Efficacy of neoadjuvant chemotherapy combined with prophylactic intraperitoneal hyperthermic chemotherapy for patients diagnosed with clinical T4 gastric cancer who underwent laparoscopic radical gastrectomy: a retrospective cohort study based on propensity score matching.

BACKGROUND: Clinical T4 (cT4) stage gastric cancer presents with frequent postoperative recurrence and poor prognosis. This study is to evaluate the oncological efficacy of laparoscopic radical total gastrectomy combined with postoperative prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with cT4N + M0 gastric cancer who received neoadjuvant chemotherapy. METHODS: We reviewed the clinicopathological data of 174 patients with clinical T4 gastric cancer who underwent neoadjuvant chemotherapy followed by laparoscopic radical total gastrectomy between June 2017 and December 2021. Among them, 142 were included in the non-HIPEC group, and 32 in the HIPEC group. Patients in both groups were paired based on propensity score in a 2:1 ratio to assess disparities in tumor recurrence and long-term survival. RESULTS: After matching, there were no significant differences in the clinicopathological data between the two groups. The peritoneum (16.1%) and distant organs (10.9%) were the most frequent locations for recurrence. Prior to matching, the recurrence rates were similar at all sites for both groups. Compared with those in the non-HIPEC cohort, the recurrence rates at all sites, the lung, and the peritoneum were notably lower in the HIPEC cohort. Prior to matching, the 3-year overall survival and disease-free survival rates were similar between the two groups; following matching, the HIPEC group exhibited notably greater survival rates than did the non-HIPEC group. The disparities in survival rates between the groups became even more pronounced after conducting a stratified analysis among patients with stage III disease. CONCLUSIONS: Neoadjuvant chemotherapy combined with prophylactic HIPEC after laparoscopic radical gastrectomy can effectively reduce the rate of peritoneal metastasis in patients with cT4N + M0 advanced gastric cancer and significantly improve the prognosis of such patients, which is of great clinical value.

The safety and efficacy of neoadjuvant immunochemotherapy following laparoscopic gastrectomy for gastric cancer: a multicentre real-world clinical study.

BACKGROUND: The safety and efficacy of neoadjuvant immunochemotherapy (nICT) for locally advanced gastric cancer (LAGC) remain controversial. METHODS: Patients with LAGC who received either nICT or neoadjuvant chemotherapy (nCT) at 3 tertiary referral teaching hospitals in China between January 2016 and October 2022 were analyzed. After propensity-score matching (PSM), comparing the radiological response, pathological response rate, perioperative outcomes, and early recurrence between the two groups. RESULTS: After PSM, 585 patients were included, with 195 and 390 patients comprising the nICT and nCT groups, respectively. The nICT group exhibited a higher objective response rate (79.5% vs. 59.0%; P <0.001), pathological complete response rate (14.36% vs. 6.41%; P =0.002) and major pathological response rate (39.49% vs. 26.15%; P =0.001) compared with the nCT group. The incidence of surgical complications (17.44% vs. 16.15%, P =0.694) and the proportion of perioperative textbook outcomes (80.0% vs. 81.0%; P =0.767) were similar in both groups. The nICT group had a significantly lower proportion of early recurrence than the nCT group (29.7% vs. 40.8%; P =0.047). Furthermore, the multivariable logistic analysis revealed that immunotherapy was an independent protective factor against early recurrence [odds ratio 0.62 (95% CI 0.41-0.92); P =0.018]. No significant difference was found in neoadjuvant therapy drug toxicity between the two groups (51.79% vs. 45.38%; P =0.143). CONCLUSIONS: Compared with nCT, nICT is safe and effective, which significantly enhanced objective and pathological response rates and reduced the risk for early recurrence among patients with LAGC. TRIAL REGISTRATION: Clinical Trials.gov.

New α-ditetralonyl glucoside from the green walnut husk of Juglans mandshurica.

One new α-ditetralonyl glucoside (1), was isolated from the green walnut husk of Juglans mandshurica (Juglandaceae), together with twelve known compounds (2-13). The structure of the new compound was determined as (2R,4S,10S,12S)-2-[7-(12,13,16-trihydroxy-α-tetralonyl-13-O-ß-D-glucopyranoside)]- 4,8-dihydroxy-α-tetralone-4-O-ß-D-glucopyranoside (1), on the basis of detailed spectroscopic analyses, and acidic hydrolysis. Compounds 6, 7 and 11 were isolated from the genus Juglans for the first time. Compound 1-13 showed weak cytotoxic against A549 and HeLa cell lines.

A two-step similarity-based method for prediction of drug's target group.

Determination of drug's target protein is very important for studying drug-target interaction network, while drug-target interaction network is a key area in the drug discovery pipeline. Thus correct prediction of drug's target protein is very helpful to promote the development of drug discovery. In this study, we developed a two-step similarity-based method to predict drug's target group. In each step, a similarity score (obtained by graph representation in the first step, and chemical functional group representation in the second step) was employed to make prediction. Since some drugs can target proteins distributing in more than one group of proteins, the method provided a series of candidate target groups for each drug. As a result, the first-order prediction accuracy on training set and test set were 79.01% and 76.43%, respectively, which were much higher than the success rate of a random guess. The results show that using graph representation to encode drug is a good choice in this area. We expect that this contribution will provide some help to understand drug-target interaction network.

Predicting Anatomical Therapeutic Chemical (ATC) classification of drugs by integrating chemical-chemical interactions and similarities.

The Anatomical Therapeutic Chemical (ATC) classification system, recommended by the World Health Organization, categories drugs into different classes according to their therapeutic and chemical characteristics. For a set of query compounds, how can we identify which ATC-class (or classes) they belong to? It is an important and challenging problem because the information thus obtained would be quite useful for drug development and utilization. By hybridizing the informations of chemical-chemical interactions and chemical-chemical similarities, a novel method was developed for such purpose. It was observed by the jackknife test on a benchmark dataset of 3,883 drug compounds that the overall success rate achieved by the prediction method was about 73% in identifying the drugs among the following 14 main ATC-classes: (1) alimentary tract and metabolism; (2) blood and blood forming organs; (3) cardiovascular system; (4) dermatologicals; (5) genitourinary system and sex hormones; (6) systemic hormonal preparations, excluding sex hormones and insulins; (7) anti-infectives for systemic use; (8) antineoplastic and immunomodulating agents; (9) musculoskeletal system; (10) nervous system; (11) antiparasitic products, insecticides and repellents; (12) respiratory system; (13) sensory organs; (14) various. Such a success rate is substantially higher than 7% by the random guess. It has not escaped our notice that the current method can be straightforwardly extended to identify the drugs for their 2(nd)-level, 3(rd)-level, 4(th)-level, and 5(th)-level ATC-classifications once the statistically significant benchmark data are available for these lower levels.

[The biomechanical study of craniovertebral junction fixation with posterior transarticular screw].

OBJECTIVE: To evaluate the stability of biomechanics of occipitoatlantoaxial reconstruction with transarticular screw fixation. METHODS: Twelve fresh human cadaveric occipitocervical spine specimens were mounted in a custom-designed, spine-testing machine that applied pure moments while recording the three-dimensional angular movement at occiput (Oc)-C(1) and C(1 - 2) segments. The specimens were tested under seven different conditions: the intact (intact group), the occipitoatlantoaxial instability (Destabilized group), fixation with Ti-cable plus bone graft group (cable + graf group), fixation with the transarticular fixation (CTS group), fixation with SUMMIT occitocervical spinal fixation system (SUMMIT group), fixation with transarticular screw plus bone graft (CTS + graf group), and fixation with SMMIT system and plus graft group (SUMMIT + graf group). The data obtained were statistically analyzed. RESULTS: The CTS group reduced motion to well within the normal rang. In the Oc-C(1) segment, The CTS group and SUMMIT group allowed a very small rang of motion (ROM) and neutral zone (NZ) during lateral bending and axial rotation. The ROM and NZ during flexion and extension of the SUMMIT group, were significantly smaller than those of cable + graf group and CTS group (6.64 degrees +/- 0.59 degrees, 2.49 degrees +/- 0.26 degrees, 0.50 degrees +/- 0.03 degrees, 0.21 degrees +/- 0.01 degrees, 0.27 degrees +/- 0.07 degrees, 0.13 degrees +/- 0.01 degrees vs 10.01 degrees +/- 1.26 degrees, 3.80 degrees +/- 0.79 degrees, 7.93 degrees +/- 1.34 degrees, 3.18 degrees +/- 0.95 degrees, 9.54 degrees +/- 0.87 degrees, 5.93 degrees +/- 0.74 degrees, P < 0.05). In the C(1 - 2) segment, ROM and NZ in all directions of CTS group were smaller in rotation than SUMMIT group (1.64 degrees +/- 0.39 degrees, 0.61 degrees +/- 0.15 degrees, 0.14 degrees +/- 0.05 degrees, 0.02 degrees +/- 0.01 degrees, 0.32 degrees +/- 0.04 degrees, 0.08 degrees +/- 0.01 degrees, vs 0.21 degrees +/- 0.04 degrees, 0.07 degrees +/- 0.03 degrees, 0.21 degrees +/- 0.12 degrees, 0.10 degrees +/- 0.02 degrees, 2.92 degrees +/- 0.28 degrees, 1.27 degrees +/- 0.11 degrees, all P < 0.05). There was no significant difference in ROM and NZ in all directions between CTS + graf group and SUMMIT + Graf group (P > 0.05). CONCLUSION: In vivo biomechanics studies show that posterior occipitocervical transarticular fixation has unique features in reconstructing dynamic stability of the occipitoatlantoaxis, especially in controlling stability of rotation and lateral flexion, thus ensuring successful fusion of the implanted bone and allowing for clinical use of the technique.