Objective To investigate the effect of the serum of patients with hepatopulmonary syndrome on the myogenic differentiation,proliferation and migration of human lung fibroblasts.Methods The human lung fibroblasts were seeded in plates or flasks and randomly divided into 2 groups (n =31each) using a random number table:serum of patients with hepato-pulmonary syndrome group and serum of healthy volunteer group.The human lung fibroblasts were incubated in the DMEM culture medium containing 10％ serum of patients with hepatopulmonary syndrome or in the DMEM culture medium containing 10％ serum of healthy volunteers.At 24,48 and 72 h of incubation (T1-T3),the expression of smooth muscle-α-actin (SM-α-actin) and smooth muscle myosin heavy chain (SM-MHC) in human lung fibroblasts was determined by Western blot,the proliferation of the human lung fibroblasts was determined using 3H-TDR incorporation assay,and the migration of the human lung fibroblasts was determined by Transwell chamber assay.Results Compared with serum of healthy volunteer group,the expression of SM-α-actin and SM-MHC in human lung fibroblasts was significantly up-regulated at each time point,and the proliferation and migration of the cells were significantly enhanced at T2,3 in serum of patients with hepatopulmonary syndrome group (P＜0.05).Compared with the value at T1,the expression of SM-α-actin and SM-MHC in human lung fibroblasts was significantly up-regulated,and the proliferation and migration of the cells were significantly enhanced at T2,3in serum of patients with hepatopulmonary syndrome group (P＜0.05).Compared with the value at T2,the expression of SM-α-actin and SM-MHC in human lung fibroblasts was significantly up-regulated,and the proliferation and migration of the cells were significantly enhanced at T3 in serum of patients with hepatopulmonary syndrome group (P＜0.05).Conclusion The serum of patients with hepatopulmonary syndrome can promote the myogenic differentiation,proliferation and migration of human lung fibroblasts.

Objective To evaluate the safety and efficacy of multi-band mucosectomy (MBM) for early esophageal cancer and precancerous lesions.Methods Data of 28 patients with early esophageal cancer or precancerous lesions undergoing MBM were reviewed in regarding of procedure complications and follow-up results.Results A total of 32 lesions were resected successfully by MBM in one session,with mean procedure time of 28.3 minutes.The mean diameter of specimens was 12mm.No residual neoplasm was found at the base of any resected specimens.The post-MBM pathological findings consisted of 2 cases of intramucosal cancer,1 case of submucosal cancer,and 25 cases of moderate-severe dysplasia.No perforation,delayed hemorrhage or subcutaneous emphysema occurred.Intraoperative bleeding occurred in 23 cases,including 3 cases of pulsatile bleeding,which were controlled with metal clip,and 20 cases of minor bleeding which were managed with APC or halted automatically at the end of procedure.Chest pain after the procedure occurred in 5 cases and were relieved soon.The patient with submucosal cancer underwent subsequent surgical resection,with no residual cancer in surgical specimen or lymph node metastasis.Twenty seven other cases were followed up endoscopically for 2-12 months.Esophageal stricture occurred in 2 cases,and were successfully relieved by dilatation with stent or bougienage.No recurrent lesion or metastasis were revealed.Conclusion MBM is a relatively safe and effective endoscopic technique for treatment of early esophageal intramucosal cancer and precancerous lesions,but further studies are needed to evaluate the long-term results.

Objective To evaluate the effect of 15-deoxy-△12,14-prostaglandin J2 (15d-PGJ2) on endotoxin-induced acute lung injury (ALI) in rats.Methods Forty healthy male Sprague-Dawley rats, aged 3-5 months, weighing 220-250 g, were randomly divided into 4 groups (n =10 each) using a random number table: control group (group C), 15d-PGJ2 group, lipopolysaccharide (LPS) group, and LPS +15d-PGJ2 group.In group 15d-PGJ2, 15d-PGJ20.3 mg/kg was injected via the tail vein, while the equal volume of normal saline was given in group C.In LPS and LPS+15d-PGJ2 groups, ALI was produced with LPS 6 mg/kg injected through the tail vein, and then the equal volume of normal saline and 15d-PGJ2 0.3 mg/kg were injected, respectively.At 4 h after LPS injection, blood samples were drawn from the abdominal aorta for blood gas analysis, and arterial oxygen partial pressure (PaO2) was recorded.The rats were then sacrificed, lungs were removed for microscopic examination, and for determination of wet/dry lung weight ratio (W/D ratio), TNF-α, IL-8 and cytokine-induced neutrophil chemoattractant-1 (CINC-1) contents (by enzyme-linked immunosorbent assay) , and nuclear factor kappa B (NF-κB) p65 and IκB-α expression (by Western blot).Results Compared with group C, no significant change was found in PaO2, W/D ratio, contents of TNF-α, IL-8 and CINC-1, and expression of NF-κB p65 and IκB-α in group 15d-PGJ2 (P＞0.05), and PaO2 was significantly decreased, W/D ratio and contents of TNF-α,IL-8 and CINC-1 were increased, the expression of NF-κB p65 was up-regulated, and the expression of IκB-α was down-regulated in LPS and LPS+ 15d-PGJ2 groups (P＜0.05).Compared with group LPS,PaO2 was significantly increased, W/D ratio and contents of TNF-α, IL-8 and CINC-1 were decreased, the expression of NF-κB p65 was down-regulated, and the expression of IκB-α was up-regulated (P＜0.05),and the pathological changes were attenuated in group LPS+ 15d-PGJ2.Conclusion 15d-PGJ2 can mitigate endotoxin-induced ALI in rats.

Objective To study the dynamic changes of plasma C-reactive protein (CRP) and cortisol (COR) and their clinical value in prognosis of patients with sepsis. Methods Daily CRP and COR detection was conducted to record the dynamic changes of CRP and COR for cases of sepsis patients in ICU then the rela-tionship between dynamic changes of serum CRP and COR and prognosis were analyzed. Results Serum CRP and COR levels of dead patients were significantly higher than those of survival patients after treatment (P <0.05). According to the difference of the dynamic changes of CRP and COR, the data were divided into typeⅠ:sustained elevated type , typeⅡ: up-and-down type , type Ⅲ: fluctuated type and type Ⅳ: normal or mild ele-vation type. The mortality of CRP typeⅠ patients was significantly higher than that of type Ⅱ and type Ⅳ(P <0.001). The mortality of COR typeⅠ and COR Ⅲ patients was significantly higher than that in COR Ⅱand COR Ⅳ (P < 0.001). Further analysis showed that the mortality of group with significant elevation of CRP and COR were obviously higher than that of group with significant increase of CRP or COR and that of group with no significant elevation of CRP and COR (P < 0.001); the mortality of group with significant increase of CRP or COR was also significantly higher than that of group with no significant elevation of CRP and COR (P < 0.001). Conclusions The dynamic changes of COR and CRP in patients with sepsis present certain regularity and monitor-ing the dynamic changes of the two provides accurate assessment of the prognosis of sepsis.

Objective To evaluate the efficacy of stroke volume variation (SVV) combined with controlled low central venous pressure (CLCVP)-directed fluid therapy in the patients undergoing liver cancer resection.Methods Seventy American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients,aged 40-60 yr,with body mass index of 20-25 kg/m2,scheduled for elective liver cancer resection under general anesthesia,were divided into 2 groups (n=35 each) using a random number table:routine fluid replacement group (R group) and SVV combined with CLCVP-guided fluid replacement group (SC group).In R group,routine fluid replacement included compensatory volume expansion,physiological requirement,cumulative loss,continued loss (intraoperative blood loss) and 3rd space losses,maintaining mean arterial pressure＞70 mmHg,central venous pressure＜4 cmH2O and heart rate ＜ 100 bpm.Central venous pressure was maintained ＜4 cmH2O and SVV ＜ 12％ during operation in SC group.The operation time,total amount of crystalloid and colloid solution infused,urine volume and development of intraoperative hypotension and bradycardia were recorded.Blood samples from the left radial artery and central vein were collected before anesthesia induction and at the end of operation for measurement of the blood lactate concentration,and the oxygen supply index,oxygen consumption index and oxygen uptake rate were calculated.Blood samples from the ulnar vein were collected before anesthesia induction and at the end of operation for determination of serum β2-microglobulin concentrations.The development of intraoperative adverse cardiovascular events was recorded,and the occurrence of postoperative complications was observed.Results Compared with R group,the total amount of crystalloid solution infused was significantly decreased,the total amount of colloid solution infused and urine volume were increased,the incidence of intraoperative hypotension and bradycardia was decreased,oxygen supply index,oxygen consumption index and oxygen uptake rate were increased at the end of operation,and the lactate concentration in arterial blood,serum β2-microglobulin concentration and rate of postoperative pulmonary infection were decreased in SC group (P＜0.05).Conclusion SVV combined with CLCVP-directed fluid therapy produces better efficacy than routine fluid replacement in the patients undergoing liver resection.

OBJECTIVES: This study aimed to investigate the associations of obesity phenotypes with hypertension stages, phenotypes, and transitions among middle-aged and older Chinese. METHODS: Using the 2011-2015 waves of the China Health and Retirement Longitudinal Study, we conducted a cross-sectional analysis included 9,015 subjects and a longitudinal analysis included 4,961 subjects, with 4,872 having full data on the hypertension stage and 4,784 having full data on the hypertension phenotype. Based on body mass index and waist circumstance, subjects were categorized into 4 mutually exclusive obesity phenotypes: normal weight with no central obesity (NWNCO), abnormal weight with no central obesity (AWNCO), normal weight with central obesity (NWCO), and abnormal weight with central obesity (AWCO). Hypertension stages were classified into normotension, pre-hypertension, stage 1 hypertension, and stage 2 hypertension. Hypertension phenotypes were categorized as normotension, pre-hypertension, isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic-diastolic hypertension (SDH). The association between obesity phenotypes and hypertension was estimated by logistic regression. A comparison between different sexes was conducted by testing the interaction effect of sex. RESULTS: NWCO was associated with normal→stage 2 (odds ratio [OR], 1.95; 95% confidence interval [CI], 1.11 to 3.42), maintained stage 1 (OR, 1.62; 95% CI, 1.14 to 2.29), and normal→ISH (OR, 1.39; 95% CI, 1.05 to 1.85). AWCO was associated with normal→stage 1 (OR, 1.75; 95% CI, 1.40 to 2.19), maintained stage 1 (OR, 2.77; 95% CI, 2.06 to 3.72), maintained stage 2 (OR, 2.80; 95% CI, 1.50 to 5.25), normal→ISH (OR, 1.56; 95% CI, 1.20 to 2.02), and normal→SDH (OR, 2.54; 95% CI, 1.72 to 3.75). An interaction effect of sex existed in the association between obesity phenotypes and hypertension stages. CONCLUSIONS This study highlights the importance of various obesity phenotypes and sex differences in hypertension progression. Tailored interventions for different obesity phenotypes may be warranted in hypertension management, taking into account sex-specific differences to improve outcomes.

Objective·To analyze the clinicopathologic characteristics,gene mutation profile,and prognostic factors of thyroid diffuse large B-cell lymphoma(DLBCL).Methods·From November 2003 to December 2021,a total of 66 patients with thyroid DLBCL[23 cases(34.8%)with primary thyroid DLBCL,and 43 cases(65.2%)with secondary thyroid DLBCL]admitted to Ruijin Hospital,Shanghai Jiao Tong University School of Medicine were retrospectively analyzed for their clinicopathological data,survival and prognostic factors.Gene mutation profiles were evaluated by targeted sequencing(55 lymphoma-related genes)in 40 patients.Results·Compared to primary thyroid DLBCL,secondary thyroid DLBCL had advanced ratio of Ann Arbor stage Ⅲ?Ⅳ(P=0.000),elevated serum lactate dehydrogenase(LDH)(P=0.043),number of affected extranodal involvement≥2(P=0.000),non-germinal center B cell(non-GCB)(P=0.030),BCL-2/MYC double expression(DE)(P=0.026),and international prognostic index(IPI)3?5-scores(P=0.000).The proportion of patients who underwent thyroid surgery(P=0.012)was lower than that of patients with primary thyroid DLBCL.The complete remission(CR)rate in primary thyroid DLBCL patients was higher than that in secondary thyroid DLBCL patients(P=0.039).Fifty-five patients(83%)received rituximab combined with cyclophosphamide,doxorubicin,vincristine,and prednisone(R-CHOP)-based first-line regimen.The estimated 5-year progression free survival(PFS)rate of primary thyroid DLBCL patients was 95.0%,higher than the 49.7%of the secondary patients(P=0.010).Univariate analysis showed that Ann Arbor Ⅲ?Ⅳ(HR=4.411,95%CI 1.373?14.170),elevated LDH(HR=5.500,95%CI 1.519?19.911),non-GCB(HR= 5.291,95%CI 1.667?16.788),and DE(HR=6.178,95%CI 1.813?21.058)were adverse prognostic factors of PFS in patients with thyroid DLBCL.Ann Arbor Ⅲ?Ⅳ(HR=7.088,95%CI 0.827?60.717),elevated LDH(HR=6.982,95%CI 0.809?60.266),and DE(HR=18.079,95%CI 1.837?177.923)were adverse prognostic factors of overall survival(OS).Multivariate analysis showed that Ann Arbor Ⅲ?Ⅳ(HR=4.693,95%CI 1.218?18.081)and elevated LDH(HR=5.058,95%CI 1.166?21.941)were independent adverse prognostic factors of PFS in patients with thyroid DLBCL.Targeted sequencing data showed mutation frequency>20%in TET2(n=14,35%),KMT2D(n=13,32%),TP53(n=11,28%),GNA13(n=10,25%),KMT2C(n=9,22%),and TP53 were adverse prognostic factors of PFS in patients with thyroid DLBCL(P=0.000).Conclusion·Patients with primary thyroid DLBCL have better PFS and OS than those with secondary thyroid DLBCL.Ann Arbor Ⅲ?Ⅳ,elevated LDH,non-GCB,and DE(MYC and BCL2)are adverse prognostic factors in thyroid DLBCL.TET2,KMT2D,TP53,GNA13,and KMT2C are commonly highly mutated genes in thyroid DLBCL,and the prognosis of patients with TP53 mutations is poor.

Objective:To investigate the clinicopathological characteristics, gene mutation profile, and prognostic factors of diffuse large B-cell lymphoma (DLBCL) in female genital tract.Methods:A retrospective analysis was performed on the clinicopathological data of 30 patients with female genital tract DLBCL who were admitted to Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from October 2003 to October 2021. Targeted sequencing was used to detect 55 lymphoma-related genes, and the gene mutation status of patients was evaluated. Kaplan-Meier method was used for survival analysis, and prognostic factors were analyzed by Cox proportional hazards model.Results:The median age of 30 female genital tract DLBCL patients at diagnosis was 58 years old (23-77 years old). The initial symptoms mainly included abdominal pain, distension, and masses (8 cases, 32%). Tumors most commonly located in the adnexal region (including ovaries and fallopian tubes) (13 cases, 45%), of which 9 cases were unilateral. Twenty-one cases (70%) had multiple extra-nodal involvements, 22 cases (73%) had Ann Arbor stage Ⅲ-Ⅳ, 8 cases (27%) had Eastern Cooperative Oncology Group (ECOG) score of ≥2, and 22 cases (73%) had elevated lactate dehydrogenase (LDH), 21 cases (70%) had International Prognostic Index (IPI) score of 3-5. Within 30 patients, 11 patients (37%) received surgery, and all patients received R-CHOP regimen-based chemotherapy. All 30 cases were evaluated for efficacy, the complete remission rate was 83% (25/30), the 5-year progression-free survival (PFS) rate was 69.7%, and the 5-year overall survival (OS) rate was 79.6%. Univariate analysis showed that ECOG score ≥2 was associated with worse OS ( P = 0.048). Among the 30 patients, 7 patients (23%) were primary and 23 patients (77%) were secondary. The proportions of patients with Ann Arbor stage Ⅲ-Ⅳ, IPI score 3-5 and elevated LDH in secondary patients were higher than those in primary patients (all P < 0.001), but there were no significant differences in PFS and OS between the two ( P values were 0.261 and 0.671). The targeted sequencing results of 16 patients showed that the mutation rates of PIM1, MYD88, KMT2D, TP53, CARD11, CCND3 and GNA13 were all > 20%, and TP53 mutation was associated with poorer PFS and OS ( P values 0.012 and 0.002). Conclusions:Female genital tract DLBCL is a rare invasive extranodal DLBCL with similar survival prognosis in primary and secondary patients. High-frequency mutations of PIM1, MYD88 and TP53 genes may provide new directions for treatment.

OBJECTIVES: Safe and effective anticoagulation is essential for hemodialysis patients who are at high risk of bleeding. The purpose of this trial is to evaluate the effectiveness and safety of two-stage regional citrate anticoagulation (RCA) combined with sequential anticoagulation and standard calcium-containing dialysate in intermittent hemodialysis (IHD) treatment. METHODS: Patients at high risk of bleeding who underwent IHD from September 2019 to May 2021 were prospectively enrolled in 13 blood purification centers of nephrology departments, and were randomly divided into RCA group and saline flushing group. In the RCA group, 0.04 g/mL sodium citrate was infused from the start of the dialysis line during blood draining and at the venous expansion chamber. The sodium citrate was stopped after 3 h of dialysis, which was changed to sequential dialysis without anticoagulant. The hazard ratios for coagulation were according to baseline. RESULTS: A total of 159 patients and 208 sessions were enrolled, including RCA group (80 patients, 110 sessions) and saline flushing group (79 patients, 98 sessions). The incidence of severe coagulation events of extracorporeal circulation in the RCA group was significantly lower than that in the saline flushing group (3.64% vs. 20.41%, P<0.001). The survival time of the filter pipeline in the RCA group was significantly longer than that in the saline flushing group ((238.34±9.33) min vs. (221.73±34.10) min, P<0.001). The urea clearance index (Kt/V) in the RCA group was similar to that in the saline flushing group with no statistically significant difference (1.12±0.34 vs. 1.08±0.34, P=0.41). CONCLUSIONS Compared with saline flushing, the two-stage RCA combined with a sequential anticoagulation strategy significantly reduced extracorporeal circulation clotting events and prolonged the dialysis time without serious adverse events.
Humans ; Citric Acid/adverse effects* ; Prospective Studies ; Sodium Citrate ; Hemorrhage/chemically induced* ; Citrates/adverse effects* ; Anticoagulants/adverse effects* ; Renal Dialysis/adverse effects*

Objective: To investigate the metabolic trajectory of kidney aging and the effects of Polygonatum sibiricum polysaccharides (PSP) against kidney aging in D-galactose (D-gal)-induced aging mice, based on ultra-performance liquid chromatography/Q-Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive MS/MS). Methods: A total of 36 C57 BL/6J mice were randomly allocated to six groups: control (CON), model (MOD), PSP low-dose (PSP-L), PSP medium-dose (PSP-M), PSP high-dose (PSP-H), and positive drug ascorbic acid (VC) groups. To create models of aging mice, D-gal was intraperitoneally administered to all other groups of mice except the CON group. After modeling, the appropriate Chinese medicine [PSP-L: 150 mg/(kg·d), PSP-M: 300 mg/(kg·d), PSP-H: 600 mg/(kg·d)] or positive drug [ascorbic acid, 300 mg/(kg·d)] was administered for intervention. Key markers of renal function in urine and serum of mice in each group, such as creatinine (Crea), urea nitrogen (BUN), and uric acid (UA) levels, as well as key indicators of oxidative stress in serum and kidney, including superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) were determined to validate the successful establishment of kidney aging models and to estimate the effects of PSP. Hematoxylin and eosin (HE), periodic acid Schiff (PAS), and β-galactosidase staining were used to assess the renal pathological changes. The metabolic profiles of serum, kidney, and urine samples from CON, MOD, and PSP-H groups were analyzed by UPLC-Q-Exactive MS/MS, and pattern recognition methods were used to outline the metabolic trajectory of kidney aging and to identify the characteristic metabolites. Results: Age-related alterations in renal histopathology and impaired renal function in mice were also associated with oxidative stress indicators. Following the injection of PSP [PSP-H: 600 mg/(kg·d)], the pathological indices associated with aging were adjusted to normal levels, renal function and oxidative stress were improved in aging mice, and renal pathological damage was markedly improved. Meanwhile, the potential biomarkers were identified by UPLC-Q-Exactive MS/MS analysis and were further analyzed to form related metabolic pathways, with P < 0.05 as a threshold. The results showed that purine, sphingolipid, glycerophospholipid, tryptophan, and riboflavin metabolisms were the main metabolic pathways associated with aging. After administration of PSP, these pathological indices returned to normal levels, and biomarkers related to the aging process, such as adenosine monophosphate (AMP), tryptophan, and 5-hydroxytryptophan, also demonstrated, to some degree, reverse regulation (promoting synthesis). Conclusion Metabolomics methods based on UPLC-Q-Exactive MS/MS and multivariate statistical analysis can be adopted to establish metabolic profiles in aging mice. PSP has been shown to protect against kidney aging by interfering with the purine, sphingolipid, glycerophospholipid, tryptophan, and riboflavin metabolisms in the kidney.