Solid forms,such as polymorphs and co-crystals,can improve the physicochemical properties of drugs without changing their molecular structure,increasing their solubility,bioavailability,stability,and thus affecting their original pharmacodynamic activity.Estradiol and its derivatives ethinylestradiol and estriol,contain steroidal parent nucleus,which results in a very low water solubility.Researches showed that polymorphism and co-crystal studies could enhance the water solubility of estradiol and its derivatives.This paper reviews the research progress on the solid forms of estradiol and its derivatives in last decade.

This document targets digital human metabolic chamber platforms and specifies construction standards and testing protocols covering the full lifecycle of " build-test-operate." It encompasses chamber engineering and environmental control, digital platform and cybersecurity architecture, metabolic measurement and multimodal data acquisition, as well as quantitative system performance and data quality indicators with verifiable acceptance tests. By standardizing architecture, interfaces, and quality control, the specification enables multicenter data interoperability and harmonized quality management, providing high-quality, verifiable, and traceable infrastructure to support precision metabolism research and clinical translation in China.

Solid forms,such as polymorphs and co-crystals,can improve the physicochemical properties of drugs without changing their molecular structure,increasing their solubility,bioavailability,stability,and thus affecting their original pharmacodynamic activity.Estradiol and its derivatives ethinylestradiol and estriol,contain steroidal parent nucleus,which results in a very low water solubility.Researches showed that polymorphism and co-crystal studies could enhance the water solubility of estradiol and its derivatives.This paper reviews the research progress on the solid forms of estradiol and its derivatives in last decade.

Objective:To explore the potential mechanisms of autophagy suppressing the activation of pro-inflammatory macro-phages.Methods:Macrophage-specific knockout mice(Atg5△mye)was generated by the hybridization of Lyz2-Cre mice and Atg 5flox/+mice.Bone marrow cells were differentiated into bone marrow-derived macrophages(BMDMs)induced by monocyte colony-stimulating factor.The expressions of endoplasmic reticulum stress(ER stress)-related proteins,such as glucose regulatory protein 78(GRP78),autophagy-related marker LC3-Ⅱ and p62,and pro-inflammatory iNOS,were detected by Western blot.GO analysis was performed on BMDMs from Atg5flox/flox and Atg5△mye mice stimulated by LPS.Tauroursodeoxycholate(TUDCA)or ATF6 inhibitor Ceapin-A7 was used to suppress the ER stress in BMDMs.Results:LPS promoted the expression of ER stress-related proteins and the activation of pro-in-flammatory macrophages,while inhibiting autophagy in BMDMs.By utilizing proteomic detection and GO enrichment analysis,it was found that the autophagy deficiency in BMDMs caused changes in the ATF6 pathway,a key downstream pathway of ER stress.Inhibi-tion of ER stress by TUDCA significantly down-regulated the expression of iNOS and the secretion of inflammatory cytokines IL-18 and IL-1β in autophagy-deficient BMDMs.ATF6-specific inhibitor(Ceapin-A7)was used to exculpate LPS-stimulated BMDMs,and it was found that Ceapin-A7 significantly down-regulated the elevated expression of iNOS and inflammatory factors caused by Atg5 deletion in BMDMs.Conclusion:Autophagy inhibits the activation of pro-inflammatory macrophages by suppressing ATF6 pathway.

Objective:To explore the potential mechanisms of autophagy suppressing the activation of pro-inflammatory macro-phages.Methods:Macrophage-specific knockout mice(Atg5△mye)was generated by the hybridization of Lyz2-Cre mice and Atg 5flox/+mice.Bone marrow cells were differentiated into bone marrow-derived macrophages(BMDMs)induced by monocyte colony-stimulating factor.The expressions of endoplasmic reticulum stress(ER stress)-related proteins,such as glucose regulatory protein 78(GRP78),autophagy-related marker LC3-Ⅱ and p62,and pro-inflammatory iNOS,were detected by Western blot.GO analysis was performed on BMDMs from Atg5flox/flox and Atg5△mye mice stimulated by LPS.Tauroursodeoxycholate(TUDCA)or ATF6 inhibitor Ceapin-A7 was used to suppress the ER stress in BMDMs.Results:LPS promoted the expression of ER stress-related proteins and the activation of pro-in-flammatory macrophages,while inhibiting autophagy in BMDMs.By utilizing proteomic detection and GO enrichment analysis,it was found that the autophagy deficiency in BMDMs caused changes in the ATF6 pathway,a key downstream pathway of ER stress.Inhibi-tion of ER stress by TUDCA significantly down-regulated the expression of iNOS and the secretion of inflammatory cytokines IL-18 and IL-1β in autophagy-deficient BMDMs.ATF6-specific inhibitor(Ceapin-A7)was used to exculpate LPS-stimulated BMDMs,and it was found that Ceapin-A7 significantly down-regulated the elevated expression of iNOS and inflammatory factors caused by Atg5 deletion in BMDMs.Conclusion:Autophagy inhibits the activation of pro-inflammatory macrophages by suppressing ATF6 pathway.

This document targets digital human metabolic chamber platforms and specifies construction standards and testing protocols covering the full lifecycle of " build-test-operate." It encompasses chamber engineering and environmental control, digital platform and cybersecurity architecture, metabolic measurement and multimodal data acquisition, as well as quantitative system performance and data quality indicators with verifiable acceptance tests. By standardizing architecture, interfaces, and quality control, the specification enables multicenter data interoperability and harmonized quality management, providing high-quality, verifiable, and traceable infrastructure to support precision metabolism research and clinical translation in China.

Objective: The genetic characteristics of the human adenovirus type 53 (HAdV-53) strains isolated from Taiyuan city of Shanxi Province were studied to obtain the baseline data of their molecular characteristics. Methods: Conjunctival swabs (n=79) were collected from epidemic keratoconjunctivitis (EKC) patients in Shanxi eye Hospital in 2016, and five HAdV-53 strains were obtained after virus isolation and identification based on the three major capsid genes sequences including Penton base, Hexon and Fiber gene. And the corresponding sequences of global epidemic HAdV-53 strains and the strains with the same genetic origin as HAdV-53 were also downloaded from GenBank database, and then the three gene database were established, respectively. With the database, phylogenetic tree was constructed, and the genetic and molecular evolutionary characteristics were analyzed with bioinformatics software. Results: Five HAdV-53 strains in Shanxi Province in 2016 showed high consistency with the HAdV-53 strains prevalent in other countries in 1996-2014 (>99.8%). All HAdV-53 strains were in the same evolutionary branch with their recombinant source genotypes (HAdV-37 and HAdV-8) in Penton base and Fiber gene, respectively, and maintained a high degree of consistency in gene sequences. In Hexon gene, HAdV-53 strains were more closed to its recombinant source genotype HAdV-22, the nucleotide and amino acid sequences between two types were highly homologous, while HAdV-53 and HAdV-22 belonged to different evolutionary branches, and the evolution rate of HAdV-53 based on Hexon gene was 3.51×10^-5 substitution/site/year. Conclusion HAdV-53 has become an important new ocular infectious pathogen of Taiyuan. HAdV-53 strain are relatively conservative and stable based on Penton base, Hexon, and Fiber gene.

Objective: To evaluate our replantation and functional reconstruction of amputated lower extremities. Methods: From February 2013 to October 2017, 13 patients with an amputated lower extremity were treated at Orthopaedic Department, The 960th Hospital of the PLA Joint Logistics Support Force. They were 10 males and 3 females, aged from 15 to 63 years (average, 39 years). In all the patients, large segmental shortening and extremity replantation was conducted at the first stage and Ilizarov extremity lengthening at the secondary stage. After desired extension was achieved, the frame of Ilizarov external fixator was removed and replaced by external fixation with a locking plate under closed reduction. Postoperatively, functions of the knee and ankle joints, sensory recovery of the foot sole, length and appearance of the extremity were observed. Results: All the 13 patients were followed up for 12 to 24 months (average, 16 months). All the limb replants survived well. Of them, 12 were satisfied with their weight-bearing walking and therapeutic outcomes. Conclusions For an amputated lower extremity, the first-stage shortening and replantation can result in fine extremity salvage and the secondary Ilizarov extremity lengthening can lead to fine therapeutic outcomes.

Objective To prepare biomimetic bone material by reconstructing type Ⅰ collagen combined with polyaspartic acid. Methods By acid hydrolysis,rat tail type Ⅰ collagen was decomposed into collagen fibers,which were then placed in the calcium phosphate mineralization solution. Under the cross-linking of glutaraldehyde,the collagen fibers were reconstructed and assembled into collagen fibers,and the calcium phosphate crystals were wrapped in the inner side of the collagen fibers for biomineralizationin. After poly aspartate acid was added,calcium hydroxyapatite calcium precursor was added into the collagen fibers to simulate thebiomimetic biomineralizationin the human body. After mineralization for 3-9 days,the bone mineralization process was observed by transmission electron microscopy and electron diffraction. Results Transmission electron microscopy and electron diffraction displayed that,after 3 days of mineralization,calcium hydroxyapatite precursor was wrapped in the collagen fiber gap,and the collagen fiber was partially mineralized. After 9 days of mineralization,calcium hydroxyapatite precursor completely infiltrated into the collagen fiber,and the amorphous calcium phosphate was transformed into hydroxyapatite calcium crystal. Thus,the simulation of bone mineralization was completed,and collagen type Ⅰ collagen/hydroxyapatite calcium biomimetic bone material was formed. Conclusion Reconstruction of type Ⅰ collagen combined with polyaspartic acid can prepare biomimetic bone material that has close chemical composition and molecular structure to the human bone tissue.

Objective To explore the curative efficacy of treating tibial transport gap fracture after bone transport by external fixation with locking compression plate(LCP) and autologous iliac grafting.Methods From February 2015 to January 2016,9 patients who had sustained tibial transport gap fracture after bone transport were treated by LCP external fixation and autologous iliac grafting.They were 7 men and 2 women,aged from 26 to 56 years (average,40.2 years).One of them received bone transport because of limb shortness after replantation and others did because of traumatic osteomyelitis.The distances of tibial transport averaged 9.2 cm (from 7 to 12 cm);the time for external fixation averaged 20.1 months (from 13 to 25 months);the time from removal of external fixator to gap fracture averaged 1.8 weeks (from 1 to 3 weeks).Two patients were complicated with docking site fracture.The durations from gap fracture to operation averaged 4.1 days (from 3 to 5 days).Five patients sustained angular deformity of various severities which could not be corrected by surgery.The curative efficacy was evaluated according to conventional criteria for fracture healing.Results The 9 patients were followed up for 11 to 15 months (average,13.1 months).The time for LCP external fixation averaged 9.0 months (from 8 to 10 months);the time for fracture union averaged 4.6 months (from 4 to 5 months).The 5 patients with angular deformity obtained fracture malunion which did not obviously affect their limb appearance.One case suffered extensive cellulitis at the leg which responded to intravenous administration of antibiotics.No pin track infection happened.The knee and ankle functions after removal of LCP external fixation were not significantly different from those after removal of external fixator following bone transport.Wounds at the iliac donor site and bone graft area all healed well.Conclusions LCP external fixation is an effective treatment for tibial transport gap fracture after bone transport,due to its stable fixation,limited injury to soft tissues,positive curative efficacy and miniature size as well.However,it requires sophisticated operative skills and demanding postoperative care.