[Prognostic factors affecting the success of conversion chemotherapy in patients with unresectable liver metastases from initially colorectal cancer].

Objective: To investigate the factors affecting the success of conversion therapy in patients with initially unresectable colorectal cancer liver metastases (CRLM) in order to provide evidence-based medical evidence for formulating individualized treatment strategies for patients. Methods: A retrospective case-control study was used in this study. Clinical data of 232 patients with initially unresectable CRLM receiving first-line systemic treatment in Sun Yat-sen University Cancer Center from January 2013 to January 2020 were collected, including 98 patients of successful conversion and 134 patients of failed conversion as control. Conversion therapy scheme: 38 patients received FOLFOXIRI regimen chemotherapy (irinotecan, oxaliplatin, calcium folinate and fluorouracil), 152 patients received FOLFOX regimen (oxaliplatin, calcium folinate and fluorouracil), 19 patients received FOLRIRI regimen (irinotecan, calcium folinate and fluorouracil), 23 patients received systemic chemotherapy combined with fluorouridine hepatic artery infusion chemotherapy; 168 patients received targeted therapy, including 68 of bevacizumab and 100 of cetuximab. Logistics analysis was used to compare the factors affecting the success of conversion therapy. The Kaplan-Meier method was used to calculate progression-free survival (PFS), and the Log-rank test was used for survival comparison. Results: Among 232 patients, 98 patients had successful conversions and 134 patients had failed conversions with a successful conversion rate of 42.2%, meanwhile 30 patients underwent simple hepatectomy and 68 underwent hepatectomy combined with intraoperative radiofrequency ablation. After first-line chemotherapy, 111 patients (47.8%) were partial remission, 57 patients (24.6%) were stable disease, and 64 patients (27.6%) were progression disease. During the median follow-up of 18.8 (1.0-87.9) months, 148 patients were dead or with tumor progression. The median PFS time of patients with successful conversion was longer than that of patients with failed conversion (31.0 months vs. 9.9 months, P<0.001). Univariate analysis found that the bilobar distribution of liver tumors (P=0.003), elevated baseline carcinoembryonic antigen (CEA) levels (P=0.024), tumor invasion of the portal vein (P=0.001), number of metastatic tumor>8 (P<0.001), non-FOLFOXIRI (P=0.005), and no targeted therapy (P=0.038) were high risk factors for the failed conversion therapy. The results of multivariate logistics analysis indicated that the number of metastatic tumor >8 (OR=2.422, 95%CI: 1.291-4.544, P=0.006), portal vein invasion (OR=2.727, 95%CI: 1.237-4.170, P=0.008) were the independent risk factors for failed conversion therapy, while FOLFOXIRI regimen (OR=0.300, 95%CI: 0.135-0.666, P=0.003) and targeted drugs (OR=0.411, 95%CI: 0.209-0.809, P=0.010) were independent protective factors for successful conversion therapy. Conclusions: The number of metastatic tumor and portal vein invasion are key factors that affect the outcomes of conversion therapy for initially unresectable CRLM. If a patient can tolerate chemotherapy, a combination program of three-drug and targeted therapy is preferred for the active conversion therapy.

Expression and clinical significance of the obesity-related gene TNFAIP9 in obese children.

To investigate the expression of tumor necrosis factor-alpha inducible protein 9 (TNFAIP9) gene in obese children and its clinical significance, 36 simple obese children and 17 non-obese children were recruited as research subjects. The adipose tissue was obtained by abdominal operation. The expression of TNFAIP9 was detected using real-time fluorescence quantitative polymerase chain reaction and western blot. The relationship between the expression of TNFAIP9 and blood lipid, blood glucose, and obesity indexes was analyzed. The levels of TNFAIP9 mRNA and protein in obese children were significantly lower than those in the control group (P < 0.05). The waist circumference (wc), body mass, body mass index (BMI), fat, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), insulin resistance index (HOMA-IR), and endothelin (ET) in obese children were significantly higher than those in the control group. The level of high-density lipoprotein cholesterol (HDL-C) was significantly lower than that in the control group (P < 0.05). The level of TNFAIP9 protein was negatively correlated with the wc, body mass, BMI, fat, TC, TG, LDL-C, HOMA-IR, and ET (P < 0.05) and was positively correlated with the level of HDL-C (P < 0.05). In conclusion, the expression of TNFAIP9 significantly decreased in the adipose tissue of obese children, and its levels are closely related to blood lipid level, insulin resistance, and obesity.

Effect of systemic morphine on neurons in the lateral reticular nucleus area of the rat.

The present study is undertaken to investigate the effect of systemic morphine on neurons in the lateral reticular nucleus (LRN) using extracellular recording techniques. The spontaneous activities of 64 neurons in the LRN area were tested with morphine (3-5 mg/kg, IV). Morphine excited 23 and inhibited 28 neurons tested, and 13 neurons were not affected. Of the 28 neurons inhibited, 20 were identified as nociceptive and the remaining 6 were nonnociceptive. Of the 23 neurons excited by morphine, 18 were nociceptive and 5 were nonociceptive. Systemic naloxone (0.3-0.5 mg/kg) significantly reversed the morphine effect in 15 out of 19 neurons excited and 19 out of 20 neurons inhibited by morphine. Thirteen out of 64 neurons were further identified as reticulospinal neurons, of which four were excited and four were inhibited by morphine. The remaining five were not affected. The results demonstrate that a similar proportion of neurons in the LRN area were either excited or inhibited by systemic morphine, and the majority of them are nociceptive neurons. It is suggested that different types of neurons in the LRN area may have different functions in morphine analgesia.

Role of the deep mesencephalic nucleus in the antinociception induced by stimulation of the anterior pretectal nucleus in rats.

The present study showed that the inhibitory effect on the tail-flick reflex (TF) of stimulating the deep mesencephalic nucleus (DpMe) was very similar to that produced by stimulation of the anterior pretectal nucleus (APtN). An electrolytic lesion of the ipsilateral DpMe greatly reduced the inhibitory effect of APtN stimulation on the TF. Furthermore, activating the neuronal cell bodies in DpMe but not the fibers of passage by microinjection of L-glutamate into this area was also shown to elicit inhibition of TF. On the other hand, inhibiting the neuronal cells in DpMe by microinjection of gamma-aminobutyric acid produced a marked reduction in the APtN-induced inhibition of TF, which was comparable to that produced by DpMe lesions. It is suggested that the APtN-induced antinociception is, at least in part, mediated via a relay through the DpMe.

Responses of reticulospinal neurons in the lateral reticular nucleus area of the rat to cutaneous noxious and non-noxious stimulation.

Response properties of reticulospinal neurons in the lateral reticular nucleus (LRN) area to natural cutaneous stimulation were investigated systematically in 45 urethane-anesthetized rats by using extracellular recording techniques. A total of 64 neurons were tested with peripheral stimuli, of which 19 were responsive only to noxious stimuli; 7 responsive to both noxious and non-noxious stimuli; 4 responsive only to non-noxious stimuli; and 34 not responsive to any cutaneous stimuli. Both the noxious and non-noxious receptive fields were large and bilateral. Among the neurons responding to noxious stimuli, the majority (72%) was excited. This study provides evidence that some reticulospinal neurons in the rat LRN area are involved in the mechanisms of nociception.

Electrophysiological identification of spinally projecting neurons in the lateral reticular nucleus of the rat.

Eighty-four neurons in the caudal ventrolateral medullary reticular formation were antidromically activated by the stimulation of the dorsolateral funiculus in 49 urethane-anesthetized rats. Of 76 neurons, 37 had no spontaneous discharge. Of the neurons that had spontaneous discharges, 80% had firing rates between 0.1 and 15 Hz. The average conduction velocity, determined among 70 neurons, was 15.20 +/- 1.23 m/s, and 87% had conduction velocities within the range of 2-30 m/s. This study further confirms the existence of spinally-projecting neurons in the lateral reticular nucleus (LRN) of the caudal medulla, and some of them are probably responsible for the descending controls of nociception from the LRN.

A study on the receptive field of acupoints and the relationship between characteristics of needling sensation and groups of afferent fibres.

We have recorded the afferent unit discharges and using it as an index, measured the locations and the volumes of nine acupoints, such as Neiguan and Shaoshang, which are innervated by median nerve. We have also investigated the relationships between electric needling sensations and afferent fibres of different groups as well as manual needling sensations by means of analysing power-spectrum of the unit discharges with FFT. It has been found that the fibres of Group II and Group IV convey numbness and soreness, respectively. The fibres of Group III relates to the conduction of heaviness and distention closely.