A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

Objective To investigate the size variation in the first metatarsal of extant primates.Methods In this study,we analyzed 135 first metatarsal specimens across 12 primate genera,quantifying eight linear measurements,articular surface areas,mid-shaft cross-sectional area,total surface area,volume,and derived indices.Multivariate patterns were assessed through mean-based correspondence analysis and principal component analysis(PCA).Results Eulemur,Otolemur,Cebus,and Perodicticus exhibited a relatively high metatarsal surface-area-to-volume ratio.Perodicticus additionally showed a low articular facet index.Propithecus,Colobus,and Macaca displayed lower values for metatarsal shaft robusticity,the ratio of shaft cross-sectional area to base articular surface area,and the proximal articular facet index.Nasalis possessed a relatively high articular facet index.Pongo,Pan,Gorilla,and Homo sapiens were characterized by higher metatarsal shaft robusticity and a lower metatarsal surface-area-to-volume ratio.Principal component analysis revealed that the 12 extant primate genera could be broadly divided into two groups.Group 1 comprised Pongo,Pan,Gorilla and H.sapiens,although H.sapiens formed a distinct cluster relative to the extant great apes.Group 2 included Eulemur,Otolemur,Perodicticus,Propithecus,Cebus,Colobus,Macaca and Nasalis.Conclusion The relative sizedistribution of the first metatarsal provides some reference value for classifying extant primates.However,it demonstrates no clear correlations with specific locomotor patterns or foot grasping ability.

Objective To explore the relationship between the M1/M2 macrophages and severity of diabetic retinopathy(DR).Methods This retrospective study included 42 patients with or without DR who had type 2 diabetes mellitus(T2DM)and 19 healthy individuals undergoing cataract intraocular surgery without systemic or ocular diseases from Handan Central Hospital between April 2022 and November 2023.Patients with T2DM were divided into three groups:diabetes mellitus with non-dominant diabetic retinopathy(T2DM non-DR group,n=20),mild and moderate non-proliferative diabetic retinopathy(NPDR)(n=10)and severe NPDR/proliferative diabetic retinopathy(PDR)(n=12).Peripheral blood and aqueous humor were obtained at surgery initiation.The levels of VEGF-A,IL-8,Elafin and TGF-β in the samples were analyzed using kits,and the ratio of M1 macrophages to M2 macrophages was analyzed by flow cytometry.Results Among patients with T2DM,there were significant differences in the duration of diabetes,insulin and metformin use among the three groups(P<0.05).Aqueous humor levels of VEGF-A,IL-8,Elafin,M1 ratio,M2 ratio and TGF-β of each group were significantly different(F=17.40,9.492,4.792,11.32,5.768 and 20.38,all P<0.01).The levels of VEGF-A,IL-8,Elafin,M1 ratio,VD86 and TGF-β in severe NPDR/PDR group were significantly higher than those in healthy control group and T2DM non-DR group(P<0.05),and the levels of VEGF-A,IL-8 and Elafin in severe NPDR/PDR group were significantly higher than those in mild and moderate NPDR group(P<0.05).The levels of M1 proportion and TGF-β in aqueous humor of the mild to moderate NPDR group were significantly higher than those in healthy control group and T2DM non-DR group(P<0.05).The level of M1 in aqueous humor was positively correlated with the levels of M2,Elafin,TGF-β and VEGF-A(r=0.260,0.411,0.726 and 0.304,all P<0.05),and the level of M2 was positively correlated with the levels of Elafin and TGF-β(r=0.865,0.552,all P<0.01).Conclusion The elevation of IL-8 and M1 macrophages in the aqueous humor may promote the occurrence of DR,while the increase of Elafin and M2 macrophages may be a compensatory regulation to chronic inflammation,which is involved in the regulation of local microvascular lesions and fibrosis.

Objective:To retrospectively analyze the anesthetic management characteristics of children undergoing resection of pheochromocytoma and paraganglioma (PPGL).Methods:The clinical data from patients undergoing resection of PPGL and confirmed histologically from January 1, 2010 to June 30, 2023 were retrospectively collected. The baseline characteristics, intraoperative conditions and postoperative complications were recorded.Results:The clinical data from 47 pediatric patients were analyzed. The overall incidence of hemodynamic instability events was 68% (32 cases). Lowering preoperative blood pressure to normal levels and the maximum diameter of tumor≥6 cm was helpful in reducing the incidence of the intraoperative hemodynamic instability events ( P<0.05). Postoperative hypotension developed in 7 cases, acute left heart failure in 1 case, arrhythmia in 1 case, adrenocortical insufficiency in 4 cases, and pulmonary infection in 13 cases. Conclusions:Thorough preoperative preparation, evidence-based anesthetic management, and meticulous postoperative vital sign monitoring can increase the perioperative safety for children undergoing resection of PPGL, thereby reducing the incidence of complications.

Objective To observe the therapeutic effect of curculioside on rats with ulcerative colitis(UC),and to explore its regulatory effect on the protein extracellular regulated kinases(PERK)/activated transcription factor 4(ATF4)/enhancer-binding protein(C/EBP)homologous protein(CHOP)pathway.Methods Sixty-one SD rats were induced by trinitrobenzene sulfonic acid(TNBS)to establish UC model.According to the random number table,they were divided into low,medium and high dose curculioside groups(25,50 and 100 mg/kg citronelioside dissolved in normal saline),mesalazine group(500 mg/kg mesalazine dissolved in normal saline),PERK inhibitor group(GSK2606414 1.0 mg/kg dissolved in normal saline),and model group(normal saline),and another 10 healthy SD rats were recorded as the normal group(normal saline),and the volume of normal saline was 1ml/100g the body weight of rats,gavaged once a day for 10 consecutive days.On the day after the end of administration,disease activity index(DAI)was evaluated.The ratio of lactulose(L)to mannitol(M)excretion rate(L/M)in the 5-hour urine of two groups of rats was determined by Gas chromatography(GC).Double antibody sandwich method was used to measure serum glucocorticoid concentration,and enzyme-linked immunosorbent assay was used to detect serum interleukin-6(IL-6),interferon-γ(IFN-γ),interleukin-8(IL-8)and tumor necrosis factor-α(TNF-α)levels.Hematoxylin eosin(HE)staining was used to observe the pathological changes of the intestinal mucosa.Real time reverse transcription fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to detect the expression of PERK,ATF4,CHOP,Bcl2 associated X protein(Bax),B lymphoblastoma 2(Bcl-2)messenger RNA(mRNA)in intestinal mucosa.Immunoblotting(WB)was used to detect the expression of PERK,ATF4,CHOP,Bax,and Bcl-2 proteins in intestinal mucosal tissue,as well as the levels of phosphorylated PERK(p-PERK).Results Visual and HE staining observations confirmed successful modeling.Compared with the normal group,the model group had L/M,DAI and intestinal mucosal pathological score,serum glucocorticoid concentration,and serum IL-6,IFN-γ,IL-8 and TNF-α levels,mRNA and protein expressions of PERK,ATF4,CHOP,Bax,and p-PERK increased(P＜0.05),while the mRNA and protein expressions of Bcl-2 decreased(P＜0.05).Compared with the model group,the L/M,DAI and intestinal mucosal pathological scores,serum glucocorticoid concentration,and serum IL-6,IFN-γ,IL-8 and TNF-αlevels,mRNA and protein expressions of PERK,ATF4,CHOP,Bax,and p-PERK of the three dose curculioside groups,mesalazine group,and PERK inhibitor group decreased(P＜0.05),while the mRNA and protein expressions of Bcl-2 increased(P＜0.05).There were no significant differences in glucocorticoid concentration,PERK,ATF4,CHOP,Bax,Bcl-2 mRNA and protein expressions,p-PERK levels between the low dose curculioside group and the mesalazine group,between the medium dose curculioside group and the PERK inhibitor group(P＞0.05),and there were significant differences between each other two groups(P＜0.05).The pathological changes of colonic mucosa in the model group were serious.The low dose curculioside group was relieved,the medium dose curculioside group,the Mesalazine group and the PERK inhibitor group were significantly relieved,and the high-dose group of citronelloside was significantly relieved.Conclusion Curculioside can improve intestinal mucosal barrier function,control disease activity,and alleviate pathological changes in UC rats,which is speculated to be related to the inhibition of the PERK/ATF4/CHOP pathway.

In recent years, with the problem of aging population in China being prominant, the number of patients with chronic wounds such as diabetic foot, pressure ulcer, and vascular ulcer is increasing. Those diseases seriously affect the life quality of patients and increase the economy and care burden of the patients' family, which have been one of the most urgent clinical problems. Many researches have confirmed that adipose stem cells can effectively promote wound healing, while exogenous protease is needed, and there are ethical and many other problems, which limit the clinical application of adipose stem cells. Adipose stem cell matrix gel is a gel-like mixture of biologically active extracellular matrix and stromal vascular fragment obtained from adipose tissue by the principle of fluid whirlpool and flocculation precipitation. It contains rich adipose stem cells, hematopoietic stem cells, endothelial progenitor cells, and macrophages, etc. The preparation method of adipose stem cell matrix gel is simple and the preparation time is short, which is convenient for clinical application. Many studies at home and abroad showed that adipose stem cell matrix gel can effectively promote wound healing by regulating inflammatory reaction, promoting microvascular reconstruction and collagen synthesis. Therefore, this paper summarized the preparation of adipose stem cell matrix gel, the mechanism and problems of the matrix gel in promoting wound repair, in order to provide new methods and ideas for the treatment of chronic refractory wounds in clinic.
Humans ; Aged ; Wound Healing/physiology* ; Adipocytes ; Adipose Tissue ; Extracellular Matrix ; Stem Cells

Objective: To prepare a composite membrane by chitosan/β-sodium glycerophosphate(CS/β-GP) thermosensitive hydrogel combined with stromal cell derived factor-1(SDF-1) and observe its biological characteristics in vitro. Methods: Different doses of SDF-1 were added into CS/β-GP solution and then the thermosensitive gel time was measured. The SDF-1/CS/β-GP solution was membrane paved and dried to prepare composite membranes. The morphological characteristics were observed by scanning electron microscope(SEM). Composite membranes were placed into cell culture medium, and the supernatant(n=3) was extracted after standing at 6, 12, 24, 36, 48, 60 h, respectively. The concentration of SDF-1 in the solution was measured. Bone mesenchymal stem cells(BMSCs) were cultured in the Transwell room, and the composite membranes containing different concentrations of SDF-1 were placed in the lower chamber. There were four groups(n=3): Group M0 used CS/β-GP membrane(control group), Group M1, M2, M3 used SDF-1/CS/β-GP membrane(SDF-1 was 100, 200, 400 ng/mL respectively). After culture for 6, 12 and 24 h, the cells under the membrane were preserved and Giemsa stained and counted. The absorbance(OD) value was measured by MTT method to calculate the cell proliferation rate. SPSS 19.0 was used for multi-factor analysis of variance. Results : After adding a certain amount of SDF-1 into CS/β-GP solution, the gel time did not change significantly(P>0.05). The SDF-1/CS/β-GP membrane was translucent and porous at 37 ℃. In this experiment, the volumic mass of SDF-1 released by SDF-1/CS/β-GP composite membrane increased gradually with the experimental time(P<0.01). Transwell cell chemotaxis test showed that the number of BMSCs cells with directional migration increased with the prolongation of observation time(P<0.01) and the increase of SDF-1 volumic mass(P<0.01). In MTT test, the OD value of migration cell solution increased with the prolongation of time(P<0.01) and the increase of SDF-1 volumic mass(P<0.01). Conclusion The SDF-1/CS/β-GP composite membrane has a porous structure and biological activity of chemotactic BMSCs directional migration. It is a potential membrane for guided tissue regeneration.

As one of the most attention-attracting immunotherapy, immune checkpoint inhibitors (ICIs) have been approved as the first-line drugs for the therapy of various types of cancers.Nevertheless, the single application of ICIs exhibited limited efficacy, and it is easy to develop drug resistance.Therefore, the development of combination therapies become a hot topic in this field to improve the efficacy of ICIs therapy.This article describes some new ICIs targets, reveals the mechanisms of resistance, and introduces the current status of combination other therapies with ICIs therapy systematically including chemotherapy, radiotherapy, hyperthermia, antiangiogenic therapy, tumor vaccines, cytokine therapy and adoptive cellular therapy.Furthermore, the synergistic mechanism of combination therapy to enhance antitumor effect.Thus, this article provides solid references for personalized combination therapy according to the pathological characteristics of patients.

ObjectiveTo validate the alleviating effect of Gegen Qinliantang （GGQLT） on insulin resistance in db/db diabetic mice by regulating the silent information regulator 1 （SIRT1）/forkhead transcription factor O1 （FoxO1） autophagy pathway. MethodSeventy-five SPF-grade spontaneous type 2 diabetic db/db mice and 15 control db/m mice were selected and maintained on regular feed for one week before measuring blood glucose. They were randomly divided into six groups， with 15 mice in each group. The groups included a normal group （physiological saline， 0.2 g·kg^-1）， a metformin group （0.2 g·kg^-1）， high-， medium-， and low-dose GGQLT groups （31.9， 19.1， 6.9 g·kg^-1）， and a model group （physiological saline， 0.2 g·kg^-1）. They were orally treated with corresponding drugs for eight weeks， once daily. Fasting blood glucose （FBG） was measured using a Roche glucometer. Serum levels of high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， triglyceride （TG）， and total cholesterol （TC） were measured using an automated biochemical analyzer. Fasting serum insulin （INS） levels were determined using enzyme-linked immunosorbent assay （ELISA）， and the homeostasis model assessment of insulin resistance （HOMA-IR） was calculated. Western blot was used to detect the expression of Beclin-1， microtubule-associated protein 1 light chain 3 （LC3）， and SIRT1/FoxO1 autophagy pathway-related proteins in liver tissues. Immunohistochemistry was performed to assess the expression of SIRT1， FoxO1， Beclin-1， and LC3B proteins in liver tissues. Transmission electron microscopy was used to observe the formation of autophagosomes in the liver. ResultCompared with the normal group， the model group showed significant increases in FBG， FINS， HOMA-IR， TC， TG， LDL-C， and HDL-C levels （P<0.01）， and significant increases in the expression of SIRT1， Beclin-1， LC3， and FoxO1 proteins in liver tissues （P<0.01）. Transmission electron microscopy revealed the highest number of autophagosomes in the model group. Compared with the model group， the metformin group and the low-， medium-， and high-dose GGQLT groups showed significant decreases in serum FBG， FINS， HOMA-IR， TC， TG， LDL-C， and HDL-C levels （P<0.05， P<0.01）， significant decreases in the expression of SIRT1， Beclin-1， LC3 （P<0.05， P<0.01）， and up-regulated FoxO1 protein （P<0.01）. Transmission electron microscopy showed a reduction in the degree of autophagy in the treatment groups. Compared with the metformin group， the medium- and high-dose GGQLT groups showed significant decreases in FBG， FINS， and TG levels （P<0.01）， significant decreases in the expression of SIRT1， Beclin-1， and LC3 in liver tissues （P<0.05， P<0.01）， and reduced FoxO1 protein （P<0.01）. The high-dose GGQLT group showed reduced HOMA-IR， TC， LDL-C， and HDL-C levels （P<0.05， P<0.01）. Transmission electron microscopy revealed a significant reduction in autophagosomes in the medium- and high-dose GGQLT groups. ConclusionGGQLT can significantly improve glucose and lipid metabolism disorders， alleviate insulin resistance in db/db mice， and prevent and treat type 2 diabetes by activating the SIRT1/FoxO1 autophagy pathway.

Objective To evaluate the efficacy and safety of the new left ventricular circulation assist device iVAC 2L in high-risk percutaneous coronaryintervention(HR-PCI)in Chinese patients.Methods We reported 6 PCIs in 5 patients supported by iVAC 2L,a new left ventricular circulation assist device,performed in Macao from September 2022 to March 2023.All patients were assessed by heart team and categorize to be high-risk for procedure.Clinical and intra-procedural data were analyzed.iVAC 2L-related complications and 30-day results were also documented.Results Insertion and removement of iVAC 2L successfully performed in all the 5 patients.Three of them underwent complete revascularization in the index procedure;one failed for the first time due to intolerance of the prolonged procedure,but succeeded for the reattempt of complete revascularization a month later,with the support of iVAC 2L.PCI was abandoned due to poor vessel condition.iVAC 2L,the new left ventricular circulation assist device,supported effectively during the 6 procedures.The patients were stable during the procedure.The success rate of hemodynamic support was 100％.No iVAC 2L-related complications and 30-day major adverse cardiac and cerebral events occurred,the 30-day survival was 100％.Conclusions Initial experience suggested that the new left ventricular circulation assist device iVAC 2L could provide effective and safe support in high-risk PCI.