[The efficacy and safety of laparoscopic radical gastrectomy after neoadjuvant chemotherapy combined with immunotherapy and targeted therapy].

Objectives: To explore the efficacy and safety of laparoscopic radical gastrectomy after neoadjuvant chemotherapy combined with immunotherapy and targeted therapy in patients with gastric cancer. Methods: A retrospective analysis of clinical and pathological data of 20 patients with locally advanced gastric cancer (clinical TNM stage T3-4aN+M0) admitted to the Cancer Hospital, Chinese Academy of Medical Sciences from July 2021 to July 2023. All patients received 3 cycles of SOX (Oxaliplatin+S-1) regimen combined with immunotherapy (Trastuzumab) and targeted therapy (Apatinib) as neoadjuvant treatment followed by laparoscopic radical gastrectomy for gastric cancer. Surgical outcomes, postoperative pathological response, and postoperative recovery were observed. Quantitative data, except for age and operation time, were expressed using Median (range). Results: Among the 20 patients, there were 18 males and 2 females, aged 41 to 73 years [(60.6±9.7) years]. All 20 patients underwent laparoscopic surgical treatment after neoadjuvant therapy, with one patient undergoing laparoscopic conversion to open total gastrectomy with partial transverse colon resection due to tumor invasion into the transverse mesocolon. Eight patients underwent totally laparoscopic radical gastrectomy, all with Billroth Ⅱ+Braun anastomosis at the distal stomach. Eleven patients underwent laparoscopic-assisted radical gastrectomy, among which total gastrectomy with Roux-en-Y anastomosis was performed in ten cases, and proximal gastrectomy with esophagogastrostomy overlap anastomosis was performed in one case. The mean operation time for the 20 patients was (165.0±34.1) minutes; intraoperative blood loss was 80 (20-100) ml; and the number of lymph nodes retrieved was 68 (21-89). Postoperative pathological TNM staging revealed stage T0N0M0 in six cases, stage Ⅰ in two cases, stage Ⅱ in three cases, and stage Ⅲ in nine cases. Six patients (30.0%) achieved pathological complete response, and nine patients (45.0%) achieved significant pathological response. The median postoperative time to flatus was 4 (1-5) days; oral intake resumed after 3 (2-5) days; and the median length of hospital stay was 13 (6-19) days. One patient developed colonic anastomotic leakage with intra-abdominal infection, and one patient developed duodenal stump leakage with intra-abdominal infection, both classified as Clavien-Dindo grade 3A complications, and improved after treatment and discharged. One patient developed gastric paresis, and two patients developed pleural effusion, classified as Clavien-Dindo grade 2 complications, and improved after treatment and discharged. There were no deaths within 30 days after discharge. Conclusions: Laparoscopic radical gastrectomy for gastric cancer after neoadjuvant treatment with the SOX regimen combined with immunotherapy and targeted therapy is safe and feasible, with satisfactory short-term efficacy. However, there is an increase in overall surgical risk and difficulty, and it is recommended to be performed in experienced gastric cancer centers.

[The clinical value of totally laparoscopic stomach-partitioning gastrojejunostomy for malignant gastric outlet obstruction].

Objective: To explore the clinical value of totally laparoscopic stomach-partitioning gastrojejunostomy (TLSPGJ) for malignant gastric outlet obstruction. Methods: The clinical data of 9 gastric cancer patients who underwent TLSPGJ in Department of Pancreatic and Gastric Surgery, Cancer Hospital between September 2018 and September 2019 were retrospectively analyzed. Results: The mean operative blood loss of 9 cases were (13.3±5.0) ml, and the average operative time was (103.3±10.6) min. All patients received clear flow food on the first day after surgery. Postoperative first exhaust time was (3.1±0.8) days and the average postoperative hospital stay was (5.4±1.1) days. All of the 9 patients could tolerate semi-liquid food at discharge, and no postoperative complications such as bleeding or delayed gastric emptying occurred. Conclusion: TLSPGJ is an effective treatment for gastric output tract obstruction caused by malignant tumor.

[Comparison of short-term clinical outcome between laparoscopic distal pancreatectomy and open distal pancreatectomy].

Objective: To compare the short-term clinical effect between laparoscopic distal pancreatectomy (LDP) and open distal pancreatectomy (ODP). Methods: We performed a retrospective study on 161 patients who underwent pancreatectomy between September 2017 to December 2018 in the Department of Pancreatic and Gastric Surgery, Cancer Hospital of Chinese Academy of Medical Sciences. According to the mode of operation, the patients were divided into the LDP group (n=43) and the ODP group (n=118). To compare the short-term clinical effect and safety between the LDP group and the ODP group, the preoperative clinical data, intraoperative related index, postoperative complication, postoperative recovery index, preoperative and postoperative inflammatory index were analyzed. Results: The preoperative clinical characteristics between the LDP group and the ODP group were not statistically different (P>0.05). The intraoperative blood loss in LDP group was (194.19±241.83) ml, significantly less than (315.17±295.94) ml in ODP group (P<0.05), and the postoperative exhaust time in LDP group was (3.00±0.72) days, significantly shorter than (4.05±0.97) days in OPD group (P<0.001). The time to get out of bed in LDP group was (3.14±1.01) days, significantly shorter than (3.55±1.05) days in OPD group (P<0.05). The postoperative eating time in LDP group was (3.88±1.61) days, significantly shorter than (5.11±1.56) days in ODP group (P<0.001). The time of the drainage tube removal in LDP group was (8.44±1.93) days, significantly shorter than (9.82±3.70) days in ODP group (P<0.05). The postoperative hospital stay in LDP group was (9.65±3.57) days, significantly shorter than (11.99±6.57) days in ODP group (P<0.05). The mean operation time in LDP group was (168.65±55.45) min, shorter than (171.23±65.61) min in ODP group, but without significant difference (P>0.05). The incidences of non-pancreatic fistula-related complications in LDP group and ODP group were 16.3% and 11.0%, respectively, without statistical significance (P>0.05). The incidences of pancreatic fistula in LDP group and ODP group were 16.3% and 19.5%, respectively, without statistical significance (P>0.05). The total incidences of complications in LDP group and ODP group were 32.6% and 30.5%, respectively, without statistical significance (P>0.05). The preoperative and postoperative inflammatory indexes between these two groups were not statistically different (P>0.05). Conclusions: Compared with ODP, LDP has the advantages of less intraoperative blood loss, faster postoperative recovery, shorter postoperative hospital stays, without increased postoperative complications and prolonged operation time. LDP is a safe and feasible operation method, and its short-term clinical effect is better than that of ODP.

LncRNA SNHG7 is an Oncogenic Biomarker Interacting with MicroRNA-193b in Colon Carcinogenesis.

BACKGROUND: The expression and significance of small nucleolar RNA host gene 7 (SNHG7) in early-stage colon carcinogenesis remains unclear. METHODS: The level of SNHG7 and microRNA-193b (miR-193b) was detected by qRT-PCR in colon tumor tissues and cells. The interaction of SNHG7 and miR-193b and the influence of SNHG7 silencing on colon tumor cells was evaluated. RESULTS: Stepwise upregulated SNHG7 in colon advanced adenomas and early-stage cancer negatively correlates with miR-193b level, the direct interaction was confirmed in vitro. SNHG7 silencing in HT29 cells decreased proliferation and promoted apoptosis by inhibiting K-ras/ERK/cyclinD1. CONCLUSIONS: SNHG7 is an oncogenic biomarker in colon carcinogenesis. The effect may be mediated by interaction with miR-193b.

[Comparison of short-term outcomes of laparoscopy-assisted and totally laparoscopic distal gastrectomy for gastric cancer].

Objective: To assess the safety, feasibility and short-term outcome of totally laparoscopic distal gastrectomy(TLDG). Methods: Seventy-five patients who underwent laparoscopic distal gastrectomy in Cancer Hospital of Chinese Academy of Medical Science between August 2015 and April 2018 were enrolled in this study. A total of 46 laparoscopy-assisted distal gastrectomy (LADG) cases and 29 TLDG cases were included. The Short-term outcomes and safeties of the two groups were compared. Results: The operation time of TLDG group was significantly longer than that of LADG group (207±41 vs. 156±34 min, P<0.001), while the length of wound was shorter in the TLDG group (3.6±0.6 vs. 5.8±0.8 cm, P<0.001). The time to first flatus in TLDG group was (3.3±0.6) days, significantly shorter than (3.7±0.8) days in LADG group (P=0.034). There were no significant differences between the two groups in the estimated blood loss, intraoperative blood transfusion, extraction of gastric tube, drainage tube removal, interval of the first time to eat semi-liquid food, postoperative hospital stays, surgical complications, number of retrieved lymph nodes, proximal and distal resection margin lengths (all P>0.05). The white blood cell count at postoperative day 1 in the TLDG group was (10.96±1.96) ×10(9)/L, significantly lower than (12.49±3.46)×10(9)/L of the LADG group (P=0.017). While the CRP level at postoperative day 1 in the TLDG group were lower than that of LADG group, no statistical difference was observed (P=0.072). Conclusions: Our study shows that TLDG is safe and feasible. TLDG has better cosmesis, less blood loss, and faster recovery compared to LADG.

Occurrence and significance of elevated D-dimer levels in different types of osteomyelitis: a clinical study.

OBJECTIVE: Plasma D-dimer levels >0.5 mg/L are encountered in various conditions besides venous thromboembolism (VTE). Recent studies use them as a prognostic indicator for systemic and inflammatory diseases. The clinical significance of abnormal levels is unclear in osteomyelitis patients with baseline elevation. Our study reviews the occurrence and significance of >0.5 mg/L D-dimer levels in different types of osteomyelitis. PATIENTS AND METHODS: This study involved 125 individuals, out of which 94 were male and 31 were female. The patients were divided into two groups based on the results of bacterial culture testing. Group A comprised those who tested positive for bacterial culture, while group B included those who tested negative. Out of 68 samples tested, 56% were found to have Staphylococcus aureus. All 125 patients underwent blood testing, which included measuring the D-dimer levels, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), and MHR monocyte to high-density lipoprotein cholesterol (HDL-C) ratio in different types of osteomyelitis. The statistical analysis of these tests was carried out. RESULTS: Although there were no significant differences in white blood cell (WBC) count, Neutrophil count, Lymphocyte count, or erythrocyte sedimentation rate (ESR) as well as the NLR, PLR, LMR, MHR, HDL-C ratio. The C-reactive protein (CRP) levels were significantly higher in group A (26.13±50.30) than in group B (10.76±18.70) (p<0.05). D-dimer levels were elevated in 40.8% of patients with bacterial culture-positive osteomyelitis, negative culture osteomyelitis, implants with fractures, and no trauma osteomyelitis. No correlation was found between the increase in D-dimer levels and the presence of bacterial culture or implant-related osteomyelitis in patients. CONCLUSIONS: No significant correlation was found between D-dimers and osteomyelitis, including positive bacterial cultures, implant-related osteomyelitis, or osteomyelitis without trauma. However, 40% of the patients had higher D-dimer levels.

Cell-free DNA from bile outperformed plasma as a potential alternative to tissue biopsy in biliary tract cancer.

BACKGROUND: Biliary tract cancers (BTCs) are rare and highly heterogenous malignant neoplasms. Because obtaining BTC tissues is challenging, the purpose of this study was to explore the potential roles of bile as a liquid biopsy medium in patients with BTC. PATIENTS AND METHODS: Sixty-nine consecutive patients with suspected BTC were prospectively enrolled in this study. Capture-based targeted sequencing was performed on tumor tissues, whole blood cells, plasma, and bile samples using a large panel consisting of 520 cancer-related genes. RESULTS: Of the 28 patients enrolled in this cohort, tumor tissues were available in eight patients, and plasma and bile were available in 28 patients. Somatic mutations were detected in 100% (8/8), 71.4% (20/28), and 53.6% (15/28) of samples comprising tumor tissue DNA, bile cell-free DNA (cfDNA), and plasma cfDNA, respectively. Bile cfDNA showed a significantly higher maximum allele frequency than plasma cfDNA (P = 0.0032). There were 56.2% of somatic single-nucleotide variant (SNVs)/insertions and deletions (indels) shared between bile and plasma cfDNA. When considering the genetic profiles of tumor tissues as the gold standard, the by-variant sensitivity and positive predictive value for SNVs/indels in bile cfDNA positive for somatic mutations were both 95.5%. The overall concordance for SNVs/indels in bile was significantly higher than that in plasma (99.1% versus 78.3%, P < 0.0001). Moreover, the sensitivity of CA 19-9 combined with bile cfDNA achieved 96.4% in BTC diagnosis. CONCLUSION: We demonstrated that bile cfDNA was superior to plasma cfDNA in the detection of tumor-related genomic alterations. Bile cfDNA as a minimally invasive liquid biopsy medium might be a supplemental approach to confirm BTC diagnosis.

Theoretical analysis for photophoresis of a microscale hydrophobic particle in liquids.

In the present study, combining the conventional photothermal analysis and the concept of interaction of solvent molecules in interfacial layer used for thermophoresis in liquid, a theory for photophoresis of a hydrophobic particle suspended in liquids is developed. To characterize hydrophobicity of the micro-particle, slip length in Navier's formula is used as an index. Analytical expressions are derived and a parametric analysis for photophoretic velocity is performed with emphasis on the influences of particle characteristics such as size, optical properties, hydrophobicity, and thermal conductivity. Heat source function and the corresponding asymmetry factor at various conditions are evaluated to interpret the mechanisms of negative and positive photophoresis and the conditions for transition between them. The present theory discloses that the particle surface hydrophobicity or fluid slippage at particle-liquid interface may lead to a remarkable enhancement in the particle photophoretic velocity in liquids. Higher particle thermal conductivity and larger size of liquid molecules both result in weaker photophoretic motion.

Modified correlation entropy estimation for a noisy chaotic time series.

A method of estimating the Kolmogorov-Sinai (KS) entropy, herein referred to as the modified correlation entropy, is presented. The method can be applied to both noise-free and noisy chaotic time series. It has been applied to some clean and noisy data sets and the numerical results show that the modified correlation entropy is closer to the KS entropy of the nonlinear system calculated by the Lyapunov spectrum than the general correlation entropy. Moreover, the modified correlation entropy is more robust to noise than the correlation entropy.

MiR-129-2 weakens proliferation and promotes apoptosis of liver cancer cells by suppressing the Wnt signaling pathway.

OBJECTIVE: To explore the effects of micro ribonucleic acid-129-2 (miR-129-2) on proliferation and migration of liver cancer cells and its possible mechanism. PATIENTS AND METHODS: The expression level of miR-129-2 was measured in liver cancer tissues and adjacent tissues from patients with liver cancer. Its level in liver cancer HepG2 cells and normal liver cells L-02 was also detected via quantitative polymerase chain reaction (qPCR). MiR-192-2 overexpression model was established in the HepG2 cell line. The proliferation and apoptosis levels of cells were determined by methyl thiazolyl tetrazolium (MTT) assay and flow cytometry, respectively. Wound healing assay was performed to detect the migration ability of cells. The expressions level of genes in the Wnt signaling pathway were measured through Western blotting. Xenograft tumor model was conducted in nude mice for exploring the in vivo effects of miR-129-2 on liver cancer growth. RESULTS: The expression level of miR-129-2 was significantly lower in liver cancer tissues than that in adjacent tissues (p<0.01), and it was overtly lower in HepG2 cells than that in L-02 cells (p<0.01). Overexpression of miR-129-2 weakened proliferation and migration abilities of liver cancer cells (p<0.01), and evidently increased apoptosis level (p<0.01). Sex-determining region Y-related HMG-box 4 (Sox4) and matrix metalloproteinase-2 (MMP-2) were downregulated, while phosphorylated glycogen synthase kinase-3ß (p-GSK3ß) was upregulated in liver cancer cells overexpressing miR-129-2. Besides, the weight and volume of tumors in nude mice bearing liver cancer were significantly smaller after overexpression of miR-129-2. CONCLUSIONS: MiR-129-2 weakens proliferation and migration and stimulates apoptosis in liver cancer cells mainly by downregulating Sox4 and inactivating the Wnt signaling pathway.

Autotrophic picoplankton in the tropical ocean.

In phytoplankton of the eastern tropical Pacific Ocean from 25 to 90 percent of the biomass (measured as chlorophyll a) and 20 to 80 percent of the inorganic carbon fixation were attributable to particles that could pass a screen with a 1-micrometer pore diameter. Evidence is presented that these are indeed autotrophic cells and not cell fragments.

A method of estimating the noise level in a chaotic time series.

An attempt is made in this study to estimate the noise level present in a chaotic time series. This is achieved by employing a linear least-squares method that is based on the correlation integral form obtained by Diks in 1999. The effectiveness of the method is demonstrated using five artificial chaotic time series, the Henon map, the Lorenz equation, the Duffing equation, the Rossler equation and the Chua's circuit whose dynamical characteristics are known a priori. Different levels of noise are added to the artificial chaotic time series and the estimated results indicate good performance of the proposed method. Finally, the proposed method is applied to estimate the noise level present in some real world data sets.

Cotrimoxazole for prophylaxis or treatment of opportunistic infections of HIV/AIDS in patients with previous history of hypersensitivity to cotrimoxazole.

BACKGROUND: Opportunistic infections continue to cause a significant amount of morbidity and mortality worldwide in patients infected with HIV. Trimethoprim-sulfamethoxazole (cotrimoxazole) is used in the treatment and prophylaxis of several opportunistic infections. In patients with HIV/AIDS, cotrimoxazole use can cause a higher rate of adverse drug reactions than in the general population. Given the cost-effectiveness of cotrimoxazole, the management of these adverse reactions has included continuing the drug (treating-through) and reintroducing the drug at a later date, either using dose-escalation (desensitization), or rechallenge at full dose. This systematic review is the first to examine the differences in patient outcomes between these strategies. OBJECTIVES: To compare the rate of discontinuation of cotrimoxazole and adverse reactions among the three strategies of treating-through, desensitization, and rechallenge in patients living with HIV who previously had an adverse reaction to cotrimoxazole. SEARCH STRATEGY: We searched MEDLINE, EMBASE, LILACS, The Cochrane Library, Meeting Abstracts, AIDSTRIALS, ACTIS, Current Controlled Trials, The National Institutes of Health Clinical Trials Registry, and CenterWatch (search date May 2006). SELECTION CRITERIA: Randomised trials comparing treating-through, rechallenge, or desensitization of cotrimoxazole treatment or prophylaxis in adults (age 18 years or over) and/or children (age 17 years or under). DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial eligibility and quality, and extracted data. Where data were incomplete or unclear, a third reviewer resolved conflicts and/or trial authors were contacted for further details. MAIN RESULTS: Three trials that examined cotrimoxazole prophylaxis and involving 268 adults were included. Meta-analysis of these studies found a beneficial effect of using a desensitization protocol over a rechallenge protocol at six months of follow-up for preventing discontinuation of cotrimoxazole (number needed to treat (NNT) 7.14, 95% confidence interval (CI) 4.0-33.0), and for lower incidence of overall hypersensitivity (NNT 4.55, 95% CI 3.03-9.09). No severe hypersensitivity reactions occurred for either protocol in the three studies. AUTHORS' CONCLUSIONS: In the small trials included in this review, when compared to cotrimoxazole rechallenge for prophylaxis of opportunistic infections, cotrimoxazole desensitization resulted in fewer treatment discontinuations and overall adverse reactions in HIV-infected patients with a previous history of mild or moderate hypersensitivity to cotrimoxazole. Paediatric data and trials in resource-poor settings are urgently required. Further randomised controlled trials are also needed for the treatment of opportunistic infections, treating-through, adjunctive medications, and different desensitization-dosing schedules.

High throughput workflow for coacervate formation and characterization in shampoo systems.

Cationic cellulosic polymers find wide utility as benefit agents in shampoo. Deposition of these polymers onto hair has been shown to mend split-ends, improve appearance and wet combing, as well as provide controlled delivery of insoluble actives. The deposition is thought to be enhanced by the formation of a polymer/surfactant complex that phase-separates from the bulk solution upon dilution. A standard characterization method has been developed to characterize the coacervate formation upon dilution, but the test is time and material prohibitive. We have developed a semi-automated high throughput workflow to characterize the coacervate-forming behavior of different shampoo formulations. A procedure that allows testing of real use shampoo dilutions without first formulating a complete shampoo was identified. This procedure was adapted to a Tecan liquid handler by optimizing the parameters for liquid dispensing as well as for mixing. The high throughput workflow enabled preparation and testing of hundreds of formulations with different types and levels of cationic cellulosic polymers and surfactants, and for each formulation a haze diagram was constructed. Optimal formulations and their dilutions that give substantial coacervate formation (determined by haze measurements) were identified. Results from this high throughput workflow were shown to reproduce standard haze and bench-top turbidity measurements, and this workflow has the advantages of using less material and allowing more variables to be tested with significant time savings.

Value at risk estimation using independent component analysis-generalized autoregressive conditional heteroscedasticity (ICA-GARCH) models.

We suggest using independent component analysis (ICA) to decompose multivariate time series into statistically independent time series. Then, we propose to use ICA-GARCH models which are computationally efficient to estimate the multivariate volatilities. The experimental results show that the ICA-GARCH models are more effective than existing methods, including DCC, PCA-GARCH, and EWMA. We also apply the proposed models to compute value at risk (VaR) for risk management applications. The backtesting and the out-of-sample tests validate the performance of ICA-GARCH models for value at risk estimation.

Coccidiosis immunization: effects of mushroom and herb polysaccharides on immune responses of chickens infected with Eimeria tenella.

An experiment was conducted to investigate the effects of polysaccharide extracts (E) of two mushrooms, Lentinus edodes (LenE) and Tremella fuciformis (TreE), and an herb, Astragalus membranaceus (AstE), on the immune responses of chickens infected with Eimeria tenella. A total of 180 broiler chickens were assigned to nine groups: three groups were fed with each of the extracts (LenE, TreE, and AstE), three groups were fed with the extracts and immunized with live oocyst vaccine (LenE+V, TreE+V, and AstE+V), a group was immunized with the vaccine only, and there were two controls (E. tenella-infected and noninfected groups). The oocyst vaccine was given at 4 days of age, and the extracts (1 g/kg of the diet) were supplemented from 8 to 14 days of age. At 18 days of age, all birds except those in the noninfected group were infected with 9 x 10(4) sporulated oocysts. The results showed that at 7 days postinfection (p.i.), birds fed the extracts without vaccination had lower body weight (BW) gain than those given the vaccine only. However, the extracts in conjunction with the vaccine significantly enhanced BW gain of the infected chickens compared with the vaccine group. Of the three extracts, LenE and TreE showed a better growth-promoting effect. The extracts largely increased oocyst excretion of droppings during the primary response postvaccination. The cecal peak oocyst output and lesion scores measured at 7 days p.i. were higher in the groups fed the extracts than in the group immunized with the vaccine only, whereas those of the groups fed with the extracts and immunized with the vaccine were not significantly different from the vaccine group. Of the three extracts, both LenE- and AstE-fed groups showed lower cecal oocyst output. Thus, as compared with the extracts, the live, attenuated vaccine showed better results with significantly increased immune response in coccidial infected birds. The polysaccharide extracts may prove useful against avian coccidiosis, and, particularly when they are used in conjunction with vaccine, they have shown preliminary promise against the experimental coccidial infection.

Flavonoids from Epimedium wanshanense.

A novel flavonol glycoside named wanepimedoside A was isolated from the whole plant of Epimedium wanshanense, along with fifteen known flavonoids, anhydroicaritin, desmethylanhydroicaritin, icarisid I and II, quercetin, ikarisoside A and B, sagittatoside B, 2"-O-rhamnosylicarisid II, icariin, 2"-O-rhamnosylikarisoside A, epimedin B, epimedin C, and diphylloside A and B.

Flavonol glycosides from Epimedium koreanum.

A novel flavonol glycoside named caohuoside-B was isolated from the aerial parts of Epimedium koreanum, along with a known flavonol glycoside, epimedokoreanoside-I. Their structures were established by spectroscopic methods. The new compound was elucidated as anhydroicaritin 3-O-beta-D-(4,6-O- diacetyl)glucopyranosyl-(1-->3)-alpha-L-(4"-O-acetylrhamnopyranoside+ ++)-7-O-beta- D-glucopyranoside.