The prerequisites and clinical outcomes of ipsilateral C7 nerve root transfer to the upper trunk for adult C5-C6 brachial plexus injuries.

PURPOSE: Although ipsilateral C7 nerve transfer is used for the treatment of C5-C6 brachial plexus injuries, accurately evaluating the functional quality of the donor nerve (ipsilateral C7 nerve root) is difficult, especially when the C7 nerve root is slightly injured. The purpose of this study was to determine the indicators to evaluate the quality of the ipsilateral C7 nerve and assess the clinical outcomes of this procedure. METHODS: This study employed the following three indicators to assess the quality of the ipsilateral C7 nerve: (1) the muscle strength and electrophysiological status of the latissimus dorsi, triceps brachii, and extensor digitorum communis; (2) the sensibility of the radial three digits, especially the index finger; and (3) the intraoperative appearance, feel and electrophysiological status of the ipsilateral C7 nerve root. Transfer of the ipsilateral C7 nerve root to the upper trunk was implemented only when the following three tests were conducted, the criteria were met, and the clinical outcomes were assessed in eight patients with C5-C6 brachial plexus injuries. RESULTS: Patients were followed-up for an average of 90 ± 42 months. At the final follow-up, all eight patients achieved recovery of elbow flexion, with five and three patients scoring M4 and M3, respectively, according to the Medical Research Council scoring. The shoulder abduction range of motor recovery averaged 86 ± 47° (range, 30°-170°), whereas the shoulder external rotation averaged 51 ± 26° (range, 15°-90°). CONCLUSION: Ipsilateral C7 nerve transfer is a reliable and effective option for the functional reconstruction of the shoulder and elbow after C5-C6 brachial plexus injuries when the three prerequisites are met.

Laparoscopic versus open gastrectomy for locally advanced gastric cancer after neoadjuvant chemotherapy: a comprehensive contrastive analysis with propensity score matching.

BACKGROUND: Laparoscopic gastrectomy (LG) is increasingly applied in locally advanced gastric cancer (LAGC) after neoadjuvant chemotherapy (NC). However, there is no study to comprehensively evaluate the clinicopathological, prognostic, and laboratory data such as nutrition, immune, inflammation-associated indexes, and tumor markers between LG and open gastrectomy (OG) for LAGC following NC. METHODS: The clinicopathological, prognostic, and laboratory data of LAGC patients with clinical stage of cT2-4aN1-3M0 who underwent gastrectomy after NC were retrospectively collected. The effects of LG and OG were compared after propensity score matching (PSM). RESULTS: This study enrolled 148 cases, of which 110 cases were included after PSM. The LG group had a shorter length of incision (P < 0.001) and was superior to OG group in terms of blood loss (P < 0.001), postoperative first flatus time (P < 0.001), and postoperative first liquid diet time (P = 0.004). No significant difference was found in postoperative complications (P = 0.482). Laboratory results showed that LG group had less reduced red blood cells (P = 0.039), hemoglobin (P = 0.018), prealbumin (P = 0.010) in 3 days after surgery, and less reduced albumin in 1 day (P = 0.029), 3 days (P = 0.015), and 7 days (P = 0.035) after surgery than the OG group. The systemic immune-inflammation index and systemic inflammatory response index were not significantly different between the two groups. As for oncological outcomes, there were no significant differences in postoperative tumor markers of CEA (P = 0.791), CA199 (P = 0.499), and CA724 (P = 0.378). The 5-year relapse-free survival rates (P = 0.446) were 46.9% and 43.3% in the LG and OG groups, with the 5-year overall survival rates (P = 0.742) being 46.7% and 52.1%, respectively; the differences were not statistically significant. Multivariate Cox regression analysis revealed that tumor size ≥ 4 cm (P = 0.021) and the absence of postoperative adjuvant chemotherapy (P = 0.012) were independent risk factors for overall survival. CONCLUSIONS: LG has faster gastrointestinal recovery, better postoperative nutritional status, and comparable oncological outcomes than OG, which can serve as an alternative surgical method for LAGC patients after NC.

Staphylococcal Enterotoxin C2 Mutant-Induced Antitumor Immune Response Is Controlled by CDC42/MLC2-Mediated Tumor Cell Stiffness.

As a biological macromolecule, the superantigen staphylococcal enterotoxin C2 (SEC2) is one of the most potent known T-cell activators, and it induces massive cytotoxic granule production. With this property, SEC2 and its mutants are widely regarded as immunomodulating agents for cancer therapy. In a previous study, we constructed an MHC-II-independent mutant of SEC2, named ST-4, which exhibits enhanced immunocyte stimulation and antitumor activity. However, tumor cells have different degrees of sensitivity to SEC2/ST-4. The mechanisms of immune resistance to SEs in cancer cells have not been investigated. Herein, we show that ST-4 could activate more powerful human lymphocyte granule-based cytotoxicity than SEC2. The results of RNA-seq and atomic force microscopy (AFM) analysis showed that, compared with SKOV3 cells, the softer ES-2 cells could escape from SEC2/ST-4-induced cytotoxic T-cell-mediated apoptosis by regulating cell softness through the CDC42/MLC2 pathway. Conversely, after enhancing the stiffness of cancer cells by a nonmuscle myosin-II-specific inhibitor, SEC2/ST-4 exhibited a significant antitumor effect against ES-2 cells by promoting perforin-dependent apoptosis and the S-phase arrest. Taken together, these data suggest that cell stiffness could be a key factor of resistance to SEs in ovarian cancer, and our findings may provide new insight for SE-based tumor immunotherapy.

[Common diseases and drug use characteristics of Chinese herbal medicines and suggestions].

Based on the data of 56 kinds of diseases and drug use in 100 kinds of cultivated Chinese herbal medicines, this paper used frequency analysis method to count the types of diseases and their drug use characteristics, and systematically analyzed the status of drug registration and monitoring standards for disease prevention and control of Chinese herbal medicines. The results showed that 14 diseases such as root rot, powdery mildew, and drooping disease were common in the production of Chinese herbal medicines. Among the 99 pesticides reported, 67.68% were chemically synthesized, 23.23% were biological pesticides, and 9.09% were mineral pesticides. Among the reported pesticides, 92.93% of them were low toxic, with relative safety. However, 70% of the production drugs were not registered in Chinese herbal medicines, and the phenomenon of overdose was serious. The current pesticide residue monitoring standards does not match well with production drugs in China. Although the matching degree between Maximum Residue Limit of Pesticide in Food Safety National Standard(GB 2763-2021) and production drugs is more than 50%, there are few varieties of Chinese herbal medicines covered. The matching degree between Chinese Pharmacopoeia(2020 edition), Green Industry Standard of Medicinal Plants and Preparations(WM/T2-2004), and production drugs is only 1.28%. It is suggested to speed up the research and registration of Chinese herbal medicine production and further improve the pesticide residue limit standard combined with the actual production, so as to promote the high-quality development of Chinese herbal medicine industry.

Staphylococcal Enterotoxin C2 Mutant-Directed Fatty Acid and Mitochondrial Energy Metabolic Programs Regulate CD8+ T Cell Activation.

CD8+ T cells can switch between fatty acid catabolism and mitochondrial energy metabolism to sustain expansion and their cytotoxic functions. ST-4 is a TCR-enhanced mutant derived from superantigen staphylococcal enterotoxin C2 (SEC2), which can hyperactivate CD4+ T cells without MHC class II molecules. However, whether ST-4/SEC2 can enhance metabolic reprogramming in CD8+ T cells remains poorly understood. In this study, we found that ST-4, but not SEC2, could induce proliferation of purified CD8+ T cell from BALB/c mice in Vß8.2- and -8.3-specific manners. Results of gas chromatography-mass spectroscopy analysis showed that fatty acid contents in CD8+ T cells were increased after ST-4 stimulation. Flow cytometry and Seahorse analyses showed that ST-4 significantly promoted mitochondrial energy metabolism in CD8+ T cells. We also observed significantly upregulated levels of gene transcripts for fatty acid uptake and synthesis, and significantly increased protein expression levels of fatty acid and mitochondrial metabolic markers of mTOR/PPARγ/SREBP1 and p38-MAPK signaling pathways in ST-4-activated CD8+ T cells. However, blocking mTOR, PPARγ, SREBP1, or p38-MAPK signals with specific inhibitors could significantly relieve the enhanced fatty acid catabolism and mitochondrial capacity induced by ST-4. In addition, blocking these signals inhibited ST-4-stimulated CD8+ T cell proliferation and effector functions. Taken together, our findings demonstrate that ST-4 enhanced fatty acid and mitochondria metabolic reprogramming through mTOR/PPARγ/SREBP and p38-MAPK signaling pathways, which may be important regulatory mechanisms of CD8+ T cell activation. Understanding the effects of ST-4-induced regulatory metabolic networks on CD8+ T cells provide important mechanistic insights to superantigen-based tumor therapy.

Pulsed High-Peak Power Microwaves at 9.4 GHz Do Not Affect Basic Endpoints in Caenorhabditis elegans.

Because of the extensive application of electromagnetic technology, its health impact on humans has attracted widespread attention. Due to the lack of a model organism with a stable response to electromagnetic waves, the research conclusions on the biological effects of electromagnetic waves have been vague. Therefore, the aim of this study was to investigate the effects of irradiation by pulsed 9.4 GHz high-power microwaves with a peak power density of 2126 W/cm2 using Caenorhabditis elegans. The development, movement, egg production, ROS, and lifespan of C. elegans were detected at different times after irradiation with different repetitive frequencies of 10, 20, and 50 Hz for 30 min. The results indicated that no obvious changes in basic life indices were induced compared with the sham radiation group, but the survival rate of positive control was significantly decreased compared with other groups, which is of interest for microwave protection research based on C. elegans and provides data for updating safety standards with respect to pulsed high-peak power microwave. © 2021 Bioelectromagnetics Society.

Lymph node ratio is a prospective prognostic indicator for locally advanced gastric cancer patients after neoadjuvant chemotherapy.

BACKGROUND: The accuracy of lymph node ratio (LNR) as a prognostic index remains to be proven for gastric cancer patients after neoadjuvant chemotherapy (NACT). This study sought to investigate the prognostic value of LNR in locally advanced gastric cancer (LAGC) patients after NACT. METHODS: LAGC patients with clinical TNM stages 2-3, Her2(-), and Eastern Cooperative Oncology Group, scores 0-2 are routinely scheduled with NACT. Patients with LAGC after NACT and surgical operation between January 2012 and October 2020 were retrospectively reviewed. The correlation between LNR and survival was investigated. RESULTS: Overall, 148 patients were enrolled: 103 with low-LNR (LNR ≤ 30%) and 45 with high-LNR (LNR > 30%). Approximately, 50.5% and 24.4% patients responded to NACT at the primary site in the low-LNR and high-LNR groups, respectively. The overall survival (OS) and progression-free survival (PFS) of low-LNR group were considerably better than those of high-LNR group (3-year OS: 81.9% vs 18.5%, P < 0.001; 3-year PFS: 72.6% vs 13.5%, P < 0.001). In the low-LNR group, OS and PFS were superior in patients with tumor regression grade (TRG) 0-2 than in those with TRG 3 (3-year OS: 89.2% vs 73.2%, P = 0.086; 3-year PFS: 80.3% vs 66.5%, P = 0.036). In association with OS and PFS, the degree of tumor differentiation, TRG, and LNR were identified as predictive factors, and LNR was identified as the independent prognostic factor in univariate and multivariate analyses, respectively. CONCLUSIONS: LNR is a prospective index of prognosis in patients with LAGC after NACT.

MFEprimer-3.0: quality control for PCR primers.

Quality control (QC) for lab-designed primers is crucial for the success of a polymerase chain reaction (PCR). Here, we present MFEprimer-3.0, a functional primer quality control program for checking non-specific amplicons, dimers, hairpins and other parameters. The new features of the current version include: (i) more sensitive binding site search using the updated k-mer algorithm that allows mismatches within the k-mer, except for the first base at the 3' end. The binding sites of each primer with a stable 3' end are listed in the output; (ii) new algorithms for rapidly identifying self-dimers, cross-dimers and hairpins; (iii) the command-line version, which has an added option of JSON output to enhance the versatility of MFEprimer by acting as a QC step in the 'primer design → quality control → redesign' pipeline; (iv) a function for checking whether the binding sites contain single nucleotide polymorphisms (SNPs), which will affect the consistency of binding efficiency among different samples. In summary, MFEprimer-3.0 is updated with the well-tested PCR primer QC program and it can be integrated into various PCR primer design applications as a QC module. The MFEprimer-3.0 server is freely accessible without any login requirement at: https://mfeprimer3.igenetech.com/ and https://www.mfeprimer.com/. The source code for the command-line version is available upon request.

Effect of operative trauma and multiple propofol anesthesia on neurodevelopment and cognitive function in developmental rats.

To investigate the effect of multiple propofol anesthesia and operative trauma on neuroinflammation and cognitive function in development rats and its mechanism. A total of 104 13-day-old neonatal Sprague-Dawley rats were randomly divided into 4 groups with 26 rats in each group: control group was treated with saline q.d for propofol group was treated with propofol q.d for surgery group received abdominal surgery under local anesthesia and then treated with saline q.d for surgery with propofol group received propofol anesthesia plus abdominal surgery under local anesthesia with ropivacaine at d1, then treated with propofol q.d for At d2 of experiment, 13 rats from each group were sacrificed and brain tissue samples were taken, the concentration of TNF-α in hippocampus was detected with ELISA, the expression of caspase-3 and c-fos in hippocampal tissue was determined with immunohistochemical method, the number of apoptotic neurons in hippocampus was examined with TUNEL assay. Morris water maze test was used to examine the cognitive function of the rest rats at the age of 60 d, and the TNF-α concentration, caspase-3, c-fos expressions and the number of apoptotic neurons in hippocampus were also detected. Compared with control group, TNF-α concentration, caspase-3, c-fos expression and the neuroapoptosis in hippocampus increased significantly in other three groups (all <0.05). Compared with surgery group, propofol group and surgery with propofol group showed increased TNF-α level, caspase-3 and c-fos expressions and apoptotic cell numbers (all <0.05), but there was no significant difference between last two groups (all >0.05). Morris water maze test showed that there were no significant differences in swimming speed, escape latency, target quadrant residence time and crossing times among groups (all >0.05). TNF-α level, expressions of caspase-3 and c-fos and apoptotic cell numbers in hippocampus had no significant differences among the 4 adult rats groups (all >0.05). Abdominal surgery and multiple propofol treatment can induce neuroinflammation and neuroapoptosis in hippocampus of neonatal rats, however, which may not cause adverse effects on neurodevelopment and cognitive function when they grown up.

Cytotoxic Diterpenoids from Caryopteris aureoglandulosa.

Seven new (1-7) and 11 known diterpenoids were isolated and identified from Caryopteris aureoglandulosa. These diterpenoids were structurally determined by HRESIMS and NMR spectroscopic analyses, single-crystal X-ray diffraction, and ECD data. Structurally, aureoglandulosin A (1) is a highly oxygenated abietane diterpenoid with an unprecedented 7/6/6/5-ring system. Aureoglandulosins B (2) and C (3) represent naturally occurring new diterpenoids with an unusual 6/6/6/5-ring system. Additionally, the configurations of two known abietane diterpenoids 11 and 12 were determined by X-ray crystallographic data analysis for the first time. A plausible biosynthetic pathway for compounds 1-3 is proposed. The cytotoxicity of all isolates was evaluated, and compounds 1 and 11 exhibited significant cytotoxic activity against some cell lines with IC50 values in the range 1.6-8.2 µM.