To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.

Purpose: Colorectal cancer (CRC) often spreads to the liver, necessitating surgical treatment for CRC liver metastasis (CRLM). Iron-deficiency anemia is common in CRC patients and is associated with fatigue and weakness. This study investigated the effects of iron-deficiency anemia on the outcomes of surgical resection of CRLM. Methods: This population-based, retrospective study evaluated data from adults ≥20 years old with CRLM who underwent hepatic resection. All patient data were extracted from the 2005–2018 US National (Nationwide) Inpatient Sample (NIS) database. The outcome measures were in-hospital outcomes including 30-day mortality, unfavorable discharge, and prolonged length of hospital stay (LOS), and short-term complications such as bleeding and infection. Associations between iron-deficiency anemia and outcomes were determined using logistic regression analysis. Results: Data from 7,749 patients (representing 37,923 persons in the United States after weighting) were analyzed. Multivariable analysis revealed that iron-deficiency anemia was significantly associated with an increased risk of prolonged LOS (adjusted odds ratio [aOR], 2.76; 95% confidence interval [CI], 2.30–3.30), unfavorable discharge (aOR, 2.42; 95% CI, 1.83–3.19), bleeding (aOR, 5.05; 95% CI, 2.92–8.74), sepsis (aOR, 1.60; 95% CI, 1.04–2.46), pneumonia (aOR, 2.54; 95% CI, 1.72–3.74), and acute kidney injury (aOR, 1.71; 95% CI, 1.24–2.35). Subgroup analyses revealed consistent associations between iron-deficiency anemia and prolonged LOS across age, sex, and obesity status categories. Conclusion In patients undergoing hepatic resection for CRLM, iron-deficiency anemia is an independent risk factor for prolonged LOS, unfavorable discharge, and several critical postoperative complications. These findings underscore the need for proactive anemia management to optimize surgical outcomes.

Purpose: Colorectal cancer (CRC) often spreads to the liver, necessitating surgical treatment for CRC liver metastasis (CRLM). Iron-deficiency anemia is common in CRC patients and is associated with fatigue and weakness. This study investigated the effects of iron-deficiency anemia on the outcomes of surgical resection of CRLM. Methods: This population-based, retrospective study evaluated data from adults ≥20 years old with CRLM who underwent hepatic resection. All patient data were extracted from the 2005–2018 US National (Nationwide) Inpatient Sample (NIS) database. The outcome measures were in-hospital outcomes including 30-day mortality, unfavorable discharge, and prolonged length of hospital stay (LOS), and short-term complications such as bleeding and infection. Associations between iron-deficiency anemia and outcomes were determined using logistic regression analysis. Results: Data from 7,749 patients (representing 37,923 persons in the United States after weighting) were analyzed. Multivariable analysis revealed that iron-deficiency anemia was significantly associated with an increased risk of prolonged LOS (adjusted odds ratio [aOR], 2.76; 95% confidence interval [CI], 2.30–3.30), unfavorable discharge (aOR, 2.42; 95% CI, 1.83–3.19), bleeding (aOR, 5.05; 95% CI, 2.92–8.74), sepsis (aOR, 1.60; 95% CI, 1.04–2.46), pneumonia (aOR, 2.54; 95% CI, 1.72–3.74), and acute kidney injury (aOR, 1.71; 95% CI, 1.24–2.35). Subgroup analyses revealed consistent associations between iron-deficiency anemia and prolonged LOS across age, sex, and obesity status categories. Conclusion In patients undergoing hepatic resection for CRLM, iron-deficiency anemia is an independent risk factor for prolonged LOS, unfavorable discharge, and several critical postoperative complications. These findings underscore the need for proactive anemia management to optimize surgical outcomes.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

Objective To investigate the efficacy of preprocedural intracoronary injections of adenosine and sodium nitroprusside in patients with intravascular ultrasound-attenuated plaques(AP).Methods In total,200 patients with AP detected using intravascular ultrasound(IVUS)at Shijiazhuang People's Hospital from January 1,2022,to January 1,2024,were selected and randomly divided into conventional treatment and pretreatment groups,with 100 patients in each group.The conventional treatment group underwent standard percutaneous coronary intervention(PCI)procedures,whereas the pretreatment group underwent intracoronary injection of sodium nitro-prusside and adenosine through a guiding catheter prior to PCI.The observation parameters included intraoperative no-reflow(NR)inci-dence,post-PCI TIMI myocardial perfusion frame count(TMPFC),perioperative myocardial infarction(PMN),and 6-month major adverse cardiac and cerebrovascular events(MACCE).Results The pretreatment group exhibited a significantly lower intraoperative NR inci-dence,reduced postoperative TMPFC,and attenuated PMN severity than the conventional treatment group(P＜0.05).Conclusion Pre-procedural intracoronary administration of adenosine and sodium nitroprusside through a guiding catheter can effectively reduce PCI-re-lated NR occurrence,improve post-PCI TMPFC,and mitigate PMN in patients with AP,although no significant improvement in MACCE incidence can be observed at the 6-month follow-up.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective To explore the clinical,radiological,and arthroscopic outcomes of anterior cru-ciate ligament(ACL)reconstruction combined with posterior tibial slope(PTS)reducing osteotomy in patients with increased PTS and excessive anterior tibial subluxation(ATS)due to primary ACL inju-ry.Methods This retrospective study included patients who underwent ACL reconstruction between 2016 and 2022 in our department.The inclusion criteria were PTS≥15° and ATS≥6 mm,and all pa-tients received ACL reconstruction combined with PTS reducing osteotomy with a follow-up of more than 2 years.Before and after the operation,they were assessed KT-1000 side-to-side difference(KT SSD),pivot shift grade,Lachman test,anterior tibial subluxation of the medial and lateral compart-ments(ASMC and ASLC),magnetic resonance imaging(MRI),and arthroscopic findings of associat-ed injuries.Moreover,graft laxity was defined as graft laxity observed on MRI or arthroscopy,KT SSD>3 mm,or pivot>1+,while graft failure was defined as graft rupture on MRI or arthroscopy,KT SSD>5 mm,or pivot>2+.Meanwhile,clinical outcomes were compared preoperatively and post-operatively,and graft status and associated injuries were described.Results A total of 30 patients were included,with an average age of 31 years,and 23%of female.The inter-observer reliability for mea-surements of PTS and ATS was greater than 0.80.Compared to preoperative values,postoperative PTS(18.2° vs.6.8°,P<0.001),KT SSD(7.8 mm vs.1.2 mm,P<0.001),ASLC(7.5 mm vs.4.5 mm,P=0.002),and ASMC(5.0 mm vs.2.7 mm,P=0.034),all showed significant improvements.In addi-tion,the proportion of patients with postoperative pivot grade of 2+to 3+(73.3%vs.6.7%,P<0.001)and Lachman grades Ⅱ-Ⅲ(70%vs.3.3%,P<0.001)reduced significantly.At the last follow-up,the incidence of graft laxity was 20%,and that of the graft failure was 13.3%.Among all pa-tients,1 patient(3.3%)had graft roof impingement or cyclops lesion,and 3(10%)suffered from concomitant cartilage injury,with 4(13.3%)undergoing intercondylar notchplasty due to intercondylar notch hyperplasia.However,no complications related to osteotomy,such as infection,non-union,or fixation failure,were observed.Conclusion Over a follow-up period of at least 2 years,for primary ACL injury patients with steep PTS and excessive ATS,combined ACL reconstruction with PTS reduc-ing osteotomy improves knee stability,but significantly reduces PTS,the incidence of severe pivot grade,anterior tibial subluxation in both medial and lateral compartments,and delays the occurrence of graft laxity and failure.

Objective:To construct a triple pre-rehabilitation intervention program for patients undergoing radical prostatectomy, to provide a basis for promoting pre-rehabilitation in patients undergoing radical prostatectomy.Methods:Literature analysis was used to search domestic and foreign databases such as China National Knowledge Infrastructure, Wanfang, PubMed, etc, on triple pre-rehabilitation and rapid rehabilitation of patients undergoing radical prostatectomy, with a search time frame from January 1, 2013 to December 31, 2023. The Delphi expert letter consultation was conducted later, and the final draft of the triple pre-rehabilitation intervention program for patients with radical prostatectomy was finally formed.Results:A total of 20 experts completed 2 rounds of inquiries, all were female, with an age of (40.85 ± 5.40) years old. The response rates for the 2 rounds of expert inquiries were both 100%(20/20). The authority coefficients of the experts were 0.87 and 0.90, respectively. Kendall coordination coefficients were 0.11 and 0.21, respectively. The coefficient of variation for each item in the second round of inquiries ranged from 0 to 0.15. The triple pre-rehabilitation intervention program for patients with radical resection of prostate cancer was constructed, including 4 primary indexes, 8 secondary indexes and 25 tertiary indexes.Conclusions:It is scientific, targeted and feasible to construct a triple pre-rehabilitation intervention program for patients undergoing radical prostatectomy based on Delphi method, which can provide clinical basis for pre-rehabilitation of elderly patients undergoing prostate cancer surgery.

In proton therapy,prompt gamma-ray imaging is considered as one of the most promising methods for assessing proton beam range.Prompt gamma-ray imaging detector evaluates the proton beam range based on the prompt gamma-ray distribution obtained by the prompt gamma-ray imaging system,which enables high-precision measurement of the proton beam range.Herein a proton beam range verification algorithm is designed for the newly developed prototype of the range verification detector(pixelated prompt gamma-ray imaging detector),which verifies the range estimation accuracy of the prototype for different phantoms and different energies of homogeneous media through Monte Carlo simulation.The results show that the accuracy of the proton beam range verification algorithm is within 0.5 mm of the safety margin error of the Bragg peak,and the measurement accuracy is significantly improved with the increase of the number of protons,indicating that the prototype algorithm is feasible for proton beam range verification.

Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.