[Establishment of Nano-ITO induced rat model of indium lung disease and exploration of its pathological characteristics].

Objective: To study the dynamic pathological characteristics of lung tissue in a Nano-ITO induced rat model of indium lung disease and to guide clinical and basic scientific research to further explore the mechanisms of pulmonary interstitial injury and pulmonary alveolar proteinosis (PAP). Methods: Dose-response (three divided doses) and time-course studies (six exposure periods) were performed to investigate the pulmonary toxicity induced by Nano-ITO. At the end of the experiment, cytokine levels and oxidative stress were analyzed in the bronchoalveolar lavage fluid. Rat lung tissues were also collected for staining with H&E, PAS, Masson's, Oil Red O, and Sirius Red. Ultrastructure of lung tissue cells was observed by transmission electron microscopy. Expression of IL-1ß, HO-1, SP-A was observed by immunohistochemistry, and the expression of α-SMA was observed by immunofluorescence. Results: Nano-ITO intratracheal instillation caused pulmonary toxicity by inducing acute inflammation at 3 days, granuloma (nodule) formation and collagen hyperplasia at 14 days, and alveolar proteinosis at 56 days post-exposure. Pathological features of lung tissue included typical alveolar exudates, cellular fibrous nodules, enlarged alveolar fat droplet fusion, cholesterol crystal granuloma and pulmonary alveolar proteinosis. The intra-alveolar eosinophilic material (multilamellated, lattice-shaped, and myelin-like structure) showed abnormal lamellar bodies (features of alveolar type Ⅱ epithelial cells) and abundant rough endoplasmic reticulum and mitochondria (features of fibroblasts) on transmission electron microscopy of the lung tissue from rats exposed to Nano-ITO on the 84th day. Cellular pathology revealed that a large amount of amorphous PAS stain-positive substances appear in BALF at 28 days post-exposure, and pink granular protein-like substances can be seen in alveolar macrophages. Conclusions: There are three characteristic developmental stages in Nano-ITO induced pulmonary injury in rats, acute inflammation, granuloma (nodule) formation and collagen proliferation, and pulmonary alveolar proteinosis, which provide a reference feature model for the pathogenesis of indium lung disease.

[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.

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.

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.

[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.

Photodissociation of ethylene sulfide at 193 nm: a photofragment translational spectroscopy study with VUV synchrotron radiation and ab initio calculations.

Photodissociation of ethylene sulfide at 193 nm has been studied using photofragment translational spectroscopy and ab initio theoretical calculations. Tunable synchrotron radiation was used as a universal but selective probe of the reaction products to reveal new aspects of the photodissociation dynamics. The channel giving S + C2H4 was found to be dominated by production of ground-state sulfur atoms (S(3P):S(1D) = 1.44:1), mostly through a spin-forbidden process. The results also suggest the presence of a channel giving S(3P) in conjunction with triplet ethylene C2H4 (3B(1u)) and allow insight into the energy of the latter species near its equilibrium geometry, in which the two methylene groups occupy perpendicular planes. In addition, a channel leading to the production of H2S with C2H2 also has been observed. Our experimental results are supported and elaborated by theoretical calculations.

Effects of euxanthone on neuronal differentiation.

The growth inhibitory and differentiation inducing effects of euxanthone (1,7-dihydroxyxanthone) from the medicinal plant Polygala caudata on the neuroblastoma (Neural 2A, subclone BU-1) were investigated. At the concentration range of 0-100 microM, euxanthone inhibits the growth of BU-1 cells in a dose dependent manner. The 50% growth inhibitory concentration (IC50) was 41 microM. Significant induction of morphological differentiation and neurite growth was observed at the concentration of 100 microM. Frequency of proliferative neuroblastoma cells was determined after induction of differentiation. The frequency of proliferating BU-1 cells was markedly reduced from 1/1.1 to <1/99. Confocal microscopy also confirmed that the morphological differentiation of BU-1 was associated with the expression of neurite specific marker MAP-2 protein in neurites. These data suggest that euxanthone may be one of the neuropharmacological active compounds in the medicinal plant Polygala caudata.

Residence times and half-lives of nicotine metabolites in rat brain after acute peripheral administration of [2'-(14)C]nicotine.

The residence times of nicotine and its metabolites in rat brain after acute peripheral nicotine administration were determined. We hypothesize that nicotine metabolites will reach pharmacologically significant concentrations in brain. Cotinine, nornicotine, and norcotinine were structurally identified by dual label radiochemical and gas chromatography-mass spectrometric analysis as biotransformation products of nicotine present in rat brain after s. c. injection of S(-)-nicotine. Two unidentified minor metabolites were also detected in brain. The half-lives in brain of nicotine metabolites were determined after a single s.c. injection of [2'-(14)C]-(+/-)nicotine (0.8 mg/kg) and analysis of radiolabeled metabolites by high pressure-liquid radiochromatography. The brain half-lives of nicotine, cotinine, and nornicotine were 52, 333, and 166 min, respectively. Peak brain concentrations of nicotine metabolites were 300, 70, and 7 nM for cotinine, nornicotine, and norcotinine, respectively. Even with potential accumulation of cotinine in brain after chronic nicotine administration, it is likely that the brain concentration of cotinine will be insufficient to produce neuropharmacological effects resulting from activation of nicotinic receptors to induce dopamine release. Conversely, the concentration of nornicotine in brain after acute nicotine approaches the range found to be neuropharmacologically active. It is likely that nornicotine will accumulate in brain on chronic nicotine administration based on the brain half-life of this metabolite. Importantly, nornicotine is also a major alkaloidal component of tobacco. Thus, as a consequence of tobacco use, alkaloidal and metabolically formed nornicotine may reach concentrations in brain sufficient to produce pharmacological effects.

[Pharmacokinetics of epostane in rabbits by HPLC method].

Epostane (Epo), a 3 beta-hydroxysteroid dehydrogenase inhibitor, interrupted pregnancy in rats, rhesus monkeys, and women. Epo concentrations in serum were determined by high performance liquid chromatography (HPLC) at 0.25, 0.5, 1, 2, 4, 8, 16, 32, and 48 h after intragastric Epo 96 mg.kg-1 in rabbits. The concentration-time curve exhibited a 2-compartment open model. The pharmacokinetic parameters were: T1/2ka 0.79 +/- 0.08 h, T1/2 alpha 0.96 +/- 0.08 h, T1/2 beta 6.6 +/- 1.5 h, Vc 14 +/- 3 ml.kg-1, AUC 12.0 +/- 1.9 micrograms.h.ml-1, Tmax 1.8 +/- 0.5 h, Cmax 3.3 +/- 0.5 microgram.ml-1. After rat copora luteum were incubated with hCG 10 IU.ml-1 and Epo 10 or 100 micrograms.ml-1 for 18 and 48 h, luteal cells showed various degrees of degeneration and progesterone production was significantly inhibited.

[Interceptive activity of epostane in pregnant rats and rhesus monkeys].

A complete interceptive action on pregnancy was shown after ig epostane (Epo) 48 and 96 mg/kg on d 10 of pregnancy in rats. ED50 (95% fiducial limits) of Epo was 20.7 (16.3-26.3) mg/kg. Epo 48 mg/kg ig on d12, 14 and 16 of pregnancy lowered rat plasma progesterone concentrations (P less than 0.05) and plasma corticosterone on d 16 of pregnancy (P less than 0.05). Epo 35 mg/(kg.d) was given ig on d 50-54 of pregnancy in rhesus monkeys. Vaginal bleeding was seen in all of the 6 treated monkeys. Complete expulsions of fetal and placental materials occurred in 5 of the treated monkeys, among which 2 aborted on d 53 and the other 3 on d 54 of pregnancy. Plasma progesterone concentrations of the treated monkeys were lowered on d 52, 53 and 54 of pregnancy (P less than 0.05) and plasma estradiol on d 51, 52, 53, 54 and 55 (P less than 0.05), while there were no significant differences in plasma hydrocortisone. Epo may be a valuable supplement to the existing methods of female contraception.

Pelvic Ewing's sarcoma. Advances in treatment.

In a study of eighteen patients with pelvic Ewing's sarcoma who were treated with a multidisciplinary approach, chemotherapy was effective in controlling systemic spread of the tumor. Surgery coupled with improved methods of chemotherapy provided results that were statistically superior to those obtained with radiation and chemotherapy alone in control of the local pelvic lesion. A twofold increase in the survival rate was seen at a median follow-up of thirty-six months in the patients who had the resection. Our results suggest that pelvic Ewing's sarcoma is best treated by initial chemotherapy, followed by local wide marginal resection of the pelvic lesion coupled with perimeter radiation therapy and concluded with additional chemotherapy. Survival rates of patients with pelvic Ewing's sarcoma may then approach the excellent survival rates of patients with lesions in more favorable anatomical locations.