. rapa and B. oleracea, yet their KNOT structures are highly divergent. We found that genes retained in less fractionated subgenomes exhibited stronger interaction strengths, and diploidization-resistant duplicates retained in pairs or triplets are more likely to be colocalized in both B. rapa and B. oleracea. These observations suggest that spatial constraint in duplicated genes is correlated to their biased retention in the diploidization process. In addition, we found strong similarities in the epigenetic modification and Gene Ontology terms of colocalized paralogues, which were largely conserved across B. rapa and B. oleracea, indicating functional constraints on their 3D positioning in the nucleus. This study presents an investigation of the spatial organization of genomes in Brassica and provides insights on the role of 3D organization in the genome evolution of this genus.

Study on efficacy and safety of Tong-luo Qu-tong plaster treatment for knee osteoarthritis: study protocol for a randomized, double-blind, parallel positive controlled, multi-center clinical trial.

BACKGROUND: Knee osteoarthritis (KOA) is a common chronic musculoskeletal disorder that seriously affects quality of life. Patients with KOA frequently develop one or more of the following typical symptoms: joint pain, stiffness, joint friction noise and impaired functionality. Traditional Chinese medicine (TCM) has been shown to have a superior effect and a particular advantage in the treatment of KOA; among TCM, the Tong-luo Qu-tong plaster is the convenient and most commonly used method in China to improve symptoms including pain, stiffness and limited mobility in patients with KOA, as it causes few adverse effects. But there is a lack of high-quality clinical evidences to support the therapeutic effect that Chinese adhesive plaster can have in relieving pain and stiffness. The purpose of this study will be to evaluate the efficacy and safety of Tong-luo Qu-tong plaster in patients with KOA. METHODS/DESIGN: This study will be a randomized, double-blind, parallel positive controlled, multi-center clinical trial, a non-inferiority trial design was adopted. A total of 2000 participants older than 40 years, with KOA, will be randomly allocated into an experimental group (n = 1500) and a control group (n = 500). All participants will receive a conventional conservative treatment lasting for 14 days as two courses, once daily. Tong-luo Qu-tong plaster will be administered externally to participants in the experimental group, while the control group will receive a Qi-zheng Xiao-tong plaster. The outcome of the total Western Ontario and McMaster Universities Arthritis Index scores, TCM syndrome quantitative score and visual analog scale scores will be measured during the assessment visits (baseline and 1-week and 2-week follow up). In addition, adverse events related to clinical symptoms and signs and results of laboratory tests will be documented during the clinical trials. DISCUSSION: This study will provide reliable evidence of the effectiveness and safety of Tong-luo Qutong plaster in patients with KOA. If the results are favorable, it is expected that the patients with KOA will benefit from this study, many patients may have a good alternative treatment for KOA. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03309501 . Registered on 8 November 2017.

Using Prognosis-Related Gene Expression Signature and Connectivity Map for Personalized Drug Repositioning in Multiple Myeloma.

BACKGROUND Multiple myeloma (MM) is the second most common hematologic cancer with poor prognosis. Novel therapeutic strategies are needed to decrease the high mortality rate. The aim of this study was to identify prospective agents for MM. MATERIAL AND METHODS A microarray dataset was mined, which contains the transcriptome profiles of 588 MM patients. Univariate Cox analysis was performed to analyze the relationships between genes and clinical outcome. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were determined. Protective and risky genes were uploaded to Connectivity Map (CMAP) database to identify the potentially unknown effects of existing drugs. An example was selected to be docked on the known molecules. RESULTS A total of 1445 genes significantly correlated with the event free survival (EFS) of MM patients were identified and included 676 protective and 769 risky indicators. KEGG pathway analysis revealed that these prognosis-associated genes were enriched in the "cell cycle," "DNA replication," and "P53 signaling pathway". The top t3 most significant potential molecules were vorinostat, trifluoperazine, and thioridazine. CDK1 (cyclin-dependent kinase-1) ranked as the core in the class of prognosis-related genes in MM based on protein-protein interaction (PPI) network analysis. With Sybyl-X 2.0, the majority of the top 10 molecules aforementioned displayed high binding forces with CDK1. Among these molecules, trichostatin A had the greatest ability in combining with CDK1. CONCLUSIONS Genes that mainly accumulate in the cell cycle pathway play an essential role in the prognosis of MM, and these prognosis-related genes also have great value in drug development.

Thoracic outlet syndrome in a postoperative cervical spondylotic myelopathy patient: A case report.

RATIONALE: Thoracic outlet syndrome (TOS) is a rare disease that presents with neurogenic and vascular symptoms similar to those of cervical spondylosis. However, making the diagnosis of TOS can be challenging due to a lack of standardized objective confirmatory tests. PATIENT CONCERNS: A 66-year-old man presented with neck, supraclavicular, and right shoulder pain as well as numbness and weakness in the right arm after surgery to correct cervical spondylotic myelopathy (CSM). DIAGNOSIS: Magnetic resonance imaging confirmed the diagnosis of CSM. He was diagnosed with TOS based on the manifestations and examination findings. INTERVENTIONS: After surgery for CSM, nonoperative management was provided. OUTCOMES: The patient reported pain relief and improving sensation in the shoulder and supraclavicular region. LESSONS: Based on this case and the reviewed literature, to optimize the diagnosis and treatment of CSM, clinicians should consider preoperative differential diagnosis to preliminarily exclude it.

Thoracic Inlet Parameters for Degenerative Cervical Spondylolisthesis Imaging Measurement.

BACKGROUND The aim of this study was to explore the diagnostic value of sagittal measurement of thoracic inlet parameters for degenerative cervical spondylolisthesis (DCS). MATERIAL AND METHODS We initially included 65 patients with DCS and the same number of health people as the control group by using cervical radiograph evaluations. We analyzed the x-ray and computer tomographic (CT) data in prone and standing position at the same time. Measurement of cervical sagittal parameters was carried out in a standardized supine position. Multivariate logistic regression analysis was performed to evaluate these parameters as a diagnostic index for DCS. RESULTS There were 60 cases enrolled in the DCS group, and 62 cases included in the control group. The T1 slope and thoracic inlet angle (TIA) were significantly greater for the DCS group compared to the control group (24.33±2.85º versus 19.59±2.04º, p=0.00; 76.11±9.82º versus 72.86±7.31º, p=0.03, respectively). We observed no significant difference for the results of the neck tilt (NT), C2-C7 angle in the control and the DSC group (p>0.05). Logistic regression analysis and receiver operating characteristic (ROC) curve revealed that preoperative T1 slope of more than 22.0º showed significantly diagnostic value for the DCS group (p<0.05). CONCLUSIONS Patients with preoperative sagittal imbalance of thoracic inlet have a statistically significant increased risk of DCS. T1 slope of more than 22.0º showed significantly diagnostic value for the incidence of DCS.

Simplified Chinese Version of the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire: Agreement, Responsiveness, and Minimal Important Change for Patients With Chronic Low Back Pain.

STUDY DESIGN: Psychometric test of the cross-cultural adaptation the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) in low back pain (LBP) patients. OBJECTIVE: To investigate the agreement, responsiveness, and minimal important change (MIC) of the simplified Chinese version of the JOABPEQ in LBP patients. SUMMARY OF BACKGROUND DATA: The factor structure, internal consistency, test-retest reliability, validity, floor and ceiling effect of simplified Chinese JOABPEQ have been tested, while the agreement, responsiveness, and MIC were required. METHODS: The agreement, responsiveness, and MIC of the simplified Chinese version were assessed by completing the Chinese JOABPEQ twice. Agreement was tested with Bland-Altman plot. Responsiveness was operationalized using receiver operating characteristic analyses. The anchor-based method was used to calculate MIC. RESULTS: One hundred sixty-two of 184 patients returned to finish the booklet twice were available for analysis (response rate: 88.0%). While the responsiveness, the area under the curves of each subscale were ranged from 0.746 to 0.875, which meant a good responsiveness. While the MIC (MIC%) of simplified Chinese JOABPEQ was 19.28 (44.98%) for Q1 Low back pain, 15.20 (24.13%) for Q2 Lumbar function, 15.79 (22.76%) for Q3 Walking ability, 9.58 (19.86%) for Q4 Social life function, 7.33 (17.28%) for Q5 Mental health. While compared with the MIC, only the Q3 Walking ability had a positive rating for agreement in the Bland-Altman plot. CONCLUSION: The simplified Chinese JOABPEQ has positive agreement of Q3 Walk ability and acceptable to excellent responsiveness of all the subscales. The MICs for subscales of the simplified Chinese JOABPEQ ranged from 7.33 to 19.28 points. LEVEL OF EVIDENCE: 3.

[Mechanism of macrophage polarization on spinal cord injury].

Spinal cord injury is a serious trauma of the spinal and nervous system, local tissue destruction and microcirculation disturbance can lead to a more serious spinal cord injury and extensive necrosis of neurons. Spinal cord injury often accompany with Inflammation reaction producing a variety of cytokines and bioactive substances, result in macrophage polarization. M1 macrophages polarization are induced by IFN-γ, LPS, TNF-α and so on, it show the damage and proinflammatory effect. M2 macrophages polarization are caused by IL-4, IL-10, IL-13 and show the recovery and anti-inflammatory effect. However, clinical treatment after spinal cord injury is very limited, inhibition of proinflammatory and promotion of anti-inflammatory by regulating the M1 macrophages and M2 macrophages is a new direction for the treatment of spinal cord injury. The article will review different phenotype and function of macrophages after spinal cord injury.

HiTAD: detecting the structural and functional hierarchies of topologically associating domains from chromatin interactions.

A current question in the high-order organization of chromatin is whether topologically associating domains (TADs) are distinct from other hierarchical chromatin domains. However, due to the unclear TAD definition in tradition, the structural and functional uniqueness of TAD is not well studied. In this work, we refined TAD definition by further constraining TADs to the optimal separation on global intra-chromosomal interactions. Inspired by this constraint, we developed a novel method, called HiTAD, to detect hierarchical TADs from Hi-C chromatin interactions. HiTAD performs well in domain sensitivity, replicate reproducibility and inter cell-type conservation. With a novel domain-based alignment proposed by us, we defined several types of hierarchical TAD changes which were not systematically studied previously, and subsequently used them to reveal that TADs and sub-TADs differed statistically in correlating chromosomal compartment, replication timing and gene transcription. Finally, our work also has the implication that the refinement of TAD definition could be achieved by only utilizing chromatin interactions, at least in part. HiTAD is freely available online.

[Status and suggestions for adjuvant standard for Chinese materia medica processing in China].

In this paper, the status of adjuvant standard for Chinese materia medica processing in the Chinese Pharmacopoeia 2015 edition, the National Specification of Chinese Materia Medica Processing, and the 29 provincial specification of Chinese materia medica was summarized, and the the status including general requirements, specific requirements, and quality standard in the three grade official specifications was collected and analyzed according to the "medicine-adjuvant homology" and "food-adjuvant homology" features of adjuvants. This paper also introduced the research situation of adjuvant standard for Chinese materia medica processing in China; In addition, analyzed and discussed the problems existing in the standard system of adjuvant for Chinese materia medica processing, such as lack of general requirements, low level of standard, inconsistent standard references, and lack of research on the standard, and provided suggestions for the further establishment of the national standards system of adjuvant for Chinese materia medica processing.

Spatial Colocalization of Human Ohnolog Pairs Acts to Maintain Dosage-Balance.

Ohnologs -paralogous gene pairs generated by whole genome duplication- are enriched for dosage sensitive genes, that is, genes that have a phenotype due to copy number changes. Dosage sensitive genes frequently occur in the same metabolic pathway and in physically interacting proteins. Accumulating evidence reveals that functionally related genes tend to co-localize in the three-dimensional (3D) arrangement of chromosomes. We query whether the spatial distribution of ohnologs has implications for their dosage balance. We analyzed the colocalization frequency of ohnologs based on chromatin interaction datasets of seven human cell lines and found that ohnolog pairs exhibit higher spatial proximity in 3D nuclear organization than other paralog pairs and than randomly chosen ohnologs in the genome. We also found that colocalized ohnologs are more resistant to copy number variations and more likely to be disease-associated genes, which indicates a stronger dosage balance in ohnologs with high spatial proximity. This phenomenon is further supported by the stronger similarity of gene co-expression and of gene ontology terms of colocalized ohnologs. In addition, for a large fraction of ohnologs, the spatial colocalization is conserved in mouse cells, suggestive of functional constraint on their 3D positioning in the nucleus.