Mulberry (Morus alba L.) leaf is a well-established traditional Chinese botanical and culinary resource. It has found widespread application in the management of diabetes. The bioactive constituents of mulberry leaf, specifically mulberry leaf flavonoids (MLFs), exhibit pronounced potential in the amelioration of type 2 diabetes (T2D). This potential is attributed to their ability to safeguard pancreatic β cells, enhance insulin resistance, and inhibit α-glucosidase activity. Our antecedent research findings underscore the substantial therapeutic efficacy of MLFs in treating T2D. However, the precise mechanistic underpinnings of MLF's anti-T2D effects remain the subject of inquiry. Activation of brown/beige adipocytes is a novel and promising strategy for T2D treatment. In the present study, our primary objective was to elucidate the impact of MLFs on adipose tissue browning in db/db mice and 3T3-L1 cells and elucidate its underlying mechanism. The results manifested that MLFs reduced body weight and food intake, alleviated hepatic steatosis, improved insulin sensitivity, and increased lipolysis and thermogenesis in db/db mice. Moreover, MLFs activated brown adipose tissue (BAT) and induced the browning of inguinal white adipose tissue (IWAT) and 3T3-L1 adipocytes by increasing the expressions of brown adipocyte marker genes and proteins such as uncoupling protein 1 (UCP1) and beige adipocyte marker genes such as transmembrane protein 26 (Tmem26), thereby promoting mitochondrial biogenesis. Mechanistically, MLFs facilitated the activation of BAT and the induction of WAT browning to ameliorate T2D primarily through the activation of AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling pathway. These findings highlight the unique capacity of MLF to counteract T2D by enhancing BAT activation and inducing browning of IWAT, thereby ameliorating glucose and lipid metabolism disorders. As such, MLFs emerge as a prospective and innovative browning agent for the treatment of T2D.
Mice ; Animals ; Adipose Tissue, Brown ; Sirtuin 1/pharmacology* ; Diabetes Mellitus, Type 2/metabolism* ; AMP-Activated Protein Kinases/metabolism* ; Morus/metabolism* ; Flavonoids/metabolism* ; Prospective Studies ; Signal Transduction ; Adipose Tissue, White ; Plant Leaves ; Uncoupling Protein 1/metabolism* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism*

Objective:To explore the predictability cytokines in aqueous humor affecting optical coherence tomography angiography (OCTA) parameters after anti-vascular endothelial growth factor (VEGF) treatment in patients with polypoidal choroidal vasculopathy (PCV).Methods:A cross-sectional study was carried out.Twenty eyes of 20 patients with PCV were included in Xuzhou First People's Hospital from July 2017 to July 2020.All PCV eyes were treated by intravitreal injection of conbercept (IVC) following 3+ PRN regimen.One hundred μl of aqueous humor was collected before treatment and before the third injection, respectively.Thirteen kinds of cytokines in the aqueous humor were detected with Luminex bead-based multiplex array.The aqueous humor of 16 eyes of 16 cataract patients with age and gender matched were collected in the same way during phacoemulsification surgery as control.The values of center macular thickness (CMT), subretinal fluid height (SRFH), pigment epithelial detachment height (PEDH) and pigment epithelial detachment diameter (PEDD) of the eyes in the PCV group were examined with OCTA system.The target cytokines in aqueous humor affecting OCTA parameter change values (the difference between before and after treatment) was analyzed.This study protocol was approved by an Medical Ethic Committee of Xuzhou First People's Hospital (No.xyyll[2020]27) and complied with Declaration of Helsinki.Written informed consent was obtained from each patient prior to any medical invention.Results:The concentration of interleukin-8 (IL-8), Leptin, hepatocyte growth factor (HGF), fibroblast growth factor-2 (FGF-2), angiopoietin-2 (Ang-2), endothelin-1 and vascular endothelial growth factor-A (VEGF-A) were significantly higher in aqueous humor of the PCV group before treatment than those in the cataract group (all at P<0.05). After treatment, the concentration of VEGF-A in aqueous humor of the PCV group was significantly lower than that before treatment ( P<0.001). The values of CMT, SRFH, PEDH and PEDD were significantly reduced in comparison with before treatment, showing statistical significances (all at P<0.05). The concentration of VEGF-A in aqueous humor was positively correlated and endothelin-1 in aqueous humor was negatively correlated with the change value of CMT ( r=0.592, -0.485, both at P<0.05). The concentration of IL-8 and HGF were positively correlated with SRFH change value ( r=0.492, 0.466, both at P<0.05). VEGF-A and IL-8 concentraions of aqueous humor before treatment were the risk factor of the change value of CMT and SRFH.Every 1pg/ml increase of baseline VEGF-A, the CMT change value reduced 0.836 μm ( P=0.006), and every 1pg/ml increase of baseline IL-8, the SRFH change value reduced 12.522 μm ( P=0.028). Conclusions:The concentrations of VEGF-A and IL-8 in aqueous humor might predict the CMT and SRFH improvement in PCV eyes after anti-VEGF therapy.

Objective To identify prognostic factors ofmotorfunctionafter surgery of metastatic spinal cord compression (MSCC).Methods The clinical data of 681 patients with spinal metastases from January 2008 to December 2017 were retrospectively analyzed.According to inclusion and exclusion criteria,a total of 206 patients with spinal metastatic were included.Postoperative neurological function was assessed using Frankel classification.The influence of age,gender,preoperative status,number of spine metastases,location of spinal metastases,visceral metastases,bone metastases,primary tumor type,interval from symptom to surgery,time of developing motor deficits,interval from primary tumor diagnosis to MSCC,preoperativethe Eastern Cooperative Oncology Group performance status (ECOG-PS),Karnofsky Performance score (KPS) and surgical procedures on postoperative function outcomes were explored.Results 140 (68.0％) patients were able to walk postoperatively compared with 88 (42.7％) patients preoperatively.Moreover,in 89.8％ of all patients,79 ambulatory patients maintained ambulation after treatment.The univariate analysis according to Ordered-logit model showed thatnumber of spine metastases,location of spinal metastases,preoperative ECOG-PS,preoperative KPS,interval from symptom to surgery and time of developing motor deficits were related with posttreatment motor functions.The multivariable analysis showed that number of spine metastases (OR=2.03;95％CI:1.12-3.33;P=0.04),preoperative ECOG-PS (OR=4.84;95％CI:2.42-8.15;P=0.038),interval from symptom to surgery (OR=3.78;95％CI:3.12-9.15;P=0.024),time of developing motor deficits(OR=2.75;95％CI:1.22-3.89;P=0.01) were independent prognostic factors for function outcomes.Conclusion 1-2 levels of metastasis,Interval from symptom to treatment ≥ 48 h,time of developing motor deficits ≥7 d,and ECOG-PS 1-2 can be considered as the most significant positive prognosticfactors for post-treatment ambulatory status.Spinal metastasis should have a higher priority,and immediate intervention should be started before the development of irreversible neurologic deficits.Increasing awareness of early symptoms and earlier screeningwith regular outpatient review might make a difference for patients with MSCC.Consequently,the identified prognostic factors can be considered as apreoperative assessment tool to predict the neurologic outcomeand guide clinical treatment for individual patients with MSCC.

Objective To investigate the effects of chemotherapeutic drugs on ER-α expression and methylation in breast cancer cells.Methods Human breast cancer cells MCF-7(ER+,Luminal A) were induced by paclitaxel(PTX) and epirubicin(EPI) for more than 6 months,with an incremental dose,respectively.The expression and methylation status of ER-α in MCF-7 cells were detected before and after drug treatment.miRNAs with consistent expression changes in MCF-7 cells after two drugs' treatment were screened by microarray,and verified by quantitative PCR (qPCR).Targets of the most significantly down-regulated miRNA were analyzed by bioinformatics.miRNA inhibitor was transfected into MCF-7 cells,miRNA mimic was transfected into MCF-7/PTX and MCF-7/EPI cells,then ER-α and DNA methyltransferase 1 (DNMT1) expression were detected by Western blot,and ER-α methylation was detected by quantitative methylation-specific PCR (qMSP).Results PTX resistant MCF-7/PTX cell line and EPI resistant MCF-7/EPI cell line were established.Both drug treatments caused a decrease in ER-α protein expression and an increase in methylation levels,with up-regulation of DNMT1 and his tone deacetylase 1 (HDAC 1) expression.miRNAs with consistent expression changes in MCF-7 cells after drug treatments were screened and verified by qPCR,the most significant down-regulation among which was miR-148b.Bioinformatics analysis,and further confirmed by luciferase reporter gene assay (Luciferas) that DNMT1 was a direct target of miR-148b.miR-148b inhibitor induced decreased expression of ER-α and increased methylation level in MCF-7 cells,accompanied by increased expression of DNMT1;whereas miR-148b mimic caused an increased expression of ER-α and decreased methylation level in MCF-7/PTX and MCF-7/EPI cells,with a decreased expression of DNMT1.Conclusion Chemotherapeutic drugs (represented by PTX and EPI) induce aberrant miRNA expression in breast cancer MCF-7 cells,and down-regulate miR-148b further to attenuate the inhibition of DNMT1 expression,which promote,hypermethylation and down-regulation of ER-α.

Objective: To compare the clinical effects of endoscopic laminectomy with traditional hemilaminectomy for lumbar spinal stenosis. Methods: From January 2016 to April 2017, 61 patients with lumbar spinal stenosis were treated surgi-cally. Percutaneous endoscopic laminectomy was performed in 32 patients (minimally invasive group), including 13 males and 19 females, aged 38-76 years, with an average age of 58.47±7.51 years. Twenty-nine patients (open group) underwent hemilaminecto-my, including 11 males and 18 females, aged 38-75 years, with an average age of 57.17±9.99 years. The operation time, bleeding, incision length, bedridden time and hospitalization time were recorded. Visual analogue scale(VAS), Oswestry disability index (ODI), dural sac cross-sectional area (DSCA), ventral intervertebral space height (VH), dorsal intervertebral space height (DH) and lumbar mobility (range of motion, ROM) were compared between the two groups. Results: All of 61 patients were followed up for 14 to 27 months, with an average of 19.2±2.95 months. The operation time was 60.88±6.49 min in the minimally invasive group, and 52.07±9.45 min in the open group (t=4.277, P=0.000). The blood loss of minimally invasive group was 55.63±10.14 ml, and that of open group was 78.79±12.58 ml (t=7.952, P=0.000). The incision length of minimally invasive group was 23.31±4.56 mm, and open group 82.59±7.66 mm (t=12.047, P=0.000). Bed rest time was 21.97±6.42 h in minimally invasive group and 78.79±12.58 h in open group (t=12.047, P=0.000). The hospitalization time of the minimally invasive group was 8.53±2.75 d and the open group 11.34±3.12 d (t=3.745, P=0.000). All these parameters had statistical significance (P<0.05). At the last follow-up, the VAS score of minimally invasive group was 1.06±0.56, and the open group was 1.14±0.74 (t=0.469, P=0.634). ROM of open group was 5.66±1.12 degree, and ROM of minimally invasive group was 5.56±1.13 degree (t=0.140, P=0.710), VH of minimally invasive group was 14.75±2.81 mm, and open group was 14.44±2.89 mm (t=0.181, P=0.672). There was no significant difference between the two groups for these parameters. At the last follow-up, ODI score was 13.25%±1.08% in the minimally invasive group and 14.28%±2.10% in open group (t=5.911, P=0.018). DSCA score was 108.56±8.69 mm² in the minimally invasive group, and 117.28±11.09 mm² in open group (t=11.774, P=0.001). There were significant differences between the two groups for ODI and DS-CA. Conclusion Both endoscopic and open laminectomy have excellent clinical effects on lumbar spinal stenosis. Endoscop-ic laminectomy has the advantages of less local trauma, less damage to the stability of the lumbar spine and faster recovery. However, there's a higher technical requirement for endoscopic spine surgery.

Objective: To explore the treatment outcome of triangular osteosynthesis (TOS) for the treatment of unilateral Isler type II lumbosacral junction injuries (LSJIs). Methods: Data of sixteen patients with unilateral Isler type II LSJIs surgically who were treated in our Hospital from March 2015 to February 2017 were retrospectively analyzed. There were 13 males and 3 females with an average age of 35.5 years (range, 24-61 years). Seven patients were multiple injuries including head, thoracic, musculoskeletal and nerve injuries. According to Isler classification of LSJIs, there were 5 cases of type IIa, 9 of type IIb and 2 of type IIc. All the LSJIs combined with ipsilateral sacral fractures. The sacral fractures were classified by Denis classification with 1 case of zone I, 13 cases of zone II and 2 cases of zone III. According to Tile classification of pelvic fractures, there were 3 cases of type B2, 11 of type C1 and 2 of type C3. There were 3 cases combined with sacral nerve injury among which there were 2 cases of grade II and 1 case of grade III according to Gibbons classification of neurologic deficits. All cases were surgically treated with triangular osteosynthesis. There were 14 cases combined with iliosacral screws fixation in S₁ and 2 cases combined with posterior locking plates. Results: All patients were followed up for 20.6 months (range, 16-30 months). CT scan was conducted 12 to 24 months after surgery which showed all the sacral fractures were union, and 2 cases achieved bony fusion in L₅S₁ facets while the other 14 didn’t. According to Majeed’s pelvic injury evaluation, clinical outcomes were rated with excellent in 12 cases, good in 2 cases, fair in 2 cases. The excellent and good rate was 87.5% (14/16) . According to Mears-Velyvis evaluation criterion, there were 14 cases with anatomical reduction and 2 cases with satisfactory reduction. Among the 3 cases with sacral nerve injury, 2 cases were improved from Gibbons grade II to grade I and the other 1 case was improved from Gibbons grade III to grade II, still feeling numbness on the lateral foot. There were no intraoperative complications in all patients such as neurovascular injuries. No incision infection, fat liquefaction and other incision related complications occurred postoperatively. Irritation and pain in iliac spine about prominent implant occurred in 1 case and lumboscaral stiffness in 1 case, in which the symptom relieved and disappeared after implants removal. Conclusion Triangular osteosynthesis can provide enough stabilization for Isler type II LSJIs and achieve satisfactory outcomes.

Objective To observe the efficacy of photodynamic therapy (PDT) based on indocyanine green angiography (ICGA) for circumscribed choroidal hemangioma (CCH).Methods A retrospective observational case series study was performed.Seventeen eyes of 17 patients were diagnosed with CCH and then underwent PDT based on ICGA image in Xuzhou Municipal Hospital from August,2010 to May,2018.The size of the treatment spot was decided according to ICGA images.The period of mean follow-up visit ranged from 6 to 36 months,with an average of (23.3± 1 1.8) months.Best corrected visual acuity (BCVA),sub-retinal fluid (SRF) and central retinal thickness (CRT) based on optical coherence tomography (OCT),the tumor diameter based on ICGA and the tumor thickness based on coloured doppler imaging (CDI) before and after treatment were analyzed.Results Sixteen cases received only one PDT session,one case had ever received PDT and another case had ever received focal laser photocoagulation.The mean BCVA (LogMAR) was 0.99±0.52,1.09±0.50,0.97±0.53,0.81±0.66,0.79±0.69,and the mean CRT was (440.76±281.34),(329.18± 175.02),(274.24± 169.55),(271.53 ± 150.00),(291.06 ± 201.41)μm before PDT,at 1 week,1 month,3 months and the last visit after treatment,with significant differences among the follow-up time (F =6.965,P =0.006;F =8.784,P =0.002).The decimal visual acuity was increased by at least 2 lines in 9 eyes (52.9％),fluctuated within 2 lines in 7 eyes (41.2％),while decreased by at least 2 lines in one eye (5.9％).SRF of all patients was involved in macular area.The absolute absorption of SRF was found in 7 eyes (41.2％) and partial absorption in 8 eyes (47.1％) at 3 months follow-up visit.In the last follow-up visit,the absolute absorption of SRF was found in 12 eyes (70.6％),partial absorption was found in 3 eyes (17.6％) and 2 eyes (11.8％) underwent no change.On FFA and ICGA,the decrease of tumor size was found in 15 patients,while the others underwent no change.All patients underwent less enhanced hyperfluorescent after treatment.The mean tumor height was (3.80± 1.13)mm before PDT and (3.42± 1.14)mm on the last visit,with a significant difference between them (t=4.101,P=0.010).Conclusions PDT with verteporfin for CCH can promote the improvement of visual acuity,the absorption of SRF,the anatomical reposition of the retina and the decrease of tumor size.The majority of patients can get therapeutic effect after one PDT session.

Objective To assess the clinical value of cross raft screws technique in preventing postoperative collapse of tibial plateau fracture.Methods From September 2014 to November 2017,data of 14 patients with tibial plateau fracture who were treated by cross raft screws technique were retrospectively analyzed.There were 9 males and 5 females aged from 30-65 years old (average,44.4± 1.7 years).There were 8 patients that the thickness of subchondral cancellous bone measured preoperatively by CT data was less than 4 mm,and 6 patients that the thickness of subchondral cancellous bone measured intraoperatively was less than 4 mm.1/4 tubular plate was placed along the anterior rim of lateral tibial plateau,and the 3.5 mm cortical bone screws were fixed as bamboo raft from anterior to posterior through the plate.The collapse of tibial plateau after surgery were measured by CT scan after union of the fracture.The function of knee was evaluated by Rasmussen Anatomical and Functional Grading.Results The time of tubular plate procedure was 18 to 35 min (average,24.1±5.4 min).All 14 patients were successfully followed-up for 13.8±5.1 months.The height of collapse preoperatively by CT scan was 5-21 mm (average,8.00± 1.40 mm).3 days after the operation,the height between articular line and lateral articular surface was 0-2 mm (average,0.80±0.06 mm).Compared with CT data preoperatively,the collapse was corrected postoperatively that was proved by CT scan (P＜ 0.05).After the fracture was healed,according to CT data,the height between articular line and lateral articular surface was 0-2 mm (average,0.70±0.08 mm).Compared with CT data postoperatively,there was no postoperative collapse happened (P=0.466).The position and length of nails were placed appropriately.The average healing time of fracture was 3.6 months.There were no infection,nonunion and pain of tendon happened.The plate could be touched subcutaneously in 2 patients,who had no discomfort feelings.The patient's postoperative Rasmussen Anatomical Grading were 13-18 (average,16.7),including 8 cases excellent and 6 cases good.The postoperative Rasmussen Functional Grading was 18-28 (average,25.7),including 11 cases excellent and 3 cases good.Conclusion The cross raft screws technique is a good way to prevent the postoperative collapse of the lateral articular surface of tibial plateau.

Objective ToanalyzethedistributionanddrugresistancesituationofKlebsiellapneumoniae(KPN)isolatedfromour hospital during 2014 .Methods The drug susceptibility test was carried out by the Siemens fully automatic bacterial identification /drug susceptibility test analyzer .The drug susceptibility test results were judged according to the (CLSI) M100‐S22 document (2012) .Results A total of 291 strains of KPN were detected from 8 486 submitted specimens ,in which 20 strains were multi‐drug resistant Klebsiella pneumoniae(MDR‐KPN)isolates were 213 strains ,48 strains were extended‐spectrum beta‐lactamases producing Klebsiella pneumoniae (ESBLs‐KPN) and 10 strains were carbapenem‐resistant Klebsiella pneumoniae(CR‐KPN) .The KPN detec‐tion rate had statistical difference among different specimens (P= 0 .000) .The constituent ratio of KPN isolation in the sputum specimen was highest(P=0 .000) .The KPN detection rate had statistical difference among different departments (P=0 .000) ,the constituent ratio of KPN isolation in the respiration department was highest (P=0 .000) .The resistance and sensitivity of KPN to different antibacterial drugs had statistical difference(P=0 .000) ,carbapenems had the lowest resistance rate .Conclusion KPN has relatively low resistance rate to commonly used antibacterial drugs ,its multi‐drug resistant strains are in the higher level ,which should arouse clinic and hospital infection management department must to pay attention to and adopt corresponding supervision measures .

This study was aimed to improve the transfer rate of sinomenine in the intermediate product of Caulis Sinomenii in order to optimize the purification process of intermediate product ofCaulis Sinomenii fromTong-An (TA) injection. The transfer rate of sinomenine and the stability of fingerprints in the intermediate product of Caulis Sinomenii were used as indexes for the investigation on the impact from different pH ofCaulis Sinomenii extract before extraction. The transfer rate of sinomenine was used as an index for the investigation on the impact by different pH of hydrochloric acid created to dry extract solution. The transfer rate of sinomenine was used as an index for the investigation of four separation ways, which included the vacuum filtration, plate and frame filters, high-speed tube separator, and flat direct centrifuge, on the liquid separation of sinomenium acutum acid. The results showed that the pH ofCaulis Sinomenii extract before extraction was 10-11; the transfer rate of sinomenine was the highest in the extraction process and the fingerprints of TA injection was stable. The pH of hydrochloric acid was 2.0-2.5; and the highest transfer rate of sinomenine in acid dissolution process was 92.94%. The high-speed tube separator had the best separation to sinomenium acutum acid-dissolving liquid. The highest transfer rate of sinomenine was 93.34%. It was concluded that the optimized process can effectively improve the transfer rate of sinomenine in the intermediate product ofCaulis Sinomenii. Meanwhile, fingerprints of the product were stable. The process was simple with good repeatability.