OBJECTIVE To evaluate the efficacy and safety of ceftazidime/avibactam （CAZ/AVI） combined with amikacin （AMK） in the treatment of carbapenem-resistant Enterobacteriaceae （CRE） severe pneumonia. METHODS A retrospective cohort study was conducted on 240 patients diagnosed with severe pneumonia caused by CRE infection in the intensive care unit （ICU） of the Affiliated Hospital of Xuzhou Medical University from January 2022 to December 2024. The patients were divided into a combination group （CAZ/AVI combined with AMK， n＝136） and a control group （CAZ/AVI alone， n＝104）. The 28-day mortality rate， clinical efficacy，mechanical ventilation time， ICU stay， infectious markers [C-reactive protein （CRP）， procalcitonin （PCT）， interleukin-6 （IL-6）， white blood cell count （WBC）， and neutrophil percentage （N%）]， Acute Physiology and Chronic Health Evaluation Ⅱ （APACHE Ⅱ） scores， and total incidence of adverse reactions were compared between two groups of patients. At the same time， subgroup analysis was conducted based on the severity of the condition， mechanical ventilation status， and baseline renal function. RESULTS The 28-day mortality rate of patients in the combination group was significantly lower than that in the control group （20.6% vs. 34.6%， P＝0.022）， and the clinical effective rate was significantly higher than that in the control group （80.1% vs. 65.4%， P＝0.004）. The mechanical ventilation time and ICU hospitalization time in the combination group were significantly shorter than those in the control group （[ 7.2±2.4） days vs. （10.4±3.6） days， （10.5±3.1） days vs. （13.7±3.8） days； P＜0.01].After 7 days of treatment， the CRP， PCT， IL-6， WBC， N% and APACHE Ⅱ scores of patients in the combination group significantly decreased compared to before treatment， and the decrease was significantly greater than that of the control group （P＜0.01）. There was no statistically significant difference in the total incidence of adverse reactions between the two groups of patients （11.8% vs. 13.5%， P＝0.690）. Subgroup analysis showed that among high-risk （APACHE Ⅱ score≥15） and mechanically ventilated patients， the 28-day mortality rate and weaning time of the combination group were significantly lower/ shorter than those of the control group （P＜0.05）， while there was no significant difference in the total incidence of adverse reactions between the combination group and the control group after dose adjustment in patients with chronic renal insufficiency （P＞0.05）. CONCLUSIONS The CAZ/AVI combined with AMK regimen has better anti-infective efficacy and good safety in patients with severe pneumonia caused by CRE infection compared to the CAZ/AVI regimen alone； the survival benefits of this joint regimen are more significant in high-risk and mechanically ventilated patients， with critically ill patients being the main beneficiaries.

Although metal blocks have been widely used for reconstructing uncontained tibial bone defects, the influence of their elastic modulus on the stability of tibial prosthesis fixation remains unclear. Based on this, a finite element model incorporating constrained condylar knee (CCK) prosthesis, tibia, and metal block was established. Considering the influence of the post-restraint structure of the prosthesis, the effects of variations in the elastic modulus of the block on the von Mises stress distribution in the tibia and the block, as well as on the micromotion at the bone-prosthesis fixation interface, were investigated. Results demonstrated that collision between the insert post and femoral prosthesis during tibial internal rotation increased tibial von Mises stress, significantly influencing the prediction of block elastic modulus variation. A decrease in the elastic modulus of the metal block resulted in increased von Mises stress in the proximal tibia, significantly reduced von Mises stress in the distal tibia, decreased von Mises stress of the block, and increased micromotion at the bone-prosthesis fixation interface. When the elastic modulus of the metal block fell below that of bone cement, inadequate block support substantially increased the risk of stress shielding in the distal tibia and fixation interface loosening. Therefore, this study recommends that biomechanical investigations of CCK prostheses must consider the post-constraint effect, and the elastic modulus of metal blocks for bone reconstruction should not be lower than 3 600 MPa.
Knee Prosthesis ; Humans ; Finite Element Analysis ; Tibia/surgery* ; Elastic Modulus ; Arthroplasty, Replacement, Knee/methods* ; Stress, Mechanical ; Metals ; Prosthesis Design ; Knee Joint/surgery* ; Biomechanical Phenomena

Objective To investigate the effects of ROCK-siRNA transfection on endothelial cell senescence and endothelial microparticles (EMPs) induced by angiotensin II (Ang II). Methods Human umbilical vein endothelial cells (HUVECs) were treated with Ang II (1.0 μmo/L) to induce cellular senescence models, followed by transfection with ROCK-siRNA. The cells were divided into four groups: control group, model group, negative transfection control group (Ang II combined with NC-siRNA), and ROCK-siRNA transfection group (Ang II combined with ROCK-siRNA). Cellular senescence was assessed by SA-β-Gal staining. EMP levels in cell supernatants and intracellular reactive oxygen species (ROS) levels were assessed using flow cytometry. The expression levels of silenced information regulator 1(SIRT1) and p53 protein in each group were analyzed by Western blotting. Results Following ROCK-siRNA transfection, the number of senescent cells induced by Ang II was significantly reduced, accompanied by decreased CD31⁺ EMP levels and suppressed intracellular ROS levels. Meanwhile, the expression levels of SIRT1 were up-regulated, while the expression levels of p53 were down-regulated. Conclusion Silencing ROCK expression suppresses EMP release, reduces ROS generation, regulates the expression of SIRT1 and p53, and ultimately attenuates Ang II-induced endothelial cell senescence.
Humans ; Angiotensin II/pharmacology* ; Cellular Senescence/genetics* ; Human Umbilical Vein Endothelial Cells/cytology* ; RNA, Small Interfering/metabolism* ; Reactive Oxygen Species/metabolism* ; Sirtuin 1/genetics* ; Transfection ; Tumor Suppressor Protein p53/genetics* ; Cell-Derived Microparticles/drug effects* ; rho-Associated Kinases/metabolism* ; Endothelial Cells/metabolism* ; Cells, Cultured

PANoptosis, a newly defined form of cell death, is characterized by the simultaneous occurrence and crosstalk of apoptosis, pyroptosis, and necroptosis. It has emerged as a promising therapeutic target for various diseases. Ovarian dysfunction is marked by oligomenorrhea or amenorrhea, elevated gonadotropin levels, and diminished estrogen levels, often accompanying subfertility or infertility. Additionally, it can manifest with perimenopausal syndrome and increase the risks of osteoporosis, cardiovascular disease, and cognitive impairments, seriously impacting patients' quality of life. While current studies have reported that ovarian hypofunction is associated with apoptosis, pyroptosis, or necroptosis, a systematic investigation into the relationship between PANoptosis and ovarian hypofunction is still absent. This review aims to elucidate the potential link between these two phenomena, providing new insights into the mechanisms underlying ovarian hypofunction and potential treatment strategies.
Humans ; Female ; Ovary/metabolism* ; Apoptosis ; Animals ; Necroptosis ; Ovarian Diseases/physiopathology*

Objective:To evaluate the immunogenicity, safety, and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years.Methods:An open-label, multi-center trial was conducted in October 2021. The eligible healthy individuals, aged 18-84 years who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, were recruited from Shangyu district of Shaoxing and Kaihua county of Quzhou, Zhejiang province. All participants were divided into three groups based on the differences in prime-boost intervals: Group A (3-4 months), Group B (5-6 months) and Group C (7-9 months), with 320 persons per group. All participants received the recombinant COVID-19 vaccine (CHO cell). Blood samples were collected before the vaccination and after receiving the booster at 14 days, 30 days, and 180 days for analysis of GMTs, antibody positivity rates, and seroconversion rates. All adverse events were collected within one month and serious adverse events were collected within six months. The incidences of adverse reactions were analyzed after the booster.Results:The age of 960 participants was (52.3±11.5) years old, and 47.4% were males (455). The GMTs of Groups B and C were 65.26 (54.51-78.12) and 60.97 (50.61-73.45) at 14 days after the booster, both higher than Group A′s 44.79 (36.94-54.30) ( P value<0.05). The GMTs of Groups B and C were 23.95 (20.18-28.42) and 27.98 (23.45-33.39) at 30 days after the booster, both higher than Group A′s 15.71 (13.24-18.63) ( P value <0.05). At 14 days after the booster, the antibody positivity rates in Groups A, B, and C were 91.69% (276/301), 94.38% (302/320), and 93.95% (295/314), respectively. The seroconversion rates in the three groups were 90.37% (272/301), 93.75% (300/320), and 93.31% (293/314), respectively. There was no significant difference among these rates in the three groups (all P values >0.05). At 30 days after the booster, antibody positivity rates in Groups A, B, and C were 79.60% (238/299), 87.74% (279/318), and 90.48% (285/315), respectively. The seroconversion rates in the three groups were 76.92% (230/299), 85.85% (273/318), and 88.25% (278/315), respectively. There was a significant difference among these rates in the three groups (all P values <0.001). During the sequential booster immunization, the incidence of adverse events in 960 participants was 15.31% (147/960), with rates of about 14.38% (46/320), 17.50% (56/320), and 14.06% (45/320) in Groups A, B, and C, respectively. The incidence of adverse reactions was 8.02% (77/960), with rates of about 7.50% (24/320), 6.88% (22/320), and 9.69% (31/320) in Groups A, B, and C, respectively. No serious adverse events related to the booster were reported. Conclusion:Healthy individuals aged 18-84 years, who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, have good immunogenicity and safety profiles following the sequential booster with the recombinant COVID-19 vaccine (CHO cell).

OBJECTIVE To explore the effect of Tuoli Xiaodusan(MDX)on ischemia-reperfusion injury of rat skin flaps and its potential mechanism.METHODS Rats were randomly divided into sham operation group(Sham group),Model group,MDX high-dose group(MDX-H group)and MDX low-dose group(MDX-L group),with 10 rats in each group.After the rat back skin flap model was successfully constructed,the drug was administered by gavage immediately,once a day for 14 consecutive days.The changes of rat skin flaps in each group after surgery were observed,and the survival rate of rat skin flaps in each group was measured on the 14th day after surgery;the histopathological changes of rat skin flaps were observed by HE staining;the protein expression of p-p65 and p-IκBα in the rat skin flap tissue was detected by Western blot;ELISA method was used to detect the expression of TNF-α,IL-1β,and IL-6 cytokines;Ki67 and CD31 immunohistochemical staining were used to observe epidermal basal layer cell prolifera-tion and vascular regeneration.RESULTS Compared with Model group,MDX-H group and MDX-L group had a small amount of e-dema and inflammatory fluid exudation after surgery,and the scab removal time was advanced;the ischemic necrosis of the skin flap was significantly improved,the area of skin flap necrosis was significantly decreased,and the survival rate of rat skin flaps was signifi-cantly increased(P<0.01).In addition,MDX could significantly improve the pathological morphology of ischemia-reperfusion injury in rat back skin flaps,reduce the expression of p-p65 and p-IκBα proteins(P<0.001),and decrease the levels of TNF-α,IL-1β,IL-6 inflammatory factor levels(P<0.05,P<0.01,P<0.001,P<0.000 1).The differences in Ki67 and CD31 also suggested that treatment with MDX accelerate re-epithelialization and blood vessel formation after ischemic flap injury.CONCLUSION MDX plays a role in improving ischemia-reperfusion injury of skin flaps by regulating the NF-κB signaling pathway and accelerating epithelializa-tion and angiogenesis.

Objective:To observe the clinical effect of lower eyelid blepharoplasty combined with micro-autologous fat transplantation (MAFT) in the rejuvenation of the infraorbital regions.Method:A retrospective analysis was conducted on the clinical data of patients with lower eyelid pouch and tear trough treated with lower eyelid blepharoplasty combined with MAFT in the Department of Plastic Surgery of Affiliated Hospital of Nanjing University of Chinese Medicine from March 2020 to March 2022. Patients seeked medical attention due to lower eyelid pouch and tear trough, with or without skin laxity, and some patients had varying degrees of midface depression. After preoperative examination and evaluation of the patient’s infraorbital area and midfacial depression, appropriate individualized plans were developed.The patient underwent lower eyelid blepharoplasty by transconjunctival approach combined with tear trough MAFT. For patients with low or depressed midface, midface MAFT was also performed, and for patients with skin laxity, skin removal surgery was performed simultaneously. Complications were recorded after the operation. Preoperative and postoperative photos of more than 6 months were taken with the same postion and delivered to the same doctor to grade the patient’s Barton classification (0-3 grades, with higher grade indicating more obvious tear trough deformity). The improvement of tear trough deformity after surgery was assessed, and the global aesthetic improvement scale (GAIS) score was also assessed. The patients evaluated their improvement using the patients aesthetic improvement scale (PAIS) score (GAIS and PAIS are both 1-5 points, with higher scores indicating more significant postoperative improvement). Normal distribution metric data was represented by Mean±SD, and count data was represented by frequency and/or percentage; skewed distribution metric data was represented by M ( Q1, Q3), and compared by rank sum test. Results:A total of 69 patients were enrolled, including 9 males and 60 females, aged 25-45 years, with an average age of 36.7 years. Among them, 35 patients had midfacial depression, and 11 patients had skin laxity. (0.37±0.07) ml (0.2-0.6 ml) of micro-autologous fat was injected into the orbicularis oculi muscle on each side; (0.18±0.06) ml (0.1-0.2 ml) of micro-autologous fat was injected into the subcutaneous layer on each side; (3.80±0.98) ml (3-5 ml) of micro-autologous fat was injected into the deep medial cheek fat compartment and pyriform aperture fat compartment on each side. No serious complications occurred after the surgery. Postoperative follow-up lasted for 6-13 months, with an average of 8.7 months. The patient’s lower eyelid pouch, tear trough deformity, and depression in the midface have all improved, presenting a youthful and smooth appearance from the infraorbital area to the midface. The skin texture in the lower eyelid area had also improved. At the last follow-up, the Barton classification of the lacrimal groove decreased compared with that before surgery, and the difference was statistically significant [grade 0 (0, 1) vs. grade 2 (1, 2), Z=-7.62, P<0.001]. At the last follow-up, the PAIS score of 69 patients was 5 points in 49 cases (71%) and 4 points in 20 cases (29%); doctor’s GAIS score was 5 points in 38 cases (55%), 4 points in 27 cases (39%), and 3 points in 4 cases (6%) . Conclusion:For those patients with aging status of infraorbital region, like lower eyelid pouch and tear trough deformities, the combination of lower eyelid blepharoplasty through the transconjunctival approach and MAFT can achieve good therapeutic effects. This method is safe with a short recovery time.

Objective:To observe the clinical effect of lower eyelid blepharoplasty combined with micro-autologous fat transplantation (MAFT) in the rejuvenation of the infraorbital regions.Method:A retrospective analysis was conducted on the clinical data of patients with lower eyelid pouch and tear trough treated with lower eyelid blepharoplasty combined with MAFT in the Department of Plastic Surgery of Affiliated Hospital of Nanjing University of Chinese Medicine from March 2020 to March 2022. Patients seeked medical attention due to lower eyelid pouch and tear trough, with or without skin laxity, and some patients had varying degrees of midface depression. After preoperative examination and evaluation of the patient’s infraorbital area and midfacial depression, appropriate individualized plans were developed.The patient underwent lower eyelid blepharoplasty by transconjunctival approach combined with tear trough MAFT. For patients with low or depressed midface, midface MAFT was also performed, and for patients with skin laxity, skin removal surgery was performed simultaneously. Complications were recorded after the operation. Preoperative and postoperative photos of more than 6 months were taken with the same postion and delivered to the same doctor to grade the patient’s Barton classification (0-3 grades, with higher grade indicating more obvious tear trough deformity). The improvement of tear trough deformity after surgery was assessed, and the global aesthetic improvement scale (GAIS) score was also assessed. The patients evaluated their improvement using the patients aesthetic improvement scale (PAIS) score (GAIS and PAIS are both 1-5 points, with higher scores indicating more significant postoperative improvement). Normal distribution metric data was represented by Mean±SD, and count data was represented by frequency and/or percentage; skewed distribution metric data was represented by M ( Q1, Q3), and compared by rank sum test. Results:A total of 69 patients were enrolled, including 9 males and 60 females, aged 25-45 years, with an average age of 36.7 years. Among them, 35 patients had midfacial depression, and 11 patients had skin laxity. (0.37±0.07) ml (0.2-0.6 ml) of micro-autologous fat was injected into the orbicularis oculi muscle on each side; (0.18±0.06) ml (0.1-0.2 ml) of micro-autologous fat was injected into the subcutaneous layer on each side; (3.80±0.98) ml (3-5 ml) of micro-autologous fat was injected into the deep medial cheek fat compartment and pyriform aperture fat compartment on each side. No serious complications occurred after the surgery. Postoperative follow-up lasted for 6-13 months, with an average of 8.7 months. The patient’s lower eyelid pouch, tear trough deformity, and depression in the midface have all improved, presenting a youthful and smooth appearance from the infraorbital area to the midface. The skin texture in the lower eyelid area had also improved. At the last follow-up, the Barton classification of the lacrimal groove decreased compared with that before surgery, and the difference was statistically significant [grade 0 (0, 1) vs. grade 2 (1, 2), Z=-7.62, P<0.001]. At the last follow-up, the PAIS score of 69 patients was 5 points in 49 cases (71%) and 4 points in 20 cases (29%); doctor’s GAIS score was 5 points in 38 cases (55%), 4 points in 27 cases (39%), and 3 points in 4 cases (6%) . Conclusion:For those patients with aging status of infraorbital region, like lower eyelid pouch and tear trough deformities, the combination of lower eyelid blepharoplasty through the transconjunctival approach and MAFT can achieve good therapeutic effects. This method is safe with a short recovery time.

Objective To investigate the biomechanical effects of the backside design of tibial trays on the bone-prosthesis fixation interfaces in unicompartmental knee arthroplasty(UKA).Methods Finite element models of medial knee arthroplasty were constructed using a fixed UKA prosthesis.The knee joint load and joint motion under walking motion were considered as boundary conditions,and the differences in tibial von Mises stress,contact stress,and micromotion of the bone-prosthesis fixation interface of the UKA tibial trays with big keel,small keel,two-peg with fin,three-oblique peg,and three-upright peg types were compared.Results At the maximum medical knee force moment,compared to the two-peg with fin type,the tibial von Mises stress,contact stress,and micromotion of the bone-prosthesis fixation interface decreased by 8%and 15.9%and increased by 9.9%for the big keel type;decreased by 12.3%and increased by 7.5%and 0.9%for the small keel type;decreased by 10%,10.5%,and increased by 1.2%for the three-oblique peg type;and decreased by 7.7%,14.7%,and 1.6%for the three-upright peg type,respectively.However,the maximum micromotion of the bone-prosthesis fixation interface occurred at 21%of the gait cycle.Compared to the two-peg with fin type,the micromotion of the bone-prosthesis fixation interface increased by 11.6%for the big keel type,increased by 1.6%for the small keel type,decreased by 0.4%for the three-oblique peg type,and decreased by 2.3%for the three-upright peg type.Conclusions To improve the long-term fixation effects of tibial prostheses,it is recommended to focus on a two-upright peg with fin or small keel designs when UKA tibial trays are designed,which can effectively balance the stress transfer and interface micromotion,thereby ensuring prosthesis stability and reducing the risk of aseptic loosening.

Objective: To explore the effects of different concentrations of glucose solution on the survival of Aedes albopictus and Culex pipiens pallens larvae, the attraction to mosquitoes and egg-laying behaviors, so as to provide the reference for developing mosquito control technology based on sugar bait. Methods: White porcelain bowls were filled with 100 mL of 3%, 5%, 8%, 10% and 15% glucose solutions. Ten of fourth instar larvae of Aedes albopictus or Culex pipiens pallens were added to each bowl, and the survival of larvae was recorded after 2, 4, 6, 24, 48 and 72 hours. Egg-laying cups containing 5%, 8% and 15% glucose solution were put in mosquito cages containing fully blooded female mosquitoes of Aedes albopictus and Culex pipiens pallens (50 mosquitoes each), and the total number of eggs laid in 72 hours was observed. The analogous site room was filled with fully blooded and starved female mosquitoes of Aedes albopictus and Culex pipiens pallens (100 mosquitoes each), and simple mosquito control buckets containing 5% and 8% glucose solution and black sticky insect plates. The number of mosquitoes and eggs was observed after 6 days. All the above experiments were repeated 3 times using dechlorinated water as the control. Results: The 72 hour corrected mortality rates of Aedes albopictus and Culex pipiens pallens larvae gradually increased with the increase of glucose concentration. The glucose solution with 5% and higher concentrations was not suitable for mosquito larvae to survive. The attraction of egg-laying behaviors to Aedes albopictus and Culex pipiens pallens gradually decreased with the increase of glucose concentration. The effects were similar between 5% and 8% glucose solution, with the averages of 686.67 and 682.33 eggs for Aedes albopictus, and 3.00 and 2.33 egg rafts for Culex pipiens pallens. In analogous site room, there were 93.33, 105.00 and 130.33 adult mosquitoes captured on average in the control group, 5% and 8% glucose solution groups, respectively, with 8% glucose solution group more attractive to adult mosquitoes than the control group (F=3.283, P=0.030); there were 70.33, 55.33 and 63.00 Aedes albopictus eggs (eggs counts+larvae counts) on average, respectively, with statistically significant differences among the three groups (H=6.761, P=0.034). Conclusion Glucose solution with concentration of 5% or higher can effectively inhibit the survival of Aedes albopictus and Culex pipiens pallens larvae, and attractive to adult mosquitoes and egg-laying behavoirs.