Despite therapy with potent antiviral agents, chronic hepatitis B (CHB) patients remain at high risk of hepatocellular carcinoma (HCC). While metabolites have been rediscovered as active drivers of biological processes including carcinogenesis, the specific metabolites modulating HCC risk in CHB patients are largely unknown. Here, we demonstrate that baseline plasma from CHB patients who later developed HCC during follow-up exhibits growth-promoting properties in a case-control design nested within a large-scale, prospective cohort. Metabolomics analysis reveals a reduction in long-chain acylcarnitines (LCACs) in the baseline plasma of patients with HCC development. LCACs preferentially inhibit the proliferation of HCC cells in vitro at a physiological concentration and prevent the occurrence of HCC in vivo without hepatorenal toxicity. Uptake and metabolism of circulating LCACs increase the intracellular level of acetyl coenzyme A, which upregulates histone H3 Lys14 acetylation at the promoter region of KLF6 gene and thereby activates KLF6/p21 pathway. Indeed, blocking LCAC metabolism attenuates the difference in KLF6/p21 expression induced by baseline plasma of HCC/non-HCC patients. The deficiency of circulating LCACs represents a driver of HCC in CHB patients with viral control. These insights provide a promising direction for developing therapeutic strategies to reduce HCC risk further in the antiviral era.

Objective To investigate the prevalence of Anisakis infections in coastal marine fishes and awareness of anisakiasis control knowledge among local residents in Yantai City, Shandong Province in 2021, so as to provide insights into formulation of anisakiasis control interventions. Methods Marine fishes were purchased from Shunxin Port, Yantai City, Shandong Province in November 2021, and the presence of Anisakis was detected in different species of fishes and different fish sites. The correlations between body length and weight of marine fish and intensity of Anisakis infections were examined using Spearman’s rank correlation analysis, and the dietary habits and anisakiasis control knowledge were investigated using questionnaire surveys among local residents. Results A total of 201 marine fishes belonging to 20 species were dissected, and Anisakis was detected in 77 marine fishes (38.31%) belonging to 11 species (55.00%), with a mean infection intensity of 45.04 parasites per fish (3 468/77). Spearman’s rank correlation analysis revealed that the body length (r_s = 0.74, P < 0.05) and weight (r_s = 0.79, P < 0.01) of the monkfish correlated positively with the intensity of Anisakis infections, and the body length (r_s = 0.68, P < 0.05) of the flatfish correlated positively with the intensity of Anisakis infections, while no correlations were examined between the body length or weight of other marine fishes and the intensity of Anisakis infections. Of all respondents, 53.38% men and 56.67% women did not know anisakiasis control knowledge at all, and there was a significant difference in the proportion of respondents using separate chopping boards for raw and cooked food from different villages (χ² = 17.89, P < 0.01), while there was an age-specific proportion of respondents with habitats of eating raw or semi-raw seafood (χ² = 28.27, P < 0.01). Conclusions The prevalence and intensity of Anisakis infections were high in coastal marine fishes in Yantai City in 2021, and the awareness of anisakiasis control knowledge was low among local residents. Intensified health education pertaining to anisakiasis control knowledge is recommended to reduce the risk of Anisakis infections.

Objective:To explore the correlation between peripheral blood B cell count and clinical features and prognosis of patients with newly diagnosed diffuse large B-cell lymphoma(DLBCL).Methods:The relationship of peripheral blood B cell count with clinical features,laboratory indexes and prognosis in 67 patients with newly diagnosed DLBCL was retrospectively analyzed.Results:Patients were divided into low B-cell count group(B cell＜0.1 × 109/L,n=34)and high B-cell count group(B cell&ge;0.1 × 109/L,n=33)according to the median B cell count values.Compared with the high B cell count group,the low B cell count group had a higher proportion of patients with Lugano stage Ⅲ-Ⅳ,elevated LDH,elevated β2-MG and IPI score 3-5 and increased CRP(P=0.033,0.000,0.023,0.001,0.033).The peripheral CD3+and CD4+cell counts of patients in the low B cell count group were significantly lower than those in the high B cell count group(P=0.010,0.017).After initial treatment,overall response rate(ORR)and complete remission(CR)rate in high B cell count group were significantly higher than those in low B cell count group(P=0.032,0.013).The median follow-up time of patients was 23(2-77)months,progression-free survival(PFS)and overall survival(OS)of patients in the high B cell count group were significantly better than those in the low B cell count group(P=0.001,0.002).Univariate analysis showed that pretreatment low B cell count in the peripheral blood was associated with shortened PFS and OS(HR=4.108,P=0.002;HR=8.218,P=0.006).Multivariate analysis showed that low B cell count was an independent prognostic factor for shortened PFS(HR=3.116,P=0.037).Conclusion:Decreased peripheral blood B cell count in newly diagnosed DLBCL patients is associated with high-risk clinical features and may affect the efficacy of immunochemotherapy,which is associated with poor clinical prognosis.

The hemodynamic characteristics of venous reflux are associated with infertility in patients with varicocele; however, an effective method for quantifying the structural distribution of the reflux is lacking. This study aimed to predict surgical outcomes using a new software for venous reflux quantification. This was a retrospective cohort study of a consecutive series of 105 patients (age range: 22-44 years) between July 2017 and September 2019. Venous reflux of the varicocele was obtained using the Valsalva maneuver during scrotal Doppler ultrasonography before microsurgical varicocelectomy. Using this software, the colored reflux signals were segmented, and the gray scale of the color pixels representing the reflux velocity was comprehensively quantified into the mean reflux velocity of the green layer (MRVG) and the reflux velocity standard deviation of the green layer (RVSDG). Spontaneous pregnancy and changes from baseline in the semen parameters were assessed during a 12-month follow-up period. Data were analyzed using logistic regression analysis. An association of the high MRVG group with impaired progressive motility (odds ratio [OR] = 2.868, 95% confidence interval [CI]: 1.133-7.265) and impaired sperm concentration (OR = 2.943, 95% CI: 1.196-7.239) was found during multivariate analysis. High MRVG (OR = 2.680, 95% CI: 1.086-6.614) and high RVSDG (OR = 2.508, 95% CI: 1.030-6.111) were found to be independent predictors of failure to achieve pregnancy following microsurgical repair. In summary, intense venous reflux is an independent predictor of impaired progressive motility, sperm concentration, and pregnancy outcomes after microsurgical varicocelectomy.
Pregnancy ; Female ; Humans ; Male ; Young Adult ; Adult ; Varicocele/surgery* ; Retrospective Studies ; Semen ; Veins/surgery* ; Sperm Count ; Infertility, Male/surgery* ; Microsurgery/methods* ; Sperm Motility

OBJECTIVE: To observe the effect of acupuncture combined with infantile tuina on intestinal flora and its efficacy in children with tic disorders (TD), and to explore its mechanism. METHODS: A total of 15 children with TD were recruited as an observation group and 10 healthy children as a healthy control group. Regulating spleen and stomach acupuncture combined with infantile tuina were received in the observation group. First, acupuncture was applied to Zhongwan (CV 12), Tianshu (ST 25), Guanyuan (CV 4), Hegu (LI 4), Zusanli (ST 36), etc., and then abdominal massage and other tuina techniques were applied, once a day, 6 times a week, 2 weeks as a course of treatment, a total of 2 courses of treatment were required. No intervention was given in the healthy control group. In the observation group, Yale global tic severity scale (YGTSS) score and TCM syndrome score were compared before treatment and after 1 and 2 courses of treatment. 16S rRNA sequencing technology was used to detect the intestinal flora in the healthy control group and before and after treatment in the observation group. RESULTS: After 1 and 2 courses of treatment, the scores of YGTSS and TCM syndrome in the observation group were lower than those before treatment (P<0.01, P<0.05). Compared with the healthy control group, the number of operational taxonomic units (OTU) and indexes of Chao1, Sobs, Ace and Shannon were decreased in the observation group before treatment (P<0.05, P<0.01). Compared with before treatment, the number of OTU and indexes of Chao1, Sobs, Ace and Shannon were increased in the observation group after treatment (P<0.01, P<0.05). Compared with the healthy control group, the relative abundance of Firmicutes in the observation group before treatment was decreased (P<0.001), while the relative abundance of Bacteroidetes, Bacteroides and Erysipelatoclostridium was increased (P<0.001, P<0.05). Compared with before treatment, the relative abundance of Bacteroidetes in the observation group was decreased (P<0.001) after treatment, while the relative abundance of Actinobacteria, Bifidobacterium and Atopobium was increased (P<0.05, P<0.01). CONCLUSION Acupuncture combined with infantile tuina based on the principle of regulating spleen and stomach could effectively improve TD symptoms in children, which may be related to regulating the diversity of intestinal flora, increasing beneficial bacteria, maintaining intestinal microecological balance, and playing a role in improving neurological disorders.
Child ; Humans ; Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; Acupuncture Therapy ; Spleen ; Tic Disorders

Objective To investigate the prevalence and changing trend of Enterobius vermicularis infections among children in Shandong Province, so as to provide the scientific evidence for the adjustment and development of the enterobiasis control strategy. Methods Soil-borne nematodiasis surveillance sites were assigned in 51 counties (districts, cities) in Shandong Province from 2016 to 2020, and the E. vermicularis infections were detected using a modified Kato-Katz technique and the cellophane tape method among children at ages of 3 to 9 years living in these surveillance sites. The epidemiological profiles of E. vermicularis-infected children were descriptively analyzed. Results A total of 5 060 children at ages of 3 to 9 years were detected in 51 soil-borne nematodiasis surveillance sites in Shandong Province from 2016 to 2020, and the overall prevalence of E. vermicularis infections was 2.23%. The annual prevalence of E. vermicularis infections was 3.99% (26/651), 1.70% (14/824), 0.96% (8/837), 2.90% (45/1 552) and 1.67% (20/1 196) from 2016 to 2020, respectively, with a significant difference detected among years ( χ² = 21.455, P < 0.01). The prevalence of E. vermicularis infections was 1.25% (15/1 198), 1.85% (14/755), 3.18% (84/2 640) and 0 (0/467) among children from central, eastern, southern and northern Shandong Province (χ² = 27.326, P < 0.01). In addition, there was no significant difference in the prevalence of E. vermicularis infections between male (1.98%, 56/2 831) and female children (2.56%, 57/2 229) (χ² = 1.916, P > 0.05); however, there was age-specific prevalence of E. vermicularis infections among children (χ² = 16.448, P < 0.05), with the greatest prevalence detected among children at ages of 6 years (3.18%, 25/786), and the lowest prevalence seen among children at ages of 3 years (0.75%, 6/800). Conclusions The prevalence of E. vermicularis infections remained at a medium level among children at ages of 3 to 9 years in Shandong Province from 2016 to 2020, with region-specific prevalence found across the province. An integrated strategy is required for enterobiasis control.

Objective To investigate the correlation between cyclin G1 expression and the efficacy of radiotherapy on HCC. Methods The expression of cyclin G1 in biopsy specimens of 68 patients who received radiotherapy was detected by immunochemistry. The correlation between cyclin G1 expression and clinicopathological characteristics was analyzed by chi-square test. The correlation between cyclin G1 expression and OS or PFS was evaluated by Kaplan-Meier analysis. Univariate and multivariate analyses were used for the relation between clinicopathological characteristics and OS or PFS. Results The expression of cyclin G1 was related to portal vein tumor embolus, clinical stage and alpha fetoprotein. Survival analysis showed that the OS and PFS of patients with low expression of cyclin G1 were significantly higher than those with high cyclin G1 expression (P < 0.05). Multivariate analysis showed that cyclin G1 was an independent risk factor for DFS of patients with HCC. Conclusion High expression of cyclin G1 is an adverse prognostic factor for HCC patients who received radiotherapy.

Adaptation, Physiological ; Adenosine Monophosphate ; administration & dosage ; analogs & derivatives ; pharmacology ; therapeutic use ; Administration, Intranasal ; Alanine ; administration & dosage ; analogs & derivatives ; pharmacology ; therapeutic use ; Animals ; Betacoronavirus ; genetics ; physiology ; Chlorocebus aethiops ; Coronavirus Infections ; drug therapy ; virology ; Disease Models, Animal ; Female ; Host Specificity ; genetics ; Lung ; pathology ; virology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mutation, Missense ; Nasal Mucosa ; virology ; Pandemics ; Pneumonia, Viral ; drug therapy ; virology ; RNA, Viral ; administration & dosage ; genetics ; Turbinates ; virology ; Vero Cells ; Viral Load ; Virus Replication

Objective To compare the clinical efficacy and safety between induction chemotherapy (IC) followed by concurrent chemotherapy (CRT) and CRT alone in patients with inoperable thoracic esophageal squamous cell carcinoma (ESCC).Methods Between 2002 and 2015,clinical data of 267 thoracic ESCC patients undergoing definitive CRT based on docetaxel combined with cisplatin were retrospectively analyzed.Through a matched case-control study,85 patients receiving IC combined with CRT were matched to those undergoing CRT alone at a ratio of 1vs.1,according to age,gender,performance status,tumor location,tumor length,and TNM staging as the matching factors.Clinical efficacy and safety between two groups were statistically compared.Kaplan-Meier survival analysis was used to analyze the survival.The log-rank test was adopted to examine within-group differences.The Cox regression model was used for multivariate analysis.Results The median follow-up time for 170 patients was 18 months (range,3-72 months).The overall objective response rates in the IC and CRT groups were 74.1％ and 58.8％(P=0.035).The 3-year overall survival (OS) and progress-free survival (PFS) rates in the IC group were 44.2％ and 34.8％,significantly higher than 29.7％ and 15.4％ in the CRT group (P=0.028,P=0.015).Subgroup analysis revealed that patients responsive to IC obtained significantly better OS (P=0.002),PFS (P=0.001),and local recurrence-free survival (LRFS)(P=0.002) compared with the IC non-responder,whereas the distant metastasis-free survival (DMFS) did not significantly differ (P=0.166).The incidence rate of grade 3-4 leukopenia in the IC group was significantly higher than that in the CRT group (38.8％ vs.24.7％,P=0.048).Multivariate analysis revealed that age and the addition of IC were independent prognostic factors for OS (P=0.003,0.016).Conclusions Compared with concurrent CRT,IC in combination with CRT can yield better short-term efficacy and longer survival for ESCC patients.The risk of hematological toxicity in the IC group is relatively higher but tolerable.Prospective randomized trials are required to confirm the clinical efficacy and safety of IC for thoracic ESCC patients.

Objective To compare the effects of dobutamine with those milrinone on myocardial strain in patients undergoing valve replacement surgery.Methods Fifty-five patients udergoing valve replacement surgery, 27 males and 28 females, aged 40-75 years, falling into ASA physical statusⅡ orⅢ, New York Heart Association (NYHA) ⅡorⅢ, were included in this study.They were divided into 3 groups by using a random number table:intravenous infusion dobutamine group (group D, n=18), intravenous infusion milrinone group (group M, n=20) and intravenous infusion saline group (group C, n=17).All patients were used general anesthesia.In groups D, the patients received intravenous infusion dobutamine (4μg·kg-1·min-1) for an hour starting from 15 min after termination of CPB.In group M, the patients did intravenous infusion milrinone (0.4μg·kg-1·min-1) in the same way.In group C, the patients got intravenous infusion saline also.After induction of anesthesia, these patients were recorded for hemodynamic measurement at three points after induction of anesthesia and before splitting of sternum (T0), starting from 15 min after termination of CPB (T1), intravenous infusion medicine for 30 min (T2), intravenous infusion medicine for one hour (T3):HR, CVP, cardiac output (CO), left ventricular ejection fraction (LVEF), right ventricular fractional area change (RVFAC), cardiac index (CI) and systemic vascular resistance index (SVRI) and strained indicator:global longitudinal strain of left ventricle (S-LVL), global circumferential strain of the left ventricle (S-LVM), global longitudinal strain of right ventricle (S-RV).Results Compared with group M, HR in group D at T2 and T3 was higher (P<0.05).Compared with group C, HR in group D at T3 was higher (P<0.05).And CI in group D at T2 was higher than that in groups C and M (P<0.05).Compared with groups C, S-LVMin groups D and M at T2 and T3 were stronger, S-LVL, S-RV in group D and S-RV in group M at T3 were stronger (P<0.05).Conclusion Intravenous infusion dobutamine can improve S-LVM, S-LVLand S-RV;Intravenous infusion milrinone can improve S-LVMand S-RV.