PURPOSE: The rate of complications among patients undergoing surgery has increased due to infection with SARS-CoV-2 and other variants of concern. However, Omicron has shown decreased pathogenicity, raising questions about the risk of postoperative complications among patients who are infected with this variant. This study aimed to investigate complications and related factors among patients with recent Omicron infection prior to undergoing orthopedic surgery. METHODS: A historical control study was conducted. Data were collected from all patients who underwent surgery during 2 distinct periods: (1) between Dec 12, 2022 and Jan 31, 2023 (COVID-19 positive group), (2) between Dec 12, 2021 and Jan 31, 2022 (COVID-19 negative control group). The patients were at least 18 years old. Patients who received conservative treatment after admission or had high-risk diseases or special circumstances (use of anticoagulants before surgery) were excluded from the study. The study outcomes were the total complication rate and related factors. Binary logistic regression analysis was used to identify related factors, and odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the impact of COVID-19 infection on complications. RESULTS: In the analysis, a total of 847 patients who underwent surgery were included, with 275 of these patients testing positive for COVID-19 and 572 testing negative. The COVID-19-positive group had a significantly higher rate of total complications (11.27%) than the control group (4.90%, p < 0.001). After adjusting for relevant factors, the OR was 3.08 (95% CI: 1.45-6.53). Patients who were diagnosed with COVID-19 at 3-4 weeks (OR = 0.20 (95% CI: 0.06-0.59), p = 0.005), 5-6 weeks (OR = 0.16 (95% CI: 0.04-0.59), p = 0.010), or ≥7 weeks (OR = 0.26 (95% CI: 0.06-1.02), p = 0.069) prior to surgery had a lower risk of complications than those who were diagnosed at 0-2 weeks prior to surgery. Seven factors (age, indications for surgery, time of operation, time of COVID-19 diagnosis prior to surgery, C-reactive protein levels, alanine transaminase levels, and aspartate aminotransferase levels) were found to be associated with complications; thus, these factors were used to create a nomogram. CONCLUSION Omicron continues to be a significant factor in the incidence of postoperative complications among patients undergoing orthopedic surgery. By identifying the factors associated with these complications, we can determine the optimal surgical timing, provide more accurate prognostic information, and offer appropriate consultation for orthopedic surgery patients who have been infected with Omicron.
Humans ; COVID-19/complications* ; Male ; Female ; Middle Aged ; Postoperative Complications/epidemiology* ; SARS-CoV-2 ; Orthopedic Procedures/adverse effects* ; Aged ; Nomograms ; Adult ; Retrospective Studies ; Risk Factors

Objective:To discuss the role of M2 macrophages in epithelial-mesenchymal transition(EMT)and cisplatin(DDP)resistance in the non-small cell lung cancer(NSCLC),and to clarify the regulatory mechanism of nuclear factor κB(NF-κB)signaling pathway.Methods:The human monocytic leukemia THP-1 cells were selected and differentiated into M0 macrophages by phorbol myristate acetate(PMA)induction,followed by M2 macrophage polarization through interleukin(IL)-4 and IL-13 stimulation.Western blotting and immunofluorescence methods were used to detect the protein expression levels of CD163,CD86,and arginase-1(Arg-1)in M0 and M2 macrophages.The human NSCLC A549 cells were co-cultured non-contactly with M0 or M2 macrophages in Transwell chambers,and the cells were divided into A549+M0 group(A549 cells co-cultured with M0 macrophages),A549+M2 group(A549 cells co-cultured with M2 macrophages),and A549+M2+BAY11-7082 group(A549 cells co-cultured with M2 macrophages and treated with 10 mmol·L-1 NF-κB inhibitor BAY11-7082).Wound healing assay was used to detect the wound healing rate of the A549 cells in various groups;Transwell assay was used to detect the number of invasion A549 cells in various groups;cell counting kit-8(CCK-8)assay was used to detect the inhibitory rate of proliferation and half maximal inhibitory concentration(IC50)value of the A549 cells after treated with DDP in the co-culture system;Western blotting method was used to detect the expression levels of vimentin,E-cadherin,N-cadherin,transcription factor Snail,phosphorylated P65(p-P65),P-glycoprotein(P-gp),and programmed death-ligand 1(PD-L1)proteins in the A549 cells in various groups.Results:The Western blotting results showed that compared with M0 group,the expression levels of CD163 and Arg-1 proteins in the macrophages in M2 group were significantly increased(P<0.05),while the expression level of CD86 protein was significantly decreased(P<0.05).The immunofluorescence results showed that compared with M0 group,the expression of CD163 protein in the macrophages in M2 group was enhanced and the expression of CD86 protein was weakened.The wound healing assay results showed that at 24 and 48 h of culture,compared with A549+M0 group,the wound healing rate of the A549 cells in A549+M2 group was significantly increased(P<0.05);in the co-culture system,compared with A549+M0 group,the wound healing rate of the A549 cells in A549+M2 group was significantly increased(P<0.05);compared with A549+M2 group,the wound healing rate of the A549 cells in A549+M2+BAY11-7082 group was significantly decreased(P<0.05).The Transwell assay results showed that compared with A549+M0 group,the number of invasion A549 cells in A549+M2 group was significantly increased(P<0.05);compared with A549+M2 group,the number of invasion A549 cells in A549+M2+BAY11-7082 group was significantly decreased(P<0.05);in the co-culture system,compared with A549+M0 group,the number of invasion A549 cells in A549+M2 group was significantly increased(P<0.05).The CCK-8 assay results showed that after treated with 2.50,5.00,10.00,20.00,and 40.00 mg·L-1 DDP,compared with A549+M0 group,the inhibitory rate of proliferation of the A549 cells in A549+M2 group was significantly decreased(P<0.05 or P<0.01),and the IC50 value was significantly increased(P<0.01);in the co-culture system,compared with A549+M0 group,the inhibitory rate of proliferation of the A549 cells in A549+M2 group was significantly decreased(P<0.05 or P<0.01),and the IC50 value was significantly increased(P<0.01);compared with A549+M2 group,the inhibitory rate of proliferation of the A549 cells in A549+M2+BAY11-7082 group was significantly increased(P<0.05),and the IC50 value was significantly decreased(P<0.05).The Western blotting results showed that compared with A549+M0 group,the expression level of E-cadherin proteins in the A549 cells in A549+M2 group was significantly decreased(P<0.05),while the expression levels of N-cadherin,vimentin,and Snail proteins were significantly increased(P<0.05);in the co-culture system,compared with A549+M0 group,the expression levels of vimentin,Snail,N-cadherin,and p-P65 proteins in the A549 cells in A549+M2 group were significantly increased(P<0.05),while the expression level of E-cadherin proteins was significantly decreased(P<0.05);compared with A549+M2 group,the expression levels of vimentin,N-cadherin,and p-P65 proteins in the A549 cells in A549+M2+BAY11-7082 group were significantly decreased(P<0.05),while the expression level of E-cadherin proteins was significantly increased(P<0.05);compared with A549+M0 group,the expression levels of P-gp and PD-L1 proteins in the A549 cells in A549+M2 group were significantly increased(P<0.05);in the co-culture system,compared with A549+M0 group,the expression levels of P-gp and PD-L1 proteins in the A549 cells in A549+M2 group were significantly increased(P<0.05);compared with A549+M2 group,the expression levels of P-gp and PD-L1 proteins in the A549 cells in A549+M2+BAY11-7082 group were significantly decreased(P<0.05).Conclusion:The M2 macrophages can regulate EMT in the NSCLC cells to promote the invasion and metastasis of tumor,and modulate the expressions of P-gp and PD-L1 to enhance DDP resistance,which is associated with the NF-κB signaling pathway.

Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.

Objective:To investigate lipid metabolism gene mutations and pathogenicity of hypertriglyceridemia acute pancreatitis (HTG-AP) patients.Methods:Clinical data of 495 HTG-AP patients admitted from June 2018 to June 2020 in the center for severe acute pancreatitis of Eastern Theater General Hospital were retrospectively analyzed. Whole-exome sequencing and mutation verification were performed by next-generation sequencing technology and Sanger sequencing. The pathogenicity of gene mutation was analyzed by population mutation ratio, pathogenicity prediction software, conservation scoring software, protein structure prediction, and in vitro experiments. Results:The mutation ratio of lipid metabolism-related genes, namely LPL, APOA5, LMF1, GPIHBP1, and APOC2, were 14.81%, 55.78%, 43.61%, 1.62%, and 0.61%, respectively. Among them, 44 heterozygous mutations in LPL gene were detected including 36 missense mutations, 5 nonsense mutations and 3 frameshift mutations, which were all rarely carried in single patient. Six HTG-AP patients carried the LPL gene heterozygous mutation c.835C>G (p.Leu279Val). The mean level of serum triglyceride at the onset of HTG-AP was 27.4 mmol/L. All of them had a history of recurrent HTG-AP, and most of them had severe acute pancreatitis. The serum LPL concentration and activity were lower than the normal level. The pathogenicity analysis results suggested that the LPL p.Leu279Val was a rare, highly possible pathogenic and highly conserved gene mutation. The in vitro results showed that the LPL p.Leu279Val could significantly reduce the synthesis and secretion ability of LPL as well as its enzymatic activity. Conclusions:The mutation ratio of lipid metabolism-related genes, including LPL, APOA5, LMF1, GPIHBP1, and APOC2, are relatively high in the HTG-AP patients. The LPL p.Leu279Val is a rare and highly possible pathogenic gene mutation, which may lead to recurrent episodes of HTG-AP.

Objective:To analyze the distribution features and pathogenicity of apolipoprotein A5 (APOA5) gene variants in patients with hypertriglyceridemia-associated acute pancreatitis (HTG-AP).Methods:Clinical data of 495 patients with HTG-AP in severe acute pancreatitis center of Eastern Theater General Hospital were collected. Next generation sequencing was performed to analyze the whole exonic regions to screen APOA5 gene variants in patients with HTP-AP. Sanger sequencing was used for validation. Bioinformative methods including mutation search, conservative analysis and pathogenicity were used to predict the functions of related mutations. 3D structural modeling were further used to evaluate the structure and function of potential mutated protein. Results:Of 495 HTG-AP patients, 275 patients (55.78%) carried APOA5 exomic variants, including 2 common missense polymorphisms as c.457G>A (100 heterozygotes and 13 homozygotes, with a prevalence of 22.83%), and c.553G>T (111 heterozygotes and 31 homozygotes, with a prevalence of 28.69%), as well as 13 rare APOA5 variants (all heterozygotes). In particular, 62 cases of enrolled patients were those suffering acute pancreatitis in pregnancy (APIP), and among them 37 carriers (58.06%) of APOA5 variants were found. Furthermore, 25(67.57%) of the APIPs carrying c.553G>T missense polymorphism, and among them 1 patient was compound with a novel APOA5 frame-shift variant c.230dupT (p.S78Efs). As bioinformatics predicted, the frame-shift variant c.230dupT was probably pathogenic and missense variant c.553G>T had potential pathogenecity, whereas the 3D-modeling of protein structure suggested that the p.Ser78fs shifting was clearly loss-of-function (LoF), and the p.Gly185Cys substitution was potential LoF. Conclusions:The current study indicates that prevalence of APOA5 gene deficiency is found in HTG-AP patients, and the interaction between APOA5 gene deficiency and pregnancy plays an important role in the development and recurrence of HTG-APIP.

Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.

Objective:To investigate the construction of fluorinated human serum albumin (F-HSA) nanoparticles loaded with epirubicin (EPI) EPI@F-HSA and its potential in urothelium penetration after bladder perfusion in female C57 mice.Methods:From January 2023 to December 2023, HSA and EPI were selected as raw materials to synthesize albumin nanoparticles loaded with EPI (EPI@HSA) based on the principles of biomineralization. EPI@F-HSA was synthesized through an amide reaction. The molecular descriptor of hydrated particles were measured by dynamic light scattering and potentiometric analyzer, and the release curve of EPI in vitro was plotted at 0.25, 0.5, 1, 2, 4, 8, 12, 24 and 48 h. The inhibitory effect of EPI@HSA and EPI@F-HSA nanoparticles on MB49 tumor cell activity was determined by MTT assay. The fluorescence distribution of EPI in mouse bladder sections after drug infusion was recorded by confocal microscope and the difference of fluorescence density of EPI was examined by Tukey post-hoc test to reflect the urothelium permeability.Results:The average hydrated particle sizes of EPI@HSA and EPI@F-HSA were 28.2 nm and 32.7 nm, respectively, and the polydispersity index (PDI) were 0.102 and 0.154. The cumulative EPI release of EPI@HSA and EPI@F-HSA nanoparticles within 12 h were 60.5% and 58.2% respectively in pH 5.0 buffer solution, and were 32.8% and 27.1% in pH 7.4 buffer solution. The median inhibitory concentrations of EPI@HSA and EPI@F-HSA nanoparticles on MB49 bladder cancer cells were 1.848 μmol/L and 1.650 μmol/L respectively. After perfusion with EPI, EPI@HSA, and EPI@F-HSA, the fluorescence intensities of EPI in the bladder wall were 2.63±0.43, 3.22±0.20 and 8.71±0.70, respectively, and the EPI fluorescence intensity of EPI@F-HSA was significantly higher than that of EPI@HSA ( P<0.01) and free EPI ( P<0.01). Conclusions:The fluorinated albumin nanoparticles had uniform particle size, good stability, significant inhibition of tumor cell activity and osmotic potential in urothelium, which had the potential to improve the anti-tumor efficacy and were expected to become a new drug delivery system targeting bladder cancer.

Objective:To investigate the construction of fluorinated human serum albumin (F-HSA) nanoparticles loaded with epirubicin (EPI) EPI@F-HSA and its potential in urothelium penetration after bladder perfusion in female C57 mice.Methods:From January 2023 to December 2023, HSA and EPI were selected as raw materials to synthesize albumin nanoparticles loaded with EPI (EPI@HSA) based on the principles of biomineralization. EPI@F-HSA was synthesized through an amide reaction. The molecular descriptor of hydrated particles were measured by dynamic light scattering and potentiometric analyzer, and the release curve of EPI in vitro was plotted at 0.25, 0.5, 1, 2, 4, 8, 12, 24 and 48 h. The inhibitory effect of EPI@HSA and EPI@F-HSA nanoparticles on MB49 tumor cell activity was determined by MTT assay. The fluorescence distribution of EPI in mouse bladder sections after drug infusion was recorded by confocal microscope and the difference of fluorescence density of EPI was examined by Tukey post-hoc test to reflect the urothelium permeability.Results:The average hydrated particle sizes of EPI@HSA and EPI@F-HSA were 28.2 nm and 32.7 nm, respectively, and the polydispersity index (PDI) were 0.102 and 0.154. The cumulative EPI release of EPI@HSA and EPI@F-HSA nanoparticles within 12 h were 60.5% and 58.2% respectively in pH 5.0 buffer solution, and were 32.8% and 27.1% in pH 7.4 buffer solution. The median inhibitory concentrations of EPI@HSA and EPI@F-HSA nanoparticles on MB49 bladder cancer cells were 1.848 μmol/L and 1.650 μmol/L respectively. After perfusion with EPI, EPI@HSA, and EPI@F-HSA, the fluorescence intensities of EPI in the bladder wall were 2.63±0.43, 3.22±0.20 and 8.71±0.70, respectively, and the EPI fluorescence intensity of EPI@F-HSA was significantly higher than that of EPI@HSA ( P<0.01) and free EPI ( P<0.01). Conclusions:The fluorinated albumin nanoparticles had uniform particle size, good stability, significant inhibition of tumor cell activity and osmotic potential in urothelium, which had the potential to improve the anti-tumor efficacy and were expected to become a new drug delivery system targeting bladder cancer.

Objective:To investigate lipid metabolism gene mutations and pathogenicity of hypertriglyceridemia acute pancreatitis (HTG-AP) patients.Methods:Clinical data of 495 HTG-AP patients admitted from June 2018 to June 2020 in the center for severe acute pancreatitis of Eastern Theater General Hospital were retrospectively analyzed. Whole-exome sequencing and mutation verification were performed by next-generation sequencing technology and Sanger sequencing. The pathogenicity of gene mutation was analyzed by population mutation ratio, pathogenicity prediction software, conservation scoring software, protein structure prediction, and in vitro experiments. Results:The mutation ratio of lipid metabolism-related genes, namely LPL, APOA5, LMF1, GPIHBP1, and APOC2, were 14.81%, 55.78%, 43.61%, 1.62%, and 0.61%, respectively. Among them, 44 heterozygous mutations in LPL gene were detected including 36 missense mutations, 5 nonsense mutations and 3 frameshift mutations, which were all rarely carried in single patient. Six HTG-AP patients carried the LPL gene heterozygous mutation c.835C>G (p.Leu279Val). The mean level of serum triglyceride at the onset of HTG-AP was 27.4 mmol/L. All of them had a history of recurrent HTG-AP, and most of them had severe acute pancreatitis. The serum LPL concentration and activity were lower than the normal level. The pathogenicity analysis results suggested that the LPL p.Leu279Val was a rare, highly possible pathogenic and highly conserved gene mutation. The in vitro results showed that the LPL p.Leu279Val could significantly reduce the synthesis and secretion ability of LPL as well as its enzymatic activity. Conclusions:The mutation ratio of lipid metabolism-related genes, including LPL, APOA5, LMF1, GPIHBP1, and APOC2, are relatively high in the HTG-AP patients. The LPL p.Leu279Val is a rare and highly possible pathogenic gene mutation, which may lead to recurrent episodes of HTG-AP.

Objective:To analyze the distribution features and pathogenicity of apolipoprotein A5 (APOA5) gene variants in patients with hypertriglyceridemia-associated acute pancreatitis (HTG-AP).Methods:Clinical data of 495 patients with HTG-AP in severe acute pancreatitis center of Eastern Theater General Hospital were collected. Next generation sequencing was performed to analyze the whole exonic regions to screen APOA5 gene variants in patients with HTP-AP. Sanger sequencing was used for validation. Bioinformative methods including mutation search, conservative analysis and pathogenicity were used to predict the functions of related mutations. 3D structural modeling were further used to evaluate the structure and function of potential mutated protein. Results:Of 495 HTG-AP patients, 275 patients (55.78%) carried APOA5 exomic variants, including 2 common missense polymorphisms as c.457G>A (100 heterozygotes and 13 homozygotes, with a prevalence of 22.83%), and c.553G>T (111 heterozygotes and 31 homozygotes, with a prevalence of 28.69%), as well as 13 rare APOA5 variants (all heterozygotes). In particular, 62 cases of enrolled patients were those suffering acute pancreatitis in pregnancy (APIP), and among them 37 carriers (58.06%) of APOA5 variants were found. Furthermore, 25(67.57%) of the APIPs carrying c.553G>T missense polymorphism, and among them 1 patient was compound with a novel APOA5 frame-shift variant c.230dupT (p.S78Efs). As bioinformatics predicted, the frame-shift variant c.230dupT was probably pathogenic and missense variant c.553G>T had potential pathogenecity, whereas the 3D-modeling of protein structure suggested that the p.Ser78fs shifting was clearly loss-of-function (LoF), and the p.Gly185Cys substitution was potential LoF. Conclusions:The current study indicates that prevalence of APOA5 gene deficiency is found in HTG-AP patients, and the interaction between APOA5 gene deficiency and pregnancy plays an important role in the development and recurrence of HTG-APIP.