OBJECTIVE: To compare the therapeutic efficacy of portal and tail vein transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) against cholestatic liver fibrosis in mice. METHODS: BMSCs were isolated and co-cultured with starvation-activated hepatic stellate cells (HSCs). HSC activation markers were identified using immunofluorescence and qRT-PCR. BMSCs were injected into the liver tissues of bile duct ligation (BDL) mice via the tail and portal veins. Histomorphology, liver function, inflammatory cytokines, and the expression of key proteins were all determined in the liver tissues. RESULTS: BMSCs inhibited HSC activation by reducing α-SMA and collagen I expression. Compared to tail vein injection, DIL-labeled BMSCs injected through the portal vein maintained a high homing rate in the liver. Moreover, BMSCs transplanted through the portal vein resulted in greater improvement in liver color, hardness, and gallbladder size than did those transplanted through the tail vein. Furthermore, BMSCs injected by portal vein, but not tail vein, markedly ameliorated liver function, reduced the secretion of inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and decreased α-SMA + hepatic stellate cell (HSC) activation and collagen fiber formation. CONCLUSION The therapeutic effect of BMSCs on cholestatic liver fibrosis in mice via portal vein transplantation was superior to that of tail vein transplantation. This comparative study provides reference information for further BMSC studies focused on clinical cholestatic liver diseases.
Animals ; Mice ; Mesenchymal Stem Cell Transplantation ; Liver Cirrhosis/etiology* ; Male ; Cholestasis/therapy* ; Mice, Inbred C57BL ; Hepatic Stellate Cells ; Mesenchymal Stem Cells

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

OBJECTIVE: To compare the therapeutic effect between Fanzhen Jieci (warming acupuncture plus fast needling) combined with conventional acupuncture and simple conventional acupuncture on discogenic sciatica. METHODS: A total of 76 patients with discogenic sciatica were randomized into a Fanzhen Jieci group and a conventional acupuncture group, 38 cases in each one. Conventional acupuncture was applied at Shenshu (BL 23), Dachangshu (BL 25), L₁-L₅ Jiaji (EX-B 2) and Huantiao (GB 30) on the affected side, etc. in the conventional acupuncture group. On the basis of the treatment in the conventional acupuncture group, Fanzhen Jieci was applied at L₁-L₅ Jiaji (EX-B 2) and Huantiao (GB 30) on the affected side in the Fanzhen Jieci group, i.e. warming acupuncture was applied at L₁-L₅ Jiaji (EX-B 2), and fast needling was applied at Huantiao (GB 30) on the affected side for a depth of 40-60 mm, so as to introduce a sensation of electric shock transmitting to lower limb, and then the needle was immediately withdrawn. The treatment was given once every other day, 3 times a week for 3 weeks in both groups. The visual analogue scale (VAS) score of leg and low back pain, the Oswestry disability index (ODI) score and the 36-item short form health survey (SF-36) score before and after treatment were compared between the two groups. RESULTS: Compared before treatment, the VAS scores of leg and low back pain and the ODI scores after treatment were decreased in both groups (P<0.001), the changes of the VAS scores of leg and low back pain in the Fanzhen Jieci group were larger than those in the conventional acupuncture group (P<0.05). After treatment, except for the role emotional and health transition scores, the various scores of SF-36 were increased compared before treatment in the Fanzhen Jieci group (P<0.01); except for the role physical, role emotional and health transition scores, the various scores of SF-36 were increased compared before treatment in the conventional acupuncture group (P<0.01). After treatment, the physical functioning, role physical, bodily pain, mental health and general health scores of SF-36 in the Fanzhen Jieci group were higher than those in the conventional acupuncture group (P<0.05). CONCLUSION Fanzhen Jieci combined with conventional acupuncture can effectively relieve the pain and improve the mental state in patients with discogenic sciatica, its therapeutic effect is superior to simple conventional acupuncture.
Acupuncture Points ; Acupuncture Therapy ; Humans ; Low Back Pain/therapy* ; Sciatica/therapy* ; Treatment Outcome

AIM: To compare and observe the characteristics of choroidal neovascularization(CNV)and polypoidal choroidal vasculopathy(PCV)in indocyanine green angiography(ICGA)and optical coherence tomography angiography(OCTA),and to discuss their differences and pros and cons.METHOD: The imaging data of 26 CNV patients(34 eyes)and 19 PCV patients(19 eyes)diagnosed at Hebei Eye Hospital from September 2018 to April 2020 were retrospectively analyzed. There were 20 cases(28 eyes)of wet age-related macular degeneration(w-ARMD)in CNV patients and 6 cases(6 eyes)of chronic central serous chorioretinopathy(CCSC)secondary to CNV. All patients underwent OCTA, fundus fluorescein angiography(FFA)+ICGA, analyzing the characteristic changes of lesions.RESULT: OCTA examination of w-ARMD patients(28 eyes)showed that, except for 2 eyes where no obvious abnormality was seen due to severe bleeding, the morphology of CNV can be seen in the remaining 26 eyes in a clear, three-dimensional way, and even the anatomical level where CNV was located could be found. Among them, 11 eyes examined by OCTA can not only show the morphology, size and affected area of CNV, but also can better distinguish the nourishing vessels, new vessels and anastomotic branches. CNV morphology not detected by FFA+ICGA was found by OCTA in 6 eyes of patients with CCSC secondary to CNV. A clearer vision of abnormal choroidal branching vascular network(BVN)can be found clearer by OCTA than ICGA in 19 eyes of PCV patients, but OCTA cannot show the number of terminal saccular dilatations(polyps)as clearly as ICGA.CONCLUSION: The positive rate of CNV detected by OCTA is higher than that of ICGA. The lesions range of CNV and PCV detected by OCTA is clearer and more stereoscopic than that of ICGA.But it cannot show all terminal saccular dilatations in PCV patients, and it cannot be used to monitor the leakage of CNV or PCV and lesion progression. So it is less effective than FFA+ICGA in this aspect. As a non-invasive examination, OCTA can be used in the follow-up to observe the changes in lesions before and after CNV or PCV treatment.

To investigate the changes of bile acid(BA) levels in mice with sleep deprivation and the regulatory effect of Jiaotai Pills(JTP) on bile acid metabolism, this study established an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of 23 BAs in mice. A total of 24 ICR mice were randomized into normal group, model group, and JTP group. Mice in the model group and JTP group were deprived of sleep at 20 h·d~(-1) by sleep deprivation apparatus for 8 consecutive days. Mice in the JTP group were given(ig, qd) JTP 3.3 g·kg~(-1) and those in the normal group and model group received(ig) the same volume of purified water. UPLC conditions are as follows: Waters ACQUITY UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm), gradient elution with the mobile phase of 0.1% formic acid in water-methanol. MS conditions are as below: negative-ion electrospray ionization, multiple reaction monitoring(MRM). Thereby, the content of 23 BAs in serum, liver, and ileum was determined and methodological investigation of the method was performed. The results showed that 23 BAs could be accurately determined within 15 min and the correlation coefficients were all higher than 0.99. The precision, accuracy, specificity, reproducibility, matrix effect, and recovery of BAs all met the requirement. The levels of BAs were significantly increased in the serum, liver, and ileum of sleep-deprived mice, but JTP can significantly reduce the levels. The UPLC-MS/MS method is simple, rapid, and accurate, which can be used for the determination of 23 BAs in biological samples, and JTP can adjust the elevated BA levels of sleep-deprived mice.
Animals ; Bile Acids and Salts ; Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Drugs, Chinese Herbal ; Mice ; Mice, Inbred ICR ; Reproducibility of Results ; Sleep ; Tandem Mass Spectrometry

Development of rapid analytical methods and establishment of toxic component limitation standards are of great importance in quality control of traditional Chinese medicine. Herein, an on-line extraction electrospray ionization mass spectrometry (oEESI-MS) coupled with a novel whole process integral quantification strategy was developed and applied to direct determination of nine key aconitine-type alkaloids in 20 proprietary Chinese medicines (APCMs). Multi-type dosage forms (, tablets, capsules, pills, granules, and liquid preparation) of APCM could be determined directly with excellent versatility. The strategy has the characteristics of high throughput, good tolerance of matrix interference, small amount of sample (∼0.5 mg) and reagent (∼240 μL) consumption, and short analysis time for single sample (<15 min). The results were proved to be credible by high performance liquid chromatography-mass spectrometry (LC-MS) and electrospray ionization mass spectrometry, respectively. Moreover, the limitation standard for the toxic aconitines in 20 APCMs was established based on the holistic weight toxicity (HWT) evaluation and the severally, and turned out that HWT-based toxicity evaluation results were closer to the real clinical applications. Hence, a more accurate and reliable APCM toxicity limitation was established and expected to play an important guiding role in clinics. The current study extended the power of ambient MS as a method for the direct quantification of molecules in complex samples, which is commonly required in pharmaceutical analysis, food safety control, public security, and many other disciplines.

Objective To investigate the bystander effect injury to lung-heart-liver-spleen caused by 12C6+ beam radiation,and explore the prevention and treatment effect of Guiqiyiyuan ointment on the injury and its mechanism.Methods Ninety healthy male Wistar rats were randomly divided into 3 groups:NC group (normal control,normal saline 2ml/kg,n=30),SR group (simple radiation,8Gy,2ml/kg,n=30),GO group (Guiqiyiyuan ointment 11.83g/kg,radiation,8Gy,n=30).All the rats received intragastric administration for 7 days.The right side of the lung was modeled by 12C6+ beam radiation.After modeling,the rats were killed at 48h.The heart,liver and spleen were taken.The malonaldehyde (MDA),glutathione (GSH),glutathione peroxidase (GSH-Px),superoxide dismutase (SOD) contents were measured by colorimetry,DNA methylation rate was assayed by ELISA,and the expressions of Dnmt1,Dnmt3a and Dnmt3b were detected by immunohistochemistry.Results Compared with NC group,the contents of SOD,GSH and GSH-Px decreased (P＜0.01),MDA increased (P＜0.01),the level of DNA methylation decreased (P＜0.01),and the expressions of Dnmt1,Dnmt3a and Dnmt3b increased in SR group (P＜0.01).Compared with SR group,the contents of SOD,GSH and GSH-Px increased (P＜0.01),MDA decreased (P＜0.01),the level of DNA methylation increased (P＜0.01),and the expressions of Dnmt1,Dnmt3a and Dnmt3b decreased in GO group (P＜0.01).Dnmtl,Dnmt3a and Dnmt3b proteins were expressed in the cytoplasm of myocardial cells,hepatocytes and peripheral B cells of the white pulp in spleen,in all the groups.The color of NC group was light brown-brown,showing a weak positive expression.The color of SR group was brown-brown,showing a strong positive expression.The color of GO group was light brown-tan,showing a moderate positive expression.Conclusion The Guiqiyiyuan ointment can reduce the bystander effect caused by the 12C6+ beam radiation,and its mechanism is related to improving the oxidative stress reaction and the level of DNA methylation.

OBJECTIVETo investigate the correlation of the fertilization strategy and embryo transfer (ET) time with the incidence of ectopic pregnancy.

METHODSWe selected 3,331 fresh and 2,706 frozen-thawed ET cycles for the patients undergoing in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). The fresh transfers included 2 546 IVF-ET and 785 ICSI-ET cycles and 2,220 day-3 embryo and 1,111 day-5 blastocyst transfers, while the frozen-thawed transfers included 2,080 IVF-ET and 626 ICSI-ET cycles and 741 day-3 embryo and 1 965 day-5 or -6 blastocyst transfers. We compared the incidence rate of ectopic pregnancy associated with different fertilization strategies and ET time.

RESULTSThe incidence rate of ectopic pregnancy was 1. 41% (36/2 546) in the IVF-ET cycles and 3.44% (27/785) in the ICSI-ET cycles of the fresh transfers, significantly lower in the IVF-ET than in the ICSI-ET cycles (P < 0.01), and it was 1.01% (21/2,080) in the IVF-ET cycles and 0.80% (5/626) in the ICSI-ET cycles of the frozen-thawed transfers, with no remarkable difference between the two groups (P > 0.05). The IVF-ET and ICSI-ET cycles included 2,220 fresh day-3 (F-D3) embryos, 1,111 F-D5 blastocysts, 741 frozen-thawed day-3 (T-D3) embryos, and 1,965 T-D5/6 blastocysts. The incidence rate of ectopic pregnancy was 1.71% (n = 38) in the F-D3, 2.25% (n = 25) in the F-D5, 1.35% (n = 10) in the T-D3, and 0.81% (n = 16) in the T-D5/6 group, respectively, significantly lower in the T-D5/6 than in the other three groups (P < 0.05).

CONCLUSIONThe incidence rate of ectopic pregnancy is associated with fertilization strategies, which is significantly lower in frozen-thawed than in fresh embryo transfers.

Blastocyst ; Embryo Transfer ; adverse effects ; methods ; statistics & numerical data ; Female ; Fertilization in Vitro ; adverse effects ; methods ; statistics & numerical data ; Humans ; Incidence ; Pregnancy ; Pregnancy Rate ; Pregnancy, Ectopic ; epidemiology ; etiology ; Sperm Injections, Intracytoplasmic ; adverse effects ; methods ; statistics & numerical data

Objective To investigate the clinical significance and influencing factors of serum levels of pro-gastrin-releasing peptide (ProGRP) and neuron-specific enolase (NSE) in the diagnosis of small cell lung cancer ( SCLC) .Methods The levels of serum ProGRP and NSE in 93 SCLC patients ( SCLC group ) , 120 non-small cell lung cancer (NSCLC) patients (NSCLC group), 120 benign pulmonary disease patients (benign disease group ) , and 90 healthy people ( healthy control group ) were determined using enzyme-linked immunosor-bent assay (ELISA).The potential impacts of the hemolysis in samples and impaired renal function on ProGRP and NSE were tested via electroluminescent and chemiluminescent immunoassay , respectively .Results The ser-um ProGRP and NSE concentrations were 90.61 (11.75-20 020.90) ng/L and 13.18 (3.05-201.88) μg/L, respectively , in SCLC group;13.26 (8.54-526.23) ng/L and 5.86 (1.80-100.90) μg/L in NSCLC group;24.65 (1.32 -802.93) ng/L and 7.22 (1.36-174.62 ) μg/L in benign disease group; and 14.74 (4.59 -100.86) ng/L and 4.95 (1.31-10.58 ) μg/L in healthy control group .The levels in the SCLC group were sig-nificantly different from those in the other three groups ( all P<0.01 ) .The area under the receiver operating characteristic curve of ProGRP was (0.856 ±0.023) (95%CI:0.811-0.901).When the cutoff value of Pro-GRP was set at 46 ng/L, the diagnostic sensitivity , specificity , positive predictive value , negative predictive val-ue, and Youden's index were 64.5% (60/93), 94.2%(311/330), 75.9%(60/79), 90.4%(311/344), and 58.7%, respectively , showing good detection performance .Sample hemolysis seriously improved the detec-tion results of NSE .Patients with impaired renal function had higher ProGRP levels .Conclusions The serum ProGRP and NSE levels are valuable tumor markers for the diagnosis of SCLC .Detection of both markers are par-ticularly useful for the monitoring of SCLC .Sample hemolysis may seriously increase the detected NSE level , whereas impaired renal function may increase the detected ProGRP level .

It has been reported that the frequency modulation (FM) or FM direction sensitivity and forward masking of central auditory neurons are related with the neural inhibition, but there are some arguments, because no direct evidence of inhibitory synaptic input was obtained in previous studies using extracellular recording. In the present study, we studied the relation between FM direction sensitivity and forward masking of the inferior collicular (IC) neurons using in vivo intracellular recordings in 20 Mus musculus Km mice. Thirty seven with complete data among 93 neurons were analyzed and discussed. There was an inhibitory area which consisted of inhibitory postsynaptic potentials (IPSP) at high frequency side of frequency tuning of up-sweep FM (FMU) sensitive neurons (n = 12) and at low frequency side of frequency tuning of down-sweep FM (FMD) selective neurons (n = 8), while there was no any inhibitory area at both sides of frequency tuning of non-FM sweep direction (FMN) sensitive neurons (n = 17). Therefore, these results show that the inhibitory area at low or high frequency side of frequency tuning is one of the mechanisms for forming FM sweep direction sensitivity of IC neurons. By comparison of forward masking produced by FMU and FMD sound stimuli in FMU, FMD and FMN neurons, the selective FM sounds could produce stronger forward masking than the non-selective in FMU and FMD neurons, while there was no forward masking difference between FMU and FMD stimuli in the FMN neurons. We suggest that the post-action potential IPSP is a potential mechanism for producing stronger forward masking in FMU and FMD neurons.
Acoustic Stimulation ; Action Potentials ; Animals ; Inferior Colliculi ; cytology ; Inhibitory Postsynaptic Potentials ; Mice ; Neurons ; cytology