Perioperative safety, oncologic outcome, and risk factors of salvage liver resection for initially unresectable hepatocellular carcinoma converted by transarterial chemoembolization plus tyrosine kinase inhibitor and anti-PD-1 antibody: a retrospective multicenter study of 83 patients.

BACKGROUND: To assess the perioperative safety, oncological outcomes, and determinants influencing the oncological outcomes of salvage liver resection for initially unresectable hepatocellular carcinoma (HCC) rendered resectable through transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies (α-PD-1). METHODS: We retrospectively reviewed data from 83 consecutive patients across six tertiary hospitals who underwent salvage liver resection for initially unresectable HCC following conversion by TACE combined with TKIs and α-PD-1, emphasizing perioperative and oncological outcomes. Multivariate Cox regression analysis was employed to discern independent risk factors for postoperative recurrence-free survival (RFS). RESULTS: The median operative duration was 200 min, with a median blood loss of 400 ml. Intraoperative blood transfusions were necessitated for 27 patients. The overall perioperative complication rate was 48.2%, with a major complication rate of 16.9%. One patient died during the perioperative period due to postoperative liver failure. During the median follow-up period of 15.1 months, 24 patients experienced recurrence, with early and intrahepatic recurrence being the most common. Seven patients died during follow-up. Median RFS was 25.4 months, with 1- and 2-year RFS rates of 68.2% and 61.8%, respectively. Median overall survival was not reached, with 1- and 2-year overall survival rates of 92.2% and 87.3%, respectively. Multivariate Cox regression analysis revealed that pathological complete response (pCR) and intraoperative blood transfusion served as independent prognostic determinants for postoperative RFS. CONCLUSIONS: Our study provides preliminary evidence suggesting that salvage liver resection may be an effective and feasible treatment option for patients with unresectable HCC who achieve resectability after conversion therapy with TACE, TKIs, and α-PD-1. The perioperative safety of salvage liver resection for these patients was manageable and acceptable. However, further research, particularly prospective comparative studies, is needed to better evaluate the potential benefits of salvage liver resection in this patient population.

Compare the clinical value of two minimally invasive approaches to locating radial nerve in the posterior humeral approach.

PURPOSE: To compare the clinical value between locating radial nerve (RN) guided by Color Doppler ultrasonography and posterior antebrachial cutaneous nerve (PACN) in the posterior humeral approach. METHODS: The five fresh adult cadavers (ten upper arms) were selected to compare the two methods of locating the RN in the posterior humeral approach (guided by ultrasound and PACN) by measuring the operation time, the length of incision, and the area of subcutaneous free. And the comparison between the two groups was statistically analyzed by paired t-test. RESULTS: The results of this study demonstrated that the length of incision and the area of subcutaneous free in the ultrasound group were smaller than that in the PACN group (P < 0.05), while the operation time was just the opposite (P < 0.05). However, after excluding the time of ultrasound location, the operation time in the ultrasound group was shorter than that in the PANC group, and the difference was statistically significant (P < 0.05). CONCLUSION: The RN can be quickly and safely exposed by both methods. The ultrasound approach requires a long learning curve, but is more minimally invasive and can help determine whether the intraoperative nerve is compressed by the plate. And the PACN method requires a longer incision and a wider area of subcutaneous free, while specialized equipment and professional training for surgeons are not required. In a word, these two methods have advantages and disadvantages, so they should be selected based on the exact situation.

PERK-STING-RIPK3 pathway facilitates cognitive impairment by inducing neuronal necroptosis in sepsis-associated encephalopathy.

AIMS: Sepsis-associated encephalopathy (SAE) is a common but serious complication in septic survivors and often causes long-term cognitive impairments. The role of RIPK3-participated necroptosis in SAE remains obscured. STING is a key molecule in regulating necroptosis and apoptosis. However, there is uncertainty as to the mechanisms of STING in CLP-induced SAE. The aim of this study was to investigate whether STING is involved in the underlying mechanism of SAE. METHODS: The contextual fear conditioning test (CFCT) assesses cognitive impairment. A transmission electron microscope (TEM) was used to notice the necroptosis. Western blotting and immunofluorescence labeling were applied for the observation of related proteins. RESULTS: The phosphorylated STING in the hippocampal neuron of SAE mice was significantly elevated. Knocking down STING inhibited necroptosis and attenuated cognitive impairment in SAE mice. Moreover, RIPK3-/- mice had less cognitive deficit in the SAE model. However, STING overexpression did not deteriorate cognitive impairment in RIPK3-/- mice with SAE, indicating that STING is upstream involved in necroptosis. Furthermore, PERK inhibition ameliorated cognitive deficits through a STING-dependent pathway in SAE mice. CONCLUSION: PERK-STING-RIPK3 pathway facilitates cognitive impairment by inducing neuronal necroptosis in the pathology of SAE, which provided a new therapeutic target in SAE treatment.

Diastereoselective Synthesis of Dihydrobenzofuran-Fused Spiroindolizidines via Double-Dearomative [3 + 2] Cycloadditions.

Spiroindolizidine oxindoles represent a kind of privileged scaffold in many biologically active natural alkaloids. 2,3-Dihydrobenzofuran derivatives exhibit significant bioactivities in a variety of pharmaceuticals. Herein, we assembled these two privileged fragments into a small molecule via double-dearomative [3 + 2] cycloadditions with pyridinium ylides and 2-nitrobenzofurans. This protocol features remarkable advantages including wide substrate scope, mild condition, high level of diastereoselectivities and yields. Thus, a collection of spiroindolizidine-fused dihydrobenzofurans/indolines were facilely produced efficiently.

Exploration of hapten-induced atopic dermatitis murine models for non-clinical pharmacodynamics study of drugs / 药学学报

Atopic dermatitis (AD) is a chronic, relapsing, inflammatory dermatosis with a variety of clinical manifestations and difficult to cure. Currently, many AD drug candidates have entered the research and development pipeline. In order to provide technical specifications for the clinical development of AD drugs, the Center for Drug Evaluation of National Medical Products Administration released the "Technical Guidelines for Clinical Trials of Drugs for AD Treatment" (Draft for Comments) in November 2022. Non-clinical pharmacodynamics evaluation is an important research before the drug enters clinical trials. Oxazolone (OXA)- and 2,4-dinitro-fluorobenzene (DNFB)-induced models are the most popular classical hapten-induced AD murine models, but variations of modeling are existing in the methods from different studies, including sensitization sites, haptens' dosages, the period of challenges, and the skin lesions severity evaluation as well. In this study, the investigation of OXA- and DNFB-induced AD murine models with various conditions of modeling was performed to compare the characteristics of hapten-induced AD murine models in the pathological process and severity according to the appearance of AD patients, and the guidance of pharmacodynamics evaluation of AD-therapeutic drugs in clinical trials as well, which may provide a proposal for AD treatment drug candidates in the non-clinical pharmacodynamics evaluation. All animal experiments were approved by the Animal Care & Welfare Committee of Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (approval No.: 00007782 and 00007784).

A case of skin ulcers secondary to extensive burns caused by flame and heavy metal-containing hydrothermal fluids / 中华烧伤杂志

On May 13, 2020, a 56-year-old man with extensive burns caused by flames and heavy metal-containing hydrothermal fluids was admitted to the General Hospital of Western Theater Command. After being admitted to the hospital, most of the burn wounds healed after treatments such as debridement, expansion, skin grafting, anti-shock, anti-infection, fluid replacement, and wound dressing change, etc. However, in the middle and late stages of treatment, the patient's burn wounds gradually showed repeated skin ulceration and inflammation. After excluding the cause of physical, bacterial infection and others, IgG4-related skin diseases was finally diagnosed by histopathological examination of tissue biopsy and concentration measurement of IgG4 in interstitial fluid, and the condition was improved after hormone treatment. This suggests that extensive burns may lead to the occurrence of autoimmune skin diseases. For the diagnosis of such diseases, it is necessary to combine clinical manifestations, serological examinations, and histopathological biopsy, etc. to avoid diagnostic pitfalls and draw correct conclusions.

Anti-diabetic Effect of Zishenwan and Its Herbal Components： A Review / 中国实验方剂学杂志

Zishenwan， also known as Tongguanwan， is composed of three herbs：Anemarrhenae Rhizoma， Phellodendri Chinensis Cortex， and Cinnamomi Cortex， which thus is thought to be the representative formula to clear heat， purge fire， nourish Yin， and tonify Qi， and it is often used for treating anuresis and renal arthralgia. In recent years， this formula has become a commonly used combination of herbs and is used to treat diabetes （consumptive thirst disease） diagnosed with "lower consumption" syndrome. This article systematically reviewed the development of traditional Chinese medicine （TCM） theory for Zishenwan. Moreover， based on modern pharmacological research， the previous studies on the components of Zishenwan， the improvement of diabetes-related diseases by Zishenwan， and the relationship between the single herd of Zishenwan and the treatment of diabetes were summarized， and the chemical components and the mechanisms for treating diabetes by the three herbs were discussed. It is found that Zishenwan can alleviate diabetes and diabetic nephropathy by performing anti-inflammation， enhancing insulin sensitivity， and inhibiting pyroptosis of renal tubular epithelial cells. Three herbs in Zishenwan and several components of them， including mangiferin， timosaponins， berberine， jatrorrhizine， cinnamaldehyde， and cinnamic acid can ameliorate diabetes and maintain stable glycometabolism by a variety of mechanisms such as improving insulin resistance in insulin target tissues， suppressing inflammation， anti-oxidation， regulating lipid metabolism， enhancing insulin secretion， and regulating gut microbiota. This review provides a theoretical foundation and reference for subsequent studies on the mechanisms of the anti-diabetic effect of Zishenwan.

Effect of Zishenwan on Intestinal Barrier and Transcriptome of Skeletal Muscle of db/db Diabetic Mice / 中国实验方剂学杂志

ObjectiveTo explore the effect of Zishenwan on glucose and lipid metabolism in spontaneous type 2 diabetes （db/db） mice and investigate the underlying mechanism for improving diabetes based on intestinal barrier function and skeletal muscle transcriptome sequencing results. MethodLiquid chromatography-tandem mass spectrometry （LC-MS/MS） was used to analyze the components of Zishenwan. Sixteen 6-week-old db/db mice were divided into a model group and a Zishenwan group， while eight wild-type mice were assigned to the normal group. The Zishenwan group received oral administration of drugs for six weeks， during which fasting blood glucose， body weight， and food intake were measured. Serum total cholesterol （TC） and triglyceride （TG） levels were determined， and fasting insulin levels were measured to calculate the homeostatic model assessment of insulin resistance （HOMA-IR）. After the treatment， skeletal muscle and ileum tissues were collected， followed by hematoxylin-eosin （HE） staining. Immunohistochemistry was used to detect the expression of tight junction proteins occludin and zonula occludens-1 （ZO-1） in the ileum. Transcriptome sequencing was performed to detect the skeletal muscle transcriptome， and enrichment analysis was conducted for differentially expressed genes. ResultMultiple active components were identified in Zishenwan. Compared with the normal group， the model group showed increased fasting blood glucose， body weight， TC， TG， and HOMA-IR （P<0.01）. Compared with the model group， Zishenwan significantly reduced fasting blood glucose， body weight， TC， TG， and HOMA-IR in db/db mice （P<0.01）， while there was no statistically significant difference in food intake. Compared with the normal group， the model group exhibited lipid deposition in skeletal muscle， as well as structural changes in the ileum， with significant decreases in the protein expression levels of intestinal occludin and ZO-1 （P<0.01）. Compared with the model group， Zishenwan improved the pathological changes in skeletal muscle and ileum， and increased the protein expression of occludin and ZO-1 in the ileum （P<0.01）. Transcriptome analysis suggested that Zishenwan might improve skeletal muscle metabolism and increase insulin sensitivity in mice. ConclusionZishenwan can improve glucose and lipid metabolism in db/db mice， and this effect may be related to its protection of intestinal barrier function and transcriptional regulation of skeletal muscle metabolism-related genes.

Application of remote ischemic preconditioning combined with controlled low central venous pressure in hepatectomy / 临床肝胆病杂志

Objective To investigate the application effect of remote ischemic preconditioning (RIPC) combined with controlled low central venous pressure (CLCVP) in hepatectomy. Methods A total of 80 patients who underwent elective partial hepatectomy in Yougchuan Hospital Affiliated to Chongqing Medical University from May 2021 to April 2022 were enrolled and divided into control group (group C), CLCVP group (group L), RIPC group (group R), and RIPC+CLCVP group (group RL) using a random number table, with 20 patients in each group. The patients in group L received CLCVP, those in group R received RIPC, and those in group RL received both CLCVP and RIPC. The patients were compared in terms of perioperative general status and the levels of tumor necrosis factor-α (TNFα), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin on preoperative day 1(D0), postoperative day 1(D1), postoperative day 3(D3), postoperative day 5(D5), and postoperative day 7(D7). A one-way analysis of variance or a repeated measures analysis of variance was used for comparison of normally distributed continuous data between groups, and the Kruskal-Wallis H test was used for comparison of continuous data with skewed distribution between groups; the chi-square test was used for comparison of categorical data. Results Compared with group R, group RL had a significantly shorter time of operation ( H =14.278, P =0.015), a significantly lower total infusion volume ( H =24.175, P =0.001), and a significantly lower estimated blood loss ( H =45.625, P < 0.001). Group and time factors had significant interaction effects on TNFα, ALT, and AST in the four groups ( P < 0.001; P =0.010; P =0.012). Group RL had a significantly lower level of TNFα than group L on D1( P < 0.001) and D3( P < 0.001). Group RL had a significantly lower level of ALT than group L on D1( P =0.008) and D7( P < 0.001). Conclusion For patients undergoing hepatectomy, RIPC combined with CLCVP can effectively reduce intraoperative blood loss, provide a clear surgical field, and shorten the time of operation; meanwhile, it can also inhibit inflammatory response by reducing TNFα, but it cannot effectively alleviate hepatic ischemia-reperfusion injury after hepatectomy under the context of CLCVP.

Construction of training indexes of post competency of dental hygienist / 中国实用护理杂志

Objective:To construct training indexes of post competency of dental hygienist, and to provide objective basis for the establishment of the index system of the transition from dental nurse to dental hygienist in the future.Methods:The relevant literature of post competency of dental hygienist was searched from the databases such as PubMed, Medline, Web of Science, China National Knowledge Internet, Wanfang database. The search time was from the establishment of the database to March 2021. The expert letter inquiry questionnaire was designed through preliminary consultation.Delphi expert consultation was conducted for 20 dental experts from Beijing city, Chongqing city, Jiangsu province, Sichuan province, Jilin province from May to November 2021, and model indexes and weight assignment of post competency of dental hygienist were determined.Results:Three rounds of Delphi expert consultation were conducted, the effective recoveries of the questionnaires were 100%, the expert authority coefficients were 0.81, 0.81, 0.83, respectively, the coefficient of variation of expert consultation was 0.000-0.386, 0.000-0.300 and 0.000-0.250, respectively, the coordination degree of expert opinions in the third round of consultation was 0.679, 0.428 and 0.389 (all P<0.01). The formed training indexes of post competency of dental hygienist included 4 first-level indexes, 20 second-level indexes and 60 third-level indexes. Conclusions:The training index system of post competency of dental hygienist in this study is scientific, reliable, and practical, to provide reference for training and assessment of post competency of dental hygienist and objective basis for establishing the indexes system of dental nurse to dental hygienist in the future.

Pathological evaluation of endoscopic submucosal dissection for early gastric cancer and precancerous lesion in 411 cases / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the pathological characteristics of endoscopic submucosal dissection (ESD) specimens for early gastric cancer and precancerous lesions, accumulating experience for clinical management and pathological analysis.@*METHODS@#A total of 411 cases of early gastric cancer or precancerous lesions underwent ESD. According to the Japanese guidelines for ESD treatment of early gastric cancer and classification of gastric carcinoma, the clinicopathological data, pathologic evaluation, concordance rate of pathological diagnosis between preoperative endoscopic forceps biopsies and their ESD specimens (in 400 cases), as well as the risk factors of non-curative resection of early gastric cancer, were analyzed retrospectively.@*RESULTS@#23.4% (96/411) of the 411 cases were adenoma/low-grade dysplasia and 76.6% (315/411) were early gastric cancer. The latter included 28.0% (115/411) non-invasive carcinoma/high-grade dysplasia and 48.7% (200/411) invasive carcinoma. The concordance rate of pathological diagnosis between endoscopic forceps biopsies and ESD specimens was 66.0% (264/400), correlating with pathological diagnosis and lesion location (P < 0.01). The rate of upgraded diagnosis and downgraded diagnosis after ESD was 29.8% (119/400) and 4.2% (17/400), respectively. Among the 315 cases of early gastric cancer, there were 277 cases (87.9%) of differentiated type and 38 cases (12.1%) of undifferentiated type. In the study, 262 cases (83.2%) met with absolute indication, while 53 cases (16.8%) met relative indication. En bloc and curative resection rates were 98.1% and 82.9%, respectively. Risk factors for non-curative resection included a long diameter >20 mm (OR=3.631, 95%CI: 1.170-11.270, P=0.026), tumor infiltration into submucosa (OR=69.761, 95%CI: 21.033-231.376, P < 0.001)and undifferentiated tumor histology (OR=16.950, 95%CI: 4.585-62.664, P < 0.001).@*CONCLUSION@#Several subjective and objective factors, such as the limitations of biopsy samples, the characteristics and distribution of the lesions, different pathological understanding, and the endoscopic sampling and observation, can lead to the differences between the preoperative and postoperative pathological diagnosis of ESD. In particular, the pathological upgrade of postoperative diagnosis was more significant and should receive more attention by endoscopists and pathologists. The curative resection rate of early gastric cancer in ESD was high. Non-curative resection was related to the long diameter, the depth of tumor invasion and histological classification. ESD can also be performed in undifferentiated early gastric cancer if meeting the indication criteria. The comprehensive and standardized pathological analysis of ESD specimens is clinically important to evaluate the curative effect of ESD operation and patient outcomes.

Preliminary clinical application of multimodal imaging combined with frameless robotic stereotactic biopsy in the diagnosis of primary central nervous system lymphoma.

Objective: To evaluate the clinical application of multimodal imaging combined with frameless robotic stereotactic biopsy in the diagnosis of primary central nervous system lymphoma (PCNSL). Methods: We retrospectively reviewed the clinical data of 8 patients who were considered suspected cases of PCNSL by multimodal imaging techniques. The final pathologic diagnosis were determined by the frameless robotic stereotactic biopsy. The postoperative related complications and pathological results were analyzed. Results: All patients underwent biopsies under general anesthesia with an average surgery time of 29.5 ± 4.5 min. The final pathological diagnostic accordant rate with the preoperative ones was 100%, and the pathologic examination of our patients showed features of diffuse large B-cell lymphoma. During the surgery, one patient suffered intratumoral hemorrhage without leading to serious cerebral edema, and conservative treatment was given. There was no death occurring during the study, and there were no significant differences in the Karnofsky Performance Scale Scores of all patients before and after surgery. Finally, they were transferred to the hematology department for standardized chemoradiotherapy according to the pathological results of PCNSL. Conclusion: This study shows that it may play a vital role in the early diagnosis of PCNSL with the technique of multimodal imaging. The technique of frameless robotic stereotactic biopsy for obtaining the pathology outcomes in suspected PCNSL patients has the advantages of safety, efficiency, and minimally invasiveness.

An Adaptive and Robust Control Strategy for Real-Time Hybrid Simulation.

A real-time hybrid simulation (RTHS) is a promising technique to investigate a complicated or large-scale structure by dividing it into numerical and physical substructures and conducting cyber-physical tests on it. The control system design of an RTHS is a challenging topic due to the additional feedback between the physical and numerical substructures, and the complexity of the physical control plant. This paper proposes a novel RTHS control strategy by combining the theories of adaptive control and robust control, where a reformed plant which is highly simplified compared to the physical plant can be used to design the control system without compromising the control performance. The adaptation and robustness features of the control system are realized by the bounded-gain forgetting least-squares estimator and the sliding mode controller, respectively. The control strategy is validated by investigating an RTHS benchmark problem of a nonlinear three-story steel frame The proposed control strategy could simplify the control system design and does not require a precise physical plant; thus, it is an efficient and practical option for an RTHS.

Meteorin links the bone marrow hypoxic state to hematopoietic stem/progenitor cell mobilization.

Hematopoietic stem/progenitor cells (HSPCs) are supported and regulated by niche cells in the bone marrow with an important characterization of physiological hypoxia. However, how hypoxia regulates HSPCs is still unclear. Here, we find that meteorin (Metrn) from hypoxic macrophages restrains HSPC mobilization. Hypoxia-induced factor 1α and Yin Yang 1 induce the high expression of Metrn in macrophages, and macrophage-specific Metrn knockout increases HSPC mobilization through modulating HSPC proliferation and migration. Mechanistically, Metrn interacts with its receptor 5-hydroxytryptamine receptor 2b (Htr2b) to regulate the reactive oxygen species levels in HSPCs through targeting phospholipase C signaling. The reactive oxygen species levels are reduced in HSPCs of macrophage-specific Metrn knockout mice with activated phospholipase C signaling. Targeting the Metrn/Htr2b axis could therefore be a potential strategy to improve HSPC mobilization for stem cell-based therapy.

Clinical Study on a Modified Hematoma Puncture Drainage Treatment in Patients with Hypertensive Basal Ganglia Hemorrhage.

OBJECTIVE: We aim to investigate the clinical efficacy and safety of a modified hematoma puncture drainage treatment through the burr hole lateral to Kocher's point from the frontal lobe in patients with hypertensive basal ganglia hemorrhage. METHODS: Twenty-six patients were enrolled in the retrospective study. The volume of hematoma in those patients was between 25 and 35 mL, and the Glasgow Coma Scale scores were between 9 and 11; they were divided into a hematoma puncture drainage treatment group and a traditional conservative treatment group. The volume of remaining hematoma, neurological function defect scores, and life quality after treatment, duration of hospitalization, and cost of hospitalization were analyzed in these 2 groups. RESULTS: The volume of remaining hematoma was significantly less in the drainage group than that in the traditional group on the first day and the third day after treatment (P < 0.05). Posttreatment neurological function defect scores in the drainage group were statistically lower than those in the traditional group (P < 0.05). The duration of hospitalization was significantly shorter and the cost of hospitalization was also significantly less in the drainage group than that in the traditional group (P < 0.05). The Extended Glasgow Outcome Scale and Barthel Index scores were significantly higher in the drainage group than those in the traditional group (P < 0.05). There were no significant differences between the 2 groups in the complication rates (P > 0.05). CONCLUSIONS: The modified hematoma puncture drainage treatment represents an effective and safe way to treat hypertensive basal ganglia hemorrhage.

Matrix metalloproteinase-25 from Japanese sea bass (Lateolabrax japonicus) is involved in pro-inflammatory responses.

Matrix metalloproteinases (MMPs) are highly expressed in leukocytes and macrophages, which play a role in the innate immune response. Here, the cDNA sequence of MMP25 from Japanese sea bass (Lateolabrax japonicus) (LjMMP25) was identified. Phylogenetic analysis revealed that LjMMP25 was most closely related to large yellow croaker MMP25. Multiple sequence alignment of LjMMP25 with MMP25 sequences from other teleosts revealed that regions of known functional importance were highly conserved. Expression analysis revealed that LjMMP25 was highly expressed in the head kidney and widely expressed in other tissues including gill, spleen, and liver. LjMMP25 was found to regulate inflammatory cytokine production and promote phagocytosis and bacterial killing in monocytes/macrophages (MO/MФ). Furthermore, LjMMP25 regulated the inflammatory response by modulating NF-κB signaling. These findings reveal new information about the role of LjMMP25 in regulating pro-inflammatory responses in this species.

Two paralogs of CXCR4 in the Japanese sea bass (Lateolabrax japonica) are involved in the immune response of B lymphocytes.

CXC chemokine receptor 4 (CXCR4), a member of the G-protein-coupled receptor family, plays an important role in host immune responses. Within the teleost lineage, there are two paralogs of CXCR4; however, the role of CXCR4 in teleost B cells is poorly understood. In this study, we determined the cDNA sequences of the two CXCR4 paralogs from the Japanese sea bass (Lateolabrax japonica; LjCXCR4a and LjCXCR4b). Sequence and phylogenetic tree analyses revealed that LjCXCR4a and LjCXCR4b are most closely related to CXCR4a and CXCR4b, respectively, in the large yellow croaker (Larimichthys crocea). CXCR4 transcripts were mainly expressed in the gills, and their expression in different tissues was altered upon infection with Vibrio harveyi. LjCXCR4a and LjCXCR4b protein levels were upregulated in infected B cells. Knockdown of LjCXCR4a and LjCXCR4b in B cells by RNA interference, the phagocytic activity of B cells was not affected. Furthermore, knockdown of LjCXCR4a, not of LjCXCR4b, was observed to inhibit LjIgM expression in lipopolysaccharide-stimulated B cells. In addition, knockdown of LjCXCR4a, not of LjCXCR4b, was found to reduce reactive oxygen species levels in B cells. Our results indicate that LjCXCR4a and LjCXCR4b modulate the immune response of Japanese sea bass B cells against bacterial infection, albeit via different pathways.

Pollution monitoring, risk assessment and target remediation of heavy metals in rice from a five-year investigation in Western Fujian region, China.

Recently, rice contamination by heavy metals (HMs) has become a severe problem. Taking the Western Fujian region as an example in this study, a total of 1311 rice samples containing eight HMs were collected from 2015 to 2019, then used to explore their pollution characteristics, health risks, and Spatio-temporal variations, finally derive the target remediation areas of the key pollutants. The results showed that average concentrations of all the HMs had not reached the limits of the National Standards of Food Safety, but pollution indexes of As (0.783) and Cu (0.665) were at accumulation level (>0.6), which posed high pollution risks. Furthermore, locations of higher HMs concentrations coincided with those of higher pollution estimation probabilities. The non-carcinogenic risk (4.150, 2.434) and carcinogenic risk (4.96 × 10-3, 2.92 × 10-3) for children and adults cannot be negligible, As and Cd were the largest contributors. Children were more susceptible than adults due to the metal concentrations and rice intake rate. The spatio-temporal changes indicated that a decreasing trend in average concentrations of HMs (except Cr), but As (0.37%-0.88%) contents increased in the west and northeast parts, and so did Cd (1.92%-5.11%) in the central region during monitoring. For the target remediation, particular regions in the western and eastern were used as risky areas of As and Cd, respectively. Our results will provide theoretical support for the pollution management of HMs in rice.

Two ACTH analogs exert differential effects on monocytes/macrophages function regulation in ayu (Plecoglossus altivelis).

Adrenocorticotropic hormone (ACTH), a bioactive peptide of the family of melanocortins, is generated from pro-opiomelanocortin (POMC). So far, the research on the specific functions of ACTH in the immune system of teleosts is limited. We determined two complementary DNA (cDNA) sequences of POMC in ayu (Plecoglossus altivelis), termed PaPOMC-A and PaPOMC-B. PaPOMCs transcripts occurred in all examined tissues, and their expression in immune tissues changed following experimental infection with Vibrio anguillarum. PaACTH-B, but not PaACTH-A, suppressed the phagocytosis of monocytes/macrophages (MO/MФ). Two isoforms of PaACTH increased the bactericidal capacity of MO/MФ. PaACTH-A increased anti-inflammatory cytokine expression, while PaACTH-B decreased pro-inflammatory cytokine expression in MO/MФ. Compared with PaACTH-B treatment, the PaACTH-A treatment improved survival rate and reduced the bacterial load in V. anguillarum-infected ayu through interleukin (IL)-10. Our results indicate that the two PaACTH isoforms exert different effects in the host defense against bacterial infection.

Analysis of HIV-1 genetic subtype and pretreatment drug resistance among men who have sex with men infected with HIV-1 from 19 cities of 6 provinces in China / 中华流行病学杂志

Objective: To investigate the distribution of HIV-1 genetic subtypes and pretreatment drug resistance (PDR) among men who have sex with men (MSM) from 19 cities of 6 provinces in China. Methods: From April to November 2019, 574 plasma samples of ART-naive HIV-1 infected MSM were collected from 19 cities in Hebei, Shandong, Jiangsu, Zhejiang, Fujian, and Guangdong provinces, total ribonucleic acid (RNA) was extracted and amplified the HIV-1 pol gene region by nested polymerase chain reaction (PCR) after reverse transcription. Then sequences were used to construct a phylogenetic tree to determine genetic subtypes and submitted to the Stanford drug resistance database for drug resistance analysis. Results: A total of 479 samples were successfully amplified by PCR. The HIV-1 genetic subtypes included CRF01_AE, CRF07_BC, B, CRF55_01B, CRF59_01B, CRF65_cpx, CRF103_01B, CRF67_01B, CRF68_01B and unrecognized subtype, which accounted for 43.4%, 36.3%, 6.3%, 5.9%, 0.8%, 0.8%, 0.4%, 0.4%, 0.2% and 5.5%, respectively. The distribution of genetic subtypes among provinces is statistically different (χ2=44.141, P<0.001). The overall PDR rate was 4.6% (22/479), the drug resistance rate of non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, and protease inhibitors were 3.5% (17/479), 0.8% (4/479) and 0.2% (1/479), respectively. The PDR rate of recent infections was significantly higher than that of long-term infections (χ2=4.634, P=0.031). Conclusions: The HIV-1 genetic subtypes among MSM infected with HIV-1 from 19 cities of 6 provinces in China are diverse, and the distribution of subtypes is different among provinces. The overall PDR rate is low, while the PDR rate of recent infections was significantly higher than that of long-term infections, suggesting the surveillance of PDR in recent infections should be strengthened.