Objective:To investigate the role and molecular mechanism of sensory neuron-derived exosomes (nExo) in mediating intervertebral disc degeneration (IDD).Methods:A rat IDD model was constructed, with nExo injected into the intervertebral disc. After 4 weeks, the degenerative grades of operated discs were evaluated using histological staining, while the senescent phenotype of nucleus pulposus stem cells (NPSC) in the tissue was evaluated using immunofluorescence staining. For in vitro experiments, 24 hours after the treatment of nExo to NPSC, immunoblotting, flow cytometry, or senescence-associated β-galactosidase staining was applied to evaluate the senescent phenotype of NPSC. Transcriptomics analysis was applied to identify the key molecules that mediate nExo-induced cells senescence. After 4 weeks of injecting nExo and TXN into the rat tail disc degeneration model.Results:nExo increased the degenerative grades of IDD and increased the proportion of TEK +p16 + and TEK +p21 + cells (from 36.32% ±4.04%, 33.69% ±4.56% in IDD group to 56.41% ±5.26%, 50.14% ±8.49% in IDD+nExo group, respectively; t=7.420, P<0.001; t=4.184, P<0.0019, respectively) in the disc tissue. Besides, nExo promoted the expression of p16 and p21 in NPSC and increased the percentage of cells with positive senescence-associated β-galactosidase staining (from 7.32%±1.73% to 58.22%±11.38%, t=7.658, P=0.002), while the percentage of G2/M cells was downregulated (from 18.10%±1.32% to 1.60%±0.67%, t=19.290, P<0.001). Transcriptomic analysis showed that the differential genes of CTRL vs. nExo were closely related to cell senescence, and TXN was screened by intersecting the differential gene set with the cellular senescence gene sets from the published database. Furthermore, we verified that nExo decreased the content of TXN in NPSC, while exogenous TXN downregulated the expression of p16 and p21 in NPSC, reduced the positive cell rate of senescence-associated β-galactosidase staining (from 58.84%±3.99% to 21.68%±8.16%, t=7.048, P=0.021), increased the percentage of G2/M cells (from 1.21%±0.34% to 15.26%±2.60%, t=9.259, P=0.001). TXN significantly reduced the grade of disc tissue degeneration (histological score: 14.33±0.82 in the nExo group; 8.17±1.17 in the nExo+TXN group, t=10.590, P<0.001), significantly increased the content of extracellular matrix (from 10.94±4.35 μg/mg to 50.55±12.16 μg/mg, t=7.512, P<0.001), and reduced the proportion of TEK +p16 + and TEK +p21 + double-positive cells (from 54.92%±4.21% and 60.31%±9.02% to 27.93%±3.26% and 33.75%±8.07%, respectively; t=12.430, P<0.001; t=5.375, P<0.001, respectively). Conclusion:nExo promotes cell senescence and IDD by downregulating TXN in NPSC.

OBJECTIVE: To evaluate the prospective association between cumulative resting heart rate (cumRHR) and rapid renal function decline (RRFD) in a cohort of individuals aged 60 and older. METHODS: In the Tianjin Chronic Kidney Disease Cohort Study, the individuals who underwent three consecutive physical examinations between 2014 and 2017, with estimated glomerular filtration rate (eGFR) greater than 60 mL/min per 1.73 m² and aged 60 years or older were enrolled. A total of 27,564 patients were prospectively followed up from January 1, 2017 to December 31, 2020. The 3-year cumRHR was calculated. The primary outcome was RRFD, defined as an annualized decline in eGFR of 5 mL/min per 1.73 m² or greater. Logistic and restricted spline regression models and subgroup analysis were used to investigate the association of cumRHR with RRFD after adjusting for all confounders. RESULTS: During a median follow-up of 3.2 years, a total of 4,347 (15.77%) subjects developed RRFD. In fully-adjusted models, compared with the lowest quartile of cumRHR, the odds ratio (OR) for the highest was 1.44 (1.28-1.61), P < 0.001. Furthermore, each 1-standard deviation (27.97 beats/min per year) increment in cumRHR was associated with a 17% (P < 0.001) increased risk of RRFD, with a linear positive correlation (P for non-linear = 0.803). Participants with a 3-year cumRHR ≥ 207 (beats/min) * year (equivalent to ≥ 69 beats/min per year in 3 years) were found to be at a higher risk of RRFD. CONCLUSIONS The cumRHR is significantly associated with a higher risk of RRFD among older adults. These results might provide an effective goal for managing and delaying the decline of renal function in the older adults.

OBJECTIVES: To explore the influencing factors of the horizontal distance of bodies in the high falling scene and the feasibility of inferring the falling mode based on it. METHODS: A total of 614 high falling deaths and 15 cases of corpse dumping from high altitudes were collected. The relationship between the horizontal distance and the falling height, as well as the sex, age and manner of death (suicide, accident and corpse dumping) were observed. RESULTS: The horizontal distance increased with the increase of falling height, and the difference among the height groups was statistically significant. The horizontal distance decreased with the increase of the age of the deceased, in each height group, the difference between the group over 60 years old and other age groups was statistically significant (P<0.05). The horizontal distance of male deceased was (1.99±0.27) m, which was greater than that of female deceased (1.88±0.19) m, and the difference was statistically significant in partial height groups (P<0.05). Roof falls had a greater horizontal movement distance than window falls. Except for the >20-30 m group, there was no significant difference in horizontal distance between suicide high falls and accidental high falls in other height groups. CONCLUSIONS The horizontal distance is affected by the falling height, the sex and age of the victim, and the spatial characteristics of the falling starting point.
Body Height ; Cadaver ; Female ; Homicide ; Humans ; Male ; Middle Aged ; Suicide

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.

Objective:To investigate the efficacy and safety of dual wavelength pulsed dye laser combined with 30% supramolecular salicylic acid in the treatment of moderate and severe facial acne.Methods:Sixty patients with moderate and severe acne that visited the Dermatology Department of the First Affiliated Hospital of Chongqing Medical University from May 2020 to January 2021, were selected and randomly divided into observation group and control group, with 30 patients in each group. The observation group was given dual-wavelength pulsed dye laser combined with 30% supramolecular salicylic acid. 30% supramolecular salicylic acid was used once every two weeks, for a total of six times. Dual-wavelength pulsed dye laser was given once a month, for a total of three times. The control group was only given dual-wavelength pulsed dye laser, once a month, a total of three times.Results:Twenty-two cases (73.33%) in the observation group were effective, while 14 cases (46.67%) in the control group were effective. The efficacy of the observation group was better than that of the control group, and the difference was statistically significant (χ 2=4.44, P<0.05). There were no obvious adverse reactions in both groups. Conclusions:Dual-wavelength pulsed dye laser combined with 30% supramolecular salicylic acid is effective and safe in the treatment of moderate and severe facial acne, which is worth popularizing.

Arbuscular mycorrhizal fungi provided is beneficial to Salvia miltiorrhiza for increasing yield, promoting the accumulation of active ingredients, and alleviating S. miltiorrhiza disease etc. However, the application of fungicides will affect the benefit of arbuscular mycorrhizal fungi and there is little research about it. This article study the effect of four different fungicides: carbendazim, polyoxin, methyl mopazine, and mancozeb on mycorrhiza benefit to S. miltiorrhiza by the infection intensity of arbuscular mycorrhizal fungi, the growth of S. miltiorrhiza, and the content of active ingredients. RESULTS:: showed that different fungicides had different effects. The application of mancozeb had the strongest inhibitory effect on the mycorrhizal benefit to S. miltiorrhiza. Mancozeb significantly reduced the mycorrhizal colonization and the beneficial effect of arbuscular mycorrhizal fungi on the growth and the accumulation of active components of S. miltiorrhiza. The application of polyoxin had no significant effect on mycorrhizal colonization. Instead, it had a synergistic effect with the mycorrhizal benefit to promoting the growth and accumulation of rosmarinic acid of S. miltiorrhiza. The inhibitory strengths of four fungicides are: mancozeb>thiophanate methyl, carbendazim>polyoxin. Therefore, we recommend applying biological fungicides polyoxin and avoid applying chemical fungicides mancozeb for disease control during mycorrhizal cultivation of S. miltiorrhiza.
Fungicides, Industrial/pharmacology* ; Mycorrhizae ; Plant Roots ; Salvia miltiorrhiza ; Symbiosis

Objective:To study the effect of transcranial direct current stimulation (tDCS) regulating excitability of the vagus nerve on dysphagia after stroke. Methods:From September, 2020 to February, 2021, 28 patients with dysphagia after stroke were randomly divided into control group (n = 14) and tDCS group (n = 14). Both groups accepted swallowing function training, and tDCS group received anodal tDCS over vagus nerve, while the control group received sham tDCS. They were assessed with modified Mann Assessment of Swallowing Ability (MMASA) and Australian Therapy Outcome Measures (AusTOMs)-swallowing scale before and after treatment. Results:The scores of MMASA (|t| > 5.593, P < 0.001) and AusTOMs swallowing scale (|Z| > 2.121, P < 0.05) increased in both groups after treatment, and were higher in tDCS group than in the control group (|t| = 2.439, |Z| = 2.079, P < 0.05). Conclusion:Anodal tDCS over vagus nerve may further release dysphagia after stroke.

Objective:To investigate the in vitro antibacterial effects of imipenem combined with common antibiotics on bla KPC-2 type carbapenem resistant klebsiella pneumoniae (CRKP) targeting bla KPC-2 gene. Methods:Six strains of unrepeated bla KPC-2 type confirmed by polymerase chain reaction and DNA sequence were isolated in Yueqing People's Hospital, China between January 2018 and January 2019 were included in this study. The susceptibility rate of imipenem against nine conventionally used antibiotics was determined. The sensitivity test of imipenem combined with eight antibiotics was performed with the checkerboard method. Fractional inhibitory concentration was calculated to assess the efficacy of imipenem combined with common antibiotics. The in vitro treatment time-antibacterial effect curve was drawn to evaluate the antibacterial effects. Results:The resistance rate of six strains of bla KPC-2 type was 100.00% (6/6) for imipenem, meropenem, ceftazidime, ciprofloxacin, rifampicin and cefotaxime, and it was 66.67% (4/6) for minocycline and clavulanic acid and 33.33% (2/6) for tigecycline. Imipenem combined with tigecycline had a better antibacterial effect and exhibited a synergistic effect on four strains of bla KPC-2 type CRKP and an additive effect on two strains of Bla KPC-2 type CRKP. The curve of time for in vitro treatment of KPN2 with imipenem combined with tigecycline against bactericidal effect revealed that the antibacterial rate of imipenem at the 1/2 minimum inhibitory concentration combined with tigecycline at the 1/4 minimum inhibitory concentration was > 95% at (t+2) and the antibacterial effect could maintain (t+10) hours to (t+12) hours. The antibacterial rate of imipenem combined with tigecycline against strain 002 was gradually decreased with time, and the growth curve of strain 002 rised gradually. Conclusion:In vitro drug sensitivity test revealed that imipenem combined with tigecycline exhibits a good synergistic effect on bla KPC-2 type CRKP. Findings from this study provide a reference for clinical treatment of bla KPC-2 type CRKP.

The exacerbation of progressive multiple sclerosis (MS) is closely associated with obstruction of the differentiation of oligodendrocyte progenitor cells (OPCs). To discover novel therapeutic compounds for enhancing remyelination by endogenous OPCs, we screened for myelin basic protein expression using cultured rat OPCs and a library of small-molecule compounds. One of the most effective drugs was pinocembrin, which remarkably promoted OPC differentiation and maturation without affecting cell proliferation and survival. Based on these in vitro effects, we further assessed the therapeutic effects of pinocembrin in animal models of demyelinating diseases. We demonstrated that pinocembrin significantly ameliorated the progression of experimental autoimmune encephalomyelitis (EAE) and enhanced the repair of demyelination in lysolectin-induced lesions. Further studies indicated that pinocembrin increased the phosphorylation level of mammalian target of rapamycin (mTOR). Taken together, our results demonstrated that pinocembrin promotes OPC differentiation and remyelination through the phosphorylated mTOR pathway, and suggest a novel therapeutic prospect for this natural flavonoid product in treating demyelinating diseases.
Animals ; Cell Differentiation ; Flavanones ; Mice ; Mice, Inbred C57BL ; Myelin Sheath/metabolism* ; Oligodendroglia/metabolism* ; Rats ; Remyelination ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism*

The exacerbation of progressive multiple sclerosis (MS) is closely associated with obstruction of the differentiation of oligodendrocyte progenitor cells (OPCs). To discover novel therapeutic compounds for enhancing remyelination by endogenous OPCs, we screened for myelin basic protein expression using cultured rat OPCs and a library of small-molecule compounds. One of the most effective drugs was pinocembrin, which remarkably promoted OPC differentiation and maturation without affecting cell proliferation and survival. Based on these in vitro effects, we further assessed the therapeutic effects of pinocembrin in animal models of demyelinating diseases. We demonstrated that pinocembrin significantly ameliorated the progression of experimental autoimmune encephalomyelitis (EAE) and enhanced the repair of demyelination in lysolectin-induced lesions. Further studies indicated that pinocembrin increased the phosphorylation level of mammalian target of rapamycin (mTOR). Taken together, our results demonstrated that pinocembrin promotes OPC differentiation and remyelination through the phosphorylated mTOR pathway, and suggest a novel therapeutic prospect for this natural flavonoid product in treating demyelinating diseases.