BACKGROUND:Fibromyalgia syndrome,as a common rheumatic disease,is related to central sensitization and immune abnormalities.However,the specific mechanism has not been elucidated,and there is a lack of specific diagnostic markers.Exploring the possible pathogenesis of this disease has important clinical significance. OBJECTIVE:To screen the potential diagnostic marker genes of fibromyalgia syndrome and analyze the possible immune infiltration characteristics based on bioinformatics methods,such as weighted gene co-expression network analysis(WGCNA),and machine learning. METHODS:Gene expression profiles in peripheral serum of fibromyalgia syndrome patients and healthy controls were obtained from the gene expression omnibus(GEO)database.The differentially co-expressed genes were screened in the expression profile by differential analysis and WGCNA analysis.Least absolute shrinkage and selection operator(LASSO)and support vector machine-recursive feature elimination(SVM-RFE)machine learning algorithm were further used to identify hub biomarkers,and draw receiver operating characteristic curve(ROC)to evaluate the accuracy of diagnosing fibromyalgia syndrome.Finally,single sample gene set enrichment analysis(ssGSEA)and gene set enrichment analysis(GSEA)were used to evaluate the immune cell infiltration and pathway enrichment in patients with fibromyalgia syndrome. RESULTS AND CONCLUSION:Eight down-regulated differentially expressed genes(DEGs)were obtained after differential analysis of the GSE67311 dataset according to the conditions of log2|(FC)|>0 and P<0.05.After WGCNA analysis,497 genes were included in the module(MEdarkviolet)with the highest positive correlation(r=0.22,P=0.04),and 19 genes were included in the module(MEsalmon2)with the highest negative correlation(r=-0.41,P=6×10-5).After intersecting DEGs and the module genes of WGCNA,seven genes were obtained.Four genes were screened out by LASSO regression algorithm and five genes were screened out by SVM-RFE machine learning algorithm.After the intersection of the two,three core genes were identified,which were germinal center associated signaling and motility like,integrin beta-8,and carboxypeptidase A3.The areas under the ROC curve of the three core genes were 0.744,0.739,and 0.734,respectively,indicating that they have good diagnostic value and can be used as biomarkers for fibromyalgia syndrome.The results of immune infiltration analysis showed that memory B cells,CD56 bright NK cells,and mast cells were significantly down-regulated in patients with fibromyalgia syndrome compared with the control group(P<0.05),and were significantly positively correlated with the above three biomarkers(P<0.05).The enrichment analysis suggested that there were nine fibromyalgia syndrome enrichment pathways,mainly related to olfactory transduction pathway,neuroactive ligand-receptor interaction,and infection pathway.The above results showed that the occurrence and development of fibromyalgia syndrome are related to the involvement of multiple genes,abnormal immune regulation,and multiple pathways imbalance.However,the interactions between these genes and immune cells,as well as their relationships with various pathways need to be further investigated.

Objective:To compare the therapeutic efficacy, safety and drug cost between generic enteric-coated mycophenolate sodium (EC-MPS) and branded EC-MPS in immunosuppressive treatment for adult recipients of renal transplantation (RT) .Methods:From January, 2022 to October, 2023, 60 adult RT patients were continuously enrolled and randomized into two groups. Patients receiving generic EC-MPS were selected as cohort 1 (n=30) while those taking branded EC-MPS designated as cohort 2 (n=30). Hepatic/renal function, blood routine parameters, drug concentrations, adverse events (AEs) and drug costs were recorded and compared between two cohorts at baseline (<3 days before/after day of RT, W0), week 1 (W1), week 4 (W4), week 8 (W8), week 12 (W12) and week 24 (W24) post-RT.Results:Only urine protein was elevated at W24[0.4 (0-0.6) vs 0 (0-0.2) g/24 h, P=0.049]in cohort 1 as compared with cohort 2. Aspartate aminotransferase at W12 (15.6±3.3 vs 20.3±9.7 U/L, P=0.010), leucocyte count at W1 (8.4±2.3 vs 10.1±3.8 ×10 9/L, P=0.045) and platelet count at W1 (158.5±51.5 vs 185.8±46.8 ×10 9/L, P=0.036) all declined in cohort 1 as compared with cohort 2. However, these parameters at other timepoints did not vary between two cohorts (all P>0.050). In addition, blood concentration of MPS after dosing, area under the concentration-time curve and trough concentration of tacrolimus at different timepoints were not different between two cohorts (all P>0.050). Similarly, helper T cells (Th), suppressor T cells (Ts), Th/Ts and B cells at W4/12 did not vary between two cohorts (all P>0.050). Concerning drug cost, no difference existed in the number of tablets or length of stay between two cohorts (both P>0.050). However, cost of EC-MPS (￥1 333.5±419.6 vs ￥2 368.6±596.0, P<0.001) and total cost during hospitalization (￥96 403.3±29 159.8 vs ￥117 062.8±28 782.1, P=0.001) were lower in cohort 1 than cohort 2. The most common AEs in cohort 1 included acid regurgitation (n=19, 63.3%), hypoalbuminemia (n=16, 53.3%), anemia (n=12, 40.0%) and hypokalemia (n=11, 36.7%). And the most common AEs in cohort 2 included acid regurgitation (n=20, 66.7%), anemia (n=14, 46.7%) and hypoalbuminemia (n=9, 30.0%). Notably, the incidence of all AEs was not different between two cohorts (all P>0.050) . Conclusion:Generic EC-MPS has comparable therapeutic efficacy and safety profile with lower drug cost in adult RT patients. It provides more options for maintenance treatment in RT patients.

Objective:To evaluate the relationship between red blood cell distribution width (RDW) and prognosis of patients with hepatocellular carcinoma (HCC) andergoing transcatheter arterial chemoembolization (TACE).Methods:Clinical data of 212 patients with HCC andergoing TACE for the first time in Department of Interventional Radiology, the Affiliated Hospital of Xuzhou Medical University from January 2011 to May 2018 were retrospectively analyzed, including 184 males and 28 females, aged (56.8±11.2) years. Follow-up for survival. X-tile software was used to determine 13.1% as the optimal threshold for preoperative RDW prediction of prognosis, and enrolled patients were divided into a low level group (RDW<13.1%, n=70) and a high level group (RDW≥13.1%, n=142). Aspartate aminotransferase, total bilirubin, albumin, hemoglobin and lipoprotein a, Barcelona clinical liver cancer (BCLC) stage and other indexes were compared between the two groups. Survival analysis was performed by Kaplan-Meier method, survival rate was compared by log-rank test, and the effect of RDW on prognosis was analyzed by Cox regression. Results:The 1-year, 2-year and 3-year cumulative survival rates in RDW high level group were 34.5%, 14.1% and 6.3%, respectively, while those in RDW low level group were 64.3%, 38.6% and 21.4%, respectively, with significant difference ( χ2=23.09, P<0.001). Compared with the low level group, the levels of aspartate aminotransferase and total bilirubin were higher, the levels of albumin, hemoglobin and lipoprotein a were lower, the proportion of portal vein cancer thrombin was higher, and the stage of BCLC was later, with statistical significance (all P<0.05). Cox regression analysis showed that HCC patients with RDW≥13.1%( HR=1.732, 95% CI: 1.223-2.452, P=0.002) had poor survival prognosis after TACE. Conclusion:Preoperative RDW≥13.1% is an independent risk factor for survival after TACE in patients with HCC. RDW has potential predictive value for prognosis of patients with HCC.

Objective:To compare the therapeutic efficacy, safety and drug cost between generic enteric-coated mycophenolate sodium (EC-MPS) and branded EC-MPS in immunosuppressive treatment for adult recipients of renal transplantation (RT) .Methods:From January, 2022 to October, 2023, 60 adult RT patients were continuously enrolled and randomized into two groups. Patients receiving generic EC-MPS were selected as cohort 1 (n=30) while those taking branded EC-MPS designated as cohort 2 (n=30). Hepatic/renal function, blood routine parameters, drug concentrations, adverse events (AEs) and drug costs were recorded and compared between two cohorts at baseline (<3 days before/after day of RT, W0), week 1 (W1), week 4 (W4), week 8 (W8), week 12 (W12) and week 24 (W24) post-RT.Results:Only urine protein was elevated at W24[0.4 (0-0.6) vs 0 (0-0.2) g/24 h, P=0.049]in cohort 1 as compared with cohort 2. Aspartate aminotransferase at W12 (15.6±3.3 vs 20.3±9.7 U/L, P=0.010), leucocyte count at W1 (8.4±2.3 vs 10.1±3.8 ×10 9/L, P=0.045) and platelet count at W1 (158.5±51.5 vs 185.8±46.8 ×10 9/L, P=0.036) all declined in cohort 1 as compared with cohort 2. However, these parameters at other timepoints did not vary between two cohorts (all P>0.050). In addition, blood concentration of MPS after dosing, area under the concentration-time curve and trough concentration of tacrolimus at different timepoints were not different between two cohorts (all P>0.050). Similarly, helper T cells (Th), suppressor T cells (Ts), Th/Ts and B cells at W4/12 did not vary between two cohorts (all P>0.050). Concerning drug cost, no difference existed in the number of tablets or length of stay between two cohorts (both P>0.050). However, cost of EC-MPS (￥1 333.5±419.6 vs ￥2 368.6±596.0, P<0.001) and total cost during hospitalization (￥96 403.3±29 159.8 vs ￥117 062.8±28 782.1, P=0.001) were lower in cohort 1 than cohort 2. The most common AEs in cohort 1 included acid regurgitation (n=19, 63.3%), hypoalbuminemia (n=16, 53.3%), anemia (n=12, 40.0%) and hypokalemia (n=11, 36.7%). And the most common AEs in cohort 2 included acid regurgitation (n=20, 66.7%), anemia (n=14, 46.7%) and hypoalbuminemia (n=9, 30.0%). Notably, the incidence of all AEs was not different between two cohorts (all P>0.050) . Conclusion:Generic EC-MPS has comparable therapeutic efficacy and safety profile with lower drug cost in adult RT patients. It provides more options for maintenance treatment in RT patients.

Objective To summarize clinical experience of transabdominal pericardial anastomosis of suprahepatic vena cava of the donor and right atrium of the recipient in liver transplantation for Budd-Chiari syndrome (BCS) complicated with liver cancer. Methods Clinical data of a BCS patient complicated with liver cancer undergoing transabdominal pericardial anastomosis of suprahepatic vena cava and right atrium in liver transplantation were retrospectively analyzed. Results The hepatic vein and suprahepatic vena cava were partially occluded in the patient. Liver transplantation was completed by transabdominal pericardial anastomosis of suprahepatic vena cava and right atrium with beating-heart. In addition, due to pathological changes of the recipient's hepatic artery, splenic artery of the recipient was cut off, distal ligation was performed, and the proximal end was reversed and anastomosed with the common hepatic artery of the donor liver, and the reconstruction of hepatic artery was completed. The surgery was successfully performed. At approximately postoperative 1 week, the function of the liver allograft was gradually restored to normal, and no major complications occurred. The patient was discharged at postoperative 25 d. No signs of BCS recurrence was reported after 8-month follow-up. Conclusions It is safe and feasible to treat BCS by liver transplantation with transabdominal pericardial anastomosis of suprahepatic vena cava and right atrium. BCS patients complicated with liver cancer obtain favorable prognosis.

A 37-year-old male patient was treated with tacrolimus, sirolimus, and methylprednisolone after renal transplantation to prevent rejection reaction. The function of the transplanted kidney recovered, serum creatinine was about 130 μmol/L, and serum uric acid was about 350 μmol/L. After 2 years and 6 months of renal transplantation, sirolimus was switched to mizolibin due to edema of his lower extremities. After taking mizolibin for 21 days, the patient developed nausea, poor appetite, and decreased urine volume (1 500 ml/24 h), and the symptoms gradually worsened. Laboratory tests showed serum creatinine 635 μmol/L and serum uric acid 1 750 μmol/L. The color Doppler ultrasonography of the transplanted kidney showed multiple stones and decreased color of blood flow signal. Acute renal failure, hyperuricemia, and calculus in transplanted kidney were diagnosed. Considering that it was related to mizolibin, the drug was discontinued and replaced by sirolimus, and hemodialysis, uric acid lowering, alkalizing urine, and other treatments were given. After 6 days of mizolibin discontinuation, the patient had no nausea or poor appetite. His urine volume was 3 000 ml/24 h, serum creatinine was 247 μmol/L and serum uric acid was 207 μmol/L. The color Doppler ultrasonography of the transplanted kidney showed no stone with abundant colorful blood flow signals. After 13 days of mizolibin discontinuation, the serum creatinine was 156 μmol/L and the serum uric acid was 123 μmol/L.

A 73-year-old male patient with right lung squamous cell carcinoma developed edema of bilateral lower limbs, poor appetite, and oliguria after targeted treatment with afatinib 30 mg once daily orally for 80 days. The laboratory tests showed serum creatinine 658 mmol/L, blood urea 26.8 mmol/L, urine protein (++++), and urine occult blood (+++). Renal biopsy showed renal tubular injury, some cells appearing as crescents, and mild IgA deposition. Acute kidney failure was diagnosed, which was considered to be caused by afatinib. Afatinib was stopped and symptomatic treatments including hemodialysis, glucocorticoids, anticoagulants, diuretics, etc. were given. Twelve days later, the edema in both lower limbs was alleviated;19 days later, his daily urine volume was approximately 800 ml; 99 days later, his renal function indicators tended to be normal. The patient did not receive targeted treatment again.

A 37-year-old male patient was treated with tacrolimus, sirolimus, and methylprednisolone after renal transplantation to prevent rejection reaction. The function of the transplanted kidney recovered, serum creatinine was about 130 μmol/L, and serum uric acid was about 350 μmol/L. After 2 years and 6 months of renal transplantation, sirolimus was switched to mizolibin due to edema of his lower extremities. After taking mizolibin for 21 days, the patient developed nausea, poor appetite, and decreased urine volume (1 500 ml/24 h), and the symptoms gradually worsened. Laboratory tests showed serum creatinine 635 μmol/L and serum uric acid 1 750 μmol/L. The color Doppler ultrasonography of the transplanted kidney showed multiple stones and decreased color of blood flow signal. Acute renal failure, hyperuricemia, and calculus in transplanted kidney were diagnosed. Considering that it was related to mizolibin, the drug was discontinued and replaced by sirolimus, and hemodialysis, uric acid lowering, alkalizing urine, and other treatments were given. After 6 days of mizolibin discontinuation, the patient had no nausea or poor appetite. His urine volume was 3 000 ml/24 h, serum creatinine was 247 μmol/L and serum uric acid was 207 μmol/L. The color Doppler ultrasonography of the transplanted kidney showed no stone with abundant colorful blood flow signals. After 13 days of mizolibin discontinuation, the serum creatinine was 156 μmol/L and the serum uric acid was 123 μmol/L.

A 73-year-old male patient with right lung squamous cell carcinoma developed edema of bilateral lower limbs, poor appetite, and oliguria after targeted treatment with afatinib 30 mg once daily orally for 80 days. The laboratory tests showed serum creatinine 658 mmol/L, blood urea 26.8 mmol/L, urine protein (++++), and urine occult blood (+++). Renal biopsy showed renal tubular injury, some cells appearing as crescents, and mild IgA deposition. Acute kidney failure was diagnosed, which was considered to be caused by afatinib. Afatinib was stopped and symptomatic treatments including hemodialysis, glucocorticoids, anticoagulants, diuretics, etc. were given. Twelve days later, the edema in both lower limbs was alleviated;19 days later, his daily urine volume was approximately 800 ml; 99 days later, his renal function indicators tended to be normal. The patient did not receive targeted treatment again.

Objective:To evaluate the effect of 2019 novel coronavirus inactivated vaccine on the disease severity of patients with Delta variant of coronavirus disease 2019.Methods:A retrospective analysis was performed on 704 patients with coronavirus disease 2019 infected with Delta variant who were older than 18 years old and admitted in the coronavirus disease 2019 designated hospital of Yangzhou (Subei Hospital New Area Branch) from July 2021 to September 2021. They were divided into severe (severe, critical) group and non-severe (light, ordinary) group according to the clinical characteristics of patients. According to the vaccination status, they were divided into 0-dose group, 1-dose group and 2-dose group. We evaluated the effects of vaccination on the severity of the disease and the production of antibodies, and analyzed the influencing factors leading to the severe group of coronavirus disease 2019.Results:The proportion of severe group in the 2-dose vaccinated group was significantly lower than that in the 1-dose vaccinated group and 0-dose vaccinated group [3.02% (7/232) vs. 9.48% (22/232), 15.83% (38/240), P < 0.05]. The time from onset to admission (day: 1.97±1.66 vs. 2.66±2.70), age (years: 45.3±12.2 vs. 63.6±17.0), direct bilirubin [DBil (μmol/L): 3.70±1.83 vs. 5.30±5.13], lactate dehydrogenase [LDH (U/L): 240.69±74.29 vs. 256.30±85.18], creatinine [SCr (μmol/L): 63.38±19.86 vs. 70.23±25.43], interleukin-6 [IL-6 (ng/L): 7.32 (1.54, 17.40) vs. 18.38 (8.83, 33.43)], creatine kinase [CK (U/L): 66.00 (43.00, 99.75) vs. 78.00 (54.50, 144.00)] and D-dimer [mg/L: 0.30 (0.08, 0.49) vs. 0.41 (0.23, 0.69)] of patients in the 2-dose group were significantly lower than those in the 0-dose group (all P < 0.05), while platelet [PLT (×10 9/L): 176.69±60.25 vs. 149.25±59.07], white blood cell count [WBC (×10 9/L): 5.43±1.77 vs. 5.03±1.88] and lymphocyte [LYM (×10 9/L): 1.34±0.88 vs. 1.17±0.50] were significantly higher than those in the 0-dose group (all P < 0.05). The titer of immunoglobulin G (IgG) in the 2-dose group was significantly higher than those in the 1-dose group and 0-dose group on the 10th day after admission [U/L: 130.94 (92.23, 326.31), 113.18 (17.62, 136.20), 117.85 (33.52, 156.73), both P < 0.05], and higher than 0-dose group on the 16th day [U/L: 156.12 (120.32, 167.76) vs. 126.52 (61.34, 149.57), P < 0.05]. The proportion of complete 2-dose vaccination [10.45% (7/67) vs. 35.32% (225/637)], LYM (×10 9/L: 1.09±0.32 vs. 1.25±0.56) and PLT (×10 9/L: 138.55±68.03 vs. 166.93±59.70) in the severe group were significantly lower than those in the non-severe group ( P < 0.05), while the time from onset to admission (day: 3.01±2.99 vs. 2.25±2.09), the length of hospital stay (day: 28±18 vs. 16±6), male proportion [77.61% (52/67) vs. 34.54% (220/637)], age (years: 69.13±12.63 vs. 52.28±16.53), DBil [μmol/L: 4.20 (3.18, 6.65) vs. 3.60 (2.80, 4.90], LDH (U/L: 310.61±98.33 vs. 238.19±72.14), SCr (μmol/L: 85.67±38.25 vs. 65.98±18.57), C-reactive protein [CRP (μmol/L): 28.12 (11.32, 42.23) vs. 8.49 (2.61, 17.58)], IL-6 [ng/L: 38.38 (24.67, 81.50) vs. 11.40 (4.60, 22.07)], CK [U/L: 140.00 (66.00, 274.00) vs. 72.80 (53.00, 11.00)] and the D-dimer [mg/L: 0.46 (0.29, 0.67) vs. 0.35 (0.19, 0.57)] in the severe group were significantly higher than those in the non-severe group (all P < 0.05). Multivariate regression analysis showed that the odds ratio ( OR) of severe group was 0.430 ( P = 0.010) in the 1-dose group and the 2-dose group compared with the 0-dose group. However, the risk of severe group was 0.381-fold in the 2-dose group compared with the 0-dose group [ OR = 0.381, 95% confidence interval (95% CI) was 0.121-1.199] which was not statistically significant, when the age was included in the regression analysis ( P > 0.05). PLT ( OR = 0.992, 95% CI was 0.986-0.998) were protective factors, but older than 60 years old ( OR = 3.681, 95% CI was 1.637-8.278), CK ( OR = 1.001, 95% CI was 1.000-1.001), IL-6 ( OR = 1.006, 95% CI was 1.002-1.010), SCr ( OR = 1.020, 95% CI was 1.007-1.033) were risk factors for severe group (all P < 0.05). Conclusions:Compared with the 0-dose vaccinated patients, the coronavirus disease 2019 patients infected with delta variant and fully vaccinated with 2-dose 2019 novel coronavirus inactivated vaccine had lower level of IL-6, SCr, CK and D-dimer, and higher PLT, LYM and IgG titer, who were not easy to develop into the severe condition.