Human bone marrow mesenchymal stem cell-derived exosomes loaded with gemcitabine inhibit pancreatic cancer cell proliferation by enhancing apoptosis

BACKGROUND Pancreatic cancer remains one of the most lethal malignancies,and has limited effective treatment.Gemcitabine(GEM),a chemotherapeutic agent,is commonly used for clinical treatment of pancreatic cancer,but it has characteristics of low drug delivery efficiency and significant side effects.The study tested the hypothesis that human bone marrow mesenchymal stem cell(MSC)-derived exosomes loaded with GEM(Exo-GEM)would have a higher cytotoxicity against human pancreatic cancer cells by enhancing their apoptosis.AIM To investigate the cytotoxicity of MSC-derived Exo-GEM against pancreatic cancer cells in vitro.METHODS Exosomes were isolated from MSCs and characterized by transmission electron microscopy and nanoparticle tracking analysis.Exo-GEM through electroporation,sonication,or incubation,and the loading efficiency was evaluated.The cytotoxicity of Exo-GEM or GEM alone against human pancreatic cancer Panc-1 and MiaPaca-2 cells was assessed by MTT and flow cytometry assays.RESULTS The isolated exosomes had an average size of 76.7 nm.The encapsulation efficacy and loading efficiency of GEM by electroporation and sonication were similar and significantly better than incubation.The cytotoxicity of Exo-GEM against pancreatic cancer cells was stronger than free GEM and treatment with 0.02μM Exo-GEM significantly reduced the viability of both Panc-1 and MiaPaca-2 cells.Moreover,Exo-GEM enhanced the frequency of GEMinduced apoptosis in both cell lines.CONCLUSION Human bone marrow MSC-derived Exo-GEM have a potent cytotoxicity against human pancreatic cancer cells by enhancing their apoptosis,offering a promising drug delivery system for improving therapeutic outcomes.

Efficacy and safety of gemcitabine plus S-1 vs. gemcitabine plus nab-paclitaxel in treatment-na?ve advanced pancreatic ductal adenocarcinoma

Objective:Gemcitabine plus nab-paclitaxel(GnP)is the standard first-line therapy for advanced pancreatic ductal adenocarcinoma(PDAC).S-1,an oral fluoropyrimidine derivative,as compared with gemcitabine,is non-inferior in terms of overall survival(OS)and is associated with lower hematologic toxicity.Accordingly,S-1 is a convenient oral alternative treatment for advanced PDAC.This study was aimed at comparing the efficacy and safety of gemcitabine plus S-1(GS)vs.GnP as first-line chemotherapy for advanced PDAC.Methods:Patients with advanced PDAC who received first-line GS or GnP at the Peking Union Medical College Hospital between March 2011 and November 2022 were evaluated.Results:A total of 300 patients were assessed,of whom 84 received GS and 216 received GnP.The chemotherapy completion rate was higher with GS than GnP(50.0%vs.30.3%,P=0.0028).The objective response rate(ORR)was slightly higher(14.3%vs.9.7%,P=0.35),and the median OS was significantly longer(17.9 months vs.13.3 months,P=0.0078),in the GS group than the GnP group.However,the median progression-free survival(PFS)did not significantly differ between groups.Leukopenia risk was significantly lower in the GS group than the GnP group(14.9%vs.28.1%,P=0.049).Conclusions:As first-line chemotherapy for advanced PDAC,the GS regimen led to a significantly longer OS than the GnP regimen.The PFS,ORR,and incidence of severe adverse events were comparable between the GS and GnP groups.

Discussion on gemcitabine combined with targeted drugs in the treatment of pancreatic cancer

Pancreatic cancer is a malignant tumor with poor prognosis.The treatment of pancreatic cancer depends on the tumor stage and type,and includes local treatment(surgery,radiotherapy and ablation intervention)and systemic therapy(chemotherapy,targeted therapy and immunotherapy).We read with great interest the review“Effective combinations of anti-cancer and targeted drugs for pancreatic cancer treatment”published on World J Gastroenterol and intended to share some of our perspectives in pancreatic cancer treatment.This review presents the therapeutic effects of the combination of gemcitabine and targeted drugs,which gives us a deeper insight into the combination treatments for pancreatic cancer.

Treatment of Primary Liver Cancer with Postoperative After-Loading Radiotherapy and Gemcitabine

Objective： To evaluate the curative effectiveness of postoperative after-loading radiotherapy with the use of gemcitabine in 22 patients with primary liver cancer. Methods： From Oct. 1999 to Dec. 2001, 22 patients with primary liver cancer underwent postoperative after-loading radiotherapy 3-10 days after hepatectomy and chemotherapy using gemcitabine （1400 mg every week for 3 weeks, repeated after one week interval, total cycles were 6） and compared with 22 cases of sole hepatectomy. Three-six catheters were placed for irradiation after hepatectomy. The single-dose of after-loading radiotherapy was 10 Gy, 24 sessions per person. Results＇. The rate of AFP negative-reversion was 100% （17/17） in the treated group, higher than in control group （62.5%, 10/16, P〈0.05）. In the treated group, the 1-year relapse rate, metastasis rate and survival rate were 18.2% （4/22）, 0 and 100% （22/22） respectively, while in the control group they were 45.5% （10/22）, 13.6% （3/22） and 77.3% （17/22） respectively. There were significant differences between the two groups in relapse rate, metastasis rate and survival rate within a year （P〈0.05）. Conclusion： Postoperative after-loading radiotherapy with gemcitabine is an effective way for the treatment of primary liver cancer.

Treatment of Unresectable Carcinoma of Pancreas with ^(125)I Implantation and ^(125)I Plus Gemcitabine

Objective: To study the role of 125 I and 125 I plus gemcitabine (GEM) in treatment of unresectable carcinoma of pancreas. Methods: From April 2000 to April 2003, 38 untreated patients with locally advanced pancreatic cancer (LAPC) were collected and randomized into two groups: Arm A 125 I (18 patients) and Arm B 125 I+GEM (20 patients). Eligibility criteria were: cytologically and pathologically proven pancreatic carcinoma, Karnofsky performance status (kps) 60 80, age 18 75 years, adequate hematological, renal and liver function, and controllable pain. Arm A patients were treated with 125 I implants. Arm B patients started chemotherapy within 10 14 d post operatively following the implant procedure. Chemotherapy doses were as follows: GEM 1 000 mg/m 2 weekly × 3 followed by 1 week of rest for 3 cycles. In addition, all patients underwent laparotomy and surgical staging. The surgical procedures performed were biopsy, gastric bypass and biliary bypass. The total activity and number of seeds used were as recommended by Anderson. The mean activity, minimal peripheral dose (MPD), and volume of implants were 20 mCi, 14 000 cGy, and 53 cm 3, respectively. Results: Overall response rate (CR+PR) in Arm A was 37.6% and in Arm B it was 44.5% ( P >0.05). PR median duration in Arm A was 6.7 months and in Arm B it was 4.8 months ( P <0.05). Clinical benefit response was experienced by 11.7 % of Arm A compared with 42.1% of Arm B ( P <0.05). The incidences of hematological toxicity (such as neutropenia) between Arm A and Arm B were 5.8% and 21.1%, respectively ( P >0.05). The survival rates of 12 and 24 month were 32.5%, 16.3% for Arm A and 61%, 38.7% for Arm B ( P =0.04). The rate of complication of Arm A was lower than that of Arm B without statistical significance. Conclusion: To some extent, 125 I or 125 I plus GEM is able to lead to a moderate objective response for LAPC with obstructive jaundice on the base of biliary bypass or/and gastric bypass, but 125 I plus GEM is more effective than 125 I in improvement of the quality of life and survival rate in patients with LAPC.

Nedaplatin/Gemcitabine Versus Carboplatin/Gemcitabine in Treatment of Advanced Non-small Cell Lung Cancer: A Randomized Clinical Trial

Objective： To evaluate the efficacy and safety of nedaplatin/gemcitabine （NG） and carboplatin/gemcitabine （CG） in the management of untreated advanced non-small cell lung cancer （NSCLC）. Methods： Sixty-two patients with previously untreated advanced NSCLC were recruited between June 2006 and November 2007. Subjects were randomly assigned to the NG arm （n=30） and the CG arm （n=32）. Only patients （24 and 25 in the NG and CG arms, respectively） who completed 〉2 chemotherapy cycles were included in the data analysis. The primary outcome measure was the objective response rate （ORR）. The secondary outcome measures included progression-free survival （PFS）, overall survival （OS） and adverse events. Results： There were no statistically significant differences in the efficacy measures （ORR, P=0.305; median PFS, P=0.298, median OS, P=0.961） or in the major adverse events （grade 3/4 neutropenia, P=0.666; grade 3/4 anemia, P=0.263; grade 3/4 thrombocytopenia, P=0.222） between the two treatment arms. However, there was a trend towards higher ORR （37.5% vs. 24.0%）, longer PFS （6.0 vs. 5.0 months）, and less adverse events in the NG arm. Conclusion： NG regimen seems to be superior over CG regimen for advance NSCLS, but further investigation is needed to validate this superiority.

Combination treatment of inflammatory bowel disease:Present status and future perspectives

The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.

Oral chemotherapy for second-line treatment in patients with gemcitabine-refractory advanced pancreatic cancer

BACKGROUND There is no standard therapy for second-line treatment of gemcitabine-refractory pancreatic cancer patients with poor performance status.A combination of chemotherapy drugs 5-fluorouracil(5-FU),leucovorin,irinotecan,and oxaliplatin(FOLFIRINOX)or 5-fluorouracil/leucovorin plus nanoliposomal irinotecan can be considered as second-line treatment for such patients;however,due to toxicity,none of the regimens are recommended for patients with poor performance.Capecitabine or S-1 has relatively low toxicity and can be considered a treatment option for gemcitabine-refractory pancreatic cancer.AIM To investigate the efficacy and toxicity of oral chemotherapy as second-line treatment in patients with pancreatic cancer.METHODS Patients who had progressive disease after first-line gemcitabine-based chemotherapy were retrospectively analyzed between January 2011 and December 2018.They were treated with capecitabine or S-1 as the second-line treatment.Capecitabine was administered as a 2500 mg/m2 divided dose on days 1-14,followed by a 1-wk rest.S-1 was taken orally based on the patient’s body surface area for 28 d,followed by 2-wk of rest.Progression-free survival and overall survival were used to compare efficacy of capecitabine and S-1.RESULTS Of the 81 patients,41 were treated with capecitabine and 40 with S-1.The median time to treatment failure in both groups was 1.5 mo(P=0.425).The objective response rate was similar in the two groups:9.8%with capecitabine and 2.5%with S-1(P=0.359).Median progression-free survival was longer in the S-1 group than in the capecitabine group(S-12.7 mo,capecitabine 2.0 mo,P=0.003).There was no significant difference in the median overall survival between the capecitabine and S-1 groups(4.3 mo vs 5.0 mo,P=0.092).Grade 3 or 4 hand-foot syndrome was significantly more common in the capecitabine group than in the S-1 group(14.6%vs 0%,P=0.026).CONCLUSION Capecitabine or S-1 can be used as a second-line treatment for patients with advanced pancreatic cancer with poor performance status after progression to a gemcitabine-based regimen.

Working toward an integrated plasticity/network framework for repetitive transcranial magnetic stimulation to inform tailored treatments

Non-invasive brain stimulation techniques(NIBS),including repetitive transcranial magnetic stimulation(rTMS) and transcranial electric stim ulation(tES),are increasingly being adopted clinically for treatment of neuropsychiatric and neurological disorders,albeit with varying success.The rationale behind the use of NIBS has historically been that stim ulation techniques modulate neuronal activity in the targeted region and consequently induce plasticity which can lead to therapeutic outcomes.

N-gamboyl Gemcitabine Inhibits Tumor Cells Proliferation and Migration

Gambogic acid(GA) is a natural substance with a good antitumor effect, but it is too lipophilic to be metabolized and excreted, thus accumulating in the body. Gemcitabine(GEM), one of the first-line antitumor drugs, has high hydrophilicity, which greatly shortens its half-life in vivo. We previously reported a compound named N-gamboyl gemcitabine(GAG), derived from the condensation of GEM and GA, whose hydrophilicity is better than GA and stability is better than GEM. Here, the antitumor performance of GAG was investigated for the first time by using several common tumor cell lines as tumor models. The results of in vitro study showed that GAG significantly inhibited the proliferation and migration of the tumor cells. The IC50 values of GAG for the tumor cells were lower than those of GEM and GA. The present study suggests that GAG has a promising potential to be developed into a broad-spectrum antitumor drug.

Targeting mitochondrial transcription factor A sensitizes pancreatic cancer cell to gemcitabine

Background:The survival of pancreatic cancer cells,particularly cancer stem cells which are responsible for tumor relapse,depends on mitochondrial function.Mitochondrial transcription factor A(TFAM)is critical for the regulation of mitochondrial DNA and thus mitochondrial function.However,the possible involvement of TFAM in pancreatic cancer is unknown.Methods:Human samples were obtained from pancreatic cancers and their adjacent tissues;human pancreatic cell lines were cultured in RPMI1640 medium.TFAM expressions in pancreatic tissues and cultured cells were determined using immunohistochemistry,ELISA,and reverse transcription polymerase chain reaction(RT-PCR).The effect of TFAM on cell growth,migration,colony formation and apoptosis were evaluated.Mitochondrial biogenesis in pancreatic cancer and normal cells were examined.Results:The majority of pancreatic cancer tissues exhibited higher TFAM expression compared to the adjacent counterparts.Consistently,TFAM mRNA and protein levels were higher in pancreatic cancer cell lines than in immortalized normal pancreatic epithelial cells.There was no difference on TFAM level between gemcitabine-sensitive and resistant pancreatic cancer cells.Functional analysis demonstrated that TFAM overexpression activated pancreatic normal and tumor cells whereas TFAM inhibition effectively inhibited the growth of pancreatic cancer cells.TFAM inhibition enhanced gemcitabine’s cytotoxicity and suppressed growth,anchorage-independent colony formation and survival of gemcitabine-resistant pancreatic cancer cells.Mechanistic studies showed that TFAM inhibition resulted in remarkable mitochondrial dysfunction and energy crisis followed by oxidative stress.The basal mitochondrial biogenesis level correlated well with TFAM level in pancreatic cancer cells.Conclusions:TFAM played essential roles in pancreatic cancer via regulating mitochondrial functions which highlighted the therapeutic value of inhibiting TFAM to overcome gemcitabine resistance.

Gut flora in multiple sclerosis:implications for pathogenesis and treatment

Multiple sclerosis is an inflammatory disorder chara cterized by inflammation,demyelination,and neurodegeneration in the central nervous system.Although current first-line therapies can help manage symptoms and slow down disease progression,there is no cure for multiple sclerosis.The gut-brain axis refers to complex communications between the gut flo ra and the immune,nervous,and endocrine systems,which bridges the functions of the gut and the brain.Disruptions in the gut flora,termed dys biosis,can lead to systemic inflammation,leaky gut syndrome,and increased susceptibility to infections.The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors,and gut flora may play a pivotal role in regulating immune responses related to multiple scle rosis.To develop more effective therapies for multiple scle rosis,we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis.This review provides an overview of the role of the gut flora in multiple scle rosis.

Influence of heat treatment on microstructure,mechanical and corrosion behavior of WE43 alloy fabricated by laser-beam powder bed fusion

Magnesium(Mg)alloys are considered to be a new generation of revolutionary medical metals.Laser-beam powder bed fusion(PBF-LB)is suitable for fabricating metal implants withpersonalized and complicated structures.However,the as-built part usually exhibits undesirable microstructure and unsatisfactory performance.In this work,WE43 parts were firstly fabricated by PBF-LB and then subjected to heat treatment.Although a high densification rate of 99.91%was achieved using suitable processes,the as-built parts exhibited anisotropic and layeredmicrostructure with heterogeneously precipitated Nd-rich intermetallic.After heat treatment,fine and nano-scaled Mg24Y5particles were precipitated.Meanwhile,theα-Mg grainsunderwent recrystallization and turned coarsened slightly,which effectively weakened thetexture intensity and reduced the anisotropy.As a consequence,the yield strength and ultimate tensile strength were significantly improved to(250.2±3.5)MPa and(312±3.7)MPa,respectively,while the elongation was still maintained at a high level of 15.2%.Furthermore,the homogenized microstructure reduced the tendency of localized corrosion and favoredthe development of uniform passivation film.Thus,the degradation rate of WE43 parts was decreased by an order of magnitude.Besides,in-vitro cell experiments proved their favorable biocompatibility.

Prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections

Osteomyelitis is a devastating disease caused by microbial infection in deep bone tissue.Its high recurrence rate and impaired restoration of bone deficiencies are major challenges in treatment.Microbes have evolved numerous mechanisms to effectively evade host intrinsic and adaptive immune attacks to persistently localize in the host,such as drug-resistant bacteria,biofilms,persister cells,intracellular bacteria,and small colony variants(SCVs).Moreover,microbial-mediated dysregulation of the bone immune microenvironment impedes the bone regeneration process,leading to impaired bone defect repair.Despite advances in surgical strategies and drug applications for the treatment of bone infections within the last decade,challenges remain in clinical management.The development and application of tissue engineering materials have provided new strategies for the treatment of bone infections,but a comprehensive review of their research progress is lacking.This review discusses the critical pathogenic mechanisms of microbes in the skeletal system and their immunomodulatory effects on bone regeneration,and highlights the prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections.It will inform the development and translation of antimicrobial and bone repair tissue engineering materials for the management of bone infections.

FOLFIRINOX vs gemcitabine/nab-paclitaxel for treatment of metastatic pancreatic cancer: Single-center cohort study

BACKGROUND FOLFIRINOX and gemcitabine plus nab-paclitaxel(Gem+nabPTX)were recently introduced for metastatic pancreatic cancer treatment.However,studies that compared these two regimens and studies in Asian populations are lacking.AIM To compare the treatment outcomes of FOLFIRINOX and Gem+nabPTX regimen for metastatic pancreatic cancer treatment in Korean population.METHODS Patients with metastatic or recurrent pancreatic cancer treated with FOLFIRINOX(n=86)or Gem+nabPTX(n=81)as the first-line since January 2015 were identified using the Severance Hospital Pancreatic Cancer Cohort Registry.Treatment efficacy,treatment-related adverse events and economic aspects were compared.RESULTS Patients in the FOLFIRINOX group were significantly younger(54 vs 65 years;P<0.001)and had better performance statuses at diagnosis.The median overall survival(10.7 vs 12.1 mo;P=0.157),progression-free survival(8.0 vs 8.4 mo;P=0.134),and objective response rates(33.7%vs 46.9%;P=0.067)were not significantly different when compared with Gem+nabPTX group.Grade≥3 neutropenia and gastrointestinal adverse events were more common in the FOLFIRINOX group.The drug costs of both regimens were similar.CONCLUSION Treatment efficacy and economic burdens were comparable between the two regimens.But,the details of adverse event were different.Gem+nabPTX regimen might be considered preferentially in certain conditions.

Nuclear PLD1 combined with NPM1 induces gemcitabine resistance through tumorigenic IL7R in pancreatic adenocarcinoma

Objective:Pancreatic ductal adenocarcinoma(PDAC)is a highly malignant gastrointestinal cancer with a 5-year survival rate of only 9%.Of PDAC patients,15%-20%are eligible for radical surgery.Gemcitabine is an important chemotherapeutic agent for patients with PDAC;however,the efficacy of gemcitabine is limited due to resistance.Therefore,reducing gemcitabine resistance is essential for improving survival of patients with PDAC.Identifying the key target that determines gemcitabine resistance in PDAC and reversing gemcitabine resistance using target inhibitors in combination with gemcitabine are crucial steps in the quest to improve survival prognosis in patients with PDAC.Methods:We constructed a human genome-wide CRISPRa/dCas 9 overexpression library in PDAC cell lines to screen key targets of drug resistance based on sgRNA abundance and enrichment.Then,co-IP,ChIP,ChIP-seq,transcriptome sequencing,and qPCR were used to determine the specific mechanism by which phospholipase D1(PLD1)confers resistance to gemcitabine.Results:PLD1 combines with nucleophosmin 1(NPM1)and triggers NPM1 nuclear translocation,where NPM1 acts as a transcription factor to upregulate interleukin 7 receptor(IL7R)expression.Upon interleukin 7(IL-7)binding,IL7R activates the JAK1/STAT5 signaling pathway to increase the expression of the anti-apoptotic protein,BCL-2,and induce gemcitabine resistance.The PLD1 inhibitor,Vu0155069,targets PLD1 to induce apoptosis in gemcitabine-resistant PDAC cells.Conclusions:PLD1 is an enzyme that has a critical role in PDAC-associated gemcitabine resistance through a non-enzymatic interaction with NPM1,further promoting the downstream JAK1/STAT5/Bcl-2 pathway.Inhibiting any of the participants of this pathway can increase gemcitabine sensitivity.

Clinical observation of gemcitabine and concomitant three-dimensional conformal radiotherapy in the treatment of locally advanced non-small cell lung cancer

Objective： To evaluate the clinical effect of gemcitabine and concurrent three-dimensional conformal radiation therapy （3D-CRT） for locally advanced non-small cell lung cancer （NSCLC）. Methods： From April 2002 to June 2005, 38 patients with inoperable stage Ⅲ NSCLC were treated with gemcitabine and 3D-CRT simultaneously. Chemotherapy consisted of intravenously gemcitabine 350 mg/m^2 on days 1, 8, 15, 22, 29, 36.3D-CRT was delivered up to a total dose of 60-64 Gy with a 2.0 Gy dose fraction per day, 5 days per week. Results： The overall response rates of primary tumor and mediastinum metastatic node were 86.8% （33/38） and 90.6% （29/32） respectively, and 91.7% （22/24） and 78.6% （11/14） for squamous cell carcinoma and adenocarcinoma respectively. The acute side effects of patients were mostly myelosuppression, nausea, vomiting, radiation-induced esophagitis and pneumonitis （RTOG 1/11）, however, all of them were cured. Conclusion： Concurrent application of gemcitabine and 3D-CRT can improve the overall response rate for locally advanced NSCLC without aggravating the side effects.

Epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China:a hospital-based retrospective study

Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national level.We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program.The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent surgery.Only 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 hours.The total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 hours,which is associated with improved sensorimotor recovery,increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.

Gemcitabine-induced peripheral vascular disease and prolonged response in a patient with metastatic pancreatic adenocarcinoma:A case report

BACKGROUND Gemcitabine is an antimetabolite used in the treatment of pancreatic cancer.One of the side effects of gemcitabine is vascular toxicity.Here,we report the case of a patient treated with gemcitabine who had peripheral vascular disease concomi-tant with a prolonged antitumor response.CASE SUMMARY A 75-year-old man was diagnosed with locally recurrent pancreatic cancer.Partial response was achieved after 9 mo of gemcitabine.At the same time,the patient reported peripheral vascular disease without necrosis.Chemotherapy was suspended,and after one month the Positron Emission Tomography(PET)scan showed locoregional tumor recurrence.Gemcitabine was resumed and partial response was obtained,but peripheral vascular disease occurred.CONCLUSION Our results suggest that the appearance of peripheral vascular disease may be related to a prolonged response to gemcitabine.

Circular RNAs in breast cancer diagnosis,treatment and prognosis

Breast cancer has surpassed lung cancer to become the most common malignancy worldwide.The incidence rate and mortality rate of breast cancer continue to rise,which leads to a great burden on public health.Circular RNAs(circRNAs),a new class of noncoding RNAs(ncRNAs),have been recognized as important oncogenes or suppressors in regulating cancer initiation and progression.In breast cancer,circRNAs have significant roles in tumorigenesis,recurrence and multidrug resistance that are mediated by various mechanisms.Therefore,circRNAs may serve as promising targets of therapeutic strategies for breast cancer management.This study reviews the most recent studies about the biosynthesis and characteristics of circRNAs in diagnosis,treatment and prognosis evaluation,as well as the value of circRNAs in clinical applications as biomarkers or therapeutic targets in breast cancer.Understanding the mechanisms by which circRNAs function could help transform basic research into clinical applications and facilitate the development of novel circRNA-based therapeutic strategies for breast cancer treatment.