OBJECTIVE: To investigate the relationship between the weight-adjusted waist index (WWI) and acute, subacute pain or chronic pain among American adults. METHODS: There was a cross-sectional study. Data from the 1999-2004 National Health and Nutrition Examination Survey (NHANES) concerning waist circumference, weight, pain status and covariates (age, gender, race, marital status, education level and income, physical activity, alcohol consumption, smoking status, and diabetes) were extracted for analysis. Multinomial Logistic regression was conducted across the three models to investigate the associations between WWI and acute, subacute and chronic pain. Model 1 did not involve any adjustments. Model 2 involved adjustments for age, gender, race, marital status, education level, and income. Model 3 was further adjusted for physical activity, alcohol consumption, smoking, and diabetes status. RESULTS: This study involved 12 694 participants with an average age of (50.6±18.7) years. Among all the participants, 9 614 people (75.74%) had no pain, 870 people (6.85%) experienced acute pain, 354 people (2.79%) suffered from subacute pain, and 1 856 people (14.62%) experienced chronic pain. The WWI of all the participants was (10.95±0.85) cm/$\sqrt{\mathrm{kg}}$, divided into four groups based on quartiles: Group Q1 (7.90-10.36) cm/$\sqrt{\mathrm{kg}}$, group Q2 (10.37-10.94) cm/$\sqrt{\mathrm{kg}}$, group Q3 (10.95-11.53) cm/$\sqrt{\mathrm{kg}}$ and group Q4 (11.54-15.20) cm/$\sqrt{\mathrm{kg}}$. With the increase of WWI, the analysis revealed a significant statistical difference in the participants' acute and chronic pain status (all P < 0.001). In Model 1, the prevalence of acute pain was lower in group Q2 and group Q4 compared with group Q1 (group Q2: OR=0.765, 95%CI: 0.615-0.953, P=0.017; group Q4: OR= 0.648, 95%CI: 0.503-0.835, P < 0.001). Compared with group Q1, the prevalence of chronic pain increased in group Q2, group Q3, and group Q4 (group Q2: OR =1.365, 95%CI: 1.149-1.622, P < 0.001; group Q3: OR=1.291, 95%CI: 1.082-1.541, P=0.005; group Q4: OR=1.874, 95%CI: 1.579-2.224, P < 0.001). In Model 2, compared with group Q1, an increase in chronic pain prevalence was still associated with an increase in WWI in other three groups (group Q2: OR=1.359, 95%CI: 1.137-1.624, P=0.001; group Q3: OR=1.260, 95%CI: 1.039-1.528, P=0.019; group Q4: OR=1.735, 95%CI: 1.413-2.132, P < 0.001). In Model 3, group Q4 had a 49.2% increased prevalence of chronic pain compared to group Q1 (OR = 1.492, 95%CI: 1.208-1.842, P < 0.001). However, in Models 2 and 3, no significant relationship was observed between acute pain and WWI (all P>0.05). And none of the three models identified a significant association between subacute pain and WWI (all P>0.05). CONCLUSION For American adults, there was no significant correlation between WWI and acute pain or subacute pain. However, as WWI increases, so does the prevalence of chronic pain. Further validation of this conclusion through large-scale prospective studies is warranted.
Humans ; Cross-Sectional Studies ; Middle Aged ; Male ; Female ; Adult ; Waist Circumference ; Chronic Pain/epidemiology* ; Aged ; Nutrition Surveys ; Pain/epidemiology* ; Body Weight ; Logistic Models ; Body Mass Index

Objective To observe the clinical efficacy of compound Wufengcao liquid combined with negative pressure wound therapy with instillation(NPWTi)for the treatment of stage Ⅲ-Ⅳ pressure injury(PI),and to preliminarily explore its action mechanism.Methods(1)Clinical research:from January 2019 to October 2022,60 PI patients who were admitted to the Scrofula Department and Wound Care Clinic at Nanjing Municipal Hospital of Traditional Chinese and Western Medicine were randomly divided into normal saline NPWTi group and compound Wufengcao liquid NPWTi group,with 30 cases in each group.Both groups underwent NPWTi under the premise of systemic basic treatment,before treatment,after removing the negative pressure device in the 1st,2nd and 3rd weeks of treatment,the pressure ulcer scale for healing(PUSH)score,the wound bacterial culture detection rate and the wound healing time were counted,and the vascular endothelial growth factor(VEGF)content of wound tissue was detected by ELISA method.(2)Animal experiments:24 SD rats were randomly divided into blank group,model group,normal saline NPWTi group and compound Wufengcao liquid NPWTi group,6 rats in each group.PI rat model was established by local tissue ischemia/reperfusion injury method,and the negative pressure device was removed at the end of each day of treatment.Before treatment and 3,7 and 10 days after treatment,the wound morphology of each group of rats was observed,the wound histopathology was observed by HE staining,the CD34 positive cells rate of wound tissue was detected by immunohistochemistry,and the expressions of p38 mitogen-activated protein kinase(p38 MAPK),nuclear factor-κB p65(NF-κB p65),inducible nitric oxide synthase(iNOS),tumor necrosis factor-α(TNF-α),arginase-1(Arg-1)and transforming growth factor-β(TGF-β)in rat blood and wound tissue were detected by ELISA and RT-qPCR.Results(1)Clinical research:Both groups could effectively reduce the PUSH score and the wound bacterial culture detection rate,shorten the wound healing time,and promote the expression of VEGF in wound tissue,the compound Wufengcao liquid NPWTi group was better than the normal saline NPWTi group(P<0.05).(2)Animal experiments:Compared with blank group,the rats in the model group showed obvious wound inflammatory response and tissue damage,and the CD34 positive cells rate,blood and wound tissue p38 MAPK,NF-κB p65,iNOS and TNF-α levels were significantly increased,Arg-1 and TGF-β level was significantly reduced(P<0.05);Compared with model group,after 7 days of treatment,the normal saline NPWTi group and the compound Wufengcao liquid NPWTi group significantly decreased the wound morphology score,the histopathological morphology was significantly improved,the CD34 positive cells rate was significantly increased(P<0.05),the levels of blood and wound tissue p38 MAPK,NF-κB p65,iNOS,and TNF-α were significantly reduced,and the levels of Arg-1 and TGF-β were significantly increased(P<0.05),and the compound Wufengcao liquid NPWTi group was better than that of the normal saline NPWTi group(P<0.05).Conclusion Compound Wufengcao liquid combined with NPWTi can effectively promote the healing of PI wounds,and its mechanism of action may be by inhibiting the activation and expression of p38 MAPK/NF-κB signaling pathway,thereby regulating the polarization balance of M1/M2 macrophages.

Objective To investigate the rate of germline variants in patients with pancreatic cancer and clinical characteristics related with germline variants.Methods A total of 271 patients diagnosed with pancreatic cancer were enrolled in this study.Germline variants of 21 tumor susceptibility genes were detected by next-generation sequencing,and the relationship between germline variants and clinical factors such as age of onset,family history and personal history was analyzed.Results The rate of germline P/LP variants was 6.3%in unselected pancreatic cancer patients,but was high as 17.1%in genetic high-risk group patients(those with a family or personal history of cancer,or early-onset).Genes with higher frequency of germline variants in pancreatic cancer patients were PALB2,BRCA2,and ATM.Conclusion The rate of germline variants in overall pancreatic cancer patients is not high,but it increases significantly in genetic high-risk group,proving the importance of clinical factors in the screening of hereditary pancreatic cancer.

Objective To evaluate the value of high-throughput sequencing(HTS)data reanalysis that does not include ERBB2 copy number variation(CNV)analysis,in identifying ERBB2 amplification in patients with colorectal cancer.Methods The HTS data of 252 cases of colorectal cancer diagnosed by pathological biopsy who received peripheral blood cfDNA HTS detection samples were retrospectively analyzed.According to the HTS data of ERBB2 non-amplified samples judged by immunohistochemistry(IHC)and/or fluorescence in situ hybridization(FISH),the number of chromosome 17(Chr17)reads in the total number of reads was calculated the range of the ratio was initially determined as the threshold for prompting ERBB2 amplification.Suspected positive samples were screened according to thresholds and verified by digital PCR,IHC and FISH.Results The proportion of the number of Chr17 reads accounts for the number of total reads in the 89 cases of ERBB2 non-amplified samples determined by IHC and/or FISH ranged from 0.188 to 0.299(0.239±0.192).Using 0.298(1.25 times the mean)as the threshold indicating ERBB2 amplification,the data of 163 samples were analyzed,of which 7 cases were suspected to be positive,and the ratio ranged from 0.302 to 0.853.Among them,5 cases were determined to be positive by IHC and/or FISH,and 6 cases were confirmed to be positive by digital PCR.The ratio of the number of Chr17 reads to the number of total reads was positively correlated with the ratio of ERBB2/EIF2C1,and the correlation was good(r2=0.909).Conclusion The high-throughput sequencing data that does not cover the ERBB2 CNV analysis has a certain hint value for ERBB2 amplification in patients with colorectal cancer.

Objective:To explore the predictive value of blood flow velocity changes in superior mesenteric artery (SMA) monitored by ultrasound on feeding intolerance (FI) of enteral nutrition (EN) in mechanically ventilated ICU patients. Methods:One-hundred and eight mechanically ventilated patients in Intensive Care Department of the Second People's Hospital of Nantong from February 2022 to February 2023 were enrolled. SMA blood flow parameters and enteral nutrition tolerance were monitored on the 1st,3rd,and 7th day (D1,D3,D7) after initiation of EN. Differences in SMA blood flow parameters between tolerant and intolerant group,as well as intolerant subgroups (mild,moderate,and severe) were analyzed. The predictive value of SMA blood flow parameters for FI and the risk factors of FI were also evaluated,and the relationship between SMA blood flow parameters and intestinal barrier function were preliminarily explored . Result:The SMA blood flow velocity parameters,peak systolic velocity (PSV) and end diastolic velocity (EDV),were higher at D1,D3,and D7 in the tolerant groups compared to the intolerant group (all P<0.05). Subgroup analysis showed that as the degree of intolerance increased,PSV gradually decreased. EDV at D1,D3,and D7 also gradually decreased with the increased severity of FI (all P<0.05);The AUC of PSV and EDV predicting FI in D1,D3,and D7 patients were 0.752 (95％ CI:0.660～0.830) and 0.773 (95％ CI:0.682～0.848),0.774 (95％ CI:0.683～0.849) and 0.796 (95％ CI:0.708～0.868),0.743 (95％ CI:0.650～0.822) and 0.713 (95％ CI:0.618～0.796). respectively. PSV,norepinephrine use,and blood phosphorus levels were independent prognostic factors for FI at D3. Patients with FI showed a negative correlation between PSV,EDV,and diamine oxidase (PSV:r=-0.857,P<0.001;EDV:r=-0.795,P<0.001). Conclusion:Changes in blood flow velocity in the superior mesenteric artery by ultrasound monitoring can effectively predict enteral nutrition intolerance in mechanically ventilated patients,it might have potential clinical application values in ICU patients.

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Objective: Cancer immunotherapy can lead to various side effects, termed immune-related adverse events (irAE). This study summarized and analyzed the clinical and pathological characteristics of immune-mediated liver injury caused by immune checkpoint inhibitors (ILICI). Methods: This is a retrospective case series study involving 11 patients diagnosed with ILICI at the Peking Union Medical College Hospital from November 2019 to November 2021. Patient demographic information and clinical data, including gender, age, ILICI onset, clinical and radiological manifestations, pathological features, treatment, and resumption of ICI were retrospectively collected and analyzed. Results: The patients were primarily males (9/11) with a median age of 65 (range: 32-73) years. ICI mainly resulted in either partial remission (4/11) or stable disease (3/11). ILICI occurred after a median of two cycles of anti-programmed cell death-1 (PD-1) therapy, with a median time from the initial and last anti-PD-1 therapy to ILICI onset of 57 days and 17 days, respectively. ILICI was mostly severe (3/11) or very severe (6/11). While the clinical and radiological manifestations were non-specific, the pathological features were active lobular hepatitis and portal inflammation, with prominent CD8⁺T lymphocyte infiltration. The basic treatment was hepatoprotective drugs (10/11). Glucocorticoids were used as the primary therapy (9/11) but were ineffective in 4 of 9 cases. Of these, 3 of 9 cases received combined treatment with mycophenolate mofetil (MMF), only one of whom achieved remission. By the end of the study, 2 of 11 cases had resumed ICI and neither had experienced an ILICI relapse. Conclusion: The ILICI patients in this study had a corresponding history of ICI treatment and pathological features. The main treatment included hepatoprotective drugs and glucocorticoids. Immunosuppressive drugs were added for some cases but had poor efficacy.
Male ; Humans ; Adult ; Middle Aged ; Aged ; Immune Checkpoint Inhibitors/adverse effects* ; Retrospective Studies ; Antineoplastic Agents, Immunological/adverse effects* ; Liver ; Glucocorticoids/therapeutic use*

Objective: To establish an ultra-sensitive, ultra-fast, visible detection method for Vibrio parahaemolyticus (VP) . Methods: We established a new method for detecting the tdh and trh genes of VP using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 12a (CRISPR/Cas12a) combined with recombinase polymerase amplification and visual detection (CRISPR/Cas12a-VD). Results: CRISPR/Cas12a-VD accurately detected target DNA at concentrations as low as 10 ^-18 M (single molecule detection) within 30 min without cross-reactivity against other bacteria. When detecting pure cultures of VP, the consistency of results reached 100% compared with real-time PCR. The method accurately analysed pure cultures and spiked shrimp samples at concentrations as low as 10 ² CFU/g. Conclusion The novel CRISPR/Cas12a-VD method for detecting VP performed better than traditional detection methods, such as real-time PCR, and has great potential for preventing the spread of pathogens.
CRISPR-Cas Systems ; Nucleic Acid Amplification Techniques/methods* ; Recombinases/genetics* ; Vibrio parahaemolyticus/genetics*

China/epidemiology* ; Diabetes Complications/epidemiology* ; Diabetes Mellitus/epidemiology* ; Humans

ObjectiveTo investigate the effect of Huangqisan pellets （HQS） on the phosphatidylinositol-3 kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway and autophagy in the kidney of diabetic nephropathy （DN） rats. MethodDN rat model was established through high-fat diet combined with intraperitoneal injection of streptozotocin （35 mg·kg^-1）. DN rats were randomly assigned into model group， irbesartan （0.027 g·kg^-1） group， low-dose HQS （0.54 g·kg^-1） group and high-dose HQS （1.08 g·kg^-1） group. The levels of 24 h urinary total protein （UTP）， serum albumin （Alb）， serum creatinine （SCr）， urea nitrogen （BUN）， triglyceride （TG） and total cholesterol （TC） were measured after 12 weeks of continuous administration. The pathological changes of renal tissue were observed via hematoxylin-eosin （HE） staining. The expression of podocyte split diaphragm proteins nephrin and podocin in the renal tissue were detected by immunohistochemistry. The protein levels and phosphorylation of key proteins in PI3K/Akt/mTOR signaling pathway， as well as the expression of yeast Atg6 homolog （Beclin1） and microtubule-associated protein 1 light chain 3 （LC3） in the renal tissue were analyzed by Western blot. ResultCompared with the control group， the model group showcased increased 24 h UTP， SCr， BUN， TG， and TC levels and decreased Alb level （P<0.01）. After modeling， the rats showed granulosity of epithelial cells of renal tubules， thickening of capillary basement membrane， proliferation of mesangial cells， and sclerosis of glomerulus. Furthermore， modeling down-regulated the expression of nephrin and podocin in the podocyte hiatus of glomerulus （P<0.01） as well as the protein levels of p-PI3K， p-Akt， and p-mTOR and the autophagy markers LC3 and Beclin1 in renal tissue （P<0.01）. Compared with model group， irbesartan and HQS decreased the 24 h UTP， Cr， BUN， TG， and TC levels， increased the Alb level， and alleviated the pathological damage of kidney. Moreover， they up-regulated the expression of Nephrin and Podocin in the podocyte hiatus of glomerulus， as well as the protein levels of p-PI3K， p-Akt， p-mTOR， LC3， and Beclin1 in renal tissue （P<0.05， P<0.01）. ConclusionHQS may inhibit the PI3K/Akt/mTOR signaling pathway to enhance podocyte autophagy and protect the glomerulus， thus slowing down the development of DN.