ObjectiveTo explore the sequential effects of hypoxic exercising on miR-27/PPARγ and lipid metabolism target gene and protein expression levels in the obesity rats’ liver. Methods13-week-old male diet-induced obesity rats were randomly divided into three groups (n＝10): normal oxygen concentration quiet group (N), hypoxia quiet group (H), hypoxic exercise group (HE). Exercise training on the horizontal animal treadmill for 1 h/d, 5 d/week for a total of 4 week, and the intensity of horizontal treadmill training was 20 m/min (hypoxic concentration was 13.6%). Comparison of the weights of perirenal fat and epididymal fat in rats across different groups and calculation of Lee’s index based on body weight and body length of rats in each group were done. And the serum concentrations of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) levels were detected. RT-PCR and Western Blot were used to detect the levels of miR-27, PPARγ, CYP7A1 and CD36. ResultsHypoxic exercise decreased the expression levels of miR-27 in the obese rats’ liver, however, the expression level of PPARγ was gradually increased. The expression levels of miR-27 in HE group were significantly lower than N group (P<0.05). The expression levels of PPARγ mRNA in N group were significantly lower than H group (P<0.05), especially lower than HE group (P<0.01). The protein expression of PPARγ protein in N group was significantly lower than that other groups (P<0.01). The expression of lipid metabolism-related genes and proteins increased in the obese rats’ liver. The expression of CYP7A1 mRNA in N group was significantly lower than H group (P<0.05), especially lower than HE group (P<0.01). The expression of CYP7A1 protein in the obese rats’ liver in N group was extremely lower than H group and HE group (P<0.01). The protein expression of CD36 in N group was significantly lower than that in HE group (P<0.05). Hypoxia exercise improved the related physiological and biochemical indexes of lipid metabolism disorder. The perirenal fat weight of obese rats in HE group was extremely lower than N group and H group (P<0.01), and the perirenal fat weight in N group was significantly higher than H group (P<0.05). The epididymal fat weight in N group was significantly higher than H group (P<0.05), and extremely higher than HE group (P<0.01). The Lee’s index in HE group was extremely lower than N group and H group (P<0.01). The serum concentration of TC in obese rats in HE group was extremely lower than N group and H group (P<0.01). The serum concentration of TG in HE group was extremely lower than N group and H group (P<0.01). The serum concentration of LDL-C in N group was extremely higher than HE group (P<0.01). The serum concentration of HDL-C in N group was extremely lower than H group (P<0.01). ConclusionHypoxia and hypoxia exercise may negatively regulate the levels of PPARγ by inhibiting miR-27 in the obese rats’ liver, thereby affecting the expression of downstream target genes CYP7A1 and CD36, and promoting cholesterol, fatty acid oxidation and HDL-C transport in the liver, and ultimately the lipid levels in obese rats were improved. The effect of hypoxia exercise on improving blood lipid is better than simple hypoxia intervention.

Objective:To evaluate the effect of combining contralateral high-frequency transcranial magnetic stimulation (rTMS) with biofeedback-controlled empty swallowing training on dysphagia among stroke survivors.Methods:Eighty dysphagic stroke survivors were divided at random into a control group, a biofeedback group, an rTMS group and a combined treatment group, each of 20. In addition to routine dysphagia rehabilitation, the biofeedback group and the rTMS group received empty swallowing training based on biofeedback or high-frequency rTMS applied to the healthy motor cortex as appropriate. The combined treatment group was given both. The treatment was administered once daily, 5 days a week for 3 consecutive weeks. Before and after the treatment, all of the subjects′ swallowing was evaluated using the penetration aspiration scale (PAS), functional oral intake scale (FOIS) and a standardized swallowing assessment (SSA). The latency and amplitude of the mylohyoid muscle′s motor evoked potentials (MEPs) were also recorded before and after the treatment.Results:After the treatment, significant improvement was observed in the average PAS, FOIS and SSA scores as well as in the latency and amplitude of the MEPs in the four groups. The average results in the combined treatment group were significantly better than in the other 3 groups. The latency of the mylohyoid muscle′s MEP was significantly shorter in the combined group than in the control and biofeedback groups on average, while the amplitude was significantly greater than in the control group.Conclusion:Combining contralateral high frequency rTMS with empty swallowing training based on biofeedback can better improve the swallowing of dysphagic stroke survivors.

Small-molecule phenolic substances widely exist in animals and plants, and have some shared biological activities. The metabolism of phenylalanine and tyrosine in the human body, and especially the metabolism of catecholamine neurotransmitters, produces endogenous small-molecule phenols. Endogenous small-molecule phenolic substances are functionally related to the important physiological processes and the occurrence of mental diseases in humans and some animals, which are systematically sorts and summarized in this review. Integrating the previous experimental research and literature analysis on natural small-molecule phenols by our research group, the understanding of the hypothesis that "small-molecule phenol are pharmacological signal carriers" was deepened. Based on above, the concept of "phenolomics" was further proposed, analyzed the research direction and research content which can bring into the knowledge framework of phenolomics. The induction of phenolomics will provide wider perspectives on explaining the pharmacological mechanism of drugs, discovering new drug targets, and finding biomarkers of mental diseases.

BACKGROUND:Although nerve conduits provide an effective treatment approach for nerve repair,traditional nerve conduits merely serve as mechanical channels in the repair process.The therapeutic effect still needs to be improved.Carbon nanomaterials have good physicochemical properties and hold great potential in fields such as electrochemistry and tissue engineering.Nerve conduits loaded with carbon nanomaterials,after appropriate functional modifications,are expected to further enhance the quality of nerve repair. OBJECTIVE:To review the recent research progress of carbon nanomaterial-loaded nerve conduits/scaffolds for peripheral nerve repair. METHODS:PubMed,Web of Science,China National Knowledge Infrastructure(CNKI),and Wanfang databases were searched for the literature on the application of carbon nanomaterial catheters in peripheral nerve regeneration.English keywords were"carbon nanomaterials,carbon-based nanomaterials,nerve conduit,nerve guidance conduit,scaffold,nerve regeneration,peripheral nerve repair,peripheral nerve injury"and Chinese keywords were"carbon nanomaterials,carbon materials,graphene,carbon nanotubes,nerve conduits,nerve scaffolds,nerve repair,nerve regeneration,peripheral nerve injury".Finally,69 articles were selected for this review. RESULTS AND CONCLUSION:(1)Carbon nanomaterials primarily restore damaged neural bioelectric signal conduction by activating calcium ion channels and inducing intracellular calcium activity.The application of various nerve conduit design strategies has improved the effectiveness of nerve repair.(2)Successful intraneural vascularization is the prerequisite for repairing peripheral nerve injuries.Reactive oxygen species and reactive nitrogen species generated by carbon nanomaterials trigger subsequent signaling pathways that promote intraneural vascularization.(3)The ratio of M1 to M2 macrophages affects the repair of peripheral nerve injuries.Carbon nanomaterials promote the polarization of macrophages into the M2 phenotype,thereby exerting their anti-inflammatory and regenerative effects.(4)Some carbon nanomaterials may induce excessive generation of reactive oxygen species intracellularly,potentially exhibiting cytotoxicity detrimental to nerve repair.However,appropriate functional modifications can improve the adverse effects caused by carbon nanomaterials.(5)Although carbon nanomaterials can restore the microenvironment of peripheral nerve injuries and play a positive role in promoting peripheral nerve regeneration,their inherent cytotoxicity and unclear in vivo degradation pathways still pose challenges for clinical application.However,by employing methods such as functional modification,it is possible to enhance the biocompatibility of carbon nanomaterials.Modified carbon nanomaterials have promising prospects in the field of neural tissue engineering.

Objective:To investigate the values of two-dimensional and three-dimensional echocardiographic parameters in predicting pulmonary vascular resistance (PVR) in chronic pulmonary thromboembolic pulmonary hypertension (CTEPH).Methods:A total of 141 patients diagnosed with CTEPH in China-Japan Friendship Hospital from November 2015 to December 2022 were included. Two-dimensional echocardiographic indicators reflecting PVR were constructed according to the calculation formula of PVR: echocardiographic estimated systolic pulmonary artery pressure (sPAP Echo)/left ventricular end-diastolic diameter (LVIDd), echocardiographic estimated mean pulmonary artery pressure (mPAP Echo)/LVIDd. sPAP Echo/left ventricular end-diastolic volume (LVEDV), sPAP Echo/left ventricular cardiac output (LVCO) were measured by three-dimensional echocardiography. The correlations between two-dimensional and three-dimensional echocardiographic ratios and invasive PVR were then analyzed using the Spearman correlation method. Using receiver operating characteristic curve analysis, cut-off values for the ratios were generated to identify patients with PVR>1 000 dyn·s -1·cm -5. Pre- and postoperative hemodynamics and echocardiographic data were analyzed, as well as the correlation between the reduction rate of the echocardiographic index and PVR in 54 patients who underwent pulmonary endarterectomy (PEA). Results:sPAP Echo/LVIDd, sPAP Echo/LVEDV and sPAP Echo/LVCO were moderately correlated with PVR( rs=0.62, 0.52, 0.63, both P<0.001). The ratio of sPAP Echo to LVEDV, when greater than or equal to 1.41, had a sensitivity of 0.800 and a specificity of 0.930 for determining PVR >1 000 dyn·s -1·cm -5 (AUC=0.860, P<0.001). Similarly, the ratio of sPAP Echo to LVIDd, when greater than or equal to 2.14, had a sensitivity of 0.647 and a specificity of 0.861 for determining PVR >1000 dyn·s -1·cm -5 (AUC=0.830, P<0.001). The sPAP Echo/LVIDd and mPAP Echo/LVIDd significantly decreased after PEA (both P<0.001). The sPAP Echo/LVIDd and mPAP Echo/LVIDd reduction rate (ΔsPAP Echo/LVIDd and ΔmPAP Echo/LVIDd) were significantly correlated with PVR reduction rate (ΔPVR), respectively ( rs=0.61, 0.63, both P<0.05). Conclusions:Two-dimensional ratio sPAP Echo/LVIDd and three-dimensional ratio sPAP Echo/LVEDV can be used to noninvasively estimate PVR in CTEPH patients. The conventional ratio sPAP Echo/LVIDd is convenient and reproducibly suitable for monitoring the improvement of PVR before and after treatment, and its ratio of 2.14 can predict the significant increase of PVR in CTEPH patients (>1 000 dyn·s -1·cm -5).

Objective:To investigate the prevalence of work-related musculoskeletal disorders (WMSDs) in rehabilitation therapists.Methods:In September 2023, the computer searched Chinese and English databases such as CNKI database, Wanfang Data Knowledge Service Platform, VIP Chinese Science and Technology Journal Database, Chinese Biomedical Literature Database, PubMed, Cochrane Library, Web of Science, Embase database, etc. The retrieval time was from the establishment of the database to September 2023. Musculoskeletal disorders, rehabilitation therapists were selected as search terms, and the author, publication time, prevalence rate, and study type were analyzed. The Agency for Healthcare Research and Quality (AHRQ) tool and The Newcastle-Ottawa Scale (NOS) were used to evaluate the quality of the literature. Stata 15.0 software was used for meta-analysis.Results:A total of 28 literatures were included, including 8039 rehabilitation therapists. Meta-analysis showed that the overall prevalence rate of WMSDs among rehabilitation therapists was 72% (95% CI: 64%-80%). The top 3 annual prevalence rates were lower back (51%, 95% CI: 38%-64%), neck (42%, 95% CI: 30%-54%) and shoulder (32%, 95% CI: 23%-41%). The top 3 weekly prevalence rates were lower back (47%, 95% CI: 28%-65%), neck (35%, 95% CI: 14%-55%) and back (30%, 95% CI: 17%-44%) . Conclusion:The higher prevalence of WMSDs in rehabilitation therapists, especially in the lower back, neck, shoulder and back, may be related to the prolonged stouching posture and the continuous or repeated exertion of the upper limbs.

Objective:To investigate the prevalence of work-related musculoskeletal disorders (WMSDs) in rehabilitation therapists.Methods:In September 2023, the computer searched Chinese and English databases such as CNKI database, Wanfang Data Knowledge Service Platform, VIP Chinese Science and Technology Journal Database, Chinese Biomedical Literature Database, PubMed, Cochrane Library, Web of Science, Embase database, etc. The retrieval time was from the establishment of the database to September 2023. Musculoskeletal disorders, rehabilitation therapists were selected as search terms, and the author, publication time, prevalence rate, and study type were analyzed. The Agency for Healthcare Research and Quality (AHRQ) tool and The Newcastle-Ottawa Scale (NOS) were used to evaluate the quality of the literature. Stata 15.0 software was used for meta-analysis.Results:A total of 28 literatures were included, including 8039 rehabilitation therapists. Meta-analysis showed that the overall prevalence rate of WMSDs among rehabilitation therapists was 72% (95% CI: 64%-80%). The top 3 annual prevalence rates were lower back (51%, 95% CI: 38%-64%), neck (42%, 95% CI: 30%-54%) and shoulder (32%, 95% CI: 23%-41%). The top 3 weekly prevalence rates were lower back (47%, 95% CI: 28%-65%), neck (35%, 95% CI: 14%-55%) and back (30%, 95% CI: 17%-44%) . Conclusion:The higher prevalence of WMSDs in rehabilitation therapists, especially in the lower back, neck, shoulder and back, may be related to the prolonged stouching posture and the continuous or repeated exertion of the upper limbs.

To analyze the prevalence, genomic characteristics and clinical relevance of carbapenem-resistant bacteria in untreated hospital wastewater, and to provide a reference basis for in-hospital assessment of public health situation and prevention of cross-infection. In March 2023, untreated wastewater in the wastewater treatment station of the Second Affiliated Hospital of Soochow University and wastewater in the U-shaped wastewater pipes of the hand-washing sinks in 26 wards were collected, centrifuged and diluted, and the drug-resistant bacteria were isolated by using LB solid plates containing meropenem (2 μg/ml) for species identification, drug sensitivity analysis, carbapenenase gene PCR detection and whole genome sequencing. The genome sequence was identified for drug resistance genes. Retrospective research was used, combining multilocus sequence typing (MLST) and single nucleotide polymorphism (SNP) analysis, to compare their homology with clinical isolates of the same quarter. The results showed that 56 carbapenem-resistant gram-negative bacteria were isolated from hospital wastewater, originating from 13 genera, of which 17 were isolated from the total hospital wastewater, with Aeromonas spp. as the most dominant genus (35.3%, 6/17), and 39 were isolated from the wastewater of 17 wards, with Pseudomonas spp. as the most dominant genus (30.8%, 12/39). All common wastewater isolates from our hospital were multidrug-resistant bacteria, with up to 100% resistant to some second-and third-generation cephalosporins. A total of 8 carbapenemase genes originated from wastewater isolates, including blaKPC, blaNDM, blaIMP, blaVIM, blaIND, blaOXA-58-like, blaOXA-48-like, and blaOXA-427-like. 39 wastewater isolates carried the carbapenemase genes, and the total wastewater of the hospital carried the highest isolation rate of blaKPC-2 bacteria (35.3%, 6/17) and the highest isolation rate of blaIMP-8 bacteria (31.8%, 7/22) were found in the wastewater from 26 wards. 14 wastewater isolates were found to carry both carbapenemase genes, with a total of 6 combinations. A new blaIMP-101 isoform was also identified for the first time. 4 wastewater isolates and 11 clinical isolates were screened for inclusion in the SNP analysis, in which only 15 SNPs differed between the two strains of ST11 Klebsiella pneumoniae of clinical and wastewater origin, which was highly homologous. In conclusion, the presence of multiple multi-drug resistant conditionally pathogenic bacteria in untreated hospital wastewater has the potential risk of spreading drug-resistant genes in the environment. The highly homologous Klebsiella pneumoniae isolated from hospital wastewater and clinics indicates the close association between hospital wastewater and clinical infections. Hospitals need to strengthen the monitoring of drug-resistant bacteria and drug-resistant genes in the wastewater environment, to prevent the widespread dissemination of drug-resistant bacteria and drug-resistant genes in hospital wastewater and to prevent nosocomial infections caused by drug-resistant bacteria in wastewater.

Objective:To investigate the value of transanal multipoint full-layer puncture biopsy (TMFP) in predicting pathological complete response (pCR) after neoadjuvant radiotherapy and chemotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) and to establish a predictive model for providing clinical guidance regarding the treatment of LARC.Methods:In this multicenter, prospective, cohort study, we collected data on 110 LARC patients from four hospitals between April 2020 and March 2023: Beijing Chaoyang Hospital of Capital Medical University (50 patients), Beijing Friendship Hospital of Capital Medical University (41 patients), Qilu Hospital of Shandong University (16 patients), and Zhongnan Hospital of Wuhan University (three patients). The patients had all received TMFP after completing standard nCRT. The variables studied included (1) clinicopathological characteristics; (2) clinical complete remission (cCR) and efficacy of TMFP in determining pCR after NCRT in LARC patients; and (3) hospital attended, sex, age, clinical T- and N-stages, distance between the lower margin of the tumor and the anal verge, baseline and post-radiotherapy serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9 concentrations, chemotherapy regimen, use of immunosuppressants with or without radiotherapy, radiation therapy dosage, interval between surgery and radiotherapy, surgical procedure, clinical T/N stage after radiotherapy, cCR, pathological results of TMFP, puncture method (endoscopic or percutaneous), and number and timing of punctures. Single-factor and multifactorial logistic regression analysis were used to determine the factors affecting pCR after NCRT in LARC patients. A prediction model was constructed based on the results of multivariat analysis and the performance of this model evaluated by analyzing subject work characteristics (ROC), calibration, and clinical decision-making (DCA) curves. pCR was defined as complete absence of tumor cells on microscopic examination of the surgical specimens of rectal cancer (including lymph node dissection) after NCRT, that is, ypT0+N0. cCR was defined according to the Chinese Neoadjuvant Rectal Cancer Waiting Watch Database Study Collaborative Group criteria after treatment, which specify an absence of ulceration and nodules on endoscopy; negative rectal palpation; no tumor signals on rectal MRI T2 and DWI sequences; normal serum CEA concentrations, and no evidence of recurrence on pelvic computed tomography/magnetic resonance imaging.Results:Of the 110 patients, 45 (40.9%) achieved pCR after nCRT, which was combined with immune checkpoint inhibitors in 34 (30.9%). cCR was diagnosed before puncture in 38 (34.5%) patients, 43 (39.1%) of the punctures being endoscopic. There were no complications of puncture such as enterocutaneous fistulae, vaginal injury, prostatic injury, or presacral bleeding . Only one (2.3%) patient had a small amount of blood in the stools, which was relieved by anal pressure. cCR had a sensitivity of 57.8% (26/45) for determining pCR, specificity of 81.5% (53/65), accuracy of 71.8% (79/110), positive predictive value 68.4% (26/38), and negative predictive value of 73.6% (53/72). In contrast, the sensitivity of TMFP pathology in determining pCR was 100% (45/45), specificity 66.2% (43/65), accuracy 80.0% (88/110), positive predictive value 67.2% (45/67), and negative predictive value 100.0% (43/43). In this study, the sensitivity of TMFP for pCR (100.0% vs. 57.8%, χ 2=24.09, P<0.001) was significantly higher than that for cCR. However, the accuracy of pCR did not differ significantly (80.0% vs. 71.8%, χ 2=2.01, P=0.156). Univariate and multivariate logistic regression analyses showed that a ≥4 cm distance between the lower edge of the tumor and the anal verge (OR=7.84, 95%CI: 1.48-41.45, P=0.015), non-cCR (OR=4.81, 95%CI: 1.39-16.69, P=0.013), and pathological diagnosis by TMFP (OR=114.29, the 95%CI: 11.07-1180.28, P<0.001) were risk factors for pCR after NCRT in LARC patients. Additionally, endoscopic puncture (OR=0.02, 95%CI: 0.05-0.77, P=0.020) was a protective factor for pCR after NCRT in LARC patients. The area under the ROC curve of the established prediction model was 0.934 (95%CI: 0.892-0.977), suggesting that the model has good discrimination. The calibration curve was relatively close to the ideal 45° reference line, indicating that the predicted values of the model were in good agreement with the actual values. A decision-making curve showed that the model had a good net clinical benefit. Conclusion:Our predictive model, which incorporates TMFP, has considerable accuracy in predicting pCR after nCRT in patients with locally advanced rectal cancer. This may provide a basis for more precisely selecting individualized therapy.

Objective:To investigate the prognosis and the factors that influence it in patients with non-gastric gastrointestinal stromal tumors (GISTs) who are at low risk of recurrence.Methods:This was a retrospective cohort study. Clinicopathologic and prognostic data from patients with non-gastric GISTs and at low risk of recurrence (i.e., very low-risk or low-risk according to the 2008 version of the Modified NIH Risk Classification), who attended 18 medical centers in China between January 2000 and June 2023, were collected. We excluded patients with a history of prior malignancy, concurrent primary malignancy, multiple GISTs, and those who had received preoperative imatinib. The study cohort comprised 1,571 patients with GISTs, 370 (23.6%) of whom were at very low-risk and 1,201 (76.4%) at low-risk of recurrence. The cohort included 799 (50.9%) men and 772 (49.1%) women of median age 57 (16–93) years. Patients were followed up to July 2024. The prognosis and its influencing factors were analyzed. Receiver operating characteristic curves for tumor diameter and Ki67 were established, and the sensitivity, specificity, area under the curve (AUC) and optimal cut-off value with 95% confidence intervals were calculated. Propensity score matching was implemented using the 1:1 nearest neighbor matching method with a matching tolerance of 0.02.Results:With a median follow-up of 63 (12–267) months, the 5- and 10-year overall survival (OS) rates of the 1,571 patients were 99.5% and 98.0%, respectively, and the 5- and 10-year disease-free survival (DFS) rates were 96.3% and 94.4%, respectively. During postoperative follow-up, 3.8% (60/1,571) patients had disease recurrence or metastasis, comprising 0.8% (3/370) in the very low-risk group and 4.7% (57/1,201) in the low-risk group. In the low-risk group, recurrence or metastasis occurred in 5.5% (25/457) of patients with duodenal GISTs, 3.9% (25/645) of those with small intestinal GISTs, 9.2% (6/65) of those with rectal GISTs, and 10.0% (1/10) of those with colonic GISTs. Among the 60 patients with metastases, 56.7% (34/60) of the metastases were located in the abdominal cavity, 53.3% (32/60) in the liver, and 3.3% (2/60) in bone. During the follow-up period, 13 patients (0.8%) died of disease. Receiver operating characteristic curves were plotted for tumor diameter and Ki67 and assessed using the Jordon index. This showed that the difference in DFS between the two groups was statistically significant when the cutoff value for tumor diameter was 3.5 cm (AUC 0.731, 95% CI: 0.670–0.793, sensitivity 77.7%, specificity 64.1%). Furthermore, the difference in DFS between the two groups was statistically significant when the cutoff value for Ki67 was 5% (AUC 0.693, 95% CI: 0.624–0.762, sensitivity 60.7%, specificity 65.3%). Multifactorial analysis revealed that tumor diameter ≥3.5 cm, Ki67 ≥5%, and R1 resection were independent risk factors for DFS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). Furthermore, age >57 years, Ki67 ≥5%, and R1 resection were also independent risk factors for OS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). We also grouped the patients according to whether they had received postoperative adjuvant treatment with imatinib for 1 or 3 years. This yielded 137 patients in the less than 1-year group, 139 in the 1-year plus group; and 44 in both the less than 3 years and 3-years plus group. After propensity score matching for age, tumor diameter, Ki67, and resection status, the differences in survival between the two groups were not statistically significant (all P>0.05). The 10-year DFS and OS were 87.5% and 95.5%, respectively, in the group treated with imatinib for less than 1 year and 88.5% and 97.8%, respectively, in the group treated for more than 1 year. The 10-year DFS and OS were 89.6% and 92.6%, respectively, in the group treated with imatinib for less than 3 years and 88.0% and 100.0%, respectively, in the group treated with imatinib for more than 3 years. Conclusion:The overall prognosis of primary, non-gastric, low recurrence risk GISTs is relatively favorable; however, recurrences and metastases do occur. Age, tumor diameter, Ki67, and R1 resection may affect the prognosis. For some patients with low risk GISTs, administration of adjuvant therapy with imatinib for an appropriate duration may help prevent recurrence and improve survival.