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

The aim of this investigation was to determine the optimal storage medium for testicular hypothermic transportation and identify the ideal concentration for the application of the protective agent 5-aminolevulinic acid (5-ALA). Furthermore, this study aimed to explore the underlying mechanism of the protective effects of 5-ALA. First, we collected and stored mouse testicular fragments in different media, including Hank's balanced salt solution (HBSS; n = 5), Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12 (DMEM/F12; n = 5), and alpha-minimum essential medium (αMEM; n = 5). Storage of testicular tissue in HBSS preserved the integrity of testicular morphology better than that in the DMEM/F12 group ( P < 0.05) and the αMEM group ( P < 0.01). Testicular fragments were subsequently placed in HBSS with various concentrations of 5-ALA (0 [control], 1 mmol l -1 , 2 mmol l -1 , and 5 mmol l -1 ) to determine the most effective concentration of 5-ALA. The 2 mmol l -1 5-ALA group ( n = 3) presented the highest positive rate of spermatogonial stem cells compared with those in the control, 1 mmol l -1 , and 5 mmol l -1 5-ALA groups. Finally, the tissue fragments were preserved in HBSS with control ( n = 3) and 2 mmol l -1 5-ALA ( n = 3) under low-temperature conditions. A comparative analysis was performed against fresh testes ( n = 3) to elucidate the underlying mechanism of 5-ALA. Gene set enrichment analysis (GSEA) for WikiPathways revealed that the p38 mitogen-activated protein kinase (MAPK) signaling pathway was downregulated in the 2 mmol l -1 5-ALA group compared with that in the control group (normalized enrichment score [NES] = -1.57, false discovery rate [FDR] = 0.229, and P = 0.019). In conclusion, these data suggest that using 2 mmol l -1 5-ALA in HBSS effectively protected the viability of spermatogonial stem cells upon hypothermic transportation.
Male ; Animals ; Testis/cytology* ; Aminolevulinic Acid/pharmacology* ; Mice ; Organ Preservation/methods* ; Organ Preservation Solutions/pharmacology* ; Cryopreservation/methods*

Eightly-four novel thioheterocyclic nucleoside derivatives were designed, synthesized, and evaluated for antitumor activity in vitro and in vivo. Most of the compounds inhibited the growth of HCT116 and HeLa cancer cells in vitro, among them 33a and 36b exhibited potent activity against HCT116 cells (IC₅₀ = 0.27 and 0.49 μmol/L, respectively). Both compounds 33a and 36b inhibited cell metastasis, arrested the cell cycle in the G₂/M phase, and induced apoptosis in vitro. Mechanistic studies revealed that 33a and 36b increased ROS levels, led to DNA damage, ER stress, and mitochondrial dysfunction, and inhibited autophagy in HCT116 cells. Biological information analysis, RNA-sequencing, Gene Set Enrichment Analysis (GSEA), drug affinity responsive target stability (DARTS) assay, cellular thermal shift assay (CETSA), and SPR experiments identified that compounds 33a and 36b showed antitumor activity by suppressing the c-MYC pathway. c-MYC silencing assays indicated that c-MYC proteins participated in 33a-mediated anticancer activities in HCT116 cells. More importantly, compound 33a presented favorable pharmacokinetic properties in mice (T _1/2 = 6.8 h) and showed significant antitumor efficacy in vivo without obvious toxicity, showing promising potential for further clinical development.

Objective:To compare the efficacy and clinical value of high-throughput sequencing(HTS)and Sanger sequencing in detecting ABL kinase domain mutations in patients with chronic myeloid leukemia(CML).Methods:A total of 198 samples of 147 CML patients from July 2017 to March 2021 in Henan Cancer Hospital were collected and underwent high-throughput sequencing and Sanger sequencing to detect the mutations in ABL kinase domain,and the relevant clinical data were collected for comparative analysis.Results:The proportion of total mutations and ≥ 2 mutations detected by high-throughput sequencing were significantly higher than those detected by Sanger sequencing(P=0.01;P=0.046).≥ 2 mutations were detected in 22 cases,of which 5 cases(22.7％)had compound mutations.High-throughput sequencing can detect low level mutations that cannot be detected by Sanger sequencing.In 198 samples,25(12.6％)were low level mutations,33(16.7％)were high level mutations and 10(5.1％)were mixed high and low level mutations.In the analysis of related clinical factors,the total mutation rate and the low level mutation rate in the optimal period,failure period and warning period were gradually increased(total mutation rate,P=0.016;low level mutation rate,P=0.005).The mutation rate of the samples with additional chromosomal abnormalities was also significantly increased(P=0.009).The mutation rate of patients who received first-and second-line treatment was significantly lower than that of patients who received third-or higher-line treatment(P=0.006).Analysis based on variant allele frequency(VAF)of the mutation site was helpful to visually evaluate the clonal evolution status of TKI-resistance CML cells.Conclusion:High-throughput sequencing is more sensitive and accurate than Sanger sequencing in mutation detection,which is helpful to accurately and visually evaluate TKI treatment response and optimize treatment strategy for CML.

Objective:To explore the genotypes and frequency distribution of thalassemia in Lingui District,Guilin City,and provide reference for the prevention and control of thalassemia in this area. Methods:The results of genetic testing for thalassemia in 1501 suspected cases at the Second Affiliated Hospital of Guilin Medical University were analyzed retrospectively. The deletional mutations of α-thalassemia were detected by gap-PCR,the non-deletional mutations of α-thalassemia and β-thalassemia mutations were detected by PCR-reverse dot blot (PCR-RDB). Results:In 1501 samples,a total of 678 cases of thalassemia carriers were detected,with a detection rate of 45.17％. Among them,379 cases were α-thalassemia (including deletional α-thalassemia and non-deletional α-thalassemia),with a detection rate of 25.25％,the most common genotype was--SEA/αα (227 cases,15.12％),followed by-α3.7/αα (53 cases,3.53％). 270 cases of β-thalassemia were detected,with a detction rate of 17.99％,and βCD41-42/βN (144 cases,9.59％) was the main genotypes,followed by βCD17/βN (66 cases,4.40％) . In addition,there were 29 cases of αβ compound thalassemia,accounting for 1.93％,and the most common genotype was--SEA/αα complex βCD41-42/βN (5 cases,0.33％). Conclusion:Lingui District in Guilin City is a high-incidence area of thalassemia,and the genotypes of carriers are complex and diverse,with genetic heterogeneity. The results of this study provide a scientific basis for genetic counseling and prenatal diagnosis in this area.

Objective To compare the lipid-lowering efficacy and safety of fixed-dose combination and free combination of rosuvastatin and ezetimibe in hypercholesterolemia patients who fail to achieve low-density lipoprotein cholesterol(LDL-C)goal with statin monotherapy.Methods A total of 45 hypercholesterolemia patients who switched from statin monotherapy to fixed-dose combination of rosuvastatin and ezetimibe after failing to achieve target LDL-C goal admitted at cardiological departments of First Affiliated Hospital of Sun Yat-sen University,Nanhai Fourth People's Hospital,Foshan First People's Hospital,and Guangdong Provincial People's Hospital between March and June 2024 were enrolled and served as the study group.Another 120 hyper-cholesterolemia patients who treated with free combination of rosuvastatin and ezetimibe were se-lected from Xiamen Regional Health Medical Big Data Platform with propensity score matching and served as control group.The LDL-C level,LDL-C reduction,and changes in TC,HDL-C and TG levels in 4-6 weeks after the medication switch,as well as the safety indicators(AST,ALT,CK,Cre and eGFR)were compared between the two groups.Results In 4-6 weeks after the medication switch,the patients in the study group exhibited a significant decrease in LDL-C level(1.70±0.44 mmol/L vs 2.12±0.87 mmol/L,P＜0.01),obvious LDL-C reduction[(43.17±16.11)％vs(29.14±29.13)％,P＜0.01]when compared to those of the control group.The LDL-C goal attainment rate was significantly higher in the study group than the control group(71.11％vs 45.00％,P=0.003).In addition,there were no statistical differences in the levels of HDL-C and TG and the reductions of HDL-C and TG between the two groups in 4-6 weeks after treatment(P＞0.05).The study group obtained notably lower TC level and TC reduction than the control group in the time(P＜/0.05,P＜0.01).After treatment,no statistical differences were observed between the two groups in terms of AST,ALT,CK,Cre and eGFR(P＞0.05).Conclusion Com-pared to free combination of rosuvastatin and ezetimibe,fixed-dose combination can further reduce LDL-C level in hypercholesterolemia patients who have not achieved LDL-C goal with statin monotherapy,with higher LDL-C goal attainment rate and good safety.

Objective To analyze the clinical characteristics and factors influencing adverse treatment outcomes in elderly patients with multidrug-resistant pulmonary tuberculosis (MDR-TB) to guide the clinical diagnosis and treatment of elderly MDR-TB patients. Methods Clinical data of elderly patients with multidrug-resistant pulmonary tuberculosis initially treated at Beijing Chest Hospital from 2008 to 2023 were retrospectively collected. Complications/comorbidities, adverse drug reactions, drug resistance during initial treatment, and retreatment were statistically described. Factors influencing adverse treatment outcomes were analyzed using the chi-square test and logistic regression analysis. Results A total of 238 elderly patients with MDR-TB were collected, of which 152 (63.9%) had adverse drug reactions, 184 (77.3%) were retreated MDR-TB, 27 (11.3%) were extensively drug-resistant tuberculosis (XDR-TB), 41 were cured, 6 completed treatment, 39 failed treatment, 6 died, 107 lost to follow-up, 31 could not be evaluated, 8 did not finish treatment, and the treatment success rate was 20.4% (47/230). The adverse outcome of treatment accounted for 79.6% (183/230). Univariate analysis showed that differences in age groups, the occurrence of drug adverse reactions, and patient sources had a statistically significant impact on treatment outcomes (P<0.05). Logistic regression analysis was performed using good and adverse treatment outcomes as dependent variables for the three factors, which showed that being aged 70 and above, the occurrence of drug adverse reactions during treatment, and being a non-local patient were factors influencing adverse treatment outcomes [OR (95%CI): 2.507 (1.027-6.121), 3.253 (1.635-6.473), 2.563 (1.285-5.111), respectively]. Conclusions Elderly patients with MDR-TB exhibit a high prevalence of complications/comorbidities, a high incidence of drug adverse reactions, and unfavorable treatment outcomes. Out-of-town medical treatment, advanced age, and experiencing drug adverse reactions are risk factors for adverse treatment outcomes.

This study systematically reviewed the randomized controlled trial(RCT) of traditional Chinese medicine(TCM) treatment of coronary heart disease patients with angina pectoris after percutaneous coronary intervention(PCI). The basic elements of these RCTs, including sample size and estimation method, randomizing scheme, allocation concealment, blind method implementation, data integrity, statistical method, TCM syndrome, intervention measures, treatment course, follow-up time, and outcome indicators, were analyzed to provide reference for the design of future RCT and the clinical application of TCM in treating angina pectoris after PCI. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, Web of Science, ClinicalTrials.gov, and Chinese Clinical Trial Registry were searched for the RCT about TCM treatment of coronary heart disease patients with angina pectoris after PCI according to pre-defined criteria, with the time interval from inception to January 31, 2024. A total of 188 RCTs were included, of which 184 were clinical research articles and 4 were clinical trial registration schemes. These RCTs involved a total of 15 521 patients, with an average sample size of 83 patients and a maximum sample size of 248 patients. Among them, 126 RCTs reported TCM syndromes, the top three of which were Qi deficiency and blood stasis(38.89%), phlegm combined with stasis(17.46%), and Qi stagnation and blood stasis(9.52%). The control group received guideline-directed medical therapy(GDMT) or GDMT combined with placebo, and the treatment group received GDMT combined with TCM. The treatment mainly lasted for 4-8 weeks, most of the RCTs did not set the follow-up period or the follow-up period was unknown. A total of 160 outcome indicators were used, with the total frequency of 1 348. According to functional attributes, the outcome indicators can be categorized into 6 groups: symptoms/signs(403, 29.90%), TCM syndromes/symptoms(182, 13.50%), physical and chemical examination(468, 34.72%), quality of life(89, 6.60%), long-term prognosis(5, 0.37%), and safety evaluation(201, 14.91%). The clinical trial design of TCM intervention in angina pectoris after PCI of coronary heart disease is becoming more and more rigorous, while it remains to be improved. It is expected that more clinical trial schemes with rigorous design and taking into account the TCM advantages can be adopted in the future to provide a basis for the TCM treatment of angina pectoris after PCI of coronary heart disease.
Humans ; Randomized Controlled Trials as Topic ; Angina Pectoris/drug therapy* ; Coronary Disease/drug therapy* ; Percutaneous Coronary Intervention ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Treatment Outcome ; Female

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ²=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male ; Humans ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV Infections/drug therapy* ; Drug Resistance, Viral/genetics* ; China/epidemiology* ; Mutation ; HIV-1/genetics* ; Protease Inhibitors/therapeutic use* ; Genotype

Objectives: To construct a nomogram for prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis based on inflammation-related markers,and to conduct its clinical verification. Methods: Clinical and pathological data of 858 ICC patients who underwent radical resection were retrospectively collected at 10 domestic tertiary hospitals in China from January 2010 to December 2018. Among the 508 patients who underwent lymph node dissection,207 cases had complete variable clinical data for constructing the nomogram,including 84 males,123 females,109 patients≥60 years old,98 patients<60 years old and 69 patients were pathologically diagnosed with positive lymph nodes after surgery. Receiver operating characteristic curve was drawn to calculate the accuracy of preoperative imaging examinations to determine lymph node status,and the difference in overall survival time was compared by Log-rank test. Partial regression squares and statistically significant preoperative variables were screened by backward stepwise regression analysis. R software was applied to construct a nomogram,clinical decision curve and clinical influence curve,and Bootstrap method was used for internal verification. Moreover,retrospectively collecting clinical information of 107 ICC patients with intraoperative lymph node dissection admitted to 9 tertiary hospitals in China from January 2019 to June 2021 was for external verification to verify the accuracy of the nomogram. 80 patients with complete clinical data but without lymph node dissection were divided into lymph node metastasis high-risk group and low-risk group according to the score of the nomogram among the 858 patients. Log-rank test was used to compare the overall survival of patients with or without lymph node metastasis diagnosed by pathology. Results: The area under the curve of preoperative imaging examinations for lymph node status assessment of 440 patients was 0.615,with a false negative rate of 62.8% (113/180) and a false positive rate of 14.2% (37/260). The median survival time of 207 patients used to construct a nomogram with positive or negative postoperative pathological lymph node metastases was 18.5 months and 27.1 months,respectively (P<0.05). Five variables related to lymph node metastasis were screened out by backward stepwise regression analysis,which were combined calculi,neutrophil/lymphocyte ratio,albumin,liver capsule invasion and systemic immune inflammation index,according to which a nomogram was constructed with concordance index(C-index) of 0.737 (95%CI: 0.667 to 0.806). The C-index of external verification was 0.674 (95%CI:0.569 to 0.779). The calibration prediction curve was in good agreement with the reference curve. The results of the clinical decision curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.32,the maximum net benefit could be obtained by 0.11,and the cost/benefit ratio was 1∶2. The results of clinical influence curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.6,the probability of correctly predicting lymph node metastasis could reach more than 90%. There was no significant difference in overall survival time between patients with high/low risk of lymph node metastasis assessed by the nomogram and those with pathologically confirmed lymph node metastasis or without lymph node metastasis (Log-rank test:P=0.082 and 0.510,respectively). Conclusion: The prediction accuracy of preoperative nomogram for ICC lymph node metastasis based on inflammation-related markers is satisfactory,which can be used as a supplementary method for preoperative diagnosis of lymph node metastasis and is helpful for clinicians to make personalized decision of lymph node dissection for patients with ICC.