Assessing the causal link between liver function and acute pancreatitis: A Mendelian randomisation study.

A correlation has been reported to exist between exposure factors (e.g. liver function) and acute pancreatitis. However, the specific causal relationship remains unclear. This study aimed to infer the causal relationship between liver function and acute pancreatitis using the Mendelian randomisation method. We employed summary data from a genome-wide association study involving individuals of European ancestry from the UK Biobank and FinnGen. Single-nucleotide polymorphisms (SCNPs), closely associated with liver function, served as instrumental variables. We used five regression models for causality assessment: MR-Egger regression, the random-effect inverse variance weighting method (IVW), the weighted median method (WME), the weighted model, and the simple model. We assessed the heterogeneity of the SNPs using Cochran's Q test. Multi-effect analysis was performed using the intercept term of the MR-Egger method and leave-one-out detection. Odds ratios (ORs) were used to evaluate the causal relationship between liver function and acute pancreatitis risk. A total of 641 SNPs were incorporated as instrumental variables. The MR-IVW method indicated a causal effect of gamma-glutamyltransferase (GGT) on acute pancreatitis (OR = 1.180, 95%CI [confidence interval]: 1.021-1.365, P = 0.025), suggesting that GGT may influence the incidence of acute pancreatitis. Conversely, the results for alkaline phosphatase (ALP) (OR = 0.997, 95%CI: 0.992-1.002, P = 0.197) and aspartate aminotransferase (AST) (OR = 0.939, 95%CI: 0.794-1.111, P = 0.464) did not show a causal effect on acute pancreatitis. Additionally, neither the intercept term nor the zero difference in the MR-Egger regression attained statistical significance (P = 0.257), and there were no observable gene effects. This study suggests that GGT levels are a potential risk factor for acute pancreatitis and may increase the associated risk. In contrast, ALP and AST levels did not affect the risk of acute pancreatitis.

Traditional Chinese medicine ointment combined with tuina therapy in treatment of pain and swelling after total knee arthroplasty.

BACKGROUND: The most effective treatment for knee joint pain is total knee arthroplasty (TKA), but the risk of pain and swelling in patients after surgery is high. Ice application, ankle pump exercise and non-steroidal anti-inflammatory painkillers are the primary clinical treatments after surgery. However, long-term use of non-steroidal anti-inflammatory pain relievers can easily cause gastrointestinal damage. Traditional Chinese medicine (TCM) ointments and tuina therapy integrate TCM and manipulation, which effectively promotes the penetration of TCM into the skin lesions, improves local blood circulation and inflammatory reaction and has good long-term effects on patients. AIM: To evaluate the efficacy of TCM ointment combined with tuina therapy in the treatment of pain and swelling after TKA. METHODS: The randomized controlled clinical trial enrolled 80 patients who underwent TKA via the same procedure. The patients were randomly divided among the treatment group (n = 40) and the control group (n = 40). The control group was given an analgesia pump in addition to oral painkillers as the postoperative intervention. The treatment group received TCM ointment with tuina therapy in addition to the analgesia pump and oral painkillers in the postoperative period. The following variables were recorded 3 d before surgery and 3 d, 7 d and 14 d after surgery: Visual analogue scale (VAS) score; skin temperature; circumferences at 15 cm above and below the patella; maximum active knee flexion angle; and the knee injury and Osteoarthritis Outcome score (KOOS). RESULTS: After treatment, VAS was significantly lower in the treatment group than the control group at 7 d (t = 7.536, P < 0.001) and 14 d (t = 8.563, P < 0.001). The skin temperature of participants in the treatment group was significantly lower than that in the control group at 7 d (t = 2.968, P = 0.004) and 14 d (t = 4.423, P < 0.001). The circumference values of the two positions in the treatment group were lower than those in the control group at 7 d [t = 2.315, P = 0.023 (above); t = 2.121, P = 0.037 (below)] and 14 d [t = 2.374, P = 0.020 (above); t = 2.095, P = 0.039 (below)]. After 14 d of treatment, the maximum active knee flexion angle and KOOS of the two groups were significantly improved but were significantly higher in the treatment group (P < 0.05 for both). CONCLUSION: TCM ointment and tuina therapy have significant advantages over standard care in the treatment of pain and swelling after TKA. This additional treatment may improve knee function but additional studies are needed to confirm our observations.

[Identification of released population of Japanese flounder based on stable isotopes analysis]. / åŸºäºŽç¨³å®šåŒä½ç´ æŠ€æœ¯çš„å¢žæ®–æ”¾æµç‰™é²†ç¾¤ä½“é‰´åˆ«.

Japanese flounder (Paralichthys olivaceus) is an important releasing fish in the Yellow and Bohai Seas of China. The identification of wild and releasing population is the premise to evaluate the enhancement effects. In order to study the application of stable isotope in the identification of released P. olivaceus population, captured juveniles in the offshore releasing area of Qinhuangdao were distinguished into wild and released population using previous method (combination of morphology and molecular). Then, the contents of carbon and nitrogen stable isotope in muscle and otoliths (including the whole and the core region) were measured. The cultured population was set as control. The results showed that δ13C values (wild population: -17.19‰±0.73‰; released population: -17.10‰±0.61‰; cultured population: -20.75‰±0.07‰) and δ15N values (wild population: 11.81‰±0.38‰; released population: 11.62‰±0.48‰; cultured population: 8.64‰±0.60‰) of muscle and δ13C value (wild popu-lation: -4.47‰±0.35‰; released population: -4.63‰±0.29‰; cultured population: -6.59‰±0.58‰) of the whole otolith could be used to identify the cultured population, but could not be used to distinguish the wild from the released population. The δ13C value (wild population: -4.66‰±0.30‰; released population: -5.41‰±0.21‰; cultured population: -5.37‰±0.19‰) of the core region of otolith could be used to identify the wild popu-lation. The δ18O values of the whole and the core region of otolith from these three groups were overlapped and could not be used to distinguish different populations. Our results indicated that the δ13C value of the core area of otolith could be used to identify wild and released population, with application prospect in the identification of broodstocks participating in spawning migration. This study provided basic data and technical methods for evaluating early resources replenishment and the effects of Japanese flounder enhancement.

ReaxFF-MPNN machine learning potential: a combination of reactive force field and message passing neural networks.

Reactive force field (ReaxFF) is a powerful computational tool for exploring material properties. In this work, we proposed an enhanced reactive force field model, which uses message passing neural networks (MPNN) to compute the bond order and bond energies. MPNN are a variation of graph neural networks (GNN), which are derived from graph theory. In MPNN or GNN, molecular structures are treated as a graph and atoms and chemical bonds are represented by nodes and edges. The edge states correspond to the bond order in ReaxFF and are updated by message functions according to the message passing algorithms. The results are very encouraging; the investigation of the potential, such as the potential energy surface, reaction energies and equation of state, are greatly improved by this simple improvement. The new potential model, called reactive force field with message passing neural networks (ReaxFF-MPNN), is provided as an interface in an atomic simulation environment (ASE) with which the original ReaxFF and ReaxFF-MPNN potential models can do MD simulations and geometry optimizations within the ASE. Furthermore, machine learning, based on an active learning algorithm and gradient optimizer, is designed to train the model. We found that the active learning machine not only saves the manual work to collect the training data but is also much more effective than the general optimizer.

LncRNA PITPNA-AS1 as a Potential Diagnostic Marker and Therapeutic Target Promotes Hepatocellular Carcinoma Progression via Modulating miR-448/ROCK1 Axis.

Background: Long non-coding RNAs are critical to hepatocellular carcinoma (HCC) developments. LncRNA PITPNA antisense RNA 1 (PITPNA-AS1) is a new regulator in several tumors. However, the mechanism by which PITPNA-AS1 mediates the tumorigenesis of HCC remains unclear. Methods: RT-qPCR was used to detect the level of PITPNA-AS1 in HCC specimens and cells. The biological functions of PITPNA-AS1 were explored by several functional experiments in vivo and in vitro. The binding relationship among PITPNA-AS1, miR-448 and ROCK1 were studied by Luciferase assay and pull-down assays. Results: We found that PITPNA-AS1 expressions were distinctly upregulated in both HCC specimens and cell lines. High PITPNA-AS1 levels were an unfavorable biomarker for patients with HCC. Functionally, knockdown of PITPNA-AS1 suppressed the proliferation, migration and invasion of HCC cells. Mechanistically, PITPNA-AS1 functioned as competing endogenous RNA to increase ROCK1 expressions via sponging miR-448. Conclusion: The newly identified PITPNA-AS/miR-448/ROCK1 axis promoted the oncogenicity of HCC cells. This novel axis is likely to be a promising HCC therapeutic aim.

An enzymatic on/off switch-mediated assay for KRAS hotspot point mutation detection of circulating tumor DNA.

BACKGROUND: To detect the mutations of KRAS gene in colorectal cancer patients and other cancer patients, it is of value to develop non-invasive, sensitive, specific, easy, and low-cost assays. METHODS: Templates harboring hotspot mutations of the KRAS gene were constructed, and primers were designed for evaluation of the specificity, and sensitivity of detection system consisted of exonuclease polymerase-mediated on/off switch; then, gel electrophoresis and real-time PCR were performed for verification. The assay was verified by testing the DNA pool of normal controls and circulating DNA (ctDNA) samples from 14 tumor patients, as compared to Sanger sequencing. RESULTS: A specific and sensitive assay consisted of exonuclease polymerase-mediated on/off switch, and multiplex real-time PCR method has been established. This assay could detect <100 copies of KRAS mutation in more than 10 million copies of wild-type KRAS gene fragments. This assay was applied to test KRAS gene mutations in three cases of fourteen ctDNA samples, and the results were consistent with Sanger sequencing. However, this PCR-based assay was more sensitive and easier to be interpreted. CONCLUSION: This assay can detect the presence of KRAS hotspot mutations in clinical circulating tumor DNA samples. The assay has a potential to be used in early diagnosis of colorectal cancer as well as other types of cancer.

Biosynthesis of an anti-tuberculosis sesterterpenoid asperterpenoid A.

A putative three-gene cluster for asperterpenoid A was identified. Step-wise reconstitution of this gene cluster in Aspergillus oryzae reveals that astC encodes a sesterterpene cyclase to synthesize preasperterpenoid A, which is dually oxidized by a P450 enzyme AstB to give asperterpenoid A along with a minor product asperterpenoid B, and asperterpenoid A is further oxidized by another P450 eznyme AstA to afford a new sesterterpenoid asperterpenoid C. Unexpectedly, asperterpenoids A and B, but not the final product asperterpenoid C, exhibit potent inhibitory activity against Mycobacterium tuberculosis protein tyrosine phosphatase B with IC50 values of 3-6 µM.

Parental Effect of Long Acclimatization on Thermal Tolerance of Juvenile Sea Cucumber Apostichopus japonicus.

To evaluate the thermal resistance of marine invertebrates to elevated temperatures under scenarios of future climate change, it is crucial to understand parental effect of long acclimatization on thermal tolerance of offspring. To test whether there is parental effect of long acclimatization, adult sea cucumbers (Apostichopus japonicus) from the same broodstock were transplanted southward and acclimatized at high temperature in field mesocosms. Four groups of juvenile sea cucumbers whose parents experienced different durations of high temperature acclimatization were established. Upper thermal limits, oxygen consumption and levels of heat shock protein mRNA of juveniles was determined to compare thermal tolerance of individuals from different groups. Juvenile sea cucumbers whose parents experienced high temperature could acquire high thermal resistance. With the increase of parental exposure duration to high temperature, offspring became less sensitive to high temperature, as indicated by higher upper thermal limits (LT50), less seasonal variations of oxygen consumption, and stable oxygen consumption rates between chronic and acute thermal stress. The relatively high levels of constitutive expression of heat-shock proteins should contribute to the high thermal tolerance. Together, these results indicated that the existence of a parental effect of long acclimatization would increase thermal tolerance of juveniles and change the thermal sensitivity of sea cucumber to future climate change.

Electrical properties and behaviors of cuprous oxide cubes under high pressure.

An accurate in situ electrical resistivity measurement of cuprous oxide cubes has been conducted in a diamond anvil cell at room temperature with pressures up to 25 GPa. The abnormal electrical resistivity variation found at 0.7-2.2 GPa is attributed to the phase transformation from a cubic to a tetragonal structure. Three other discontinuous changes in the electrical resistivity are observed around 8.5, 10.3, and 21.6 GPa, corresponding to the phase transitions from tetragonal to pseudocubic to hexagonal to another hexagonal phase, respectively. The first-principles calculations illustrate that the electrical resistivity decrease of the tetragonal phase is not related to band-gap shrinkage but related to a higher quantity of electrons excited from strain-induced states increasing in band gap with increasing pressure. The results indicate that the Cu(2)O cubes begin to crush at about 15 GPa and completely transform into nanocrystalline at 25 GPa.

Physiological responses in a variable environment: relationships between metabolism, hsp and thermotolerance in an intertidal-subtidal species.

Physiological responses to temperature reflect the evolutionary adaptations of organisms to their thermal environment and the capability of animals to tolerate thermal stress. Contrary to conventional metabolism theory, increasing environmental temperatures have been shown to reduce metabolic rate in rocky-eulittoral-fringe species inhabiting highly variable environments, possibly as a strategy for energy conservation. To study the physiological adaptations of an intertidal-subtidal species to the extreme and unpredictable heat stress of the intertidal zone, oxygen consumption rate and heat shock protein expression were quantified in the sea cucumber Apostichopus japonicus. Using simulate natural temperatures, the relationship between temperature, physiological performance (oxygen consumption and heat shock proteins) and thermotolerance were assessed. Depression of oxygen consumption rate and upregulation of heat shock protein genes (hsps) occurred in sequence when ambient temperature was increased from 24 to 30°C. Large-scale mortality of the sea cucumber occurred when temperatures rose beyond 30°C, suggesting that the upregulation of heat shock proteins and mortality are closely related to the depression of aerobic metabolism, a phenomenon that is in line with the concept of oxygen- and capacity-limited thermal tolerance (OCLTT). The physiologically-related thermotolerance of this sea cucumber should be an adaptation to its local environment.

[Shistosoma japonicum: dynamics of cytokine production induced by immunization of mice with recombinant GST-Sj32 protein before and after challenge infection].

AIM: To explore the mechanism of protective immunity of rGST-Sj32. METHODS: BALB/c mice were immunized subcutaneously with rGST-Sj32 emulsified with Freund's complete adjuvant. Five mice from each group were killed prior to immunization, prior to challenge and 10 days, 30 days and 45 days post-challenge, respectively. Spleen cells from these mice were cultured and levels of cytokine secreted by splenocytes were detected by ELISA. RESULTS: Compared with the control group, the quantity of IL-4, IL-5 and IFN-gamma released from rGST-Sj32-primed splenocytes were increased to varying degrees, being (10.21+/-3.65) ng/L, (19.89+/-9.57) ng/L and (5.09+/-2.51) microg/L, respectively. The level of IFN-gamma post challenge did not increase in control group and immunization group. The levels of IL- 4 and IL-5 in the control group were elevated gradually following challenge, and were much higher than those in immunization group. CONCLUSION: The immunization with rGST-Sj32 elicited mainly a Th1 type immune response in BALB/c mice, whereas the immune response induced by challenge was a Th2 type.

Cloning, expression and immunization of the new antigen gene Sj-Ts4 of Schistosoma japonicum.

In order to explore the molecular mechanism of high immune protection against schistosomes infection in animals infected with Trichinella spiralis, and to provide several cross-protective antigen genes for developing anti-schistosomiasis vaccine, a Schistosoma japonicum adult worm cDNA library was immunoscreened using sera taken from mice infected with Trichinella spiralis. Nine positive clones were obtained after 3 rounds of immunoscreening. Among them, Sj-Ts4 represents a novel gene of S. japonicum, which coding for a novel protein of 210 amino acids. The protein has a deduced molecular mass of 23 kD and isoelectric point of 7.72. Sj-Ts4 was expressed as a glutathione-S-transferase (GST) fusion protein by cloning into the prokaryotic expression vector pGEX-5X-3. The recombinant Sj-Ts4 protein (rSj-Ts4) was purified and could be recognized by sera of mice infected with S.japonicum. Vaccination of several groups of mice with rSj-Ts4 or rSj-Ts4 incorporated into Freund's complete adjuvant induced high titers of specific IgG antibodies. Two vaccination groups all obtained significant reduction in worm burden (31.36%, 36.80%, P<0.01), compared with the control groups.