[Prognostic values of stromal tumor-infiltrating lymphocytes and lymphocyte-activation gene-3 in advanced gastric adenocarcinoma].

Objective: To analyze density of stromal tumor-infiltrating lymphocytes (sTIL) and expression of lymphocyte-activation gene-3 (LAG-3) protein in advanced gastric adenocarcinomas, and to investigate the correlation of sTIL and LAG-3 with the prognosis in patients with advanced gastric adenocarcinoma. Methods: The clinicopathological characteristics and follow-up data of 260 patients with advanced gastric adenocarcinoma were collected at Fujian Cancer Hospital, from January 2011 to December 2014. The percentage of sTILs was reported semi-quantitatively using histological section evaluation, the LAG-3 protein was detected using immunohistochemistry, and the expression was correlated with the clinicopathological features and patient outcomes. Results: Among the 260 cases, high density of sTIL was detected in 173 cases (66.5%) while LAG-3 high expression was observed in 160 cases (61.5%). These cases were divided into four groups. Group Ⅰ: 48 cases (18.5%) were sTIL low/LAG-3 low; group Ⅱ: 52 cases (20.0%) were sTIL high/LAG-3 low; group Ⅲ: 39 cases (15.0%) were sTIL low/LAG-3 high; group Ⅳ: 121 cases (46.5%) were sTIL high/LAG-3 high. Kaplan-Meier survival analyses showed that patient prognoses were related to age, tumor size, tumor location, Lauren classification, perineural invasion, vascular invasion, TNM staging, postoperative adjuvant chemotherapy and molecular classification (P<0.05). Meanwhile, higher densities of sTIL and higher expression of LAG-3 were associated with better prognosis. Multivariate survival analysis showed age, tumor size, Lauren classification and postoperative adjuvant chemotherapy were independent prognostic factors for patient survival. The results showed a poor prognosis in low-sTIL/low-LAG-3 patients. Conclusions: Compared with low density of sTIL and low expression of LAG-3, high density of sTIL and high expression of LAG-3 are associated with better outcomes in patients with advanced gastric adenocarcinoma, respectively. Combined detecton of sTIL and LAG-3 may be more useful in gastric cancer than using either alone. Age, tumor size, Lauren classification and postoperative adjuvant chemotherapy are independent prognostic factors for patients with advanced gastric adenocarcinoma.

[Analysis of the new WHO guideline to accelerate the progress towards elimination of schistosomiasis in China].

On February 2022, WHO released the evidence-based guideline on control and elimination of human schistosomiasis, with aims to guide the elimination of schistosomiasis as a public health problem in disease-endemic countries by 2030 and promote the interruption of schistosomiasis transmission across the world. Based on the One Health concept, six evidence-based recommendations were proposed in this guideline. This article aims to analyze the feasibility of key aspects of this guideline in Chinese national schistosomiasis control program and illustrate the significance to guide the future actions for Chinese national schistosomiasis control program. Currently, the One Health concept has been embodied in the Chinese national schistosomiasis control program. Based on this new WHO guideline, the following recommendations are proposed for the national schistosomiasis control program of China: (1) improving the systematic framework building, facilitating the agreement of the cross-sectoral consensus, and building a high-level leadership group; (2) optimizing the current human and livestock treatments in the national schistosomiasis control program of China; (3) developing highly sensitive and specific diagnostics and the framework for verifying elimination of schistosomiasis; (4) accelerating the progress towards elimination of schistosomiasis and other parasitic diseases through integrating the national control programs for other parasitic diseases.

[Contribution to global implementation of WHO guideline on control and elimination of human schistosomiasis by learning successful experiences from the national schistosomiasis control program in China].

Schistosomiasis is a parasitic disease that seriously hinders socioeconomic developments and threatens public health security. To achieve the global elimination of schistosomiasis as a public health problem by 2030, WHO released the guideline on control and elimination of human schistosomiasis on February, 2022, with aims to provide evidence-based recommendations for schistosomiasis morbidity control, elimination of schistosomiasis as a public health problem, and ultimate interruption of schistosomiasis transmission in disease-endemic countries. Following concerted efforts for decades, great achievements have been obtained for schistosomiasis control in China where the disease was historically highly prevalent, and the country is moving towards schistosomiasis elimination. This article reviews the successful experiences from the national schistosmiasis control program in China, and summarizes their contributions to the formulation and implementation of the WHO guideline on control and elimination of human schistosomiasis. With the progress of the "Belt and Road" initiative, the world is looking forward to more China's solutions on schistosomiasis control.

[Progress of researches on the diagnostic techniques for schistosomiasis].

Schistosomiasis is an important zoonotic parasitic disease, and is categorized as a neglected tropical disease by the World Health Organization. Following the concerted efforts for more than 70 years, great achievements have been made in the national schistosomiasis control program in China, and the prevalence, disability and mortality due to schistosomiasis has remarkably dropped. Nevertheless, the frequent identification of imported schistosomiasis and the resulting potential transmission risk in mainland China have been recently paid much attention following the implementation of the "Belt and Road Initiative" and the China-Africa Cooperation Forum. This review describes the advances in the diagnostic tools for schistosomiasis, including pathogenic techniques, immunodiagnostic techniques and nucleic acid assays, in order to consolidate schistosomiasis control achievements and promote the capability for detection of external biological safety risks.

Interactions of Mutiple Biological Fields in Stored Grain Ecosystems.

Biological entities such as fungi in stored grain evolve and interact with the environment in similar fashions as physical fields. An experiment was conducted to study the behavior of the biological field of fungi in stored grain, as well as the interactions between the biological field of fungi and the physical fields of temperature and moisture. A framework of the biological field is presented to describe biological systems in which multiple biological entities co-exist and interact among themselves and with the surrounding environment. The proposed biological field describes the spatio-temporal distribution of a biological entity and its ability of influencing (or being influenced by) the surrounding biotic and abiotic entities through exchange of energy, matter, and/or information. The strength of a biological field of fungi was quantified as the rate of energy conversion by fungi from grain starch to heat. The experimental data showed that the strength of biological field of fungi in stored grain varied in both space and time, with the maximum field strength of 120-133 W m-3 occurred at the location where the biological field of fungi interacted strongly with the temperature and moisture fields.

[Advances in the research of Fournier gangrene].

Fournier gangrene is a relatively rare clinical critical disease, and its clinical symptoms are not specific and easily unrecognized by some clinicians. It has the features of acute onset, quick development, severe illness, and often accompanied by infection shock which is seriously life-threatening. It is difficult in treatment with high medical costs and long length of hospitalization, which increases pain for patients and relatives and brings heavy economic and psychological burden on patients, society, and medical workers. By reviewing the literature home and abroad and combined with clinical practice, I summarize the researches on concept, epidemiology, clinical manifestation, diagnosis and treatment of Fournier gangrene, in order to provide reference for vast number of clinical workers.

[Application of and progress in computer aided design and computer aided manufacture materials by chairside digital workflow in implant prosthodontics].

With the emergence and development of new dental materials, chairside computer aided design/computer aided manufacture (CAD/CAM) materials, as an important part of digital technology, is gaining increasing progress to meet the needs of implant restorations and digital processing technology for the mechanical properties, chemical stability, biocompatibility and processing properties. A large number of in-vitro experiments and clinical studies have been reported on various materials, such as polycrystalline ceramic, glass ceramic and indirect composite. The purpose of this article is to review the performance, the clinical indications and applications of the CAD/CAM materials for chairside digital workflow in implant prosthodontics.

[Transmission electron microscopic observation on gonad of Oncomelania hupensis offspring bred in Weishan Lake areas].

OBJECTIVE: To observe the morphological changes in the testes and ovaries of adult 12th-generation Oncomelania hupensis bred for 12 winters in Weishan Lake areas. METHODS: The offspring of the adult O. hupensis snails bred in the Weishan Lake that were originated from the Yangzhou section of the Yangtze River was defined as the experiment group, while uninfected, adult O. hupensis snails captured from the marshland of the Yangzhou section of the Yangtze River served as the control group. Snails were dissected and intact testicular and ovarian specimens were sampled, routinely fixed, dehydrated, embedded, polymerized in an oven and sliced on an ultramicrotome. The sections were visualized under a transmission electron microscope, and the ultrastructure of the snail gonad was compared between the experiment and control groups. RESULTS: Transmission electron microscopy showed "9 + 2" microtubules on the transverse sections of the tails of sperm cells in the testes of male snails in the control group, with triangular acrosomes and spiral, dense nuclei seen in the tip, while in the experiment group, the "9 + 2" microtubules disappeared on the transverse sections of the tails of sperm cells in the testes of male snails, with low chromatin density found in the tip. Transmission electron microscopy revealed clear nucleolus and nuclear membranes in the ova of female snail ovaries, and displayed yolk body, liposomes and endoplasmic reticulum in the cytoplasm, bilayer twists of nuclear membrane and a uniform nucleolus in the control group, while in the experiment group, smooth nuclear membrane and unclear nucleolus were observed in the ova of female snail ovaries, with few contents seen within cells. CONCLUSIONS: Following breeding for 12 winters in the Weishan Lake, the 12th-generation O. hupensis snails fail to fully adapt to the natural environment in northern China, and the remarkable changes in the ultrastructure of the snail gonad may be a cause of gradual decline and even extinction of O. hupensis in the Weishan Lake areas.

Is the Dispersion Relation Applicable for Exotic Nuclear Systems? The Abnormal Threshold Anomaly in the

The threshold anomaly of the phenomenological potential has been known for a long time in nuclear reactions at energies around the Coulomb barrier, where the connection between the real and imaginary potentials is well described by the dispersion relation. However, this connection is not clear yet for some weakly bound nuclear systems, especially for reactions induced by exotic radioactive nuclei. In this study, precise optical potentials of the halo nuclear system ^{6}He+^{209}Bi were extracted via ^{208}Pb(^{7}Li,^{6}He) transfer reactions with energies measured downward to the extremely sub-barrier region. The real potential presents a bell-like shape around the barrier as a normal threshold anomaly in tightly bound nuclear systems. However, the imaginary potential shows an abnormal behavior: it increases first with energy decreasing below the barrier and then falls quickly down to 0. It is the first time the threshold of the imaginary potential has been determined in an exotic nuclear system. Moreover, experimental results show the dispersion relation is not applicable for this system, which may be a common phenomenon for exotic nuclear systems. We discuss possible explanations for such a peculiar behavior, but further study is still desired for the underlying physics.

[Giant cell reparative granuloma originating from the paranasal sinus: a case report].

A 40-year-old man presented with a 10-year history of nasal obstruction of his left nose, a 1-year history of headache and orbital pain. Radiologically, an extensive paranasal sinus mass was seen. Superiorly ,the cribriform plate was demineralized, and the lesion had intracranial extension with mild mass effect over the basal frontal lobes. Histologic examination revealed a central giant cell reparative granuloma. After endoscopic removal, the patient was symptom free at the 2-month follow-up.

Development and evaluation of loop-mediated isothermal amplification (LAMP) for rapid detection of Clonorchis sinensis from its first intermediate hosts, freshwater snails.

Clonorchiasis, caused by Clonorchis sinensis, is a key foodborne zoonosis, which is mainly found in China, Korea and Vietnam. Detection of this parasite from the second intermediate host, the freshwater fish is the common method for epidemiological surveys of this parasite, but is time consuming, labour intensive and easily leads to misdiagnosis. In this study, we have developed a rapid, sensitive and reliable molecular method for the diagnosis of C. sinensis from its first intermediate hosts, freshwater snails, based on a loop-mediated isothermal amplification (LAMP) method. The specific amplified fragment from genomic DNA of C. sinensis did not cross-react with those from other relevant trematodes and a range of hosts (freshwater fish, shrimps and snails) of C. sinensis living in similar environments. The detection limit of the LAMP method was as low as 10 fg which was 1000 times more sensitive than conventional PCR, which was also demonstrated by successful application to field samples. These results show that the LAMP method is a more sensitive tool than conventional PCR for the detection of C. sinensis infection in the first intermediate hosts and, due to a simpler protocol, is an ideal molecular method for field-based epidemiological surveys of this parasite.

Unique roles of Schistosoma japonicum protein Sj16 to induce IFN-γ and IL-10 producing CD4(+)CD25(+) regulatory T cells in vitro and in vivo.

Various proteins are expressed during different stages of schistosome development that are essential for cercarial penetration of vertebrate skin and evasion of host immune response. CD4(+)CD25(+) regulatory T cells are important in modulating immune responses towards helminth infections. Schistosoma japonicum protein Sj16 present in the secretions of schistosomula has been shown to have anti-inflammatory effects; however, it is uncertain whether Sj16 can induce CD4(+)CD25(+) regulatory T cells to participate in the regulation of early infection. In this study, we demonstrate a relationship between recombinant Sj16 (rSj16) and the induction of CD4(+)CD25(+) Foxp3(+) regulatory T cells. An increase in CD4(+)CD25(+) T cells was observed both in splenic cells from mice injected with rSj16 and the cells pretreated with rSj16, respectively. The induced CD4(+)CD25(+) T cells suppressed CD4(+)CD25(-) T-cell proliferation; furthermore, IFN-γ and IL-10 released from rSj16-stimulated cells contribute to this suppression. Additionally, rSj16-treated bone marrow dendritic cells (BMDCs) demonstrate an immature phenotype and play a role in the conversion of CD4(+)CD25(-) T cells into suppressive CD4(+)CD25(+) regulatory T cells. Our study identified a new CD4(+)CD25(+) T-cell population that induced by rSj16 and suggests that an IFN-γ-biased microenvironment during early infection of schistosome may favour the establishment of infection.

Human Angiostrongylus cantonensis: an update.

Angiostrongylus cantonensis was first discovered in 1935 and has become an important emerging pathogen causing human angiostrongyliasis. Major outbreaks of human angiostrongyliasis have been reported in endemic regions. Thousands of cases of human angiostrongyliasis have been documented worldwide. A. cantonensis has spread from its traditional endemic regions of the Pacific islands and Southeast Asia to the American continent including the USA, Caribbean islands and Brazil. Humans acquire A. cantonensis by consumption of raw or undercooked intermediate snail hosts or paratenic hosts. The main clinical manifestations of human angiostrongyliasis are eosinophilic meningitis and ocular angiostrongyliasis. The treatment of this disease includes supportive treatment, corticosteroid therapy, and combined therapy with corticosteroids and anthelminthics. The most effective method for prevention is to persuade people not to eat raw or undercooked intermediate and paratenic hosts.

Efficacy of albendazole combined with a marine fungal extract (m2-9) against Angiostrongylus cantonensis-induced meningitis in mice.

The pathogenesis of angiostrongyliasis, resulting from Angiostrongylus cantonensis invasion of the human central nervous system, remains elusive. Anthelmintics are usually used to kill worms, although dead worms in the brain may cause severe inflammation which will lead to central nervous system damage. Therefore, combination therapy with anthelmintics and anti-inflammatory drugs in the treatment of human angiostrongyliasis needs further study. To evaluate the efficacy of albendazole combined with a marine fungal extract (m2-9) in A. cantonensis infection, BALB/c mice infected by the third-stage larvae of A. cantonensis were divided into three groups: mice treated with albendazole or m2-9 alone or in combination from day 5 post-inoculation (PI). Several efficacy parameters were recorded, including weight change, worm recovery, neurological function, behavioural analysis, eosinophil and leucocyte counts. The results showed that combination therapy increased body weight, reduced worm burden, improved learning ability, memory and action, decreased neurological dysfunction and leucocyte response in these mice. The combination of albendazole and m2-9 treatment significantly decreased leucocyte response and increased the frequency of rearing, compared to infected mice treated with either drug alone. Therefore, m2-9 is a natural product with potentially significant therapeutic value for angiostrongyliasis and is worthy of further study.

rSj16, a recombinant protein of Schistosoma japonicum-derived molecule, reduces severity of the complete Freund's adjuvant-induced adjuvant arthritis in rats' model.

Sj16, a 16-kDa protein produced by Schistosoma japonicum, has been demonstrated to have anti-inflammatory effect. However, the possible mechanism of these phenomena has not been discovered. Here, we tried to touch it with arthritis rats' model induced by injection of complete Freund's adjuvant (CFA). A set of pathogenic characters were observed in CFA-treated rat, including local and systematic read-out, which showed the model successfully set up. After administration of rSj16 (recombinant Sj16) in vivo, paw swelling reduced significantly and in a dose-dependent manner, the level of TNF-α, IL-1ß and NO decreased and IL-10 in the serum increased. In vitro, rSj16 reversed the augmented surface expression of CD80, CD86, CD54 and OX6 induced by lipopolysaccharide (LPS) in bone marrow-derived DCs (BMDCs), whereas endocytotic capacity of rSj16-treated dendritic cell (DC) was profoundly increased. IL-12p70 released from rSj16-treated BMDC was decreased but IL-10 increased. Further, following incubation with rSj16 primed BMDCs, the sensitized T cells exhibited increased production of anti-inflammatory IL-10 and IL-4 and decreased production of IL-12p70 and IFN-γ. Collectively, these results implied that rSj16 alleviated CFA-induced arthritis, and the possible mechanisms may be its interruption of maturation and function of DCs. rSj16 could be a potential therapeutic agent against rheumatoid arthritis.

Long-term outcome of resection of large hepatocellular carcinoma.

BACKGROUND: The role of hepatectomy in the treatment of large hepatocellular carcinoma (HCC) is still controversial. This retrospective study evaluated whether the long-term outcome of hepatectomy for large HCC improved over 14 years in one centre. METHODS: Data from 2102 patients who underwent hepatectomy for large HCC were collected prospectively and divided into two time intervals for analysis: before end of December 1996 (group 1) and after December 1996 (group 2). Clinicopathological data for the two groups were compared, and factors associated with long-term prognosis were further analysed. RESULTS: Cumulative 1-, 3- and 5-year overall survival rates were 71.2, 58.8 and 38.7 per cent respectively in group 2, and were significantly better than respective rates of 67.8, 50.7 and 27.9 per cent in group 1. Cumulative 1-, 3- and 5-year disease-free survival rates were 61.5, 38.6 and 23.8 per cent respectively in group 2, and 56.5, 34.7 and 18.9 per cent in group 1. There was a significant difference in median survival time after recurrence between groups 2 and 1 (17 and 10 months respectively; P = 0.043). CONCLUSION: Hepatic resection in patients with large HCC has improved overall and disease-free survival during the past decade at this institute. Long-term survival can be improved significantly by aggressive treatment of recurrent tumours.

Use of hepatectomy and splenectomy to treat hepatocellular carcinoma with cirrhotic hypersplenism.

BACKGROUND: The aim of this study was to compare the outcome after simultaneous hepatectomy and splenectomy with that after hepatectomy alone for hepatocellular carcinoma with associated hypersplenism. METHODS: Two hundred and four patients with hepatocellular carcinoma and cirrhotic hypersplenism were divided non-randomly into two groups. Ninety-four underwent simultaneous hepatectomy and splenectomy and 110 underwent hepatectomy alone. White blood cell (WBC) and platelet counts, total serum bilirubin levels, immune function, incidence of complications and 5-year survival rates in the two groups were compared. RESULTS: WBC and platelet counts, distribution of T cell subsets, and levels of bilirubin, interferon gamma and interleukin 2 were different between the two groups after operation. All patients who underwent hepatectomy and splenectomy but only 15.5 per cent of those who had hepatectomy alone completed adjuvant chemotherapy. The 5-year tumour-free survival rate was significantly higher after hepatectomy and splenectomy than after hepatectomy alone (37 versus 27.3 per cent; P = 0.003), although overall survival rates were similar. CONCLUSION: Simultaneous hepatectomy and splenectomy was associated with improved 5-year tumour-free survival in patients with hepatocellular carcinoma and hypersplenism.