OBJECTIVE To explore the intervention mechanism of Shangke Lengtongtie on cold hyperalgesia in KOA mice based on the HMGB1/CXCL12/CXCR4 signaling axis.METHODS Monosodium iodoacetate(MIA)was used for the intra-articular injec-tion into the knee joint to establish mice model of knee osteoarthritis(KOA).Peripheral blood monocytes were extracted from mice,cultured,and then reinfused into the tail vein of the mice.Subsequently,in vivo animal imaging was used to observe the recruitment sites of these monocytes.The cold hyperalgesia threshold was measured at various time points in each group of mice.Hematoxylin and eosin(HE)staining was used to evaluate the level of synovial pathological changes.ELISA was employed to detect the expression of in-flammatory factors IL-1β,TNF-α,and pain mediators CGRP and Substance P in mouse serum.Western blot and qPCR methods were used to detect the protein and gene expression of cold hyperalgesia-related indicators such as TRPA1,TRPM8,HMGB1,CXCL12,CXCR4,Collagen Ⅰ,and Netrin-1 in synovial tissue,as well as DCC in dorsal root ganglia(DRG)tissue.RESULTS In vivo ima-ging showed that after the monocytes were reinfused into KOA mice,they were recruited to the knee joint area,with the HMGB1 group exhibiting a greater recruitment of circulating monocytes at the knee joint.Additionally,compared to the control group,the KOA group and HMGB1 group showed inflammatory pathological changes in the synovium,increased expression of serum inflammatory factors and pain mediators,reduced cold hyperalgesia threshold,and upregulated protein and gene expression of cold hyperalgesia-related indica-tors in synovial and DRG tissues.The changes were more significant in the HMGB1 group compared to the KOA group(P<0.05).Af-ter treatment with Shangke Lengtongtie or GL intervention,synovial inflammation was alleviated,serum inflammatory factors and pain mediators decreased,cold hyperalgesia threshold increased,and the upregulation of cold hyperalgesia-related indicator protein and gene expression levels was significantly reversed(P<0.05).CONCLUSION Shangke Lengtongtie exerts a beneficial effect on the mitigation of synovitis and cold hyperalgesia in KOA mice,a therapeutic mechanism that possibly mediated through the inhibition of the HMGB1/CXCL12/CXCR4 signaling axis.

Objective:This study analyzed the epidemiological characteristics of the clustered cases of severe fever with thrombocytopenia syndrome (SFTS) in Jiangsu province, so as to provide a scientific basis for prevention and control efforts.Methods:In this study we searched for cases related to clustered outbreaks and conducted epidemiological investigations of the cases, their co-exposed individuals, and close contacts. The basic information of the cases and their disease progression were collected and documented. The source of infection and transmission routes were analyzed. Fisher’s exact probability test and independent samples t-test were used to compare the differences between index and secondary cases. Results:From 2018 and 2024, a total of nine cluster outbreaks were reported in Jiangsu province, involving 32 cases of SFTS with 12 fatalities. Seven clustered outbreaks occurred in rural communities, while two occurred in medical institutions. The primary cause of these outbreaks was direct contact with confirmed cases.Conclusions:In recent years, Jiangsu province has experienced multiple clustered outbreaks of SFTS. Targeted health education should be implemented in high-risk areas to increase awareness of personal protective measures. Medical institutions should standardize the management of confirmed cases, educate patients′ families about prevention and control measures, and strengthen training for healthcare workers to ensure effective infection control within hospitals.

OBJECTIVE To explore the intervention mechanism of Shangke Lengtongtie on cold hyperalgesia in KOA mice based on the HMGB1/CXCL12/CXCR4 signaling axis.METHODS Monosodium iodoacetate(MIA)was used for the intra-articular injec-tion into the knee joint to establish mice model of knee osteoarthritis(KOA).Peripheral blood monocytes were extracted from mice,cultured,and then reinfused into the tail vein of the mice.Subsequently,in vivo animal imaging was used to observe the recruitment sites of these monocytes.The cold hyperalgesia threshold was measured at various time points in each group of mice.Hematoxylin and eosin(HE)staining was used to evaluate the level of synovial pathological changes.ELISA was employed to detect the expression of in-flammatory factors IL-1β,TNF-α,and pain mediators CGRP and Substance P in mouse serum.Western blot and qPCR methods were used to detect the protein and gene expression of cold hyperalgesia-related indicators such as TRPA1,TRPM8,HMGB1,CXCL12,CXCR4,Collagen Ⅰ,and Netrin-1 in synovial tissue,as well as DCC in dorsal root ganglia(DRG)tissue.RESULTS In vivo ima-ging showed that after the monocytes were reinfused into KOA mice,they were recruited to the knee joint area,with the HMGB1 group exhibiting a greater recruitment of circulating monocytes at the knee joint.Additionally,compared to the control group,the KOA group and HMGB1 group showed inflammatory pathological changes in the synovium,increased expression of serum inflammatory factors and pain mediators,reduced cold hyperalgesia threshold,and upregulated protein and gene expression of cold hyperalgesia-related indica-tors in synovial and DRG tissues.The changes were more significant in the HMGB1 group compared to the KOA group(P<0.05).Af-ter treatment with Shangke Lengtongtie or GL intervention,synovial inflammation was alleviated,serum inflammatory factors and pain mediators decreased,cold hyperalgesia threshold increased,and the upregulation of cold hyperalgesia-related indicator protein and gene expression levels was significantly reversed(P<0.05).CONCLUSION Shangke Lengtongtie exerts a beneficial effect on the mitigation of synovitis and cold hyperalgesia in KOA mice,a therapeutic mechanism that possibly mediated through the inhibition of the HMGB1/CXCL12/CXCR4 signaling axis.

Objective:This study analyzed the epidemiological characteristics of the clustered cases of severe fever with thrombocytopenia syndrome (SFTS) in Jiangsu province, so as to provide a scientific basis for prevention and control efforts.Methods:In this study we searched for cases related to clustered outbreaks and conducted epidemiological investigations of the cases, their co-exposed individuals, and close contacts. The basic information of the cases and their disease progression were collected and documented. The source of infection and transmission routes were analyzed. Fisher’s exact probability test and independent samples t-test were used to compare the differences between index and secondary cases. Results:From 2018 and 2024, a total of nine cluster outbreaks were reported in Jiangsu province, involving 32 cases of SFTS with 12 fatalities. Seven clustered outbreaks occurred in rural communities, while two occurred in medical institutions. The primary cause of these outbreaks was direct contact with confirmed cases.Conclusions:In recent years, Jiangsu province has experienced multiple clustered outbreaks of SFTS. Targeted health education should be implemented in high-risk areas to increase awareness of personal protective measures. Medical institutions should standardize the management of confirmed cases, educate patients′ families about prevention and control measures, and strengthen training for healthcare workers to ensure effective infection control within hospitals.

BACKGROUND:Osteoporosis is a common comorbidity in patients with knee osteoarthritis.The impact of osteoporosis on the prognosis of unicompartmental knee arthroplasty is a trending topic of current research. OBJECTIVE:To investigate the effect of different bone densities on the stress value and stress distribution of each structure in the joint after unicompartmental knee arthroplasty using finite element analysis,and to evaluate the correlation between osteoporosis and complications. METHODS:CT and MRI were adopted to obtain the lower limb image data of a volunteer.Geomagic Studio,Ansys workbench,and Mimics were used to establish a finite element model of the knee joint with normal sclerotin condition(T-value≥-1.0).The finite element model of the knee joint with osteopenia(-2.5

Objective To investigate the clinicopathological features,immunophenotypes,molecular genetic alterations,and prognosis of succinate dehydrogenase-deficient renal cell carcinoma(SDH-RCC).Methods A total of 11 cases of SDH-RCC diagnosed at West China Hospital,Sichuan University between 2016 and 2023 were selected for clinicopathological,immunohistochemical,and DNA sequencing analyses.Results Among the 11 cases of SDH-RCC,there were 5 male patients and 6 female patients.The patients'ages ranged from 12 to 71 years,with an average age of 39.7 years.Among them,5 patients had tumors located in the right kidney,5 had tumors located in the left kidney,and 1 patient had bilateral tumors.Microscopic observation showed that the tumor cells of the SDH-RCC patients displayed a wide spectrum of structures,forming sheet-like,nested,and glandular structures.In addition,tumor cells in papillary structures were observed in some cases.The tumor cells had abundant cytoplasm,was eosinophilic,and contained flocculent materials.Intracytoplasmic vacuolations were observed in some of the cells.Among all the patients,7(7/11,63.6％)showed typical low-grade features(grade 1-2 according to the International Society of Urological Pathology[ISUPJ/WHO 2016 classification),and 4(4/11,36.4％)showed high-grade features(grade 3 according to the ISUP/WHO 2016 classification).The average ages of patients with low-grade and high-grade features were 32.1 years and 58.0 years,respectively.Immunohistochemical staining of all 11 cases demonstrated negative results for SDHB and cytokeratin 7(CK7),and positive staining results for paired box 8(PAX-8),fumarate hydratase(FH),and epithelial membrane antigen(EMA).Their Ki-67 index was l％-30％.In one case,the loss of SDHB expression was also accompanied by a loss of SDHA expression.Sanger sequencing was performed to examine all the exons of SDHB in 7 cases.One case showed a frameshift mutation,c.236Tdel(p.K80Rfs*),and another case harbored a missense mutation,c.725G＞A(p.Arg242His).In another case,next generation sequencing revealed that large fragments of SDHB(Exon 4-8 del)were missing.Follow-up data were available for 10 patients.The follow-up time ranged from 4 to 138 months,with the average being 32.8 months,and all patients survived.Metastasis and recurrence were reported in 5 cases,with 3 of them showing high-grade features and 2 showing low-grade features.Conclusion SDH-RCC is rare and the patients demonstrate a relatively young age of onsets.Patients may present with bilateral tumors.Tumors with low-grade features usually occur in young patients,with their Ki-67 index usually being lower than 5％.Individual cases may experience tumor recurrence and metastasis over a long period of follow-up.Tumors with high-grade features tend to occur in older patients who have a higher Ki-67 index,and who are prone to recurrence and metastasis.Negative immunohistochemical staining results for SDHB can assist in tumor diagnosis,but the loss of SDHB protein expression does not necessarily lead to the detection of SDHB gene mutation.

Objective:To investigate the effects of Satir model group intervention on stress coping style, self-consistency and congruence and subjective well-being of re-employment nurses, in order to provide evidence for nursing managers to take targeted intervention measures.Methods:This was a quasi-experimental study. Convenience sampling was used to select 63 re-employment nurses from Shandong Provincial Third Hospital in 2021 as the research objects. The re-employment nurses were divided into control group (32 cases) and observation group (31 cases) by random number table method. The control group received humanistic care including heart-to-heart talk, group discussion and psychological lecture, and the observation group received Satir model group intervention for 6 weeks. Simplified Coping Style Questionnaire, Self Consistency and Congruence Scale and General Well-Being Scale were used to evaluate the intervention effect before intervention, immediately after intervention, 3 months after intervention, and 6 months after intervention.Results:There was no significant difference in coping style, self-consistency and congruence and subjective well-being between the two groups before intervention ( P>0.05). The positive coping scores of the observation group immediately after intervention, 3 months after intervention and 6 months after intervention were (28.94 ± 2.99), (28.71 ± 4.70) and (29.16 ± 3.23) points, significantly higher than the control group (23.38 ± 5.50), (24.72 ± 5.91), (24.65 ± 5.65) points, the differences were statistically significant ( t=4.96, 2.96, 3.87, all P<0.01); the total self-consistency and congruence scores were (94.52 ± 14.00), (99.87 ± 16.82), (91.84 ± 10.36) points, significantly lower than the control group (105.72 ± 10.75), (114.23 ± 20.10), (107.41 ± 13.39) points, the differences were statistically significant ( t=-3.57, -3.07, -5.15, all P<0.01); the total subjective well-being scores were (84.97 ± 7.37), (84.58 ± 10.33), (91.84 ± 7.01) points, which were higher than the control group (75.69 ± 7.94), (77.28 ± 8.27), (77.00 ± 8.48) points, and the differences were statistically significant ( t=4.80, 3.69, 7.56, all P<0.01). Conclusions:Satir model group intervention can improve the coping style, enhance the level of self-consistency and congruence and subjective well-being among re-employment nurses.

Self-organized blastoids from extended pluripotent stem (EPS) cells possess enormous potential for investigating postimplantation embryo development and related diseases. However, the limited ability of postimplantation development of EPS-blastoids hinders its further application. In this study, single-cell transcriptomic analysis indicated that the "trophectoderm (TE)-like structure" of EPS-blastoids was primarily composed of primitive endoderm (PrE)-related cells instead of TE-related cells. We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure. Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation. Furthermore, we demonstrated that blastocyst-like structures reconstituted by combining the EPS-derived bilineage embryo-like structure (BLES) with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses. In summary, our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.
Pregnancy ; Female ; Animals ; Mice ; Tetraploidy ; Blastocyst ; Embryo, Mammalian ; Cell Differentiation ; Embryonic Development

Chemically defined medium is widely used for culturing mouse embryonic stem cells (mESCs), in which N2B27 works as a substitution for serum, and GSK3β and MEK inhibitors (2i) help to promote ground-state pluripotency. However, recent studies suggested that MEKi might cause irreversible defects that compromise the developmental potential of mESCs. Here, we demonstrated the deficient bone morphogenetic protein (BMP) signal in the chemically defined condition is one of the main causes for the impaired pluripotency. Mechanistically, activating the BMP signal pathway by BMP4 could safeguard the chromosomal integrity and proliferation capacity of mESCs through regulating downstream targets Ube2s and Chmp4b. More importantly, BMP4 promotes a distinct in vivo developmental potential and a long-term pluripotency preservation. Besides, the pluripotent improvements driven by BMP4 are superior to those by attenuating MEK suppression. Taken together, our study shows appropriate activation of BMP signal is essential for regulating functional pluripotency and reveals that BMP4 should be applied in the serum-free culture system.
Animals ; Bone Morphogenetic Protein 4/metabolism* ; Cell Differentiation ; Chromosomal Instability ; Endosomal Sorting Complexes Required for Transport ; Mice ; Mitogen-Activated Protein Kinase Kinases/metabolism* ; Mouse Embryonic Stem Cells/cytology* ; Pluripotent Stem Cells/cytology* ; Signal Transduction ; Ubiquitin-Conjugating Enzymes

Objective: To investigate the content of persistent organic pollutants (POPs) in fish from Dongting Lake. Methods: Ten sample collection points were set in lakeside city Yueyang and Yuanjiang. In July (wet season) and November (dry season) of 2012, 13 common fish species were captured by convenience sampling in Dongting Lake. Two to three fish with similar weight were selected in each season for the same species of fish. After sample preparation and pretreatment, the contents of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), dioxin-like polychlorinated biphenyls (dl-PCBs), indicator polychlorinated biphenyls and polybrominated diphenyls ether (PBDEs) in the samples were determined by high resolution gas chromatographer-high resolution mass spectrometry. Toxicity Equivalents (TEQ) of PCDD/Fs and dl-PCBs were calculated according to the revised toxicity equivalent factor (TEF) of WHO in 2005. The contents of POPs were expressed by median and quavtile. The differences of POPs in fish in different periods were compared by Wilcoxon rank sum test. Results: The content of PCDD/Fs of fish in Dongting Lake in wet season was 12.397 (8.865, 24.964) pg/g, higher than that in the dry season 0.771 (0.490, 1.442) pg/g (P<0.001), and the toxicity equivalent quantity (TEQ) were 0.150 (0.066,0.528) and 0.143 (0.066, 0.235) pg-TEQ/g without statistically significant difference (P>0.05). For the fish in wet and dry season from Dongting Lake,∑dl-PCBs of fish were 66.475 (28.065, 77.794) and 24.205 (18.237, 90.777) pg/g, respectively, and the TEQ were 0.061 (0.046, 0.268) and 0.075 (0.054, 0.182) pg-TEQ/g; ∑ indicative PCBs were 237.764 (153.896, 335.483) and 119.711 (52.171, 408.696) pg/g, respectively; ∑ PBDEs were 106.513 (64.834, 164.860) and 86.837 (61.872, 177.108) pg/g, respectively. The highest content of PCDD/Fs was found in grass carp (198.360 pg/g) in wet season. The higher content of PCBs was found in long-necked fish (2 332.509 pg/g) and PBDEs was found in pelteobagrus fulvidraco (343.857 pg/g), respectively. Conclusion A lower burden was found in fishes from Dongting Lake, and the content of POPs varied in different seasons and fishes.