Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Objective:To learn about the clinical manifestations, laboratory test results, and prognosis of patients with acute and chronic brucellosis, and to provide a scientific basis for clinical diagnosis and treatment.Methods:A retrospective study was conducted to collect the clinical data of 776 patients with brucellosis admitted to the First Affiliated Hospital of Xinjiang Medical University from January 2013 to December 2023. The patients were divided into acute phase group and chronic phase group according to the course of disease. Their clinical manifestations, laboratory test results, and prognosis were compared and analyzed between the two groups.Results:Out of 776 patients with brucellosis, 649 were in the acute phase group and 127 were in the chronic phase group. Male accounted for 71.6% (556/776). The age was (44.91 ± 0.60) years old, mainly concentrated in the age range of 46 - 60 years old (38.0%, 295/776). Farmers were the main occupation, accounting for 58.4% (453/776). The disease occurred in all months of the year, with autumn being the peak period (33.9%, 263/776). The primary clinical manifestations were fever (64.7%, 502/776) and fatigue (40.5%, 314/776). The incidence rates of fever and fatigue in the acute phase group were higher than those in the chronic phase group [70.4% (457/649) vs. 35.4% (45/127), 42.5% (276/649) vs. 29.9% (38/127)], with statistically significant differences ( χ2 = 56.91, 7.01, P < 0.05). Complications of the osteoarticular system were the most common, accounting for 47.8% (371/776). Abnormal results of blood routine examinations were mainly characterized by decreased hemoglobin, decreased lymphocytes, and decreased white blood cells, accounting for 53.7% (417/776), 32.6% (253/776), and 22.6% (175/776), respectively. The incidence rate of decreased hemoglobin in the acute phase group was higher than that in the chronic phase group [63.5% (412/649) vs. 3.9% (5/127)], with a statistically significant difference ( χ2 = 151.49, P < 0.001). The remaining abnormal laboratory test results were mainly characterized by elevated erythrocyte sedimentation rate, elevated C-reactive protein, and elevated aspartate aminotransferase, accounting for 75.1% (583/776), 50.6% (393/776), and 39.8% (309/776), respectively. The incidence rates of elevated erythrocyte sedimentation rate and elevated aspartate aminotransferase in the acute phase group were higher than those in the chronic phase group [77.8% (505/649) vs. 61.4% (78/127), 43.3% (281/649) vs. 22.0% (28/127)], with statistically significant differences ( χ2 = 15.28, 20.02, P < 0.001). The overall positive rate of Brucella blood culture was 57.5% (446/776), and there was a statistically significant difference in blood culture between the two groups ( χ2 = 17.08, P = 0.002). The positive rate of blood culture in the acute phase group was higher than that in the chronic phase group [60.1% (390/649) vs. 44.1% (56/127)]. Ninety-four point three percent (732/776) of patients were treated with antibiotics, with rifampicin + doxycycline as the main treatment regimen (45.2%, 331/732). The median of antibiotic types used in the acute and chronic phase groups were 3 and 4, respectively. The overall incidence rate of adverse drug reactions was 3.8% (28/732). Eighty-seven point five percent (625/714) of patients improved or recovered after treatment, while 12.5% (89/714) did not recover or experienced relapse. Conclusions:The main clinical manifestations of brucellosis patients are fever and fatigue, with a higher incidence of complications in the osteoarticular system, and a better prognosis. The incidence of fever, fatigue, decreased hemoglobin, elevated erythrocyte sedimentation rate, elevated aspartate aminotransferase, and positive Brucella blood culture in patients in the acute phase are higher, and the types of antibiotics used are fewer than those in patients in the chronic phase.

Objective:To learn about the clinical manifestations, laboratory test results, and prognosis of patients with acute and chronic brucellosis, and to provide a scientific basis for clinical diagnosis and treatment.Methods:A retrospective study was conducted to collect the clinical data of 776 patients with brucellosis admitted to the First Affiliated Hospital of Xinjiang Medical University from January 2013 to December 2023. The patients were divided into acute phase group and chronic phase group according to the course of disease. Their clinical manifestations, laboratory test results, and prognosis were compared and analyzed between the two groups.Results:Out of 776 patients with brucellosis, 649 were in the acute phase group and 127 were in the chronic phase group. Male accounted for 71.6% (556/776). The age was (44.91 ± 0.60) years old, mainly concentrated in the age range of 46 - 60 years old (38.0%, 295/776). Farmers were the main occupation, accounting for 58.4% (453/776). The disease occurred in all months of the year, with autumn being the peak period (33.9%, 263/776). The primary clinical manifestations were fever (64.7%, 502/776) and fatigue (40.5%, 314/776). The incidence rates of fever and fatigue in the acute phase group were higher than those in the chronic phase group [70.4% (457/649) vs. 35.4% (45/127), 42.5% (276/649) vs. 29.9% (38/127)], with statistically significant differences ( χ2 = 56.91, 7.01, P < 0.05). Complications of the osteoarticular system were the most common, accounting for 47.8% (371/776). Abnormal results of blood routine examinations were mainly characterized by decreased hemoglobin, decreased lymphocytes, and decreased white blood cells, accounting for 53.7% (417/776), 32.6% (253/776), and 22.6% (175/776), respectively. The incidence rate of decreased hemoglobin in the acute phase group was higher than that in the chronic phase group [63.5% (412/649) vs. 3.9% (5/127)], with a statistically significant difference ( χ2 = 151.49, P < 0.001). The remaining abnormal laboratory test results were mainly characterized by elevated erythrocyte sedimentation rate, elevated C-reactive protein, and elevated aspartate aminotransferase, accounting for 75.1% (583/776), 50.6% (393/776), and 39.8% (309/776), respectively. The incidence rates of elevated erythrocyte sedimentation rate and elevated aspartate aminotransferase in the acute phase group were higher than those in the chronic phase group [77.8% (505/649) vs. 61.4% (78/127), 43.3% (281/649) vs. 22.0% (28/127)], with statistically significant differences ( χ2 = 15.28, 20.02, P < 0.001). The overall positive rate of Brucella blood culture was 57.5% (446/776), and there was a statistically significant difference in blood culture between the two groups ( χ2 = 17.08, P = 0.002). The positive rate of blood culture in the acute phase group was higher than that in the chronic phase group [60.1% (390/649) vs. 44.1% (56/127)]. Ninety-four point three percent (732/776) of patients were treated with antibiotics, with rifampicin + doxycycline as the main treatment regimen (45.2%, 331/732). The median of antibiotic types used in the acute and chronic phase groups were 3 and 4, respectively. The overall incidence rate of adverse drug reactions was 3.8% (28/732). Eighty-seven point five percent (625/714) of patients improved or recovered after treatment, while 12.5% (89/714) did not recover or experienced relapse. Conclusions:The main clinical manifestations of brucellosis patients are fever and fatigue, with a higher incidence of complications in the osteoarticular system, and a better prognosis. The incidence of fever, fatigue, decreased hemoglobin, elevated erythrocyte sedimentation rate, elevated aspartate aminotransferase, and positive Brucella blood culture in patients in the acute phase are higher, and the types of antibiotics used are fewer than those in patients in the chronic phase.

The objective of present study was to develop a simple and reliable voiding spot assay (VSA) system to evaluate the lower urinary tract function of mice, and to establish it as a standardized protocol. Ultraviolet (UV) light was used to screen out the filter paper without autofluorescence and with optimal urine diffusion properties. Next, the appropriate wavelength of UV was determined based on the quality of the photographic image of urine spots on the filter paper. To confirm that the urine stain area on the filter paper was correlated with the amount of urine, a volume-area standard curve was constructed. The utility of this VSA system was validated using female wild-type C57BL/6J mice aged 12-13 weeks, and the data generated under identical procedural settings were compared among laboratories. Furthermore, this VSA system was employed to analyze the changes in voiding patterns in mice with urinary tract infections or transportation stress. No. 4 filter paper with a thickness of 0.7 mm was identified as the most suitable material for VSA, exhibiting no autofluorescence and facilitating optimal urine diffusion. The filter paper retained its integrity during the assay, and there was a linear correlation between urine volume and stained area under 365 nm UV light. Utilizing this VSA system, we determined that female wild-type C57BL/6J mice produced approximately 695.8 μL total urine and 5.5 primary voiding spots (PVS) with an average size of 126.4 μL/spot within 4-h period. Over 84% of PVS volumes ranged from 20 to 200 μL. Notably, PVS volumes of mice were similar across different laboratories. Mice with urinary tract infections or transportation stress exhibited significant changes in VSA parameters, including increased voiding frequency, PVS number, and decreased PVS volume. Therefore, this VSA system can be used to evaluate the urinary function of normal mice, as well as those with urinary tract infection or transportation stress.
Mice ; Female ; Animals ; Urodynamics ; Mice, Inbred C57BL ; Urination ; Urinary Bladder ; Urinary Tract Infections

This study aimed to investigate the effect and molecular mechanism of sinomenine on proliferation, apoptosis, metastasis, and combination with inhibitors in human hepatocellular carcinoma HepG2 cells and SK-HEP-1 cells. The effect of sinomenine on the growth ability of HepG2 and SK-HEP-1 cells were investigated by CCK-8 assay, colony formation assay, and BeyoClick~(TM) EdU-488 staining. The effect of sinomenine on DNA damage was detected by immunofluorescence assay, and the effect of sinomenine on apoptosis of human hepatocellular carcinoma cells was clarified by Hoechst 33258 staining and CellEvent~(TM) Cystein-3/7Green ReadyProbes~(TM) reagent assay. Cell invasion assay and 3D tumor cell spheroid invasion assay were performed to investigate the effect of sinomenine on the invasion ability of human hepatocellular carcinoma cells in vitro. The effect of sinomenine on the regulation of protein expression related to the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription 3(STAT3) signaling pathway in HepG2 and SK-HEP-1 cells was examined by Western blot. Molecular docking was used to evaluate the strength of affinity of sinomenine to the target cysteinyl aspartate specific proteinase-3(caspase-3) and STAT3, and combined with CCK-8 assay to detect the changes in cell viability after combination with STAT3 inhibitor JSI-124 in combination with CCK-8 assay. The results showed that sinomenine could significantly reduce the cell viability of human hepatocellular carcinoma cells in a concentration-and time-dependent manner, significantly inhibit the clonogenic ability of human hepatocellular carcinoma cells, and weaken the invasive ability of human hepatocellular carcinoma cells in vitro. In addition, sinomenine could up-regulate the cleaved level of poly ADP-ribose polymerase(PARP), a marker of apoptosis, and down-regulate the protein levels of p-Akt, p-mTOR, and p-STAT3 in human hepatocellular carcinoma cells. Molecular docking results showed that sinomenine had good affinity with the targets caspase-3 and STAT3, and the sensitivity of sinomenine to hepatocellular carcinoma cells was diminished after STAT3 was inhibited. Therefore, sinomenine can inhibit the proliferation and invasion of human hepatocellular carcinoma cells and induce apoptosis, and the mechanism may be attributed to the activation of caspase-3 signaling and inhibition of the Akt/mTOR/STAT3 pathway. This study can provide a new reference for the in-depth research and clinical application of sinomenine and is of great significance to further promote the scientific development and utilization of sinomenine.
Humans ; Carcinoma, Hepatocellular/genetics* ; Proto-Oncogene Proteins c-akt/metabolism* ; Caspase 3/metabolism* ; Liver Neoplasms/genetics* ; Molecular Docking Simulation ; Sincalide/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; Hep G2 Cells ; TOR Serine-Threonine Kinases/metabolism* ; Apoptosis

This study investigated the effect and mechanism of morin in inducing autophagy and apoptosis in hepatocellular carcinoma cells through the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription protein 3(STAT3) pathway. Human hepatocellular carcinoma SK-HEP-1 cells were stimulated with different concentrations of morin(0, 50, 100, 125, 200, and 250 μmol·L~(-1)). The effect of morin on the viability of SK-HEP-1 cells was detected by Cell Counting Kit-8(CCK-8). The effect of morin on the proliferation and apoptosis of SK-HEP-1 cells was investigated using colony formation assay, flow cytometry, and BeyoClick~(TM) EdU-488 with different concentrations of morin(0, 125, and 250 μmol·L~(-1)). The changes in the autophagy level of cells treated with morin were examined by transmission electron microscopy and autophagy inhibitors. The impact of morin on the expression levels of proteins related to the Akt/mTOR/STAT3 pathway was verified by Western blot. Compared with the control group, the morin groups showed decreased viability of SK-HEP-1 cells in a time-and concentration-dependent manner, increased number of apoptotic cells, up-regulated expression level of apoptosis marker PARP, up-regulated phosphorylation level of apoptosis-regulating protein H2AX, decreased number of positive cells and the colony formation rate, an upward trend of expression levels of autophagy-related proteins LC3-Ⅱ, Atg5, and Atg7, and decreased phosphorylation levels of Akt, mTOR, and STAT3. These results suggest that morin can promote apoptosis, inhibit proliferation, and induce autophagy in hepatocellular carcinoma cells, and its mechanism of action may be related to the Akt/mTOR/STAT3 pathway.
Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; TOR Serine-Threonine Kinases/metabolism* ; Apoptosis ; Autophagy ; Cell Proliferation ; Cell Line, Tumor ; STAT3 Transcription Factor/metabolism*

Objective:To study the policy framework and core content of assistive technology (AT) services, compare the current status of AT in countries with different levels of development, and discuss the future development of international policies and services of AT. Methods:Based on the policy and theoretical framework of AT of the United Nations (UN) and World Health Organization (WHO), the policy framework and main contents of international AT services were analyzed; the policies, assistive products and service development of AT services in countries with different levels of development worldwide were compared; and the policy and innovative technology development hotspots of international AT were explored. Results:AT service is an important component of rehabilitation services, and the development of AT services is a key step toward achieving the UN Sustainable Development Goal 3, "Ensure healthy lifestyles and promote the well-being of people of all ages". UN and WHO advocated AT services policy. The framework is based on the UN Convention on the Rights of Persons with Disabilities (CRPD) on articles related to AT, and WHO documents of AT and rehabilitation, such as World Report on Disability, the Global Plan of Action on Disability, Rehabilitation in the Health System, and Rehabilitation in the Health System: A Guide to Action, as well as WHA 71.8 on Assistive Technology, Improving Access to Assistive Technology. The core elements of the international AT policy aim to build integrated, people-centered health services, emphasize the integration of AT into the health system and rehabilitation services, establish and develop AT services in six building blocks of WHO health system, thereby improving access to quality AT to achieve universal health coverage. Further in the fields of technology and service innovation, it proposed to establish a 5P model. High-income countries and low- and middle-income countries are facing many difficulties and large differences in AT service policies, assistive product provision, and service coverage. In the future, adoption of the 5P model proposed by WHO for policy and service delivery and technological changes, and the innovation of assistive product development and AT service models will be the hot spots of AT development. Conclusion:The policy on AT at international level is centered on the concept of UN CRPD and is based on prospect of policy documents issued by the UN and WHO on AT services, with the core objective of developing AT services to provide timely, appropriate, and affordable to persons with disabilities, aging, and people needed to improve their health, quality of life and well-being. It proposes to integrate AT into universal health coverage and to deliver AT service through primary health care in order to achieve the UN SDG 3 goal with full coverage of AT. It proposes to integrate AT into rehabilitation services, i.e. leadership and governance, financing, AT professionals, AT delivery, medicine and technology, and health information system monitoring AT services. There are differneces in AT products and AT delivery due to the globel differneces in economic and social development levels and challenges in access to AT services. It is necessary to develop relevant policies, planning and innovations in assistive products and AT services. AT development in the future will focus on the 5P model of AT to implement reforms in the field of product and service delivery as well as technological innovation in order to improve the coverage, availability, accessibility and affordability, integrate AT into the health system within the framework of universal health coverage, achieve full coverage of universal AT services, and enhance the quality of AT and improve consumers' well-being.

Objective:To study the prevalence of people with disability, and the demand, service policies and service system for assistive technology (AT) services in Australia. Methods:Referring to policy recommendation and indicators in World Health Organizaion's Rehabilitation in Health Systems, Australia's assistive technology service policy framework, services development and trend of development were analyzed by the means of content analysis and development research. Results:There are about 4.4 million people with disability in Australia, of which 1.4 million (32%) with severe or profound disabilities. Federal, state and territorial governments have respectively issued legislation, policy and related service project, including the National Disability Strategy, National Disability Agreement, the National Disability Insurance Scheme, National Standards for Disability Services and others assistance programs to support disability services. There are about two million Australians with disabilities received AT services support from the mentioned programme and scheme. Australia provides more than ten thousands kinds of AT appliances per year, covering all kinds of products in WHO's Priority Assistive Products List. Conclusion:Australia has developed a federal National Disability Strategy, AT service policies and standards, and established federal and state AT insurance and financial support programs for people with disabilities based on the unmet needs of AT services, and federal and state networks for AT services have been established, and service coordination mechanisms at federal and state levels have been established through the National Disability Agreement, covering all types of people with demand of AT in Australia. It meets the requirements of the policy recommendations and assessment indicators in the WHO's Rehabilitation in Health Systems policy guidelines involving AT services. The future development areas in AT will focus on the fields of policy development, ICF implementation, service delivery system, upgrading of service quality and standard, and new technology application.

Objective:To evaluate the clinical effect of applying peroneal artery perforator flap with super-draining techniques in repairing skin defects of extremities.Methods:The data of patients with limb wounds admitted to the 990th Hospital of the Joint Logistics Support Force of the People’s Liberation Army from March 2014 to August 2019 were analyzed retrospectively. All were repaired with peroneal artery perforator flaps with super-draining techniques.Cutaneous nerves and perforating vessels were anastomosed according to the routine ratio of 1∶2.The superficial vein and the recipient veinwere matched and marked according to the relative position the diameter and length.Then one to three superficial veins were anastomosed in sequence according to the vein mark number.Upper limb wounds were evaluated by the trial standard of upper limb function evaluation of the Hand Surgery Branch of the Chinese Medical Association.Patients with lower limb wounds were evaluated by the American Orthopaedic Foot and Ankle Surgery Association Ankle-Hindfoot Score System.All patients were evaluated according to the sensory function evaluation standard of the British Medical Research Association.Results:A total of 67 cases were included in this cohort. There were 54 males and 13 females, aged from 21 to 65 years, with an average of 44 years.Eight cases were anastomosed with three superficial veins, 38 cases were anastomosed with two flaps, and 21 cases were anastomosed with one flap.The donor sites were closed directly in 56 cases.Eleven cases received full-thickness skin grafting to cover the donor site.One case showed necrosis of the half flap for the arterial crisis. The wound was repaired by full-thickness skin grafting in further treatment. Three cases had hemorrhage under the free flap, which was healed secondarily after debridement. The remaining were healed well.All patients were followed for 6 to 44 months. There was no obvious swelling and blisters in the early postoperative period.The texture of the flap was the same as the surrounding area.In the later stage, the atrophy and scar were not obvious, without pigmentation. The sensation recovered quickly. The donor site healed without dysfunction.Sixteen patients with upper limb wounds were evaluated by the trial standard of upper limb function evaluation of the Chinese Medical Association Hand Surgery Branch. Twelve cases were excellent, 3 cases were good, and one case was fair. Fifty-one cases of lower limb wounds were evaluated by the American Orthopaedic Foot and Ankle Surgery Association Ankle-Hind Foot Score System. Thirty-eight cases were excellent, 11 cases were good, and two cases were fair. All patients were evaluated according to the sensory function evaluation standard of the British Medical Research Association. The two-point distance discrimination was 8-10 mm, with an average of 9.1 mm. The sensory function of the flaps reached S3+ in 48 cases and S3 in 19 cases.Conclusions:Application of super-draining technique in peroneal artery perforator flap surgery can effectively prevent blood congestion and reduce the necrosis risk of the free flap and complication rate. It can improve the survival quality of the flap and facilitate the recovery of the function of the receiving area.

Objective:To evaluate the clinical effect of applying peroneal artery perforator flap with super-draining techniques in repairing skin defects of extremities.Methods:The data of patients with limb wounds admitted to the 990th Hospital of the Joint Logistics Support Force of the People’s Liberation Army from March 2014 to August 2019 were analyzed retrospectively. All were repaired with peroneal artery perforator flaps with super-draining techniques.Cutaneous nerves and perforating vessels were anastomosed according to the routine ratio of 1∶2.The superficial vein and the recipient veinwere matched and marked according to the relative position the diameter and length.Then one to three superficial veins were anastomosed in sequence according to the vein mark number.Upper limb wounds were evaluated by the trial standard of upper limb function evaluation of the Hand Surgery Branch of the Chinese Medical Association.Patients with lower limb wounds were evaluated by the American Orthopaedic Foot and Ankle Surgery Association Ankle-Hindfoot Score System.All patients were evaluated according to the sensory function evaluation standard of the British Medical Research Association.Results:A total of 67 cases were included in this cohort. There were 54 males and 13 females, aged from 21 to 65 years, with an average of 44 years.Eight cases were anastomosed with three superficial veins, 38 cases were anastomosed with two flaps, and 21 cases were anastomosed with one flap.The donor sites were closed directly in 56 cases.Eleven cases received full-thickness skin grafting to cover the donor site.One case showed necrosis of the half flap for the arterial crisis. The wound was repaired by full-thickness skin grafting in further treatment. Three cases had hemorrhage under the free flap, which was healed secondarily after debridement. The remaining were healed well.All patients were followed for 6 to 44 months. There was no obvious swelling and blisters in the early postoperative period.The texture of the flap was the same as the surrounding area.In the later stage, the atrophy and scar were not obvious, without pigmentation. The sensation recovered quickly. The donor site healed without dysfunction.Sixteen patients with upper limb wounds were evaluated by the trial standard of upper limb function evaluation of the Chinese Medical Association Hand Surgery Branch. Twelve cases were excellent, 3 cases were good, and one case was fair. Fifty-one cases of lower limb wounds were evaluated by the American Orthopaedic Foot and Ankle Surgery Association Ankle-Hind Foot Score System. Thirty-eight cases were excellent, 11 cases were good, and two cases were fair. All patients were evaluated according to the sensory function evaluation standard of the British Medical Research Association. The two-point distance discrimination was 8-10 mm, with an average of 9.1 mm. The sensory function of the flaps reached S3+ in 48 cases and S3 in 19 cases.Conclusions:Application of super-draining technique in peroneal artery perforator flap surgery can effectively prevent blood congestion and reduce the necrosis risk of the free flap and complication rate. It can improve the survival quality of the flap and facilitate the recovery of the function of the receiving area.