AIM: To investigate and clarify the intervention mechanism of trigonelline(TRG)in preventing ferroptosis in ARPE-19 cells based on the Nrf2/HO-1/GPX4 pathway.METHODS: The ARPE-19 cells were cultured and subsequently treated with varying concentrations of trigonelline to ascertain the most effective concentration for modulating the cells. Then the cells were categorized into distinct groups, including normal control(NC)group, high glucose(HG)group, Fer-1 group, TRG group based on the determined concentration. Samples from each group were then gathered to assess relevant indicators. The intracellular levels of glutathione(GSH), malondialdehyde(MDA), and Ferrion were quantified in accordance with the protocols provided by the GSH, MDA, and Ferrion detection kits. Flow cytometry was employed to measure the ROS levels within each group. Additionally, Western blot analysis was conducted to examine the expression of nuclear factor erythroid 2-related factor 2(Nrf2), heme oxygenase-1(HO-1), glutathione peroxidase(GPX4), and acyl-CoA synthetase long-chain family member 4(ACSL4)across the different groups.RESULTS: The preconditioning intervention with 40 μg/mL TRG effectively mitigated the decline in cell activity induced by high glucose levels. The levels of reactive oxygen species(ROS)and MDA in the HG group were markedly elevated compared to the NC group; and the TRG group exhibited significantly reduced levels of ROS and MDA compared to those of the HG group, with the antioxidant stress index GSH showing opposite trends to those of ROS and MDA across all the groups. Whereas the Fer-1 and TRG groups showed decreased expression levels of ACSL4 protein and iron ions, and the expression levels of Nrf2, HO-1 and GPX4 in the Fer-1 and TRG groups were increased.CONCLUSION: TRG protects ARPE-19 cells from the detrimental effects of high glucose by targeting the Nrf2/HO-1/GPX4 signaling pathway to counter ferroptosis.

BACKGROUND:Streptococcus mutans is an important pathogen of dental caries,and timely detection of its levels is of great significance for early detection and treatment of dental caries. OBJECTIVE:To evaluate the effect of loop-mediated isothermal amplification(FTA-LAMP)direct extraction of Streptococcus mutans DNA. METHODS:(1)Bacterial suspensions containing ATCC standard strains(Streptococcus mutans)were prepared and inoculated into the brain-heart leachate medium.After mixed thoroughly,the mixture was then diluted in a 10-fold gradient into seven concentrations(4.2×107,4.2×106,4.2×105,4.2×104,4.2×103,4.2×102,4.2×10 CFU/mL),two parallel controls were made for each dilution level,and sterile water was used as a blank control.(2)The DNA of Streptococcus mutans was extracted using FTA Elute card,boiling method,kit extraction and lysate extraction methods separately and then amplified using LAMP technology was amplified.A specificity test was also performed to compare the differences between the four DNA extraction methods.RESULTS AND CONCLUSION:The DNA extracted by all four methods met the requirements for LAMP amplification.Specificity test results showed that only Streptococcus mutans could specifically amplify the target gene.The detection limit value of the DNA concentration was 4.2×103 CFU/mL for the lysate method,4.2×104 CFU/mL for the FTA Elute card extraction method,4.2×106 CFU/mL for the kit extraction method,and 4.2×107 CFU/mL for the boiling method.In the other aspects of the four extraction methods,the kit extraction method had the highest experimental cost,number of steps and time;the other three methods had the same number of steps,with the FTA Elute card method requiring the least amount of instruments,the boiling method having the lowest single cost,and the lysate extraction method taking the least amount of time.Only a small amount of bacteria were needed for successful extraction using both the FTA Elute card and lysate extraction methods.Compared with the FTA Elute card method,the lysate extraction method was superior in terms of time,but it had a high single cost and required more equipment.To conclude,the FTA-LAMP technology established in this study has the advantages of ease of operation,high specificity,high sensitivity,and visualization,which is expected to be a new way for efficient extraction and detection of Streptococcus mutans.

BACKGROUND:The plantarflexor weakness is a common muscle defect in patients with spastic cerebral palsy and Charcot-Marie-Tooth,which clinically manifests abnormal gaits,and the relationship between plantarflexor weakness and abnormal gaits is unclear. OBJECTIVE:To explore the biomechanical behavior of the lower limb under the action of a single factor of plantarflexor weakness to reveal the mechanism of abnormal gait induced by plantarflexor weakness and to provide guidance for the rehabilitation training of patients with plantarflexor weakness. METHODS:A predictive framework of musculoskeletal multibody dynamics in the sagittal plane was established based on OpenSim Moco to predict lower limb joint angles and muscle activation changes during walking in normal subjects.The validity of the framework was verified by combining the inverse kinematics and electromyogram activation time of the experimental data.Reduced isometric muscle forces were used to model plantarflexor weakness and to compare predicted lower extremity joint angles,joint moments,and muscle energy expenditure with normal subjects to analyze the effects of plantarflexor weakness on lower extremity biomechanics. RESULTS AND CONCLUSION:(1)The Moco-based prediction framework realistically predicted the biomechanical changes of the lower limbs during walking in normal subjects(joint angles:normalized correlation coefficient≥0.73,root mean square error≤7.10°).(2)The musculoskeletal model used a small stride support phase to increase the"heel-walking"gait during plantarflexor weakness.When the plantarflexor weakness reached 80%,the muscle energy expenditure was 5.691 4 J/kg/m,and the maximum activation levels of the gastrocnemius and soleus muscles were 0.72 and 0.53,which might cause the plantarflexor weakness patients to be more prone to fatigue when walking.(3)Muscle energy expenditure was significantly higher when the weakness of plantarflexors exceeded 40%,and the joint angles and moments of the lower limbs deteriorated significantly when the weakness of plantarflexors exceeded 60%,suggesting that there may be a"threshold"for the effect of plantarflexor weakness on gait,which may correspond to the point at which health care professionals should intervene in the clinical setting.

BACKGROUND: The FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial demonstrated that percutaneous coronary intervention (PCI) lesion selection using quantitative flow ratio (QFR) measurement, a novel angiography-based approach for estimating fractional flow reserve, improved two-year clinical outcomes compared with standard angiography guidance. This study aimed to assess the cost-effectiveness of QFR-guided PCI from the perspective of the current Chinese healthcare system. METHODS: This study is a pre-specified analysis of the FAVOR III China trial, which included 3825 patients randomized between December 25, 2018, and January 19, 2020, from 26 centers in China. Patients with stable or unstable angina pectoris or those ≥72 hours post-myocardial infarction who had at least one lesion with a diameter stenosis between 50% and 90% in a coronary artery with a ≥2.5 mm reference vessel diameter by visual assessment were randomized to a QFR-guided strategy or an angiography-guided strategy with 1:1 ratio. During the two-year follow-up, data were collected on clinical outcomes, quality-adjusted life-years (QALYs), estimated costs of index procedure hospitalization, outpatient cardiovascular medication use, and rehospitalization due to major adverse cardiac and cerebrovascular events (MACCE). The primary analysis calculated the incremental cost-effectiveness ratio (ICER) as the cost per MACCE avoided. An ICER of ¥10,000/MACCE event avoided was considered economically attractive in China. RESULTS: At two years, the QFR-guided group demonstrated a reduced rate of MACCE compared to the angiography-guided group (10.8% vs . 14.7%, P <0.01). Total two-year costs were similar between the groups (¥50,803 ± 21,121 vs . ¥50,685 ± 23,495, P = 0.87). The ICER for the QFR-guided strategy was ¥3055 per MACCE avoided, and the probability of QFR being economically attractive was 64% at a willingness-to-pay threshold of ¥10,000/MACCE avoided. Sensitivity analysis showed that QFR-guided PCI would become cost-saving if the cost of QFR were below ¥3682 (current cost: ¥3800). Cost-utility analysis yielded an ICER of ¥56,163 per QALY gained, with a 53% probability of being cost-effective at a willingness-to-pay threshold of ¥85,000 per QALY gained. CONCLUSION: In patients undergoing PCI, a QFR-guided strategy appears economically attractive compared to angiographic guidance from the perspective of the Chinese healthcare system. TRIAL REGISTRATION ClinicalTrials.gov , NCT03656848.
Humans ; Cost-Benefit Analysis ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Angiography/methods* ; Middle Aged ; Aged ; Coronary Artery Disease/surgery* ; Quality-Adjusted Life Years ; Fractional Flow Reserve, Myocardial/physiology*

Objective:To investigate the efficacy of computed tomographic angiography (CTA) three-dimensional reconstruction technology in the repair of limb wounds using free double-leaf anterolateral thigh perforator flaps.Methods:A retrospective analysis was conducted on 30 patients with varying degrees of skin damage on their limbs who were admitted to the Hand and Foot Surgery Department of Yiwu Central Hospital in Zhejiang Province and Zhejiang Provincial People's Hospital from January 2015 to March 2022. The patients were divided into observation group ( n=15) and control group ( n=15) based on whether CTA three-dimensional reconstruction was performed preoperatively. In the observation group, CTA three-dimensional reconstruction was performed preoperatively, including 9 males and 6 females, aged 17-67 (49.7±4.2) years. In the control group, handheld Doppler ultrasound angiography was performed preoperatively, including 10 males and 5 females, aged 20-69 (50.4±5.0) years. Relevant intraoperative and postoperative indicators were compared between the two groups, including operation duration, anesthesia recovery time, blood loss, perforator localization accuracy, vascular anastomosis rate between the donor and recipient sites, flap harvesting time, flap survival rate, and incidence of adverse reactions. Follow-up visits were conducted via telephone or outpatient clinic for 3 months postoperatively, with one visit per month, to assess patient satisfaction rates. A multi-criteria decision-making model was established, and the benefit values, risk values, and stability of the decision-making model were evaluated for both groups. Results:Compared with the control group, the observation group had significantly reduced operation duration, anesthesia recovery time, blood loss, and flap harvesting time (all P<0.05). The patient satisfaction rate, perforator localization accuracy, and vascular anastomosis rate between the donor and recipient sites were significantly better in the observation group than in the control group (all P<0.05). The incidence of adverse reactions was 13.3% (2/15) in the observation group, which was lower than 53.3% (8/15) in the control group ( P=0.020). Among the benefit indicators, the vascular anastomosis rate between the donor and recipient sites and flap survival rate had the greatest impact on treatment outcomes. Among the risk indicators, venous crisis and flap necrosis had a greater impact. The benefit-risk value was 77 in the observation group and 56 in the control group, with a difference of 21 (95% CI: 14-26) between the two groups. The observation group had higher values than the control group within the range of 0-100% relative risk weight, indicating good stability of the multi-criteria decision-making evaluation model. Conclusion:CTA three-dimensional reconstruction technology can improve the vascular anastomosis rate between the donor and recipient sites and patient satisfaction rates in the repair of limb wounds using free double-leaf anterolateral thigh perforator flaps.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective:To analyze the time to reach full enteral feedings (TFEF) among preterm infants with gestational age (GA)<32 weeks admitted to the neonatal intensive care unit (NICU) of Chinese Neonatal Network (CHNN).Methods:This was a retrospective analysis based on the database from the CHNN 89 participating centers between January 1 st, 2019 and December 31 st, 2022. All 16 155 preterm infants with a GA <32 weeks and a birth weight <1 500 g, admitted to the NICU within 24 h after birth, hospitalization for at least 7 d and achieved full enteral feedings before discharge were included. According to the birth weight, these infants were divided into extremely low birth weight (ELBW) group and very low birth weight (VLBW) group. The practice characteristics of TFEF across different GA, the severity of neonatal admission, the NICU interventions before reaching full enteral feeding, and relevant neonatal diseases were described. Mann-Whitney U tests or Kruskal-Wallis H tests was used for comparison between groups. Results:Among the 16 155 preterm infants with a GA <32 weeks, 8 505 case (52.6%) were male. The TFEF in 3 374 cases of ELBW groups was 32 (22, 46) d, 351 cases (10.4%) with TFEF ≤2 weeks, 1 050 cases (31.1%) with TFEF >2-4 weeks, 964 cases (28.6%) with TFEF >4-6 weeks, and 1 009 cases (29.9%) with TFEF >6 weeks. The TFEF in 12 781 cases of VLBW group was 22 (15, 32) d, 439 cases (3.4%) with TFEF ≤1 week, 2 565 cases (20.1%) with TFEF >1-2 weeks, 5 526 cases (43.2%) with TFEF >2-4 weeks, and 4 251 cases (33.3%) with TFEF >4 weeks. The TFEF was 36(23, 52) d of 625 preterm infants at a GA ≤25 weeks and 20 (13, 28) d of 2 606 preterm infants at a GA 31 weeks. Inborn infants had a shorter TFEF than those outborn infants and the infants with breast-fed achieved shorter than formula and mixed feeding both in ELBW and VLBW groups (all P<0.001). The earlier enteral feeding started, the shorter TFEF will be both in ELBW and VLBW groups (both P<0.001). The TFEF of preterm infants who were treated before full enteral feeding like peripherally inserted central catheters, and blood transfusions and blood product providers were all longer than those who were not treated (all P<0.001). The TFEF of preterm infants with complications like hemodynamically significant patent ductus arteriosus, necrotizing enterocolitis, late onset sepsis, severe retinopathy of prematurity and bronchopulmonary dysplasia were all longer than those without (all P<0.001). Conclusions:The distribution of TFEF in VLBW and ELBW has a large difference. The TFEF of preterm infants varies with different GA, treatment measures and complications. Further quality improvement is required to shorten TFEF.

Objective:To investigate the treatment strategies for vesicovaginal fistula（VVF）in women following cervical cancer radiotherapy.Methods:A retrospective analysis was performed on the clinical data of 33 female patients with post-radiotherapy VVF after cervical cancer treatment at Shanghai Sixth People’s Hospital between January 2020 and June 2024. The patients were categorized into three groups based on surgical approaches：Group A（11 patients）：Underwent prone-position VVF repair. Mean age：（50.0±9.6）years；mean radiotherapy sessions：（22.6±2.2）. All had simple VVF without concurrent intestinal or surrounding soft-tissue fistulas. Among them，1 patient previously received laparoscopic VVF repair，1 transvaginal VVF repair，and 2 gracilis muscle flap packing for VVF repair. One month prior to surgery，the average daily usage of urine pads was 16.7（12.8，25.7）pieces，and the quality of life（QOL）score stood at 4.0（4.0，5.0）points. Preoperative cystoscopy revealed that 8 cases had fistulas located in the trigonal region of the bladder，while 3 cases had fistulas on the posterior bladder wall. The diameter of the fistula openings，measured under a microscope，was 1.2（0.8，1.6）cm. Based on the Goh classification criteria for vesicovaginal fistulas，this group included 3 cases of type 1，4 cases of type 2，2 cases of type 3，and 2 cases of type 4；7 cases of type A and 4 cases of type B；as well as 3 cases of typeⅠ，7 cases of type Ⅱ，and 1 case of type Ⅲ.Group B（20 patients）：Underwent gracilis muscle flap packing for VVF repair. Mean age：（58.6±8.8）years；mean radiotherapy sessions：（29.8±3.9）. Three patients had concurrent rectovaginal fistulas and received colostomy for fecal diversion. History of previous interventions：3 had laparoscopic VVF repair，4 transvaginal VVF repair，and 1 both transvaginal and laparoscopic VVF repair. One month prior to surgery，the average daily usage of urine pads was 19.7（15.8，27.7）pieces，and the QOL score stood at 5.0（5.0，6.0）points. Preoperative cystoscopy revealed that 13 cases had fistulas located in the trigonal region of the bladder，while 7 cases had fistulas on the posterior bladder wall. The diameter of the fistula openings，measured under a microscope，was 1.8（1.0，3.2）cm. Based on the Goh classification criteria for vesicovaginal fistulas，this group included 4 cases of type 1，9 cases of type 2，3 cases of type 3，and 4 cases of type 4；6 cases of type A，11 cases of type B and 3 cases of type C；as well as 1 cases of type Ⅱ，and 19 case of type Ⅲ. Group C（2 patients）：Underwent ureterocutaneous diversion. Ages：67 and 73 years；radiotherapy sessions：51 and 60，respectively. Both had concurrent rectovaginal fistulas and bladder soft-tissue fistulas. The patient presented with recurrent thigh abscesses accompanied by fever. One month prior to surgery，the daily usage of urine pads was 29 and 23 pieces，respectively，and the QOL score was 6 points. Cystoscopic examination revealed that the vesicovaginal fistulas were located in the trigone of the bladder，with diameters of 3 cm and 4 cm，respectively. Additionally，partial defects were noted in the ventral wall of the urethra，while no bladder soft tissue fistulas were detected. According to the Goh classification for vesicovaginal fistulas，both cases were categorized as type 4，type C，and type Ⅲ. For Groups A and B，urinary catheters were indwelled for 3 weeks postoperatively，then removed to assess spontaneous urination and incontinence. QOL was evaluated，with a minimum 6-month follow-up. For confirmed postoperative VVF recurrence，re-repair was performed 3?6 months later based on patient preference. For Group C，double-J stents were placed in the ureters，and stoma bags were applied 3 days postoperatively. Stents were replaced every 1?2 months，with QOL assessment. Successful fistula repair in Groups A and B was defined as the absence of vaginal leakage confirmed by cystoscopy after six months of the procedure with no vaginal leakage. For Group C，surgical success was determined by the resolution of perineal urinary leakage and improvement in QOL.Results:All 33 patients completed surgery successfully. Group A：Follow-up duration：16.3（9.6，24.6）months. Surgical repair succeeded in 7 patients，with unobstructed spontaneous urination and no vaginal incontinence. Four patients had VVF recurrence：2 refused further treatment，and 2 underwent repeat gracilis muscle flap packing. One was successfully repaired，while one recurrence case refused further treatment. Group B：Follow-up duration：17.0（9.5，24.8）months（8?32 months）. Thirteen patients restored spontaneous urination without recurrence. Seven had recurrence：5 refused further surgery，and 2 underwent re-repair. One repair succeeded without incontinence，while one recurrence case refused treatment. Group C：Follow-up durations were 6 and 22 months. Perineum remained dry without incontinence（no urine pads needed），and no recurrence of thigh soft-tissue redness/infection occurred. QOL scores were 2 and 3，respectively.Conclusions:Post-radiotherapy VVF in women after cervical cancer presents complex and variable conditions. The primary goal of treatment should be to improve patients’ quality of life. Treatment approaches should be selected based on the complexity of urinary fistulas and local tissue conditions. In general，patients who are younger，have received lower doses of radiation therapy，present with smaller fistula diameters，have well-vascularized and elastic perifistular tissues，and have no concurrent tissue fistulas are candidates for prone-position VVF repair. Patients who do not meet the criteria for transvaginal repair，have a history of at least two previous repair attempts，or have concurrent vaginorectal fistulas require gracilis muscle flap packing for VVF repair. Patients with three or more types of concurrent tissue fistulas，extensive pale and inelastic perifistular tissues，and who are not amenable to repair surgery undergo ureterocutaneous diversion.

China emerges as a major country in nuclear energy development and the application of nuclear and radiologic technology. The diagnosis and treatment of acute radiation syndrom (ARS) caused by external irradiation represent a core function in the country′s medical rescue of nuclear and radiological emergencies. Clinically, ARS manifests hematopoietic, gastrointestinal, cutaneous, and central nervous system syndromes, with specific clinical manifestations, signs, severity, and prognosis strongly correlated with radiation dose. China has established a number of national and provincial centers for treating radiation-induced damage. Nevertheless, most medical staff have limited experience in ARS treatment. This consensus presents a summary of recent experience in treating ARS of China. In combination with recommendations from international organizations such as the World Health Organization (WHO), this consensus proposes key evidence of critical clinical issues of ARS, covering all links in the rescue of external irradiation-induced ARS. Initially, clinical diagnosis, syndromes, and severe degrees should be determined based on clinical symptoms and dose estimates. It is necessary to normalize clinical treatment measures for hematopoietic recovery, gastrointestinal injury treatment, infection control, symptomatic treatment, and multi-organ function preservation. To this end, this consensus offers cautions. This consensus provides principles of treatment with traditional Chinese medicine, psychological intervention, and follow-up. Additionally, it highlights multidisciplinary collaboration. It is recommended that this consensus be applied in relevant treatment centers.

Polygonati Rhizoma demonstrates significant potential for addressing both chronic and hidden hunger. The supply of high-quality seedlings is a primary factor influencing the development of the Polygonati Rhizoma industry. Warm water soaking is often used in agriculture to promote the rapid germination of seeds, while its application and molecular mechanism in Polygonati Rhizoma have not been reported. To rapidly obtain high-quality seedlings, this study treated Polygonatum kingianum var. grandifolium seeds with sand storage at low temperatures, warm water soaking, and cultivation temperature gradients. The results showed that the culture at 25 ℃ or sand storage at 4 ℃ for 2 months rapidly broke the seed dormancy of P. kingianum var. grandifolium, while the culture at 20 ℃ or sand storage at 4 ℃ for 1 month failed to break the seed dormancy. Soaking seeds in 60 ℃ warm water further increased the germination rate, germination potential, and germination index. Specifically, the seeds soaked at 60 ℃ and cultured at 25 ℃ without sand storage treatment(Aa25) achieved a germination rate of 78. 67%±1. 53% on day 42 and 83. 40%±4. 63% on day 77. The seeds pretreated with sand storage at 4 ℃ for 2 months, soaked in 60 ℃ water, and then cultured at 25 ℃ achieved a germination rate comparable to that of Aa25 on day 77. Transcriptomic analysis indicated that warm water soaking might promote germination by triggering reactive oxygen species( ROS), inducing the expression of heat shock factors( HSFs) and heat shock proteins( HSPs), which accelerated DNA replication, transcript maturation, translation, and processing, thereby facilitating the accumulation and turnover of genetic materials. According to the results of indoor controlled experiments and field practices, maintaining a germination and seedling cultivation environment at approximately 25 ℃ was crucial for the one-year seedling cultivation of P. kingianum var. grandifolium.
Germination ; Seedlings/genetics* ; Water/metabolism* ; Seeds/metabolism* ; Polygonatum/genetics* ; Temperature ; Plant Proteins/genetics* ; Plant Dormancy