[Analysis of safety and efficacy of laparoscopic surgery for gallbladder carcinoma].

Objective: To examine the efficacy and safety of laparoscopic surgery for gallbladder carcinoma. Methods: The data of 197 gallbladder carcinoma patients admitted at Peking Union Medical College Hospital between January 2012 and September 2022 were analyzed retrospectively. There were 86 males and 111 females,with age of (64.4±9.8)years(range:35 to 89 years). Patients were divided into laparoscopic group(n=53) and open group(n=144) according to different surgical methods. The general information of the two groups were matched by propensity score matching,and the clinical data and prognosis were compared between the two groups. Categorical variables were analyzed using χ2 test or Fisher's exact test,as appropriate. Continuous variables with and without normal distribution were analyzed using t-test and Mann-Whitney U test,respectively. Kaplan-Meier curves with Log-rank test were used to analyze the cumulative survival rates. Results: Forty-eight pairs of patients were matched successfully. There was no difference in general information,cholecystolithiasis,partial hepatectomy,and tumor stage between two groups(all P>0.05). The laparoscopic group had shorter operation time(t=-3.987,P<0.01),less bleeding(Z=-4.862,P<0.01),shorter total(Z=-5.009,P<0.01) and postoperative(Z=-5.412,P<0.01) hospital stay. Seventeen patients had postoperative complications. According to the Clavien-Dindo system,there were 4,11,1,and 1 patient with grade Ⅰ,Ⅱ,Ⅲa,and Ⅲb,respectively. All complications were improved after active treatment. After a median follow-up of 24(36) months(range:3 to 130 months),56 patients(58.3%) survived without tumor,7 patients(7.3%) survived with tumor,and 33 patients(34.4%) died. According to the Kaplan-Meier curves,there was no significant difference between laparoscopic and open groups in disease free(χ2=0.399,P=0.528) and overall(χ2=0.672,P=0.412) survival rates. Conclusions: The laparoscopic surgery is safe and effective in selected patients with gallbladder carcinoma. It can reduce surgical trauma and enhance patient recovery without increasing complication. Its prognosis is similar to that of open surgery.

[Application of enhanced recovery after surgery in perioperative management of patients with gallbladder carcinoma].

Objective: To investigate the efficacy and safety of enhanced recovery after surgery (ERAS) in perioperative management of patients with gallbladder carcinoma. Methods: The data of the patients with gallbladder carcinoma admitted at Peking Union Medical College Hospital between January 2017 and December 2021 were analyzed retrospectively. There were 69 males(42.1%) and 95 females(57.9%),with age of (64.0±10.3) years(range:37 to 89 years). Patients were divided into ERAS group(n=53) and normal group(n=111) according to whether they were treated with ERAS measures during the perioperative period.The basic characteristics of the two groups were matched by propensity score matching,and then the perioperative information was compared between the two groups. Categorical variables were presented as absolute numbers or frequencies. Differences between study groups were analyzed using χ2 test, Fisher's exact test, t-test, or Mann-Whitney U test, as appropriate. Results: Each group had 45 patients after propensity score matching with well-balanced basic characteristics. There was no difference in basic characteristics, operation time,bleeding,complication,and hospitalization expenses between two groups(all P>0.05). Compared with the normal group,time of ambulation (M(IQR)) (1(1) day vs. 2(2) days;Z=-3.839,P<0.01),postoperative anal exhaust time (2(1) days vs. 3(1) days;Z=-3.013,P=0.003),feeding time(2(1) days vs. 2(1) days;Z=-3.647,P<0.01),postoperative (5(2) days vs. 7(4) days;Z=-3.984,P<0.01) and total(8(4) days vs. 13(6) days;Z=-3.605,P<0.01) hospitalization time were shorter in ERAS group. Postoperative complications occurred in 12 patients. According to the Clavien-Dindo classification,6,4,and 2 patients were classified as grade Ⅰ,Ⅱ,and Ⅲa,respectively. Conclusion: The ERAS measures is safe and effective for perioperative management of patients with gallbladder carcinoma, enhancing patient recovery and shortening hospitalization time without increasing complication or hospitalization cost.

[Epidemiological characteristics of amoebic dysentery in China, 2015-2018].

Objective: To understand the characteristics and changes of the incidence of amoebic dysentery in China during 2015-2018, explore the causes of high incidence in some areas and provide a data base for the development of national prevention and control strategies and measures. Methods: Data were collected from the infectious disease reporting management information system from Chinese Disease Control and Prevention. To understand the seasonal, population and area distributions of amoebic dysentery, descriptive epidemiological method and software SPSS 16.0 were used to analyze the amoebic dysentery data. Results: A total of 4 366 amoebic dysentery cases were reported without death in China during 2015-2018. The reported average annual incidence was 0.08/100 000, and the overall proportion of laboratory confirmed cases was 68.23%(2 979/4 366). Amoeba dysentery mainly occurred during May to October. One seasonal peak was observed in 2015 and 2017 (July and June, respectively), and two seasonal peaks were observed in 2016 and 2018 (June and October). The patients were mainly children aged under 5 years (42.28%, 1 846/4 366), and the incidence rate decreased with age in children aged under 10 years. Of these, children under 1 years of age had the highest incidence rate (1.28/100 000). The number of cumulative reported cases in Guangxi, Henan, Guangdong, Heilongjiang and Jiangxi provinces ranked top five from 2015-2018, accounting for 64.50% (2 816/4 366) of the total. The cumulative cases in Dongxing county, Guangxi, in Suixian county, Henan and in Ranghulu district, Heilongjiang, respectively accounted for more than 50.00% of the total number of cases in their provinces. Conclusions: The incidence rate of amoebic dysentery reported in China during 2015-2018 showed a decreasing trend, with a higher incidence in children under 5 years old and a higher number of cases in some areas. It is suggested to further investigate and analyze the diagnosis and reporting of amoeba dysentery in key areas and promote the update of the diagnostic standards for amoeba dysentery.

Hsa-miR-203 inhibits fracture healing via targeting PBOV1.

OBJECTIVE: To explore the role of hsa-miR-203 in fracture healing and its underlying mechanism. PATIENTS AND METHODS: Expression levels of hsa-miR-203 and PBOV1 in patients with hand fractures and intra-articular fractures after treatment were detected by quantitative Real-Time-Polymerase Chain Reaction (qRT-PCR). Viability and apoptosis of osteoblast cell line hFOB1.19 after hsa-miR-203 overexpression or knockdown were detected by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. The target gene of hsa-miR-203 was predicted by bioinformatics and verified by dual-luciferase reporter gene assay. Rescue experiments were conducted to further verify whether hsa-miR-203 could participate in fracture healing via PBOV1. RESULTS: No significant hsa-miR-203 expression was found in patients with hand fractures and intra-articular fractures after treatment for 7 days, which was remarkably upregulated on the 14th day. PBOV1 expression was gradually downregulated as treatment time prolongation. Overexpression of hsa-miR-203 decreased cell viability, but induced apoptosis of hFOB1.19 cells. Bioinformatics predicted that PBOV1 might be the target gene of hsa-miR-203, which was further verified by dual-luciferase reporter gene assay. The effect of hsa-miR-203 on viability and apoptosis of hFOB1.19 cells was reversed after the PBOV1 knockdown. CONCLUSIONS: Hsa-miR-203 inhibits fracture healing by regulating osteoblast viability and apoptosis via targeting PBOV1.

miR-485-5p promotes osteoporosis via targeting Osterix.

OBJECTIVE: To investigate the effect and related mechanisms of miR-485-5p on the osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs). PATIENTS AND METHODS: The expression level of miR-485-5p was detected in clinical cases and during the osteogenic differentiation. Three group were established to study the potential function between miR-485-5p and osteogenic differentiation: miR-NC group (negative control), miR-485-5p mimics (BMSCs transfected by miR-485-5p mimics), and mimics + si-Osx (BMSCs transfected by miR-485-5p mimics and si-Osx), after the induction of osteogenic differentiation, the cell viability of BMSCs and osteogenic markers were determined. RESULTS: In our work, miR-485-5p was found up-regulated in patients with osteoporosis by comparing with health cases. Besides, during osteogenic differentiation, miR-485-5p was suppressed. These results suggest miR-485-5p has a negative regulating effect. To research potential target of miR-485-5p, we checked it in three publicly available algorithms, TargetScan, miRDB and microRNA. We found that Osterix (Osx) is a direct target of miR-485-5p, and Luciferase assays confirmed our hypothesis, the subsequent experiments showed that decreased expression of Osx resulting from the up-regulation of miR-485-5p could restrain the cell viability and the expression level of osteogenic markers CONCLUSIONS: Our research revealed the promote function of miR-485-5p on osteoporosis, indicating that miR-485-5p could be a potential therapeutic strategy for the treatment of osteoporosis.

[Epidemiological characteristics of Kala-azar disease in China, during 2005-2015].

Objective: To explore the epidemiological characteristics of Kala-azar disease in China from 2005 to 2015, to provide evidence for the development of related control and measurement strategies. Methods: Data was obtained from Disease Reporting Information System of China CDC, to compare factors on type, distribution, peak season and the age of onset of the cases. Results: Epidemic of Kala-azar had been persistent in China. Number of the reported cases declined in Sichuan and Gansu provinces but two outbreaks had occurred in Xinjiang Uygur autonomous region. The epidemic was confined in few areas. The reported cases were mainly from Xinjiang, Gansu and Sichuan, with the total cases in these three provinces accounted for 95.29% of all the cases seen in the country. The main peak season was from October to November, followed by April. There were significant differences seen in the age distributions of canine Kala-azar, anthroponotic Kala-azar and wildlife-oriented Kala-azar (P<0.05) cases. Majority of the cases involved under 3-year-olds, with peak age in under 1-year-olds for wildlife-oriented Kala-azar. For anthroponotic and canine Kala-azar cases, most of them were seen among the under 10 years old, with the peak among the 5-year-olds. Conclusions: In recent years,Kala-azar had been seen endemic and persistent, in the mid-west regions of China, but with different epidemiological characteristics. Further study on Kala-azar should be carried on to include appropriate measurements and strategies, according to the features of the disease, in the mid-western areas of China.

Outbreak of Occupational Brucellosis at a Pharmaceutical Factory in Southeast China.

Brucellosis is an occupational disease affecting workers in butcher shops, the milking and dairy product industry, causing more than 500 000 new cases around the world. As a national statutory B infectious disease in China, morbidity of brucellosis is rapidly increasing in recent years. We report an occupational outbreak of brucellosis infection in a pharmaceutical factory. Exposure was a result of manual operation in the process line, close contact with sheep placentas, insufficient disinfection and repeated using of protective suits and infected by aerosol dissemination. Improved preventive methods, appropriate public health measures and spread of health education would be helpful to prevent the occupational outbreak of brucellosis in future.

Synergistic therapeutic actions of herbal ingredients and their mechanisms from molecular interaction and network perspectives.

Opinions about the therapeutic efficacy of medicinal herbs differ significantly. Some reported herbal efficacies at low doses of active ingredients suggest a need for investigating whether these are because of placebo or multi-ingredient synergistic effects. This review discusses the opinions, methods and outcomes of herbal synergism investigations and analyzes indications from 48 in vivo tests and 106 rigorous clinical trials. Analyses of ingredient-mediated interactions at molecular and pathway levels indicate multi-ingredient synergism in 27 of the 39 reported cases of herbal synergism with available ingredient information. Synergistic actions may be responsible for the therapeutic efficacy of a substantial number of herbal products and their mechanisms may be studied by analyzing ingredient-mediated molecular interactions and network regulation.

Bioactivity-guided fractionation for analgesic properties and constituents of Vitex negundo L. seeds.

This study was undertaken to ascertain the analgesic properties of Vitex negundo L. seeds and to isolate and characterize the active constituents. Among the 80% ethanol extract and some fractions with different polarity, the acetoacetate fraction showed the highest anti-nociceptive activity in acetic acid-induced writhing test in ICR mice. The analgesic bioguided isolation of the acetoacetate fraction yielded two major lignans: 6-hydroxy-4-(4-hydroxy-3-methoxy-phenyl)-3-hydroxymethyl-7-methoxy-3,4-dihydro-2-naphthaldehyde (1) and vitedoamine A (2). Given orally, compound (1), which was more productive, produced significant inhibitions on chemical nociception induced by intraperitoneal acetic acid and subplantar formalin injections and exhibited notable anti-inflammatory activities in dimethyl benzene-induced ear edema test in a dose-dependent manner. Since co-administration of naloxone fails to antagonize the analgesic activity of compound (1) in the formalin test, we suggest that compound (1) possesses potent analgesic effects which are most likely to be mediated by its anti-inflammatory activity rather than through opioid receptor system and therefore could partially explain the anti-nociceptive effect of V. negundo L. seeds.

Trends in the exploration of anticancer targets and strategies in enhancing the efficacy of drug targeting.

A number of therapeutic targets have been explored for developing anticancer drugs. Continuous efforts have been directed at the discovery of new targets as well as the improvement of therapeutic efficacy of agents directed at explored targets. There are 84 and 488 targets of marketed and investigational drugs for the treatment of cancer or cancer related illness. Analysis of these targets, particularly those of drugs in clinical trials and US patents, provides useful information and perspectives about the trends, strategies and progresses in targeting key cancer-related processes and in overcoming the difficulties in developing efficacious drugs against these targets. The efficacy of anticancer drugs directed at these targets is frequently compromised by counteractive molecular interactions and network crosstalk, negative and adverse secondary effects of drugs, and undesired ADMET profiles. Multi-component therapies directed at multiple targets and improved drug targeting methods are being explored for alleviating these efficacy-reducing processes. Investigation of the modes of actions of these combinations and targeting methods offers clues to aid the development of more effective anticancer therapies.

Trends in the exploration of therapeutic targets for the treatment of endocrine, metabolic and immune disorders.

A number of therapeutic targets have been explored for developing drugs in the treatment of endocrine, metabolic and immune disorders. Continuous efforts and increasing interest have been directed at the search of new targets. Data from the therapeutic target database at http://bidd.nus.edu.sg/group/cjttd/ttd.asp, shows that there are 26, 24, and 22 targets of marketed drugs for the treatment of these three classes of diseases, respectively. The number of targets of investigational agents has reached 98, 124, and 72, respectively. An analysis of these targets, particularly those of recently approved drugs and patented investigational agents, provides useful hint about the general trends of target exploration, with current focus on drug discovery and the difficulties encountered in developing drugs against these targets. Multiple profiles of these targets have been analyzed to probe the sequence, structural, physicochemical and systems-related features contributing to the successful exploration of a target against these diseases.

Occupational medicine physicians in the United States: demographics and core competencies.

OBJECTIVE: We assessed the demographic profile and opinions of current occupational medicine (OM) physicians on the importance of specific core competencies. METHODS: A random sample of 1500 OM physicians listed in the membership directory of the American College of Occupational and Environmental Medicine (ACOEM) were asked to complete a voluntary survey. RESULTS: Six hundred and ten OM physicians completed the survey. Fifty two percent worked in clinical settings, and 16% worked in corporate or industrial settings. Eighty percent were satisfied with their choice of careers. CONCLUSIONS: OM physicians appeared to be highly trained, with 60% certified in OM and 68% board certified in other specialties. The OM physicians valued staying current in the field, understanding the relationship between occupational exposure and health, and communicating with stakeholders most highly. Occupational physicians are an important source of knowledge regarding what competencies and core knowledge areas are important for OM practice.

Prediction of MHC-binding peptides of flexible lengths from sequence-derived structural and physicochemical properties.

Peptide binding to MHC is critical for antigen recognition by T-cells. To facilitate vaccine design, computational methods have been developed for predicting MHC-binding peptides, which achieve impressive prediction accuracies of 70-90% for binders and 40-80% for non-binders. These methods have been developed for peptides of fixed lengths, for a limited number of alleles, trained from small number of non-binders, and in some cases based straightforwardly on sequence. These limit prediction coverage and accuracy particularly for non-binders. It is desirable to explore methods that predict binders of flexible lengths from sequence-derived physicochemical properties and trained from diverse sets of non-binders. This work explores support vector machines (SVM) as such a method for developing prediction systems of 18 MHC class I and 12 class II alleles by using 4208-3252 binders and 234,333-168,793 non-binders, and evaluated by an independent set of 545-476 binders and 110,564-84,430 non-binders. Binder accuracies are 86-99% for 25 and 70-80% for 5 alleles, non-binder accuracies are 96-99% for 30 alleles. Binder accuracies are comparable and non-binder accuracies substantially improved against other results. Our method correctly predicts 73.3% of the 15 newly-published epitopes in the last 4 months of 2005. Of the 251 recently-published HLA-A*0201 non-epitopes predicted as binders by other methods, 63 are predicted as binders by our method. Screening of HIV-1 genome shows that, compared to other methods, a comparable percentage (75-100%) of its known epitopes is correctly predicted, while a lower percentage (0.01-5% for 24 and 5-8% for 6 alleles) of its constituent peptides are predicted as binders. Our software can be accessed at .

PharmGED: Pharmacogenetic Effect Database.

Prediction and elucidation of pharmacogenetic effects is important for facilitating the development of personalized medicines. Knowledge of polymorphism-induced and other types of drug-response variations is needed for facilitating such studies. Although databases of pharmacogenetic knowledge, polymorphism and toxicogenomic information have appeared, some of the relevant data are provided in separate web-pages and in terms of relatively long descriptions quoted from literatures. To facilitate easy and quick assessment of the relevant information, it is helpful to develop databases that provide all of the information related to a pharmacogenetic effect in the same web-page and in brief descriptions. We developed a database, Pharmacogenetic Effect Database (PharmGED), for providing sequence, function, polymorphism, affected drugs and pharmacogenetic effects. PharmGED can be accessed at http://bidd.cz3.nus.edu.sg/phg/ free of charge for academic use. It currently contains 1825 entries covering 108 disease conditions, 266 distinct proteins, 693 polymorphisms, 414 drugs/ligands cited from 856 references.

Therapeutic targets: progress of their exploration and investigation of their characteristics.

Modern drug discovery is primarily based on the search and subsequent testing of drug candidates acting on a preselected therapeutic target. Progress in genomics, protein structure, proteomics, and disease mechanisms has led to a growing interest in and effort for finding new targets and more effective exploration of existing targets. The number of reported targets of marketed and investigational drugs has significantly increased in the past 8 years. There are 1535 targets collected in the therapeutic target database compared with approximately 500 targets reported in a 1996 review. Knowledge of these targets is helpful for molecular dissection of the mechanism of action of drugs and for predicting features that guide new drug design and the search for new targets. This article summarizes the progress of target exploration and investigates the characteristics of the currently explored targets to analyze their sequence, structure, family representation, pathway association, tissue distribution, and genome location features for finding clues useful for searching for new targets. Possible "rules" to guide the search for druggable proteins and the feasibility of using a statistical learning method for predicting druggable proteins directly from their sequences are discussed.

Prediction of compounds with specific pharmacodynamic, pharmacokinetic or toxicological property by statistical learning methods.

Computational methods for predicting compounds of specific pharmacodynamic, pharmacokinetic, or toxicological property are useful for facilitating drug discovery and drug safety evaluation. The quantitative structure-activity relationship (QSAR) and quantitative structure-property relationship (QSPR) methods are the most successfully used statistical learning methods for predicting compounds of specific property. More recently, other statistical learning methods such as neural networks and support vector machines have been explored for predicting compounds of higher structural diversity than those covered by QSAR and QSPR. These methods have shown promising potential in a number of studies. This article is intended to review the strategies, current progresses and underlying difficulties in using statistical learning methods for predicting compounds of specific property. It also evaluates algorithms commonly used for representing structural and physicochemical properties of compounds.

Prediction of the functional class of lipid binding proteins from sequence-derived properties irrespective of sequence similarity.

Lipid binding proteins play important roles in signaling, regulation, membrane trafficking, immune response, lipid metabolism, and transport. Because of their functional and sequence diversity, it is desirable to explore additional methods for predicting lipid binding proteins irrespective of sequence similarity. This work explores the use of support vector machines (SVMs) as such a method. SVM prediction systems are developed using 14,776 lipid binding and 133,441 nonlipid binding proteins and are evaluated by an independent set of 6,768 lipid binding and 64,761 nonlipid binding proteins. The computed prediction accuracy is 78.9, 79.5, 82.2, 79.5, 84.4, 76.6, 90.6, 79.0, and 89.9% for lipid degradation, lipid metabolism, lipid synthesis, lipid transport, lipid binding, lipopolysaccharide biosynthesis, lipoprotein, lipoyl, and all lipid binding proteins, respectively. The accuracy for the nonmember proteins of each class is 99.9, 99.2, 99.6, 99.8, 99.9, 99.8, 98.5, 99.9, and 97.0%, respectively. Comparable accuracies are obtained when homologous proteins are considered as one, or by using a different SVM kernel function. Our method predicts 86.8% of the 76 lipid binding proteins nonhomologous to any protein in the Swiss-Prot database and 89.0% of the 73 known lipid binding domains as lipid binding. These findings suggest the usefulness of SVMs for facilitating the prediction of lipid binding proteins. Our software can be accessed at the SVMProt server (http://jing.cz3.nus.edu.sg/cgi-bin/svmprot.cgi).

PEARLS: program for energetic analysis of receptor-ligand system.

Analysis of the energetics of small molecule ligand-protein, ligand-nucleic acid, and protein-nucleic acid interactions facilitates the quantitative understanding of molecular interactions that regulate the function and conformation of proteins. It has also been extensively used for ranking potential new ligands in virtual drug screening. We developed a Web-based software, PEARLS (Program for Energetic Analysis of Ligand-Receptor Systems), for computing interaction energies of ligand-protein, ligand-nucleic acid, protein-nucleic acid, and ligand-protein-nucleic acid complexes from their 3D structures. AMBER molecular force field, Morse potential, and empirical energy functions are used to compute the van der Waals, electrostatic, hydrogen bond, metal-ligand bonding, and water-mediated hydrogen bond energies between the binding molecules. The change in the solvation free energy of molecular binding is estimated by using an empirical solvation free energy model. Contribution from ligand conformational entropy change is also estimated by a simple model. The computed free energy for a number of PDB ligand-receptor complexes were studied and compared to experimental binding affinity. A substantial degree of correlation between the computed free energy and experimental binding affinity was found, which suggests that PEARLS may be useful in facilitating energetic analysis of ligand-protein, ligand-nucleic acid, and protein-nucleic acid interactions. PEARLS can be accessed at http://ang.cz3.nus.edu.sg/cgi-bin/prog/rune.pl.