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Shao-Jun Huang,1 Xian-Hua Wang,2 Zhi-Dong Liu,1 Wen-Li Cao,3 Yi Han,1 Ai-Guo Ma,2 Shao-Fa Xu1 1Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Nutrition and Food Hygiene, Institute of Human Nutrition, Medical College of Qingdao University, Qingdao, People’s Republic of China; 3Department of Pulmonary Medicine, Beijing Geriatric Hospital, Beijing, People’s Republic of China Background and aim: To conduct meta-analyses of all published studies on various aspects of association between vitamin D and tuberculosis (TB).Methods: PubMed and Web of Knowledge were searched for all properly controlled studies on vitamin D and TB. Pooled odds ratio, mean difference or standardized mean difference, and its corresponding 95% confidence interval were calculated with the Cochrane Review Manager 5.3.Results: A significantly lower vitamin D level was found in TB patients vs controls; vitamin D deficiency (VDD) was associated with an increased risk of TB, although such an association was lacking in the African population and in the human immunodeficiency virus-infected African population. A significantly lower vitamin D level was found in human immunodeficiency virus-TB-coinfected African patients receiving antiretroviral treatment who developed TB-associated immune reconstitution inflammatory syndrome vs those who did not develop TB-associated immune reconstitution inflammatory syndrome. VDD was associated with an increased risk of developing active TB in those subjects with latent TB infection and with an increased risk of tuberculin skin test conversion/TB infection conversion, and the trend toward a lower vitamin D level in active TB patients vs latent TB infection subjects did not reach statistical significance, indicating that VDD was more likely a risk factor than a consequence of TB. This concept was further strengthened by our result that anti-TB treatment did not affect vitamin D level in TB patients receiving the treatment.Conclusion: Our analyses revealed an association between vitamin D and TB. VDD is more likely a risk factor for TB than its consequence. More studies are needed to determine whether vitamin D supplementation is beneficial to TB prevention and treatment. Keywords: vitamin D, vitamin D deficiency, tuberculosis, 25-hydroxyvitamin D, meta-analysis

Increased levels of lactoferrin (Lf) are present in the aged brain and in the lesions of various neurodegenerative diseases, including Parkinson's disease (PD), and may contribute to the cascade of events involved in neurodevelopment and neuroprotection. However, whether Lf originates from astrocytes and functions within either the normal or pathological brain are unknown. Here, we employed mice with specific knockout of the astrocyte lactoferrin gene (named Lf-cKO) to explore its specific roles in the pathological process of PD. We observed a decrease in tyrosine hydroxylase-positive cells, mitochondrial dysfunction of residual dopaminergic neurons, and motor deficits in Lf-cKO mice, which were significantly aggravated after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. To further explore how astrocytic lactoferrin deficiency exacerbated PD-like manifestation in MPTP-treated mice, the critical molecules involved in endoplasmic reticulum (ER)-mitochondria contacts and signaling pathways were investigated. In vitro and in vivo models, we found an aberrant level of effects implicated in glutamate and calcium homeostasis, mitochondrial morphology and functions, mitochondrial dynamics, and mitochondria-associated ER membranes, accompanied by signs of oxidative stress and ER stress, which increase the fragility of dopaminergic neurons. These findings confirm the existence of astrocytic Lf and its influence on the fate of dopaminergic neurons by regulating glutamate/calcium metabolism and ER-mitochondria signaling. Our findings may be a promising target for the treatment of PD., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The outbreak of coronavirus disease 2019 (COVID-19) infection posed a huge threat and burden to public healthcare in late 2022. Non-drug measures of traditional Chinese medicine (TCM), such as acupuncture, cupping and moxibustion, are commonly used as adjuncts in China to help in severe cases, but their effects remain unclear., Objectives: To observe the clinical effect of TCM non-drug measures in improving respiratory function and symptoms among patients with severe COVID-19., Design, Setting, Participants and Interventions: This study was designed as a multicenter, assessor-blind, randomized controlled trial. Hospitalized patients with COVID-19 were randomly assigned to the treatment or control group. The treatment group received individualized TCM non-drug measures in combination with prone position ventilation, while the control group received prone position ventilation only for 5 consecutive days., Main Outcome Measures: The primary outcome measures were the percentage of patients with improved oxygen saturation (SpO 2 ) at the end of the 5-day intervention, as well as changes of patients' respiratory rates. The secondary outcome measures included changes in SpO 2 and total score on the self-made respiratory symptom scale. The improvement rate, defined as a 3-day consecutive increase in SpO 2 , the duration of prone positioning, and adverse events were recorded as well., Results: Among the 198 patients included in the intention-to-treat analysis, 159 (80.3%) completed all assessments on day 5, and 39 (19.7%) patients withdrew from the study. At the end of the intervention, 71 (91%) patients in the treatment group had SpO 2 above 93%, while 61 (75.3%) in the control group reached this level. The proportion of participant with improved SpO 2 was significantly greater in the intervention group (mean difference [MD] = 15.7; 95% confidence interval [CI]: 4.4, 27.1; P = 0.008). Compared to the baseline, with daily treatment there were significant daily decreases in respiratory rates in both groups, but no statistical differences between groups were found (all P ≥ 0.05). Compared to the control group, the respiratory-related symptoms score was lower among patients in the treatment group (MD = -1.7; 95%CI: -2.8, -0.5; P = 0.008) after day 3 of treatment. A gradual decrease in the total scores of both groups was also observed. Thirty-one adverse events occurred during the intervention, and 2 patients were transferred to the intensive care unit due to deterioration of their illness., Conclusion: TCM non-drug measures combined with prone positioning can effectively treat patients with severe COVID-19. The combined therapy significantly increased SpO 2 and improved symptom scores compared to prone positioning alone, thus improving the patients' respiratory function to help them recover. However, the improvement rate did not differ between the two groups., Trial Registration: Chinese Clinical Trial Registry (ChiCTR2300068319). Please cite this article as: Yin X, Jin Z, Li F, Huang L, Hu YM, Zhu BC, Wang ZQ, Li XY, Li JP, Lao LX, Mi YQ, Xu SF. Effectiveness and safety of adjunctive non-drug measures in improving respiratory symptoms among patients with severe COVID-19: A multicenter randomized controlled trial. J Integr Med. 2024; Epub ahead of print., (Copyright © 2024 Shanghai Yueyang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. Published by Elsevier B.V. All rights reserved.)

A new polyketide, mauritone A ( 1 ) with six known polyketides curvulone B ( 2 ), curvularin ( 3 ), 12-oxocurvularin ( 4 ), (10 E ,15 S )-10,11-dehydrocurvularin ( 5 ), (11 R ,15 S )-11-hydroxycurvularin ( 6 ), and (11 S ,15 S )-11-hydroxycurvularin ( 7 ) were isolated from the fungal-bacterial symbiont Aspergillus spelaeus GXIMD 04541/ Sphingomonas echinoides GXIMD 04532 derived from Mauritia arabica . Their structures were elucidated by extensive spectral analysis. All compounds ( 1 - 7 ) were evaluated for their anti-inflammatory effects. The inhibitory effects of 4 , 5 , and 7 on nitric oxide (NO) production were found to be significant, with IC 50 values of 5.5 ± 0.26, 2.0 ± 0.31, and 8.3 ± 0.62 μM, respectively, surpassing that of the positive control quercetin (10.6 ± 0.64 μM). Compounds 3 and 6 exhibited moderate inhibition of NO, with IC 50 values of 18.6 ± 0.53 and 12.7 ± 0.45 μM, respectively.

Flexible electronics are highly developed nowadays in human-machine interfaces (HMI). However, challenges such as lack of flexibility, conductivity, and versatility always greatly hindered flexible electronics applications. In this work, a multifunctional hybrid hydrogel (H-hydrogel) was prepared by combining two kinds of 1D polymer chains (polyacrylamide and polydopamine) and two kinds of 2D nanosheets (Ti 3 C 2 T x MXene and graphene oxide nanosheets) as quadruple crosslinkers. The introduced Ti 3 C 2 T x MXene and graphene oxide nanosheets are bonded with the PAM and PDA polymer chains by hydrogen bonds. This unique crosslinking and stable structure endow the H-hydrogel with advantages such as good flexibility, electrical conductivity, self-adhesion, and mechanical robustness. The two kinds of nanosheets not only improved the mechanical strength and conductivity of the H-hydrogel, but also helped to form the double electric layers (DELs) between the nanosheets and the bulk-free water phase inside the H-hydrogel. When utilized as the electrode of a triboelectric nanogenerator (TENG), high electrical output performances were realized due to the dynamic balance of the DELs between the nanosheets and the H-hydrogel's inside water molecules. Moreover, flexible sensors, including triboelectric, and strain/pressure sensors, were achieved for human motion detection at low frequencies. This hydrogel is promising for HMI and e-skin., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Recent studies have indicated that platelets may play a role in the advancement of pancreatic cancer by supporting tumor growth and increasing resistance to chemotherapy. This study aims to develop a prognostic model for pancreatic cancer using a platelet-related gene risk score. Prognostic platelet-related genes (PRGs) were identified from public databases and analyzed using cluster analysis. We investigated the microenvironment signatures and gene mutation patterns across different PRG-based molecular subtypes of pancreatic cancer. A prognostic model based on PRGs was developed using LASSO-Cox Regression Analysis. Additionally, we examined the correlation between the risk score and tumor clinical characteristics, as well as drug sensitivity. Two molecular subtypes, cluster C1 and C2, were identified. Cluster C2 was associated with a poorer prognosis compared to Cluster C1. The C1 group exhibited higher scores for activated CD8+ T cells, central memory CD4+ T cells, and natural killer T cells. The C2 group demonstrated a higher frequency of gene mutations. We established and validated a novel prognostic prediction model and platelet-related gene risk score for pancreatic cancer. The risk score was positively correlated with T stage, N stage, and tumor grade, and it presented a significant prognostic value compared to other clinical factors. In conclusion, a novel prognostic prediction model focusing on platelet involvement in pancreatic cancer has been developed, offering potential benefits for future drug therapies and clinical prognostic assessments., Competing Interests: None., (AJCR Copyright © 2023.)

Background: There are few studies comparing recurrences between endoscopic retrograde cholangiopancreatography (ERCP) and open choledochotomy (OCT)., Aims: To compare the effect of different surgical methods on single and multiple recurrences of choledocholithiasis., Methods: A total of 1255 patients with choledocholithiasis who underwent ERCP or OCT were retrospectively studied. The recurrence of choledocholithiasis was calculated by the Kaplan-Meier method with the log-rank test. Multivariate analyses of recurrent choledocholithiasis were performed by introducing variables with P < 0.20 in univariate analysis into the logistic regression model., Results: A total of 204 (16.7%, 204/1225) patients relapsed. Among the 204 patients, 74.5% relapsed within three years after surgery, of whom 39.7% (81/204) had multiple relapses (≥ 2). The recurrence rate of ERCP (17.2%, 119/692) was higher than that of OCT (15.1%, 85/563), but the difference was not statistically significant. The independent risk factors for a single recurrence of choledocholithiasis were diabetes, stone number ≥ 2, maximum stone diameter ≥ 15 mm, sedentary occupation, the approach of ERCP (EST or EPBD), periampullary diverticulum, primary suture, high-fat diet (postoperative), frequency of weekly vegetable intake (< 4, postoperative), and drinking (postoperative). However, the ERCP approach (EST or EPBD), OCT approach (LCBDE), primary suture, high-fat diet (postoperative), and frequency of weekly vegetable intake (< 4, postoperative) were independent risk factors for multiple recurrences of choledocholithiasis., Conclusion: Patients with choledocholithiasis should be followed up regularly for one to three years after treatment. Stone number  ≥ 2, diabetes mellitus, periampullary diverticulum, surgical methods, and lifestyle are all risk factors for the recurrence of choledocholithiasis. ERCP is still the preferred surgical method based on the advantages of low risk of cholangitis recurrence, less hospital stay, minimally invasive surgery, fewer postoperative complications, and easier acceptance by elderly patients. In addition to optimizing the treatment plans, postoperative lifestyle management is also vital., Competing Interests: The authors have declared that no competing interest exists., (Copyright © 2023 Yao Wu et al.)

Singapore grouper iridovirus (SGIV) is a new ranavirus species in the Iridoviridae family, whose high lethality and rapid spread have resulted in enormous economic losses for the aquaculture industry. Curcumin, a polyphenolic compound, has been proven to possess multiple biological activities, including antibacterial, antioxidant, and antiviral properties. This study was conducted to determine whether curcumin protected orange-spotted grouper ( Epinephelus coioides ) from SGIV-induced intestinal damage by affecting the inflammatory response, cell apoptosis, oxidative stress, and intestinal microbiota. Random distribution of healthy orange-spotted groupers (8.0 ± 1.0 cm and 9.0 ± 1.0 g) into six experimental groups (each group with 90 groupers): Control, DMSO, curcumin, SGIV, DMSO + SGIV, and curcumin + SGIV. The fish administered gavage received DMSO dilution solution or 640 mg/L curcumin every day for 15 days and then were injected intraperitoneally with SGIV 24 h after the last gavage. When more than half of the groupers in the SGIV group perished, samples from each group were collected for intestinal health evaluation. Our results showed that curcumin significantly alleviated intestine damage and repaired intestinal barrier dysfunction, which was identified by decreased intestine permeability and serum diamine oxidase (DAO) activity and increased expressions of tight junction proteins during SGIV infection. Moreover, curcumin treatment suppressed intestinal cells apoptosis and inflammatory response caused by SGIV and protected intestinal cells from oxidative injury by enhancing the activity of antioxidant enzymes, which was related to the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. Moreover, we found that curcumin treatment restored the disruption of the intestinal microbiota caused by SGIV infection. Our study provided a theoretical basis for the functional development of curcumin in aquaculture by highlighting the protective effect of curcumin against SGIV-induced intestinal injury.

An unexpected Ugi cascade reaction was developed for the facile construction of γ-lactam-fused pyridone derivatives with high tolerance of substrates. A C(sp 3 )-N bond and a C(sp 2 )-C(sp 2 ) bond were formed together, accompanied by a chromone ring-opening in Ugi adducts, under the basic conditions without any metal catalyst for the whole process. Screening data of several difficult-to-inhibit cancer cell lines demonstrated that 7l displayed a high cytotoxicity against HCT116 cells (IC 50 = 5.59 ± 0.78 μM). Taken together, our findings revealed new insights into the molecular mechanisms underlying compound 7l and provided potential usage of this scaffold for cancer therapeutics.

Objective: To investigate the feasibility of laser speckle contrast imaging (LSCI) for monitoring urethral blood flow (UBF)., Materials and Methods: In this study, 18 healthy, virgin female Sprague-Dawley rats aged 8-week-old were used. The animals were divided into the sham group (n = 9) and the vaginal distension (VD) group (n = 9). The sham group underwent one catheterization of the vagina without distension and the VD group underwent one VD. Following the VD or sham treatment for one week, LSCI assessment of urethral blood flow was performed during bladder filling and leak point pressure (LPP) process., Results: During the LPP process, in the VD group, the mean LPP was significantly lower than in the sham group (p < 0.05) and the mean UBF level was also significantly lower than in the sham group (p < 0.05) in the LPP condition. The mean relative change of UBF (Δ Flow) was significantly different between the sham group and VD group. The value was 0.646 ± 0.229 and 0.295 ± 0.19, respectively (p < 0.05). During the bladder filling process, the VD group had a significant lower mean UBF level than the sham group under full bladder conditions (p = 0.008). The mean ΔFlow was also significantly lower than in the sham group. The value was 0.115 ± 0.121 and 0.375 ± 0.127, respectively (p = 0.016)., Conclusions: The results confirmed that LSCI was able to determine UBF in female rats. The VD group had lower baseline UBF and lower increases in UBF during bladder filling and LPP process compared with the sham group., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To observe the effect of acupuncture at Weizhong (BL 40) with deqi on bladder urination function., Methods: A total of 60 healthy subjects were randomized into an observation group and a control group, 30 subjects in each group. Under the guidance of ultrasound, acupuncture was applied Weizhong (BL 40) on both sides. In the observation group, the needling depth was reached to the tibial nerve, and lifting-thrusting twirling method was used to induce deqi . In the control group, the needling depth was reached to the superficial fascia, and no manipulation was operated to induce deqi . The needles were retained for 10 min and acupuncture was given once in both groups. The bilateral ureteral ejection frequency and volume of the bladder were observed by ultrasound before and after acupuncture, and the score of clinical evaluation scale of deqi sensation was observed in both groups., Results: After acupuncture, the frequency of bilateral ureteral ejection in the observation group and the bladder volume in the two groups were increased compared before acupuncture ( P <0.05), and the frequency of bilateral ureteral ejection, bladder volume and score of clinical evaluation scale of deqi sensation in the observation group were higher than those in the control group ( P <0.05, P <0.01)., Conclusion: Acupuncture at Weizhong (BL 40) with deqi improves the bladder urination function. Ultrasound visualization improves the standardization and safety of acupuncture, intuitively evaluates the acupuncture effect, and provides an objective basis for the correlation between meridian points specificity and zang - fu organs.

Objective: To observe the clinical efficacy and safety of Jianpi Peiyuan acupoint thread embedding therapy on perimenopausal obesity (PMO)., Methods: Ninety-six patients of PMO were randomly divided into an observation group (48 cases) and a control group (48 cases). The control group received health education and lifestyle intervention. On the basis of the treatment in the control group, the observation group was treated with acupoint thread embedding at the main acupoints of Shangwan (CV 13), Zhongwan (CV 12), Xiawan (CV 10), Yinlingquan (SP 9) and Fenglong (ST 40), etc. as well as the supplementary acupoints in accordance with the syndrome differentiation, once every 2 weeks for 8 weeks (4 times in total). The indexes of obesity (body mass index [BMI], waist circumference, hip circumference and body mass), modified Kupperman score, insomnia severity index (ISI) score, self-rating anxiety scale (SAS) score, and self-rating depression scale (SDS) score of the two groups were observed before and after treatment, and the safety was evaluated., Results: After treatment, BMI, waist circumference, hip circumference and body mass in the two groups were lower than before treatment ( P <0.05), and those in the observation group were lower than the control group ( P <0.05). After treatment, Kupperman, ISI and SAS scores in the observation group were lower than before treatment ( P <0.05), and ISI score in the control group was lower than before treatment ( P <0.05). Kupperman, ISI and SAS scores in the observation group were lower than those in the control group ( P <0.05). There was no significant difference in SDS between the two groups or within groups ( P >0.05). No serious adverse reactions occurred during the experiment., Conclusion: Jianpi Peiyuan acupoint thread embedding therapy can reduce the degree of obesity in PMO patients, and improve patients' the perimenopausal symptoms, insomnia and anxiety, with good safety.

Objective: Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors., Methods: From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13 hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge., Results: Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9%) were men. Among them, nearly two-thirds (62.5%) of the survivors were moderate, three (9.4%) were severe, and more than half (59.4%) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6% at 3 months to 15.8% at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1%) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period., Conclusion: The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention., (Copyright © 2022 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Growing evidence indicates that circulating lactoferrin (Lf) is implicated in peripheral cholesterol metabolism disorders. It has emerged that the distribution of Lf changes in astrocytes of aging brains and those exhibiting neurodegeneration; however, its physiological and/or pathological role remains unknown. Here, we demonstrate that astrocyte-specific knockout of Lf (designated cKO) led to decreased body weight and cognitive abnormalities during early life in mice. Accordingly, there was a reduction in neuronal outgrowth and synaptic structure in cKO mice. Importantly, Lf deficiency in the primary astrocytes led to decreased sterol regulatory element binding protein 2 (Srebp2) activation and cholesterol production, and cholesterol content in cKO mice and/or in astrocytes was restored by exogenous Lf or a Srebp2 agonist. Moreover, neuronal dendritic complexity and total dendritic length were decreased after culture with the culture medium of the primary astrocytes derived from cKO mice and that this decrease was reversed after cholesterol supplementation. Alternatively, these alterations were associated with an activation of AMP-activated protein kinase (AMPK) and inhibition of SREBP2 nuclear translocation. These data suggest that astrocytic Lf might directly or indirectly control in situ cholesterol synthesis, which may be implicated in neurodevelopment and several neurological diseases., (© 2022 Wiley Periodicals LLC.)

Background: To date, there has been little focus on research into acupuncture for insomnia after ischemic stroke. Insomnia is one of the most common sequelae after ischemic stroke, and it is the most unrecognized modifiable risk factor., Objective: To evaluate the efficacy and safety of acupuncture for insomnia after ischemic stroke., Methods: In this assessor-participant blinded, randomized, controlled trial, 144 ischemic stroke patients with insomnia meeting Diagnostic and Statistical Manual of Mental Disorders (fifth edition, DSM -5) criteria were assigned to verum or sham acupuncture treatment (n = 72 per group) for three sessions per week over 4 weeks. The outcomes were the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), stroke-specific quality of life (SSQoL), and Hospital Anxiety and Depression Scale (HADS) scores. Multiple objective sleep variables were recorded using actigraphy. Assessment was conducted at baseline, and thereafter once biweekly for the 4-week treatment and at 4 weeks of follow-up., Results: The verum acupuncture group had significantly greater improvements than the sham acupuncture group in sleep quality from 2 weeks into treatment throughout the follow-up, indicated by ISI scores and actigraphic variable SE (sleep efficiency). This greater improvement was also observed in the PSQI after 4 weeks of treatment throughout follow-up, as well as actigraphic variable TST (total sleep time), SSQoL and HADS scores at the end of treatment, and SSQoL and depression scores at follow-up. There was no significant difference between groups in the actigraphic variable SA (sleep awakenings). Adverse events were mild in severity, and their incidence was not significantly different between the two groups., Conclusion: Acupuncture appears to be efficacious, in terms of improving insomnia, related quality of life, and affective symptoms, for patients with ischemic stroke., Trial Registration Number: ChiCTR-IIC-16008382 (Chinese Clinical Trial Registry).

The purpose of this study was to investigate the morphological and histological changes in the urethra in beagle dogs after intraurethral Er:YAG laser irradiation in nonablative mode to confirm the safety of this therapy. Six 2-year-old healthy female virgin beagle dogs (13 ± 1.51 kg) were used in this study. The animals were divided into 2 groups: the sham group, which received sham treatment (n = 3) involving insertion of an intraurethral cannula and laser delivery handpiece into the urethra without laser irradiation, and the experimental group (n = 3), which received intraurethral Er:YAG laser irradiation. The laser irradiation parameters were set according to clinical criteria (4 mm spot size, 1.5 J/cm 2 , 1.4 Hz, and 4 pulses) in nonablative mode. All animals received three sequential sessions at 4-week intervals. Urethrography and urethroscopy were performed in the 12th week and 13th week, respectively, after the first treatment. After urethroscopy, the animals were sacrificed, and urethral tissue was harvested for histological investigations. All procedures were performed under general anesthesia (40 mg/kg 3% sodium pentobarbital, i.v.). Transforming growth factor β1 (TGF-β1) and α-smooth muscle actin (α-SMA) expression levels were measured to evaluate the biochemical characteristics of the scar. Urethral stricture was not found by urethrography or urethroscopy in either group. Urethral epithelium thickness and collagen expression under the urethral mucosa were significantly increased in the experimental group compared with the sham group. However, there were no significant differences in TGF-β1 and α-SMA expression between the experimental group and sham group (p > 0.05). Urethral stricture is not found in beagle dogs after clinically relevant intraurethral nonablative mode Er:YAG laser irradiation. Proliferation of urethral collagen and the urethral mucosa may be one of the mechanisms by which urine leakage symptoms can be improved., (© 2022. The Author(s).)

Abstract: Sodium ferulate (SF) is the sodium salt of ferulic acid, which is one of the effective components of Angelica sinensis and Lignsticum chuanxiong , and plays an important role in protecting the cardiovascular system. In this study, myocardial hypertrophy was induced by angiotensin II 0.1 μmol/L in neonatal Sprague-Dawley rat ventricular myocytes. Nine groups were designed, that is, normal, normal administration, model, L-arginine (L-arg 1000 μmol/L), SF (50, 100, 200 μmol/L) group, and N G -nitro-L-arg-methyl ester 1500 μmol/L combined with SF 200 μmol/L or L-arg 1000 μmol/L group, respectively. Cardiomyocyte hypertrophy was confirmed by observing histological changes and measurements of cell diameter, protein content and atrial natriuretic factor, and β-myosin heavy chain levels of the cells. Notably, SF could inhibit significantly myocardial hypertrophy of neonatal rat cardiomyocytes in a concentration-dependent manner without producing cytotoxicity, and the levels of nitric oxide, NO synthase (NOS), endothelial NOS, and cyclic guanosine monophosphate were increased, but the level of cyclic adenosine monophosphate was decreased in cardiomyocytes. Simultaneously, levels of protein kinase C beta, Raf-1, and extracellular regulated protein kinase 1/2 (ERK1/2) were downregulated, whereas levels of mitogen-activated protein kinase phosphatase-1 were significantly upregulated. All the beneficial effects of SF were blunted by N G -nitro-L-arg-methyl ester. Overall, these findings reveal that SF can inhibit angiotensin II-induced myocardial hypertrophy of neonatal rat cardiomyocytes, which is closely related to activation of endothelial NOS/NO/cyclic guanosine monophosphate, and inhibition of protein kinase C and mitogen-activated protein kinase signaling pathways., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Depression is one of the most prevalent mental illnesses in the world today, and the onset of depression is usually accompanied by neuroinflammation and impaired adult neurogenesis. As a new potential member of the endocannabinoid (eCB) system, G protein coupled receptor 55 (GPR55) has been associated with mood regulation. However, the role of GPR55 in the pathophysiology of depression remains poorly understood. Thus, a 10-day chronic social defeat stress (CSDS) paradigm was utilized as an animal model of depression to explore the potential role of GPR55 in depression. After CSDS, the protein level of GPR55 decreased significantly, but the mRNA expression did not change significantly, highlighting that although the GPR55 protein was involved in the progression of the depression- and anxiety-like phenotypes, its mRNA was not. Additionally, depression- and anxiety-like behaviors were also accompanied by neuroinflammation and impaired adult neurogenesis in the hippocampus. Interestingly, O-1602, a GPR55 agonist, remarkably prevented the development of depression- and anxiety-like behaviors as well as hippocampal neuroinflammation and neurogenesis deficits induced by CSDS. However, after electroacupuncture (EA) alleviated depression- and anxiety-like behaviors induced by CSDS, treatment with a GPR55 antagonist (CID16020046) reversed this effect. Our research demonstrated that downregulation of GPR55 expression in the hippocampus might mediate CSDS-induced depression- and anxiety-like phenotypes, and activation and upregulation of GPR55, which might be correlated with its anti-inflammatory and subsequent neuroprotective effects, could be a potential treatment for depression., (Copyright © 2022. Published by Elsevier Inc.)

Background: Metagenomic next-generation sequencing (mNGS) exerts a vital part in accurately diagnosing pulmonary infection. However, the diagnostic value of different samples obtained by virtual bronchoscopic navigation (VBN) combined with mNGS for pathogen detection in infections located in the peripheral lung field (PLF) is still unclear., Methods: Patients infected from July 2018 to February of the following year were carefully analyzed and divided into two parts, namely, non-infectious disease group and the infectious disease group. Then bronchial expansion tests were performed for each subject, collected liquid specimens and tissue standards, and conducted regular mNGS and microbiological detection and analysis. The value of mNGS and culture in pathogen detection was compared, at the same time, the performance of tissue mNGS and bronchoalveolar lavage fluid (BALF) mNGS in the diagnosis process was compared. When discrete variables were processed, Pearson χ2 and Fisher's exact test could be used to perform categorical variables analysis. Continuous variables were analyzed and compared by Mann-Whitney U test., Results: After mNGS diagnosis, Acinetobacter baumannii, Pseudomonas aeruginosa and Rothia mucilaginosa were the bacterial species showing the highest abundances. In addition, mNGS achieved the sensitivities in the detection of pathogens in tissues and BALF of 72.9% and 81.4%, respectively, and it is higher than conventional culture. Bacterial diagnostic sensitivity was significantly different between BALF and tissue using mNGS (95.0% vs. 62.5%, P=0.03). The sensitivity and specificity of BALF in detecting fungal infections were not significantly different from those of mNGS. A consistency test showed that these two methods had some degree of consistency (k=0.673, P=0.000)., Conclusions: This study showed that the mNGS in BALF samples and the mNGS in tissue samples which could be used to test for pathogens in the lungs. The sensitivity will increase when mNGS is combined with culture. Also, mNGS of BALF and tissues had some degree of consistency to detect fungal infections, whereas mNGS of BALF had better sensitivity to detect bacterial infection than mNGS of tissues.

Background: The endoscopic resection of suspected gastric high-grade intraepithelial neoplasia (HGIN) may incidentally cause the patient to suffer from early gastric cancer (EGC), complicating the subsequent clinical management. Identifying the risk factors for such misstaging may help guide the clinical management. Methods: The information obtained from 123,460 patients, who underwent conventional upper gastrointestinal endoscopy at the First Affiliated Hospital of Nanjing Medical University from January 2010 to December 2015, were retrospectively reviewed. Patients with an initial diagnosis of HGIN underwent endoscopic submucosal dissection (ESD), and received a final diagnosis of EGC. The risk factors for the upgraded pathology and noncurative resection were analyzed. Results: Among the 134 patients initially diagnosed with HGIN, 35 (26.12%) patients were finally diagnosed with EGC after ESD. A lesion size of ≥2 cm (odds ratio [OR] = 5.16, 95% confidence interval [CI] = 2.04-13.05; P  < .01), ≤4 biopsies taken (OR = 2.73, 95% CI = 1.15-6.48; P  < .05), and the presence of upper gastrointestinal bleeding (UGIB; OR = 15.64, 95% CI = 1.29-189.75; P  < .05) were the independent risk factors for upgraded pathology. In addition, patients >65 years old (OR = 0.022, 95% CI = 0.901-6.549; P  < .05) or with a lesion size of ≥2 cm (OR = 4.237, 95% CI = 1.650-10.878; P  < .01) were more likely to endure the noncurative resection. Conclusion: For suspected gastric HGIN patients, age, lesion size, the number of biopsies, and UGIB should be taken into account before deciding on the ESD.

Objective: To analyze the clinical features and spinal lesions related to micturitionin of chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS) patients. Methods: Patients with CP/CPPS were enrolled to this study at the outpatient department of Tongji Hospital between January and June 2019. The data of clinical features was collected and analyzed, including lower urinary tract symptoms(LUTS), bowel syndrome and pain over different parts of body, as well as lower urinary tract dysfunction, spinal lesions and pelvic organ morphological changes demonstrated by MRI. The potential role of spinal lesions in the development of CP/CPPS syndrome was investigated. Results: A total of 126 CP/CPPS patients were included, with an age［ M （ Q 1 ， Q 3 ）］of 41(31,53) years and a course of disease of 2(1,20) years. Among them, 126 (100.0%) were complicated with LUTS, 72(57.1%) with bowel dysfunction and 88(69.8%) with pain. MRI showed the cervical central disc herniation(126 cases, 100.0%), the ischemic changing in the cervical area of visceral efferant pathway(82 cases, 65.1%), the lumbar central disc herniation(65 cases, 51.6%), and the sacral nerve cysts(97 cases, 77.0%) are commonly seen. In addition, the morphological changes in the visceral organs containing smooth muscle were demonstrated, including thickened bladder wall(91 cases, 72.2%), distended seminal vesicles(70 cases, 55.6%) and distended sigmoid colon/rectum(59 cases, 46.8%). Conclusions: CP/CPPS patients were characterized by the co-existence of LUTS, bowel dysfunction and somatic pain in one individual. The presence of multi-organ symptoms, combined with the high prevalence of spinal lesions associated with micturition reflex, suggesting the potential role of the spinal lesions in the development of CP/CPPS.

Background: Hua-Feng-Dan is a patent Chinese medicine for stroke recovery and various diseases. This study used GC-MS to profile its ingredients and RNA-Seq to analyze the induced adaptive response in the liver. Methods: Hua-Feng-Dan was subjected to steam distillation and solvent extraction, followed by GC-MS analysis. Mice were orally administered Hua-Feng-Dan and its "Guide drug" Yaomu for 7 days. Liver pathology was examined, and total RNA isolated for RNA-Seq, followed by bioinformatic analysis and quantitative real-time PCR (qPCR). Results: Forty-four volatile and fifty liposoluble components in Hua-Feng-Dan were profiled and analyzed by the NIST library and their concentrations quantified. The major components (>1%) in volatile (5) and liposoluble (10) were highlighted. Hua-Feng-Dan and Yaomu at hepatoprotective doses did not produce liver toxicity as evidenced by histopathology and serum enzyme activities. GO Enrichment revealed that Hua-Feng-Dan affected lipid homeostasis, protein folding, and cell adhesion. KEGG showed activated cholesterol metabolism, bile secretion, and PPAR signaling pathways. Differentially expressed genes (DEGs) were identified by DESeq2 with p < 0.05 compared to controls. Hua-Feng-Dan produced more DEGs than Yaomu. qPCR on selected genes largely verified RNA-Seq results. Ingenuity Pathways Analysis of the upstream regulator revealed activation of MAPK and adaptive responses by Hua-Feng-Dan, and Yaomu was less effective. Hua-Feng-Dan-induced DEGs were highly correlated with the Gene Expression Omnibus database of chemical-induced adaptive transcriptome changes in the liver. Conclusion: GC-MS primarily profiled volatile and liposoluble components in Hua-Feng-Dan. Hua-Feng-Dan at the hepatoprotective dose did not produce liver pathological changes but induced metabolic and signaling pathway activations. The effects of Hua-Feng-Dan on liver transcriptome changes point toward induced adaptive responses to program the liver to produce hepatoprotective effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Liang, Zhang, Wu, Song, Zhang, Shi, Liu, Xu and Wang.)

Background: Bioassessment and biomonitoring of meat products are aimed at identifying and quantifying adulterants and contaminants, such as meat from unexpected sources and microbes. Several methods for determining the biological composition of mixed samples have been used, including metabarcoding, metagenomics and mitochondrial metagenomics. In this study, we aimed to develop a method based on next-generation DNA sequencing to estimate samples that might contain meat from 15 mammalian and avian species that are commonly related to meat bioassessment and biomonitoring., Results: In this project, we found the meat composition from 15 species could not be identified with the metabarcoding approach because of the lack of universal primers or insufficient discrimination power. Consequently, we developed and evaluated a meat mitochondrial metagenomics (3MG) method. The 3MG method has four steps: (1) extraction of sequencing reads from mitochondrial genomes (mitogenomes); (2) assembly of mitogenomes; (3) mapping of mitochondrial reads to the assembled mitogenomes; and (4) biomass estimation based on the number of uniquely mapped reads. The method was implemented in a python script called 3MG. The analysis of simulated datasets showed that the method can determine contaminant composition at a proportion of 2% and the relative error was < 5%. To evaluate the performance of 3MG, we constructed and analysed mixed samples derived from 15 animal species in equal mass. Then, we constructed and analysed mixed samples derived from two animal species (pork and chicken) in different ratios. DNAs were extracted and used in constructing 21 libraries for next-generation sequencing. The analysis of the 15 species mix with the method showed the successful identification of 12 of the 15 (80%) animal species tested. The analysis of the mixed samples of the two species revealed correlation coefficients of 0.98 for pork and 0.98 for chicken between the number of uniquely mapped reads and the mass proportion., Conclusion: To the best of our knowledge, this study is the first to demonstrate the potential of the non-targeted 3MG method as a tool for accurately estimating biomass in meat mix samples. The method has potential broad applications in meat product safety., (© 2022. The Author(s).)

The objective of this study was to evaluate the toxic effects of Cr 6+ on bioaccumulation, digestion, immunity, oxidative stress, apoptosis and inflammation-related genes in Channa asiatica. The fish was exposed to waterborne Cr 6+ concentrations (0, 0.5, 1.0 and 2.0 mg/L) for 28 and 56 days. Our results demonstrated that the accumulation of Cr 6+ in tissues increased in a concentration-dependent manner, and the content in tissue was liver > gill > gut > muscle. Meanwhile, Cr 6+ exposure led to a remarkable suppression of digestion, immunity and antioxidant capacity in C. asiatica. Inversely, MDA and PC content were positively correlated with Cr 6+ exposure concentration. Furthermore, the expression of genes went up with the increase of waterborne Cr 6+ concentration. Among them, HSP90, NF-κB and TNF-α have a sharp increase. These results elucidate that waterborne Cr 6+ exposure may induce bioaccumulation, inhibit digestion and immunity, promote oxidative stress and up-regulate the expression of apoptosis and inflammation-related genes in C. asiatica., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: This study explored the early predictive value of volume and mean CT density of necrosis for adverse outcomes in patients with acute necrotising pancreatitis (ANP)., Methods: A total of 155 patients with ANP who underwent CECT within 7 days of symptom onset were included. The necrosis volume, mean CT density, and modified CT severity index (mCTSI) were calculated. C-reactive protein (CRP) and blood urea nitrogen (BUN) levels both 48 h after symptom onset were reviewed. Adverse outcomes were recorded. The predictive value of each indicator was assessed using ROC curve analysis., Results: There were significant associations between necrosis volume and mean CT density and organ failure (OF), persistent OF (POF), and need for intervention (p < 0.001 for all). For predicting OF, the area under the curve (AUC) was significantly higher for necrosis volume than for mCTSI and BUN (AUC: 0.84 vs 0.67, p = 0.0011; 0.84 vs 0.71, p = 0.0193, respectively). For predicting POF and need for intervention, the AUCs for necrosis volume were significantly higher than those for mCTSI (AUC: 0.79 vs 0.66, p = 0.0045; 0.77 vs 0.61, p = 0.0019, respectively), but did not significantly differ from those for CRP and BUN. For predicting OF, a significantly better predictive value was achieved with mean CT density than with mCTSI (AUC: 0.79 vs 0.67, p = 0.0163). There were no significant differences in predictive value between mean CT density, CRP, and BUN., Conclusions: The volume and mean CT density of necrosis based on CECT can provide early prediction of OF, POF, and need for intervention., Key Points: • Compared to mCTSI, necrosis volume might be used to more accurately diagnose organ failure and persistent organ failure and might be better associated with the need for intervention. • Necrosis volume and mean CT density based on CECT are reliable quantitative predictors for organ failure, persistent organ failure, and intervention in acute pancreatitis., (© 2021. European Society of Radiology.)

Constitutive activation of Hedgehog (Hh) pathway is intimately related with the occurrence and development of several malignancies, such as medulloblastoma (MB) and other tumors. Therefore, small molecular inhibitors of Hh pathway are urgently needed. In this study, three new steroidal alkaloids, ⊿ 5 (20R, 24R) 23-oxo-24-methylsolacongetidine, ⊿ 5 (20S, 24R) 23-oxo-24-methylsolacongetidine and veralinine 3-O-α-l-rhamnopyranosyl-(1 → 2)-β-D-glucopyranoside, together with six known alkaloids, 20-epi-verazine, verazine, protoverine 15-(l)-2'-methylbutyrate, jervine, veramarine and β1-chaconine, were isolated and determined from Veratrum grandiflorum Loes. The dual-luciferase bioassay indicated that all compounds exhibited significant inhibitions of Hh pathway with IC 50 values of 0.72-14.31 μM against Shh-LIGHT 2 cells. To determine whether these Hh pathway inhibitors act with the Smoothened (Smo) protein, which is an important oncoprotein and target for this pathway, BODIPY-cyclopamine (BC) competitive binding assay was preferentially performed. Compared with BC alone, all compounds obviously reduced the fluorescence intensities of BC binding with Smo in Smo-overexpression HEK293T cells through fluorescence microscope and flow cytometer. By directly interacting with Smo, it revealed that they were actually novel natural Smo inhibitors. Then, their anti-tumor effects were investigated against the human MB cell line DAOY, which is a typical pediatric brain tumor cells line with highly expressed Hh pathway. Interestingly, most of compounds had slight proliferation inhibitions on DAOY cells after treatment for 24 h same as vismodegib, while β1-chaconine showed the strongest inhibitory effect on the growth of DAOY with IC 50 value of 5.35 μM. In conclusion, our studies valuably provide several novel natural Smo inhibitors for potential targeting treatment of Hh-dependent tumors., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Zuotai (mainly β-HgS)-containing 70 Wei-Zhen-Zhu-Wan (70W, Rannasangpei ) is a famous Tibetan medicine for treating cardiovascular and gastrointestinal diseases.  We have shown that 70W protected against CCl 4 hepatotoxicity.  CCl 4 is metabolized via cytochrome P450 (CYP) to produce reactive metabolites. Whether 70W has any effect on CYPs is unknown and such effects should be compared with mercury compounds for safety evaluation.   Methods: Mice were given clinical doses of 70W (0.15-1.5 g/kg, po), Zuotai (30 mg/kg, po), and compared to HgCl 2 (33.6 mg/kg, po) and MeHg (3.1 mg/kg, po) for seven days. Liver RNA and protein were isolated for qPCR and Western-blot analysis. Results: 70W and Zuotai had no effects on hepatic mRNA expression of Cyp1a2, Cyp2b10, Cyp3a11, Cyp4a10 and Cyp7a1, and corresponding nuclear receptors [aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor-α (PPARα); farnesoid X receptor (FXR)]. In comparison, HgCl 2 and MeHg increased mRNA expression of Cyp1a2, Cyp2b10, Cyp4a10 and Cyp7a1 except for Cyp3a11, and corresponding nuclear receptors except for PXR. Western-blot confirmed mRNA results, showing increases in CYP1A2, CYP2B1, CYP2E1, CYP4A and CYP7A1 by HgCl 2 and MeHg only, and all treatments had no effects on CYP3A. Conclusions: Zuotai and Zuotai-containing 70W at clinical doses had minimal influence on hepatic CYPs and corresponding nuclear receptors, while HgCl 2 and MeHg produced significant effects.  Thus, the use of total Hg content to evaluate the safety of HgS-containing 70W is inappropriate., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Nie Y et al.)

Aim: We aimed to perform a meta-analysis to determine whether antibiotic prophylaxis reduces the incidence of urinary tract infections (UTIs) after urodynamic studies (UDS)., Methods: We conducted a systematic search of PubMed, Web of Science, Ovid, Elsevier, ClinicalKey, Embase, Cochrane Library, Medline, and Wiley Online Library. Randomized controlled trials (RCTs) comparing the effectiveness of prophylactic antibiotics with placebo or no treatment in preventing UTI after UDS were included. Two reviewers extracted data independently, and RevMan 5.3 software was used to analyze relative risk (RR) with 95% confidence intervals (CI). Heterogeneity was assessed by the Q test and I 2 test., Results: The final meta-analysis included 1829 patients in 13 RCTs. Compared with the placebo or no treatment group, prophylactic antibiotics could significantly reduce the risk of bacteriuria (RR = 0.42, 95% CI: 0.30-0.60) and the risk of symptomatic UTI (RR = 0.65, 95% CI: 0.48-0.88). In addition, there was no statistically significant difference in the risk of adverse events (RR = 4.93, 95% CI: 0.61-40.05). No significant heterogeneity or publication bias was found in this study., Conclusions: Current evidence showed that prophylactic antibiotics could reduce the risk of asymptomatic bacteriuria and symptomatic UTI after UDS without increasing the incidence of adverse events., Competing Interests: The authors declared that they have no conflicts of interest to this work., (Copyright © 2021 Xiao-yu Wu et al.)

Objective: To understand the knowledge attitude and practice (KAP) on vaccination among children's parents in Jiangxi, Shanghai, and Qinghai and explore the factors influencing KAP. Methods: The study selected two counties/districts in Jiangxi, Shanghai, and Qinghai, respectively, by stratified sampling and used a unified questionnaire to investigate the parental KAP of vaccination. A structural equation model (SEM) was used to explore factors influencing parental KAP, as well as the relationship between knowledge and behavior. Results: Of the 760 valid questionnaires, the knowledge of vaccination among children's parents was better, and the vaccination knowledge of parents in Qinghai and Shanghai were slightly better than those in Jiangxi. Parents mainly obtained vaccination knowledge through medical staff and vaccination manuals. The fitting degree of SEM was relatively good; the root mean square error of approximation of the model is 0.033. The higher the parents' education level, the better their knowledge of vaccination (β̂=0.082). Parental vaccination knowledge could influence whether the vaccinated children stay for half an hour in the clinics (β̂=0.541). It could also impact whether parents giving up vaccinating their children in the face of media reports about the adverse effects of vaccinations (β̂=0.515). Conclusions: The knowledge of vaccination among the parents in Jiangxi, Shanghai, and Qinghai was quite good. Moreover, we should pay more attention to the mass media programs and vaccination knowledge among parents with low or middle education backgrounds. Vaccination knowledge can be disseminated through medical staff, vaccination manuals, or mobile applications.

This study was aimed to explore the effect and mechanisms of action of perfluorocarbon on LPS-induced apoptosis of pulmonary microvascular endothelial cells (PMVEC) isolated from Sprague-Dawley rats. Apoptosis rates were assessed by flow cytometry. Ultrastructural characteristics of PMVEC were evaluated by transmission electron microscopy. The protein expression of cleaved caspase-3 was measured using Western blotting. LPS significantly increased the level of apoptosis, induced the appearance of ultrastructural changes typical of apoptosis, up-regulated the expression of active caspase-3 protein. These effects of LPS were attenuated by co-administration of perfluorocarbon. These results suggest that perfluorocarbon can attenuate LPS-induced apoptosis of PMVEC by inhibiting TLR-4 signaling and caspase-3 activation.

Background: Pathogenesis of Helicobacter Pylori (HP) vacuolating toxin A (vacA) depends on polymorphic diversity within the signal (s), middle (m), intermediate (i), deletion (d) and c-regions. These regions show distinct allelic diversity. The s-region, m-region and the c-region (a 15 bp deletion at the 3'-end region of the p55 domain of the vacA gene) exist as 2 types (s1, s2, m1, m2, c1 and c2), while the i-region has 3 allelic types (i1, i2 and i3). The locus of d-region of the vacA gene has also been classified into 2 genotypes, namely d1 and d2. We investigated the "d-region"/"loop region" through bioinformatics, to predict its properties and relation to disease. One thousand two hundred fifty-nine strains from the NCBI nucleotide database and the dryad database with complete vacA sequences were included in the study. The sequences were aligned using BioEdit and analyzed using Lasergene and BLAST. The secondary structure and physicochemical properties of the region were predicted using PredictProtein., Results: We identified 31 highly polymorphic genotypes in the "d-region", with a mean length of 34 amino acids (9 ~ 55 amino acids). We further classified the 31 genotypes into 3 main types, namely K-type (strains starting with the KDKP motif in the "d-region"), Q-type (strains starting with the KNQT motif), and E-type (strains starting with the ESKT motif) respectively. The most common type, K-type, is more prevalent in cancer patients (80.87%) and is associated with the s1i1m1c1 genotypes (P < .01). Incidentally, a new region expressing sequence diversity (2 aa deletion) at the C-terminus of the p55 domain of vacA was identified during bioinformatics analysis., Conclusions: Prediction of secondary structures shows that the "d-region" adopts a loop conformation and is a disordered region.

Choledocholithiasis is a chronic common disease. The incidence of cholelithiasis is 5%-15%, of which 5%-30% are combined with Choledocholithiasis. Although endoscopic cholangiopancreatography (ERCP) + endoscopic sphincterotomy (EST) is the most common treatment procedure, which clearance rate is up to 95%, the incidence of recurrent choledocholithiasis was 4%-25%. The risk factors of recurrence after choledocholithiasis clearance are the focuses of current researches, which are caused by multiple factors. We first systematically summarize the risk factors of common bile duct stones (CBDS) recurrence into five aspects: first-episode stone related factors, congenital factors, biological factors, behavioral intervention factors, and the numbers of stone recurrence., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear., Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( OR ) and 95% confidence interval (95% CI ) of the associations between comorbidities (cardiometabolic or non-cardiometabolic diseases), clinical severity, and treatment outcomes of COVID-19., Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks., Conclusion: Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes., (Copyright © 2020 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Background: Hemorrhoids are one of the most common conditions that lead to surgery, and until now surgical hemorrhoidectomy has been the major effective treatment. Post-operative pain from hemorrhoidectomy has been experienced by thousands of patients and remains a major inconvenience of the operation., Objective: This study evaluates the clinical efficacy of the pestle needle therapy, an acupoint stimulation method, for relief of post-hemorrhoidectomy pain., Design, Setting, Participants and Interventions: This was a single-center, patient-assessor-blinded and randomized controlled trial with 154 patients receiving Milligan hemorrhoidectomy surgery. Eligible patients were randomly assigned to either a treatment group or a control group at a ratio of 1:1. The treatment group received the pestle needle therapy, with manual stimulation at Yaoshu (DU2), Mingmen (DU4), Changqiang (DU1), Chengshan (BL57), Erbai (EX-UE2) and the perianal points (1, 3, 5, 7, 9, and 11o'clock around the lesion); while the control group received a sham treatment with very light pressure. Three sessions of treatment were performed at 30 min, 4 h and 12 h after the surgery, and each lasted for 15 min., Main Outcome Measures: The primary outcome was post-operative pain measured with the visual analogue scale (VAS) at 12 h after surgery. The secondary outcomes included the VAS scores measured at 0.5, 2, 4, 6, 8, 24 and 48 h after surgery, the analgesic dose, the time and the VAS score of the patients' first defecation after surgery, as well as the Hamilton Rating Scale for Anxiety (HAMA) evaluated before discharge., Results: The mean pain score of the treatment group was significantly lower than that of the control group (3.10 ± 1.27 vs 4.82 ± 1.29; P < 0.001) at 12 h after surgery. Compared with the control group, patients in the treatment group needed a smaller dose of analgesic within the first 24 hours after surgery (P = 0.002); and their HAMA scores before discharge were lower (4.07 ± 2.40 vs 5.10 ± 2.45, P = 0.009). Compared to the treatment group, patients in the control group had a greater time to the first defecation after surgery ([52.34 ± 15.72] h vs [27.08 ± 13.68] h; P < 0.001), but there was no difference in their VAS scores at the first defecation (P = 0.092)., Conclusion: The pestle needle therapy was effective for relieving pain, reducing anxiety and improving bowel function after hemorrhoidectomy, and it is worthy of clinical application., Competing Interests: Conflicts of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.)

(1) Background: Along with an increasing risk caused by migrant workers returning to the urban areas for the resumption of work and production and growing epidemiological evidence of possible transmission during the incubation period, a study of Coronavirus Disease 2019 (COVID-19) is warranted among key populations to determine the serum antibody against the SARS-CoV-2 and the carrying status of SARS-CoV-2 to identify potential asymptomatic infection and to explore the risk factors. (2) Method: This is a cross-sectional seroepidemiologic study. Three categories of targeted populations (close contacts, migrant workers who return to urban areas for work, and school children) will be included in this study as they are important for case identification in communities. A multi-stage sampling method will be employed to acquire an adequate sample size. Assessments that include questionnaires and blood, nasopharyngeal specimens, and feces collection will be performed via home-visit survey. (3) Ethics and Dissemination: The study was approved by the Institute Review Board of School of Public Health, Fudan University (IRB#2020-04-0818). Before data collection, written informed consent will be obtained from all participants. The manuscripts from this work will be submitted for publication in quality peer-reviewed journals and presented at national or international conferences., Competing Interests: The authors declare no conflict of interest.

Objective: To understand the genetic variation of soft tissue sarcomas, and to provide a scientific evidence for the individualized treatment. Methods: The somatic mutation and germline mutation of 45 adult soft tissue sarcomas had been detected by high-throughput sequencing technology, the clinical data were also analyzed. Results: A total of 88 gene mutations were detected in 45 samples, including 78 single nucleotide variation (SNV), 13 insertion/deletion (Indel) and 19 copy number variation (CNV). The most common mutant genes are TP53, CDKN2A, MDM2, CDK4, NF1 and PTEN. Among them, the mutation rates of TP53-MDM2/MDM4-CDKN2A pathway, CDKN2A/CDK4/RB1 pathway, and RAS/NF1/PTEN/PI3K pathway were more frequent (32/88, 36%). In terms of immunotherapy biomarkers among 10 samples, the median value of tumor mutation burden was 2.02 muts/Mb (0-4.24 muts/Mb), and all were microsatellite stable. Conclusions: This study analyzes the genetic variation of soft tissue sarcoma, and determines the high-frequency gene mutations and pathways, which may be the potential drug targets. This finding can provide scientific evidences for the personalized treatment of soft tissue sarcoma.

Introduction: Intrahepatic cholangiocarcinoma (ICC) exhibited increasing incidence and mortality around the world, with a 35% five-year survival rate. In this study, the genetic alteration of primary ICC and metastasis ICC was exhibited to discover novel personalized treatment strategies to improve the clinical prognosis., Methods: Based on 153 primary and 49 metastasis formalin-fixed paraffin-embedded ICC samples, comprehensive genomic profiling was carried out., Results: In primary tumor samples (PSs) and metastasis tumor samples (MSs), the top alteration genes were TP53 (41.8% vs 36.7%), KRAS (30.7% vs 36.7%), and ARID1A (22.2% vs 14.2%). In the top 20 most frequent alteration genes, BRAF showed lower mutation frequency in MSs as compared to PSs (0 vs 11.1%, P =0.015), while LRP1B exhibited opposed trend (22.4% vs 10.4%, P =0.032). In PSs, patients with MSI-H showed all PDL1 negative, and patients with PDL1 positive exhibited MSS both in PSs and MSs. It was found that the Notch pathway had more alteration genes in MSI-H patients ( P =0.027). Furthermore, the patients with mutated immune genes in PSs were more than that in MSs (28.8% vs 8.2%, P =0.003, odd ratio = 0.2). Interestingly, the platinum drug resistance pathway was only enriched by mutated genes of MSs., Conclusions: In this study, the identification of two meaningful mutated genes, BRAF and LRP1B, highly mutated immune gene harbored by primary ICC patients. Both in PSs and MSs, no patients with MSI-H showed PDL1 positive. The Notch pathway had more alteration genes in patients with MSI-H. And the enrichment of the platinum drug resistance pathway in MSs might offer reference for the novel therapeutic strategy of ICC., Competing Interests: Xin Zhang is an employee of OrigiMed. The remaining authors declare that they have no conflicts of interest., (Copyright © 2020 Shi-Feng Xu et al.)

Background: The aim of this study was to evaluate the landscape of gene mutations and the clinical significance of tumor mutation burden (TMB) in patients with soft tissue sarcoma who underwent surgical resection and received conventional adjuvant therapy., Methods: A total of 68 patients with soft tissue sarcoma were included. Postoperative tumor tissue specimens from the patients were collected for DNA extraction. Targeted next-generation sequencing of cancer-relevant genes was performed for the detection of gene mutations and the analysis of TMB. Univariate analysis between TMB status and prognosis was carried out using the Kaplan-Meier survival analysis, and multivariate analysis was adjusted by the Cox regression model., Results: No specific genetic mutations associated with soft tissue sarcoma were found. The mutation frequency of TP53, PIK3C2G, NCOR1, and KRAS of the 68 patients with soft tissue sarcoma were observed in 19 cases (27.94%), 15 cases (22.06%), 14 cases (20.59%), and 14 cases (20.59%), respectively. With regard to the analysis of TMB, the overall TMB of the 68 patients with soft tissue sarcoma was relatively low (median: 2.05 per Mb (range: 0∼15.5 per Mb)). Subsequently, TMB status was divided into TMB-Low and TMB-Middle according to the median TMB. Patients with TMB-Low and TMB-Middle were 37 cases (54.41%) and 31 cases (45.59%), respectively. Overall survival analysis indicated that the median overall survival of patients with TMB-Low and TMB-Middle was not reached, and 4.5 years, respectively ( P =0.015)., Conclusion: This study characterizes the genetic background of patients with STS soft tissue sarcoma. The TMB was of clinical significance for patients with soft tissue sarcoma who underwent surgical resection and received conventional adjuvant therapy.

The microtubule-associated protein tau is closely correlated with hypometabolism in Alzheimer's disease (AD). α-lipoic acid (LA), which is a naturally occurring cofactor in mitochondrial, has been shown to have properties that can inhibit the tau pathology and neuronal damage in our previous research. However, if LA affects glucose metabolism when it reverses tau pathology remains unclear, especially concerning the potential mechanism. Therefore, we make a further study using the P301S mouse model (a tauopathy and AD mouse model which overexpressing fibrillary tau) to gain a clear idea of the aforementioned problems. Here, we found chronic LA administration significantly increased glucose availability by elevating glucose transporter 3 (GLUT3), GLUT4, vascular endothelial growth factor (VEGF) protein and mRNA level, and heme oxygenase-1 (HO-1) protein level in P301S mouse brains. Meanwhile, we found that LA also promoted glycolysis by directly upregulating hexokinase (HK) activity, indirectly by increasing proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and DNA repair enzymes (OGG1/2 and MTH1). Further, we found the underlying mechanism of restored glucose metabolism might involve in the activation of brain-derived neurotrophic factor (BDNF)/tyrosine Kinase receptor B (TrkB)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway by LA treatment., (Copyright © 2020 Zhang, Yan, Xu, Pang, Li, Yang, Fan, Wang, Yu, Guo and Ao.)

Objectives: To evaluate the effects of pentobarbital dosages on lower urinary tract function and to define an appropriate dosage of sodium pentobarbital that would be suitable for urodynamic studies in which recovery from anesthesia and long term survive were needed for subsequent experiment., Methods: Twenty-four 8-week-old, female, virgin, Sprague-Dawley rats (200-250 g) were used in this study. Rats in study groups received gradient doses of pentobarbital intraperitoneally, and those in the control group received urethane intraperitoneally. External urethral sphincter electromyography (EUS-EMG) was recorded simultaneously during cystometry and leak point pressure tests. The toe-pinch reflex was used to determine the level of anesthesia., Results: Micturition was normally induced in both the urethane group and 32 mg/kg pentobarbital group. However, in groups of 40 mg/kg or 36 mg/kg pentobarbital, micturition failed to be induced; instead, nonvoiding contractions accompanied by EUS-EMG tonic activity were observed. There were no significant differences in leak point pressure or EUS-EMG amplitude or frequency between the urethane and 32 mg/kg pentobarbital groups., Conclusions: This study confirmed significant dose-dependent effects of pentobarbital on lower urinary tract function and 32 mg/kg pentobarbital as an appropriate dosage for recovery urodynamic testing, which enable the achievement of expected essential micturition under satisfactory anesthesia in female rats., Competing Interests: The authors declared that they have no conflicts of interest to this work., (Copyright © 2020 Sheng-Fei Xu et al.)

Reactive oxygen species (ROS), as primary intermediates formed during photocatalytic reactions, are critical for a photocatalyst to realize high activity. The major objective of this study was to investigate the regulation of ROS involved in the photocatalytic degradation process via constructing a typical metal-semiconductor hybrid heterojunction using Ag nanoparticles/anatase TiO₂ as an example. Based on radical capturing, electron paramagnetic resonance, and electron spin resonance experiments, an increase in the available ROS can be achieved in the Ag/TiO₂ heterojunction due to the fast separation of photogenerated carriers. In addition, due to the change in the electron transfer pathway, superoxide radicals (·O - ₂) are the dominant reactive species responsible for dye degradation using Ag/TiO₂ rather than hydroxyl radicals (·OH) as the main free radicals in pristine TiO₂. This study offers fresh insight into the regulation of ROS in photodegradation via the construction of a Ag/TiO₂ heterojunction.

Ethnopharmacological Relevance: Mercury sulfides (HgS) are frequently included in Ayurveda, Tibetan and Chinese medicines to assist the presumed therapeutic effects, but the ethnopharmacology remains elusive. The present study examined the protective effects of α-HgS-containing Hua-Feng-Dan and β-HgS-containing 70 Wei-Zhen-Zhu-Wan (70W, Rannasangpei) against Parkinson's disease mice induced by lipopolysaccharide (LPS) plus 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)., Method: A single injection of LPS (5 mg/kg ip) was given to adult male C57BL/6 mice, and 150 days later, the low dose of MPTP (15 mg/kg, ip, for 4 days) was given to produce the "two-hit" Parkinson's disease model. Together with MPTP treatment, mice were fed with clinically-relevant doses of Hua-Feng-Dan (0.6 g/kg) and 70W (0.2 g/kg) for 35 days. Rotarod test was performed to examine muscle coordination capability. At the end of the experiment, brain was transcardially perfused with paraformaldehyde, the substantia nigra was sectioned for microglia (Iba1 staining) and dopaminergic neuron (THir staining) determination. Colon bacterial DNA was extracted and subjected to qPCR analysis with 16S rRNA probes., Results: The low-grade, chronic neuroinflammation produced by LPS aggravated MPTP neurotoxicity, as evidenced by decreased motor activity, intensified microglia activation and loss of dopaminergic neurons. Both Hua-Feng-Dan and 70W increased rotarod activity and ameliorated the pathological lesions in the brain. In gut microbiomes examined, LPS plus MPTP increased Verrucomicrobiaceae, Methanobacteriaceae, Pronicromonosporaceae, and Clostridaceae species were attenuated by Hua-Feng-Dan and 70W., Conclusions: α-HgS-containing Hua-Feng-Dan and β-HgS-containing 70W at clinical doses protected against chronic LPS plus MPTP-induced toxicity to the brain and gut, suggesting HgS-containing traditional medicines could target gut microbiota as a mechanism of their therapeutic effects., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Nonalcoholic fatty liver disease (NAFLD) increases the risk of hepatocellular carcinoma, which is currently the leading cause of obesity-related cancer deaths in middle-aged men., Methods: Probiotics with lipid-lowering function were screened from the fecal microbiota of healthy adults. Polysaccharide from different sources was screened for improving insulin resistance. The combination of probiotics and Salvia miltiorrhiza polysaccharide (LBM) was investigated for alleviating hepatic steatosis., Results: First, Bifidobacterium bifidum V (BbV) and Lactobacillus plantarum X (LpX) were obtained from the fecal microbiota of healthy adults. Second, to improve insulin resistance, a Salvia miltiorrhiza Bunge polysaccharide showing good performance in reducing insulin resistance was obtained. The liver total cholesterol (TC) and total triglyceride (TG) levels and the serum levels of free fatty acid, alanine transaminase, aspartate transaminase, low density lipoprotein cholesterol, TG, and TC can be significantly reduced through supplementation with LpX-BbV (LB) in NAFLD mice. Interestingly, the function of the probiotic LB can be enhanced by S. miltiorrhiza Bunge polysaccharide. Furthermore, the gut microbiota was modulated by LpX-BbV+ S. miltiorrhiza Bunge polysaccharide (LBM). The lipopolysaccharide concentration of the LBM group was decreased by 73.6% compared to the NAFLD group. Ultimately, the mRNA concentrations of the proinflammatory cytokines (tumor necrosis factor α, interleukin 1β [IL-1β], and IL-6) decreased with LB and LBM treatment., Conclusion: The results of this this study indicate that the LBM combination can be used as a therapeutic for ameliorating NAFLD via modulating the gut microbiota and improving insulin resistance., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2020 Korean Diabetes Association.)

Background : Domestic migrant populations are highly mobilized at a sexually active age, and often fail to meet their needs for contraception. Moreover, they assume sexual and reproductive health (SRH) risks and utilize fewer family planning services. Method : A quasi-experimental trial (community intervention) was adopted. Two-stage stratified cluster sampling was applied to recruit participants in Beijing and Chongqing. A comprehensive SRH/family planning intervention was implemented from August 4 2014 to August 3 2015. Propensity score matching (PSM) and multivariate probit models were adopted. Results: In total, 2100 and 2024 eligible participants were involved, and 815 and 629 pairs were matched by PSM in Beijing and Chongqing, respectively. The knowledge and attitudes of the participants regarding SRH and contraception were significantly improved through the comprehensive intervention. Reversible contraceptive methods were the most prevalent; couples largely decided to utilize condoms and family planning services. Conclusions : The comprehensive intervention had positive effects on knowledge, attitudes, and practices (KAP) for SRH/family planning among the domestic migrant population. The results acquired can be extrapolated to some extent, and the pattern of this intervention is well geared toward other similar settings in China.

The intestinal epithelium acts as a barrier that prevents luminal contents, such as pathogenic microbiota and toxins, from entering the rest of the body. Epithelial barrier function requires the integrity of intestinal epithelial cells. While epithelial cell proliferation maintains a continuous layer of cells that forms a barrier, epithelial damage leads to barrier dysfunction. As a result, luminal contents can across the intestinal barrier via an unrestricted pathway. Dysfunction of intestinal barrier has been associated with many intestinal diseases, such as inflammatory bowel disease. Isolated mouse intestinal crypts can be cultured and maintained as crypt-villus-like structures, which are termed intestinal organoids or "enteroids". Enteroids are ideal to study the proliferation and cell death of intestinal epithelial cells in vitro. In this protocol, we describe a simple method to quantify the number of proliferative and dead cells in cultured enteroids. 5-ethynyl-2'-deoxyuridine (EdU) and propidium iodide are used to label proliferating and dead cells in enteroids, and the proportion of proliferating and dead cells are then analyzed by flow cytometry. This is a useful tool to test the effects of drug treatment on intestinal epithelial cell proliferation and cell survival.

Long non-coding RNAs (lncRNAs) have emerged as key regulators of cellular progress in lung adenocarcinoma. In this study, to identify cancer-related lncRNAs and genes, we screened for those lncRNAs that were differentially expressed in lung adenocarcinoma, which revealed LINC00628 overexpression and low expression of laminin subunit alpha 3 (LAMA3). This was further validated in the cancerous tissues from patients diagnosed with lung adenocarcinoma. Thereafter, we explored the functional relevance of LINC00628 and LAMA3 in lung adenocarcinoma by analyzing the recruitment of DNA methyltransferase (DNMT) and the cellular processes of lung adenocarcinoma cells following treatments that induced LINC00628 overexpression or LINC00628 silencing or with 5-azacytidine (5-Aza, a DNMT inhibitor). The results showed that LINC00628 silencing decreased cell proliferation, migration, and invasion as well as the drug resistance of lung adenocarcinoma cells to vincristine (VCR). The results were opposite in the cells with LAMA3 demethylation induced by 5-Aza treatment. Further research indicated that LINC00628 recruited DNMT1, DNMT3A, and DNMT3B to promote the methylation of LAMA3 promoter, thereby decreasing its expression. Moreover, an in vivo experiment was performed in nude mice to assess the tumor growth ability and drug resistance of human lung adenocarcinoma cells. It was observed that LINC00628 silencing or 5-Aza treatment inhibited the in vivo tumor growth ability of the human lung adenocarcinoma cells and reduced their resistance to VCR. Altogether, our results provide evidence of a mechanism by which LINC00628 silencing exerts an inhibitory role in lung adenocarcinoma by modulating the DNA methylation of LAMA3, indicative of a novel molecular target for treatment of lung adenocarcinoma patients showing resistance to VCR., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)