Glioma is difficult to treat due to the unique tumor microenvironment and blood-brain barrier. (13aS)-3-Hydroxyl-6,7-dimethoxyphenanthro[9,10-b] indolizidine (PF403), a phenanthroindolizidine alkaloid, has been identified as a promising therapeutic agent for the treatment of glioma. However, the anti-glioma mechanism of PF403 in vivo has not been conclusively verified and must be further elucidated. Hence, a strategy without chemical modification was applied to identify the target of PF403. In this study, we identified nicotinamide phosphoribosyl transferase (NAMPT) as the target of PF403 by using thermal proteome profiling (TPP). Moreover, microscale thermophoresis (MST), surface plasmon resonance (SPR), and isothermal titration calorimetry (ITC) experiments confirmed that NAMPT exhibits good affinity for PF403. Direct and indirect enzyme activity assays revealed that PF403 inhibited the catalytic activity of NAMPT, leading to a decrease in the concentration of nicotinamide adenine dinucleotide (NAD⁺) in U87 cells. X-ray diffraction and amino acid spot mutation experiments revealed that PF403 primarily relies on the formation of pi-pi interactions with residue Tyr188 to maintain binding with NAMPT (PDB code 8Y55). After NAMPT was knocked down with lentivirus, PF403 lost or partially lost its antitumor activity at the cellular and animal levels. These findings suggest that PF403 exerts antitumor activity by directly targeting NAMPT.

AIM: To investigate the factors influencing non-response to intravitreal injection of anti-vascular endothelial growth factor(VEGF)therapy in fundus vascular diseases in a real-world setting.METHODS: A retrospective analysis was conducted on 160 patients(160 eyes)with fundus vascular diseases, including 64 eyes(40.0%)of wet age-related macular degeneration(wARMD), 17 eyes(10.6%)of polypoidal choroidal vasculopathy(PCV), 45 eyes(28.1%)of diabetic macular edema(DME), 26 eyes(16.3%)of retinal vein occlusion-macular edema(RVO-ME), and 8 eyes(5.0%)of choroidal neovascularization(PM-CNV). All patients received 3+PRN anti-VEGF therapy. Factors influencing anti-VEGF treatment on the fundus vascular diseases were analyzed.RESULTS: There were statistical significant difference in age, preoperative best corrected visual acuity(BCVA), hyper reflective dots(HRD), PCV, subretinal hyperreflective material(SHRM), and PM-CNV(all P<0.05). Logistics regression analysis noted that poor preoperative BCVA, age, intraretinal HRD, SHRM, PCV and PM-CNV were influencing factors of non-response to intravitreal injection of anti-VEGF in the treatment of fundus vascular diseases.CONCLUSION: Non-response to anti-VEGF therapy in patients with fundus vascular diseases is associated with various factors, including age, baseline visual acuity, and disease pathology. Individualized treatment strategies should be explored to optimize outcomes for non-responding patients.

Objective To develop a highly sensitive and rapid nucleic acid detection method for the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2). Methods We designed,developed,and manufactured an integrated disposable device for SARS-CoV-2 nucleic acid extraction and detection.The precision of the liquid transfer and temperature control was tested.A comparison between our device and a commercial kit for SARS-Cov-2 nucleic acid extraction was performed using real-time fluorescence reverse transcription polymerase chain reaction(RT-PCR).The entire process,from SARS-CoV-2 nucleic acid extraction to amplification,was evaluated. Results The precision of the syringe transfer volume was 19.2±1.9 μL(set value was 20),32.2±1.6(set value was 30),and 57.2±3.5(set value was 60).Temperature control in the amplification tube was measured at 60.0±0.0 ℃(set value was 60)and 95.1±0.2 ℃(set value was 95)respectively.SARS-Cov-2 nucleic acid extraction yield through the device was 7.10×106 copies/mL,while a commercial kit yielded 2.98×106 copies/mL.The mean time to complete the entire assay,from SARS-CoV-2 nucleic acid extraction to amplification detection,was 36 min and 45 s.The detection limit for SARS-CoV-2 nucleic acid was 250 copies/mL. Conclusion The integrated disposable devices may be used for SARS-CoV-2 Point-of-Care test(POCT).

Objectives The combined use of bedaquiline and delamanid(BDQ-DLM)is limited by an increased risk of prolonging the QTc interval.We retrospectively evaluated patients who received DLM/BDQ-containing regimens at a TB-specialized hospital.We aimed to present clinical efficacy and safety data for Chinese patients. Methods This case-control study included patients with multidrug-resistant tuberculosis(MDR-TB)treated with BDQ alone or BDQ plus DLM. Results A total of 96 patients were included in this analysis:64 in the BDQ group and 32 in the BDQ+DLM group.Among the 96 patients with positive sputum culture at the initiation of BDQ alone or BDQ combined with DLM,46 patients(71.9%)in the BDQ group and 29(90.6%)in the BDQ-DLM group achieved sputum culture conversion during treatment.The rate of sputum culture conversion did not differ between the two groups.The time to sputum culture conversion was significantly shorter in the BDQ-DLM group than in the BDQ group.The most frequent adverse event was QTc interval prolongation;however,the frequency of adverse events did not differ between the groups. Conclusion In conclusion,our results demonstrate that the combined use of BDQ and DLM is efficacious and tolerable in Chinese patients infected with MDR-TB.Patients in the BDQ-DLM group achieved sputum culture conversion sooner than those in the BDQ group.

Objective:This study aimed to develop a rapid and accurate integrated nucleic acid detection method tailored for the influenza virus.Methods:We designed primers and probes targeting the predominant influenza virus strains circulating in China in recent years. These were integrated with extraction and amplification reagents and a point of care testing (POCT) system to facilitate a seamless and expedited process involving nucleic acid extraction, reaction system preparation, amplification, and result interpretation for the influenza virus. The specificity of the POCT system was evaluated using cultured influenza viruses, while its cross-reactivity was assessed against common respiratory pathogens, including adenovirus and respiratory syncytial virus.Results:Our study successfully developed duplex amplification primers and probes for both influenza A and B viruses, achieving a detection threshold as low as 500 copies/ml. Specificity tests confirmed that the detection reagents did not show cross-reactivity with other respiratory pathogens such as adenovirus and respiratory syncytial virus. The POCT-based rapid nucleic acid detection method for influenza virus was established, it is capable of completing the entire process from nucleic acid extraction to amplification and result interpretation within 50 minutes, while enabling real-time data upload.Conclusions:The POCT-based rapid influenza virus detection kit developed in this study offers a " sample in, results out" convenience, making it suitable for rapid influenza virus detection in primary care settings. This innovation has significant potential for clinical application.

Objective To investigate the effect of esketamine combined with sufentanil for postoperative patient-controlled intravenous analgesia(PCIA)on rebound pain after single nerve block.Methods From January 2021 to December 2022,80 patients undergoing upper limb fracture surgery in Jinshan Hospital,Fudan University with single nerve block anesthesia were included and randomly divided into two groups:the Ket group(esketamine combined with sufentanil PCIA)and the Ctrl group(sufentanil PCIA),with 40 patients in each group.Several indicators were recorded,including pain scores at 8 h,12 h,24 h,and 48 h postoperatively,the time to first pain and its score,pain scores 30 min after pressing the PCIA pump self-control button,as well as opioid consumption at 24 h and 48 h postoperatively,and the number of PCIA button presses.Rebound pain was defined as a sudden transition from"no pain"to"severe pain"(NRS ≥ 7)requiring pressing the PCIA self-control button.Results Rebound pain occurred in 17(45.95％)patients in the Ctrl group and 12(36.36％)patients in the Ket group,with no statistically significant difference.The Ket group had significantly lower sufentanil consumption and fewer PCIA presses at 24 h postoperatively compared to the Ctrl group(P=0.007).At 48 h postoperatively,there was no significant difference in sufentanil consumption and PCIA presses among patients who experienced rebound pain in the two groups.At 30 min after pressing the PCIA button for breakthrough pain,12 patients(100.00％)in the Ket group had NRS＜4,compared to 3 patients(17.65％)in the Ctrl group,with a statistically significant difference(P=0.02).Conclusions Compared with using sufentanil alone for PCIA,the combination of esketamine and sufentanil does not reduce the incidence of rebound pain following single nerve block in upper limb fracture surgery.However,the combination of esketamine and sufentanil may provide a faster relief of rebound pain.

【Objective】 To investigate the condition of confidential unit exclusion(CUE) in Guangzhou, so as to ensure blood safety. 【Methods】 The number of CUE donors, demographic characteristics of CUE donors, reasons for CUE, and response time of CUE after blood donation in Guangzhou from 2009 to 2022 were statistically analyzed. 【Results】 From 2009 to 2022, the response ratios of CUE was 0.006 2% (260/4 170 984) and the ratios had statistically significant difference between different years(P<0.05). For the response ratios of CUE, no statistically significant difference was noticed in gender and occupation (P>0.05), but statistically significant differences were found in age, number of blood donations, education background, and marital status (P<0.05). Blood donors aged 18~30 (0.007 3%, P<0.05) and first-time blood donors (0.010 8%, P<0.05) were the main groups of CUE. High risk sexual behavior (28.46%, 74/260) was the primary reason for CUE. The CUE response peak was within 72 hours after blood donation, and the response ratios within 24-72 hours after blood donation was the highest (68.46%, 178/260). 【Conclusion】 CUE is a crucial measure to ensure blood safety. Detailed pre-donation health consultations are suggested for blood donors aged 18-30 and first-time blood donors so as to better excluding high-risk blood donors. Strengthening the publicity of CUE response and process, registering and classifying the reasons for CUE are also important.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

BACKGROUND:Achilles tendon adhesion after Achilles tendon injury can lead to decreased biomechanical properties,weakened healing ability,and ultrastructural changes of Achilles tendon,which further affects patients'daily life and work ability.Therefore,how to effectively deal with and prevent Achilles tendon adhesion has become a hot and difficult problem in clinical treatment. OBJECTIVE:To analyze the effects of biological amniotic membranes on postoperative Achilles tendon adhesion,biomechanics,and ultrastructural changes in rats with Achilles tendon rupture. METHODS:Sixty 6-week-old SD rats were selected to establish bilateral Achilles tendon rupture models and divided into two groups(n=30 per group)by the random number table method.In the model group,the severed end of the tendon was sutured directly.In the amniotic membrane group,the biological amniotic membrane was wrapped around the broken anastomosis and fixed by a suture.The adhesion,biomechanics,morphology,and structure of the Achilles tendon and the expression of p38 and ERK1/2 protein were evaluated 1,2,and 4 weeks after surgery. RESULTS AND CONCLUSION:(1)1 week after operation,the Achilles tendon and peritendinous tissues of the two groups were mildly edema,and the adhesion of the Achilles tendon tissues in the model group was more obvious.2 weeks after the intervention,the Achilles tendon and peritendinous tissues of the model group still had edema,and the adhesion degree between the Achilles tendon and the surrounding tissues was heavier than that of the amniotic membrane group.4 weeks after operation,there was no edema around the Achilles tendon in both groups,and the healing was well.The adhesion degree of the Achilles tendon in the amniotic membrane group was less than that in the model group.The maximum tension of Achilles tendons in the amniotic membrane group was higher than that in the model group at 2 and 4 weeks after operation(P<0.001).(2)Hematoxylin-eosin staining and transmission electron microscopy revealed that 1 week after operation,the tendon structure of rats of the two groups was disordered and the collagen fibers were sparsely arranged,in which the model group demonstrated obvious inflammatory reaction and adhesion to the Achilles tendon.Two weeks after operation,the model group still demonstrated obvious inflammatory response,adhesion of Achilles tendon,and irregular ordering of collagen fibers.The amniotic membrane group exhibited an orderly arrangement of collagen fibers and expansion of the endoplasmic reticulum of fibroblasts.At 4 weeks after operation,the collagen fibers of the Achilles tendon in the model group were thickened and disordered,and the rough endoplasmic reticulum was less in the fibroblasts,while the collagen fibers in the amniotic membrane group were ordered and thin,and the fibroblasts contained a large number of rough endoplasmic reticulum.(3)Four weeks after operation,western blot assay exhibited that the expressions of p38 and ERK1/2 protein in the Achilles tendon tissue of rats in the amniotic membrane group were lower than those in the model group(P<0.05).(4)The results confirm that the biologic amniotic membrane can promote the healing and inhibit the adhesion of Achilles tendon after the operation of the ruptured Achilles tendon,which may be associated with the regulation of the MAPK/ERK signaling pathway.

BACKGROUND:Osteoporotic vertebral compression fracture is a common fracture secondary to osteoporosis.At present,there is no effective prediction index and method for osteoporotic vertebral compression fracture. OBJECTIVE:To investigate the predictive effect of the comprehensive index of lumbar vertebral body bone strength on osteoporotic vertebral compression fracture. METHODS:233 patients with osteoporosis were divided into a fracture group and a non-fracture group according to whether a vertebral fracture occurred.The demography,body mass index,vertebral bone mineral density and other details were collected.Lateral X-ray films of the lumbar spine were photographed.The vertebral body width,vertebral body length,sacral slope,pelvic tilt,pelvic incidence,lumbar compressive strength index and the lumbar impact strength index were measured,calculated,and analyzed by univariate and multivariate,and the receiver operating characteristic curve was analyzed.The survival analysis was conducted according to the cut-off value. RESULTS AND CONCLUSION:(1)All patients were followed up for 2-4 years,with an average of 3.1 years.During the follow-up period,99 cases(38 cases of L1 vertebral body,61 cases of L2 vertebral body)had fractures(fracture group),and 134 cases(52 cases of L1 vertebral body,82 cases of L2 vertebral body)had no fractures(non-fracture group).Univariate analysis showed that there was no significant difference in age,sex,height,body mass,body mass index and fracture segment between the two groups(P>0.05).(2)Lumbar compressive strength index and lumbar impact strength index in the fracture group were lower than those in the non-fracture group(P<0.05).Pelvic incidence and pelvic tilt in the fracture group were higher than those in the non-fracture group(P<0.05).(3)Multivariate analysis showed that lumbar compressive strength index,lumbar impact strength index and pelvic tilt were risk factors for osteoporotic vertebral compression fractures(P<0.05).(4)Receiver operating characteristic curve analysis showed that the cutoff values of vertebral bone mineral density,lumbar compressive strength index,lumbar impact strength index,pelvic tilt and pelvic incidence were 0.913 5 g/cm2,1.932,0.903,21.5° and 55°,respectively;areas under the curve were 0.630,0.800,0.911,0.633 and 0.568,respectively.(5)According to the survival analysis(with osteoporotic vertebral compression fracture as the end point),the average survival time of the patients with lumbar impact strength index≥0.903 was significantly longer than that of the patients with lumbar impact strength index<0.903(P<0.05).(6)These findings conclude that the comprehensive index of lumbar vertebral body bone strength is more accurate than the bone mineral density of the vertebral body and spine-pelvis sagittal parameters in predicting osteoporotic vertebral compression fractures,which is helpful for early prevention and treatment of osteoporotic vertebral compression fractures.