AIM:This study aimed to establish a model of functional impairment in INS-1 cells(rat insulino-ma cells)induced by prolonged exposure to a low level of interleukin-1β(IL-1β),and to investigate the underlying mech-anisms.METHODS:INS-1 cells were treated with different concentrations of IL-1β for 10 d.The cells were divided into control,0.05 μg/L IL-1β,0.1 μg/L IL-1β,and 0.2 μg/L IL-1β groups(n=3).Flow cytometry was employed to assess cell apoptosis,facilitating the identification of IL-1β concentrations that did not significantly induce apoptosis.Subse-quently,INS-1 cells were divided into control and IL-1β groups(n=3)and treated with 0.1 μg/L IL-1β for 10 days.The intracellular insulin content and glucose-stimulated insulin secretion level were detected by immunofluorescence and en-zyme-linked immunosorbent assay(ELISA).Differential proteins and associated signaling pathways were screened using 4D label-free proteomics technology.Moreover,fluorescent probes were used to detect glucose-stimulated calcium ion in-flux,and Western blot was conducted to verify the expression changes of relevant proteins in the nuclear factor kappa-B(NF-κB)signaling pathway and calcium signaling pathway.RESULTS:Treatment with 0.1 μg/L IL-1β for 10 days ex-hibited minimal impact on the survival of INS-1 cells but significantly reduced the intracellular insulin content and glucose-stimulated insulin secretion(P<0.01).Therefore,0.1 μg/L IL-1β was chosen for in vitro induction of functional impair-ment in INS-1 cells.Proteomic analysis showed no significant differences in the expression of apoptosis-related factors,such as caspase-3,B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),and Bcl-2-associated death promoter(Bad),compared with the control(P>0.05).However,the expression of insulin,v-maf avian musculoaponeurotic fibro-sarcoma oncogene family protein A(Mafa),calcium/calmodulin-dependent protein kinase II(CaMKII),inositol 1,4,5-triphosphate receptor(IP3R),and NF-kappa-B inhibitor alpha(IκBα)was significantly reduced(P<0.01),while the protein expression levels of NF-κB and inducible nitric oxide synthase(iNOS)were significantly increased(P<0.05,P<0.01).Fluorescence probe results showed that,compared to the control,the calcium ion influx induced by glucose stimu-lation in the IL-1β group was significantly reduced(P<0.01).Western blot results demonstrated that the expression lev-els of IP3R,CaMKII,and IκBα in the IL-1β group were significantly reduced(P<0.05,P<0.01),while the expression levels of NF-κB and iNOS were significantly increased(P<0.01).CONCLUSION:A model of functional impairment in rat INS-1 cells induced by prolonged exposure to low levels of IL-1β has been successfully established,and it has been pre-liminarily confirmed that this impairment may be related to the activation of the NF-κB signaling pathway and dysfunction of the calcium signaling pathway.

Acute lung injury （ALI） is one of the most common and critical diseases in clinical practice， with extremely high morbidity and mortality， seriously threatening human life and health. The pathogenesis of ALI is complex， in which the inflammatory response is a key factor. Studies have shown that NOD-like receptor protein 3 （NLRP3） inflammasomes are involved in ALI through mechanisms such as inflammation induction， increased microvascular permeability， recruitment of neutrophils， oxidative stress， and pyroptosis， playing a key role in the occurrence and progression of ALI. Therefore， regulating NLRP3 inflammasomes and inhibiting the release of inflammatory factors can alleviate the damage in ALI. At present， ALI is mainly treated by mechanical ventilation and oxygen therapy， which have problems such as high costs and poor prognosis. In recent years， studies have shown that traditional Chinese medicine （TCM） can reduce the inflammatory response and the occurrence of oxidative stress and pyroptosis by regulating the NLRP3 inflammasome， thus alleviating the damage and decreasing the mortality of ALI. Based on the relevant literature in recent years， this article reviews the research progress in TCM treatment of ALI by regulating NLRP3 inflammasomes， discusses how NLRP3 inflammasomes participate in ALI， and summarizes the active ingredients， extracts， and compound prescriptions of TCM that regulate NLRP3 inflammasomes， aiming to provide new ideas for the clinical treatment of ALI and the development of relevant drugs.

ObjectiveTo investigate the processing technology of calcined Haematitum based on the concept of quality by design（QbD） and to assess its health risk. MethodsTaking whole iron content， Fe²⁺ dissolution content and looseness as critical quality attributes（CQAs）， and calcination temperature， calcination time， spreading thickness and particle size as critical process parameters（CPPs） determined by the failure mode and effect analysis（FMEA）， the processing technology of calcined Haematitum was optimized by orthogonal test combined with analytic hierarchy process-criteria importance through intercriteria correlation（AHP-CRITIC） hybrid weighting method. The contents of heavy metals and harmful elements were determined by inductively coupled plasma mass spectrometry， and the health risk assessment was carried out by daily exposure（EXP）， target hazard quotient（THQ） and lifetime cancer risk（LCR）， and the theoretical value of the maximum limit was deduced. ResultsThe optimal processing technology for calcined Haematitum was calcination at 650 ℃， calcination time of 1 h， particle size of 0.2-0.5 cm， spreading thickness of 1 cm， and vinegar quenching for 1 time［Haematitum-vinegar（10：3）］. The contents of 5 heavy metals and harmful elements in 13 batches of calcined Haematitum were all decreased with reductions of up to 5-fold. The cumulative THQ of 2 batches of samples was>1， while the cumulative THQ of all batches of Haematitum was>1. The LCR of As in 1 batches of Haematitum was 1×10^-6-1×10^-4， and the LCR of the rest was<1×10^-6， and the LCRs of calcined Haematitum were all<1×10^-6， indicating that the carcinogenic risk of calcined Haematitum was low， but special attention should still be paid to Haematitum medicinal materials. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg were formulated as 1 014， 25， 17， 27， 7 mg·kg^-1. ConclusionThe optimized processing technology of calcined Haematitum is stable and feasible， and the contents of heavy metals and harmful elements are reduced after processing. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg are formulated to provide a scientific basis for the formulation of standards for the limits of harmful elements in Haematitum.

ObjectiveTo investigate the processing technology of calcined Haematitum based on the concept of quality by design（QbD） and to assess its health risk. MethodsTaking whole iron content， Fe²⁺ dissolution content and looseness as critical quality attributes（CQAs）， and calcination temperature， calcination time， spreading thickness and particle size as critical process parameters（CPPs） determined by the failure mode and effect analysis（FMEA）， the processing technology of calcined Haematitum was optimized by orthogonal test combined with analytic hierarchy process-criteria importance through intercriteria correlation（AHP-CRITIC） hybrid weighting method. The contents of heavy metals and harmful elements were determined by inductively coupled plasma mass spectrometry， and the health risk assessment was carried out by daily exposure（EXP）， target hazard quotient（THQ） and lifetime cancer risk（LCR）， and the theoretical value of the maximum limit was deduced. ResultsThe optimal processing technology for calcined Haematitum was calcination at 650 ℃， calcination time of 1 h， particle size of 0.2-0.5 cm， spreading thickness of 1 cm， and vinegar quenching for 1 time［Haematitum-vinegar（10：3）］. The contents of 5 heavy metals and harmful elements in 13 batches of calcined Haematitum were all decreased with reductions of up to 5-fold. The cumulative THQ of 2 batches of samples was>1， while the cumulative THQ of all batches of Haematitum was>1. The LCR of As in 1 batches of Haematitum was 1×10^-6-1×10^-4， and the LCR of the rest was<1×10^-6， and the LCRs of calcined Haematitum were all<1×10^-6， indicating that the carcinogenic risk of calcined Haematitum was low， but special attention should still be paid to Haematitum medicinal materials. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg were formulated as 1 014， 25， 17， 27， 7 mg·kg^-1. ConclusionThe optimized processing technology of calcined Haematitum is stable and feasible， and the contents of heavy metals and harmful elements are reduced after processing. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg are formulated to provide a scientific basis for the formulation of standards for the limits of harmful elements in Haematitum.

Arachidonic acid can be transformed into a variety of metabolites that trigger an inflammatory response through cyclooxygenase, lipoxygenase, cytochrome P450 enzymes, and other metabolic pathways. Moreover, it plays a key role in the occurrence and development of inflammatory diseases. In recent years, multi-target drugs based on the arachidonic acid metabolic pathway have become an important direction of anti-inflammatory drug research. This article summarizes the opportunities and challenges of arachidonic acid metabolic pathways as well as their interference in the development of anti-inflammatory drugs, reviews the research progress of multi-target drug design, synthesis, and anti-inflammatory activity based on the arachidonic acid metabolic pathway, and discusses the difficulties and prospects of multi-target drugs based on metabolic pathways in anti-inflammatory drug development, aiming to provide some reference and inspiration for the study of multi-target anti-inflammatory drugs based on the arachidonic acid metabolic pathway.

Microplastics and nanoplastics(MPs/NPs)are ubiquitous environmental pollutants that act as endocrine-disrupting chemicals(EDCs),raising significant concerns about their impact on human health,Research highlights the hazardous effects of MPs/NPs on both male and female reproductive systems,influencing germ cells,embryo development,and progeny.Additionally,studies show that MPs/NPs affect the gene expression of anabolic steroid hormones in vitro and in vivo,inducing reproductive toxicity through mechanisms such as oxidative stress and inflammation,Considering these adverse effects,identifying natural compounds that can mitigate the toxicity of MPs/NPs is increasingly important.Plants offer a wealth of antioxidants and anti-inflammatory compounds that can counteract these harmful effects.Among these,anthocyanins,natural colorants responsible for the vibrant hues of fruits and flowers,exhibit a wide range of biological activities,including antioxidant,anti-inflammatory,and anti-neoplastic properties.Moreover,anthocyanins can modulate sex hormone levels and alleviate reproductive toxicity.Cyanidin-3-glucoside(C3G),one of the most extensively studied anthocyanins,shows promise in reducing reproductive toxicity,particularly in females,and in protecting male reproductive organs,including the testis and epididymis.This protective effect is believed to result from its interaction with steroid receptors,specifically the androgen and estrogen receptors(ERs).These findings highlight the need to explore the mechanisms by which anthocyanins mitigate the reproductive toxicity caused by MPs/NPs.This review provides novel insights into how natural compounds can be leveraged to lessen the impact of environmental contaminants on human health,especially concerning reproductive health.

Microplastics and nanoplastics (MPs/NPs) are ubiquitous environmental pollutants that act as endocrine-disrupting chemicals (EDCs), raising significant concerns about their impact on human health. Research highlights the hazardous effects of MPs/NPs on both male and female reproductive systems, influencing germ cells, embryo development, and progeny. Additionally, studies show that MPs/NPs affect the gene expression of anabolic steroid hormones in vitro and in vivo, inducing reproductive toxicity through mechanisms such as oxidative stress and inflammation. Considering these adverse effects, identifying natural compounds that can mitigate the toxicity of MPs/NPs is increasingly important. Plants offer a wealth of antioxidants and anti-inflammatory compounds that can counteract these harmful effects. Among these, anthocyanins, natural colorants responsible for the vibrant hues of fruits and flowers, exhibit a wide range of biological activities, including antioxidant, anti-inflammatory, and anti-neoplastic properties. Moreover, anthocyanins can modulate sex hormone levels and alleviate reproductive toxicity. Cyanidin-3-glucoside (C3G), one of the most extensively studied anthocyanins, shows promise in reducing reproductive toxicity, particularly in females, and in protecting male reproductive organs, including the testis and epididymis. This protective effect is believed to result from its interaction with steroid receptors, specifically the androgen and estrogen receptors (ERs). These findings highlight the need to explore the mechanisms by which anthocyanins mitigate the reproductive toxicity caused by MPs/NPs. This review provides novel insights into how natural compounds can be leveraged to lessen the impact of environmental contaminants on human health, especially concerning reproductive health.

Objective:To compare the efficacy of robot system-assisted versus freehand screw revision for ankylosing spondylitis (AS) with lower cervical fractures.Methods:A multicenter retrospective cohort study was conducted to analyze the clinical data of 57 patients with AS combined with lower cervical fractures admitted to Honghui Hospital Affiliated to Xi'an Jiaotong University School of Medicine, Henan Provincial People's Hospital, Zhengzhou Orthopedic Hospital, and Qilu Hospital of Shandong University, including 46 males and 11 females, aged 38-77 years [(65.4±9.5)years]. Injury segments involved C 3 in 7 patients, C 4 in 13, C 5 in 25, C 6 in 10, and C 7 in 2. All the patients underwent revision surgery, among whom, 22 patients were treated with robot system-assisted cervical pedicle screw placement (robot nailing group, with 190 screws), and 35 with freehand cervical pedicle screw placement (freehand nailing group, with 300 screws). The operative duration, intraoperative bleeding volume, frequency of intraoperative fluoroscopy, incision length, and length of hospital stay of the two groups were compared; the time of single nscrew insertion, the number of single nail revisions, the distance between screws and the anterior cortex, the accuracy of screw placement of grade 0 and grade 0+1 were recorded in the two groups. The visual analogue scale (VAS), Japanese Orthopedic Society (JOA) score, neck dysfunction index (NDI), American Spine Injury Association (ASIA) classification before operation, at 3 days, 3 months after operation and at the last follow-up were compared between the two groups. The complication rate was also noted. Results:All the patients were followed up for 12-16 months [(14.3±2.1)months]. The operative duration, intraoperative bleeding volume, and frequency of intraoperative fluoroscopy were (186.4±12.9)minutes, (486.1±68.6)ml, and (3.4±1.3)times in the robot nailing group, which were shorter or less than (206.7±14.4)minutes, (660.3±45.2)ml, and (13.5±3.6)times in the freehand nailing group ( P<0.01). The incision length was (9.4±2.4)cm in the robot nailing group, longer than (5.6±1.2)cm in the freehand nailing group ( P<0.01), and the length of hospital stay was (3.7±0.4)days, shorter than (4.4±1.4)days in the freehand nailing group ( P<0.01). The length of single nail insertion, the number of single nail revision, and the distance between the screws and the front cortex were (6.5±0.4)minutes, (1.1±0.1)times, and (3.5±1.3)mm in the robot nailing group, which were shorter or less than (11.6±0.2)minutes, (1.5±0.2)times, and (12.4±4.7)mm in the freehand nailing group ( P<0.01). The accuracy of the screw placement in the robot nailing group was 90.0% (171/190) and 95.8% (182/190) with level 0 and 0+1 screws, better than 80.0% (240/300) and 89.0% (267/300) in the freehand nailing group ( P<0.05). There was no significant difference in VAS, JOA score, NDI, or ASIA grading between the two groups before operation ( P>0.05). The VAS, JOA, and NDI scores at 3 days after operation were (3.1±0.6)points, (12.1±1.2)points, and (15.6±2.9)points, respectively in the robot nailing group, which were better than (5.0±1.4)points, (11.3±1.1)points and (22.5±3.7)points, respectively in the freehand nailing group ( P<0.05). No statistically significant difference was observed in the ASIA grade between the two groups at 3 days after operation ( P>0.05). There were no significant differences in VAS, JOA, NDI scores, or ASIA grading between the two groups at 3 months after operation and at the last follow-up ( P>0.05). Compared with those before operation, the VAS, JOA, NDI scores, and ASIA grading were significantly improved at 3 days, 3 months after operation and at the last follow-up in the two groups, which were further improved with the passage of time. Two patients in the robot nailing group had pneumonia, with a complication rate of 9% (2/22), while 2 patients in the freehand nailing group had dural sac rupture and cerebrospinal fluid leakage and 3 had lung infection after operation, with a complication rate of 14% (5/35) ( P<0.05). Conclusion:Compared with freehand nailing, the robot system-assisted nailing revision for AS with lower cervical fracture has more advantages in terms of the operative duration, length of hospital stay, intraoperative bleeding volume, frequency of intraoperative fluoroscopy nailing speed and accuracy, screw holding force, early pain relief, function restoration, and complication rate, despite longer surgical incision.

Objective:To compare the clinical efficacy of navigation system and orthopedic robot-assisted nail placement in the treatment of lower cervical fracture and dislocation.Methods:A retrospective cohort study was conducted to analyze the clinical data of 49 patients with fracture and dislocation of the lower cervical spine who were admitted to Honghui Hospital, Xi′an Jiaotong University School of Medicine from May 2021 to October 2022, including 38 males and 11 females, aged 29-61 years [(39.3±7.3)years]. Injury segments involved C 3 in 12 patients, C 4 in 11, C 5 in 8, C 6 in 9 and C 7 in 9. Twenty-one patients were treated with S8 navigation system (navigation group, 84 screws), and 28 with TINAVI orthopedic robot (robot group, 112 screws). The two groups were compared in terms of the total surgical duration, single screw placement time, total screw placement time, distance between the screw and the anterior cortex, incision length, intraoperative radiation dose, intraoperative blood loss and length of hospital stay. The height of intervertebral space, Cobb angle, sliding distance between vertebral bodies and American Spinal Injury Association (ASIA) grade were assessed before surgery and at 3 days after surgery. Visual analogue scale (VAS), Japanese Orthopedic Association (JOA) score and neck dysfunction index (NDI) before surgery, at 3 days, 3 months after surgery and at the last follow-up were compared. The accuracy of screw placement, intraoperative invasion rate of adjacent facet joints and rate of postoperative complications (infection, screw loosening, etc.) were evaluated. Results:All the patients were followed up for 12-16 months [(13.6±1.9)months]. In the navigation group, the total surgical duration, distance from the screw to the anterior cortex and the intraoperative radiation dose were (236.2±30.6)minutes, (2.0±0.2)mm and (374.3±90.3)mGy respectively, which were significantly shorter or less than those in the robot group [(278.4±20.7)minutes, (10.6±2.9)mm and (448.4±77.9)mGy] ( P<0.01). The single screw placement time, total screw placement time, incision length and intraoperative blood loss were (3.5±0.4)minutes, (23.9±0.5)minutes, (9.1±2.4)cm and (422.2±30.4)ml respectively, which were significantly longer or more than those in the robot group [(2.6±0.2)minutes, (17.9±0.7)minutes, (6.6±2.6)cm and (360.3±56.3)ml] ( P<0.01). There was no significant difference in the length of hospital stay between the two groups ( P>0.05). No significant differences were observed in the height of the intervertebral space, Cobb angle, sliding distance between the vertebral bodies and ASIA grade between the two groups ( P>0.05). At 3 days after surgery, the height of intervertebral space, Cobb angle, sliding distance between vertebral bodies and ASIA grade in both groups were significantly improved when compared with those before surgery ( P<0.05 or 0.01). There were no significant differences in VAS, JOA scores or NDI between the two groups before surgery, at 3 days, 3 months after surgery and at the last follow-up ( P>0.05). The VAS, JOA scores and NDI in both groups were gradually improved at 3 days, 3 months and at the last follow-up after surgery when compared with those before surgery ( P<0.05). There was no significant difference in the accuracy of screw placement of levels 0 and 0+1 between the two groups ( P>0.05). No significant difference in the intraoperative invasion rate of adjacent facet joints between the two groups was found ( P>0.05). There were no serious complications such as infection or screw loosening after surgery in both groups. Conclusions:For lower cervical fracture and dislocation, although there are more advantages in total surgical duration, screw holding force and radiation control regarding the navigation system, and more outstanding performance in screw placement efficiency, incision length and intraoperative blood loss regarding the orthopedic robot, both of them can effectively rebuild the cervical structure, improve neurological function, relieve postoperative pain, improve screw placement accuracy and reduce facet joint injury and serious complications. Selection of the best auxiliary screw placement system should comprehensively consider patients′ conditions and the experience of the surgical team.

AIM:This study aimed to establish a model of functional impairment in INS-1 cells(rat insulino-ma cells)induced by prolonged exposure to a low level of interleukin-1β(IL-1β),and to investigate the underlying mech-anisms.METHODS:INS-1 cells were treated with different concentrations of IL-1β for 10 d.The cells were divided into control,0.05 μg/L IL-1β,0.1 μg/L IL-1β,and 0.2 μg/L IL-1β groups(n=3).Flow cytometry was employed to assess cell apoptosis,facilitating the identification of IL-1β concentrations that did not significantly induce apoptosis.Subse-quently,INS-1 cells were divided into control and IL-1β groups(n=3)and treated with 0.1 μg/L IL-1β for 10 days.The intracellular insulin content and glucose-stimulated insulin secretion level were detected by immunofluorescence and en-zyme-linked immunosorbent assay(ELISA).Differential proteins and associated signaling pathways were screened using 4D label-free proteomics technology.Moreover,fluorescent probes were used to detect glucose-stimulated calcium ion in-flux,and Western blot was conducted to verify the expression changes of relevant proteins in the nuclear factor kappa-B(NF-κB)signaling pathway and calcium signaling pathway.RESULTS:Treatment with 0.1 μg/L IL-1β for 10 days ex-hibited minimal impact on the survival of INS-1 cells but significantly reduced the intracellular insulin content and glucose-stimulated insulin secretion(P<0.01).Therefore,0.1 μg/L IL-1β was chosen for in vitro induction of functional impair-ment in INS-1 cells.Proteomic analysis showed no significant differences in the expression of apoptosis-related factors,such as caspase-3,B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),and Bcl-2-associated death promoter(Bad),compared with the control(P>0.05).However,the expression of insulin,v-maf avian musculoaponeurotic fibro-sarcoma oncogene family protein A(Mafa),calcium/calmodulin-dependent protein kinase II(CaMKII),inositol 1,4,5-triphosphate receptor(IP3R),and NF-kappa-B inhibitor alpha(IκBα)was significantly reduced(P<0.01),while the protein expression levels of NF-κB and inducible nitric oxide synthase(iNOS)were significantly increased(P<0.05,P<0.01).Fluorescence probe results showed that,compared to the control,the calcium ion influx induced by glucose stimu-lation in the IL-1β group was significantly reduced(P<0.01).Western blot results demonstrated that the expression lev-els of IP3R,CaMKII,and IκBα in the IL-1β group were significantly reduced(P<0.05,P<0.01),while the expression levels of NF-κB and iNOS were significantly increased(P<0.01).CONCLUSION:A model of functional impairment in rat INS-1 cells induced by prolonged exposure to low levels of IL-1β has been successfully established,and it has been pre-liminarily confirmed that this impairment may be related to the activation of the NF-κB signaling pathway and dysfunction of the calcium signaling pathway.