Cryoablation (CRA) and microwave ablation (MWA) are two main local treatments for hepatocellular carcinoma (HCC). However, which one is more curative and suitable for combining with immunotherapy is still controversial. Herein, CRA induced higher tumoral PD-L1 expression and more T cells infiltration, but less PD-L1^highCD11b⁺ myeloid cells infiltration than MWA in HCC. Furthermore, CRA had better curative effect than MWA for anti-PD-L1 combination therapy in mouse models. Mechanistically, anti-PD-L1 antibody facilitated infiltration of CD8⁺ T cells by enhancing the secretion of CXCL9 from cDC1 cells after CRA therapy. On the other hand, anti-PD-L1 antibody promoted the infiltration of NK cells to eliminate PD-L1^highCD11b⁺ myeloid cells by antibody-dependent cell-mediated cytotoxicity (ADCC) effect after CRA therapy. Both aspects relieved the immunosuppressive microenvironment after CRA therapy. Notably, the wild-type PD-L1 Avelumab (Bavencio), compared to the mutant PD-L1 atezolizumab (Tecentriq), was better at inducing the ADCC effect to target PD-L1^highCD11b⁺ myeloid cells. Collectively, our study uncovered the novel insights that CRA showed superior curative effect than MWA in combining with anti-PD-L1 antibody by strengthening CTL/NK cell immune responses, which provided a strong rationale for combining CRA and PD-L1 blockade in the clinical treatment for HCC.

Objective:To investigate the predictive value of neutrophil/lymphocyte ratio (NLR) on the discharge outcome in elderly patients with acute ischemic stroke (AIS) receiving intravenous thrombolysis (IVT).Methods:Elderly patients with AIS received IVT in the Department of Neurology, the Second Affiliated Hospital of Soochow University from August 2018 to August 2020 were retrospectively included. The modified Rankin Scale was used to evaluate discharge outcome, and the score >2 was defined as poor outcome. Symptomatic intracranial hemorrhage (sICH) was defined as any intracranial hemorrhage found on imaging examination accompanied by neurological deterioration, where the National Institutes of Health Stroke Scale (NIHSS) score increased by ≥4 from baseline or bleeding led to death. Multivariate logistic regression analysis was used to determine independent risk factors for sICH and poor discharge outcome. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of NLR for sICH and poor discharge outcome. Results:A total of 228 elderly patients with AIS receiving IVT were enrolled, including 118 males (51.8%), aged 73.64±8.16 years, with a baseline NIHSS score of 6.23±6.54. Ninety patients (39.5%) had poor outcome at discharge, and 16 (7.0%) developed sICH. Univariate analysis showed that the NLR in the poor outcome group was significantly higher than that in the good outcome group ( P<0.01). Multivariate logistic regression analysis showed that a higher NLR was an independent risk factor for poor discharge outcome (odds ratio [ OR] 1.245, 95% confidence interval [ CI] 1.044-1.484; P< 0.05) and sICH ( OR 1.124, 95% CI 1.010-1.251; P<0.05). ROC curve analysis showed that the area under the curve of NLR for predicting poor discharge outcome was 0.693 (95% CI 0.620-0.765; P<0.01). The optimal cutoff value was 4.345. Its corresponding sensitivity and specificity were 47.8% and 87.7%, respectively. The area under the curve of NLR for predicting sICH was 0.651 (95% CI 0.498-0.804; P<0.05). The optimal cutoff value was 3.515. Its corresponding sensitivity and specificity were 68.8% and 61.8%, respectively. Conclusions:A higher NLR is independently associated with sICH and poor discharge outcome in elderly patients with AIS receiving IVT, and have certain predictive value for sICH and poor discharge outcome.

Objective:Heart failure(HF),a worldwide health condition,is the result of many cardiovascular diseases.The traditional Chinese medicine(TCM)Xiaoyu Jiangzhi capsule(XYC)has long been in use in China to treat hyperlipidemia and inhibit platelet aggregation.This study explores the effects of XYC on heart failure(HF)and its detailed mechanisms.Methods:Isoproterenol(ISO,30 mg/kg)was injected intraperitoneally for 7 days to copy a HF model of 10-12 weeks old,20-30 g male mice.We then compared the CON(control)group,ISO(HF model)group,MET(metoprolol)group,and XYC group.Cardiac systolic function and left wall thickness were evaluated by echocardiograph.Using western blot analysis,we detected the proteins of calmodulin dependent protein kinase Ⅱ(CaMKII)and sarco/endoplasmic reticulum Ca2+-ATPase(Serca).Further-more,tsA201 cells were cultured and the human CaV1.2 calcium channel current(hCaV1.2)were detected by patch clamp experiments.Results:XYC reduced HF,inhibiting the protein expression of CaMKII,but Serca did not change signifi-cantly.Moreover,XYC inhibited the peak amplitude of the hCaV1.2 current,depolarizing shifted the activation curve 27.6 mV,and shifted the inactivation curve toward a positive potential 17.6 mV.The fraction recovered from inaction was reduced in XYC group compared with that in CON group.Conclusion:XYC could inhibit ISO-induced HF by reducing the Ca2+/CaMKII signaling pathway in mice.

OBJECTIVETo compare the effects of electroacupuncture (EA) at "Dachangshu" (BL 25) or "Tianshu" (ST 25) for visceral sensitivity, gene expression product c-kit of colonic Cajal interstitial cells (ICC) and capsaicin receptor 1 (TRPV1) of irritable bowel syndrome (IBS) rats, so as to investigate the effect and mechanism differences of EA at the back point and the front point of large intestine for IBS rats.

METHODSForty-two Wistar neonatal rats were randomly divided into a blank group (9 rats) and a model group (33 rats). IBS model was established with mother and child separation, acetic acid enema in young rats and colorectal dilatation method. Twenty-seven IBS rats in life were randomly divided into a model control group, a Dachangshu group and a Tianshu group, 9 rats in each group. EA (disperse-dense wave, 2 Hz/100 Hz, 0.1-0.3 mA) for 20 min was used at "Dachangshu" (BL 25) and "Tianshu" (ST 25) respectively in the Dachangshu and Tianshu groups, once every other day, totally 5 times. The rats in the model control group were fixed with soft cloth sleeve for 20 min, without acupuncture. No intervention was used in the blank group. The stool property Bristol grading score was recorded before and after intervention in each group. The visceral sensitivity was evaluated by abdominal withdrawal reflex. The latency until the first systolic wave occurred and the number of systolic wave within 90 s were observed. Immunohistochemical was used to detect the positive expressions of c-kit and TRPV1, the ICC colon specific marker.

RESULTSCompared with the blank group, the Bristol score increased，latency period shortened, systolic wave number increased, c-kit and TRPV1 positive expressions increased in the model control group (all <0.01). Compared with the model control group, the Bristol score decreased, latency period increased, systolic wave number decreased, c-kit and TRPV1 positive expressions decreased after intervention in the Dachangshu and Tianshu groups (<0.05, <0.01). Compared with the Dachangshu group, the TRPV1 positive expression decreased after intervention in the Tianshu group (<0.05).

CONCLUSIONEA at "Dachangshu" (BL 25) or "Tianshu"(ST 25) can improve the diarrhea in IBS model rats, reduce the visceral sensitivity, and its mechanism may be related to regulating the expressions of colon c-kit and TRPV1. EA at "Tianshu" (ST 25) is more apparent for TRPV1 than at "Dachangshu" (BL 25).

Objective: To observe the therapeutic efficacy of Fu's subcutaneous needling (FSN) in treating scapulohumeral periarthritis (SP). Methods: Eighty patients with SP were randomly divided into an observation group and a control group, 40 cases in each group. Patients in the observation group received FSN treatment while those in the control group received conventional acupuncture treatment. Visual analogue scale (VAS) and range of motion (ROM) were observed before and after the treatment, and the therapeutic efficacy was also evaluated. Results: After the treatment, the VAS scores decreased significantly in the two groups, and the VAS score in the observation group was significantly lower than that in the control group (P<0.01). After the treatment, the ROM increased significantly in both groups (both P<0.01), and the ROM in the observation group was significantly higher than that in the control group (P<0.01). The recovery rate and the total effective rate in the observation group were respectively 40.0% and 95.0%, significantly higher than 12.5% and 77.5% in the control group (P<0.01, P<0.05). Conclusion: FSN can effectively relieve pain and improve the joint motion in treating SP, thus offering a novel option to the treatment of this kind of musculoskeletal disorder.

OBJECTIVEThe aim of this study was to analyze the clinical features and prognostic factors in patients with brain metastasis from colorectal cancer (CRC).

METHODSClinical materials of 45 colorectal cancer patients who developed brain metastasis were collected, and the data and follow-up data of those patients were retrospectively analyzed.

RESULTSMost brain metastases were from rectal cancer (64.4%), and 80.0% of the 45 cases had extracranial metastases. The most common extracranial metastatic site was the lung (57.8%), followed by the liver (35.6%). All the brain metastases in patients with liver metastases were supratentorial, while in contrast, 44.8% of the patients without liver metastasis had subtentorial metastasis, showing a significant difference between them (P<0.05). The interval time from diagnosis of CRC to the development of brain metastases in case of Dukes D stage was 12.0 months, significantly shorter than that in the cases of Dukes A stage (24.0 months), B (36.0 months) and C (29.0 months) (P<0.05). The interval time was also shorter in the patients who developed extracranial metastasis within one year than those more than one year (12.0 months vs. 38.0 months)( P<0.05). The median survival time of patients with brain metastasis from colorectal was 6.0 months, with a 1-year survival rate of 21.1% and 2-year survival rate of 3.3% only. Univariate analysis showed that the median survival of patients with a KPS score of ≥70 was 8.0 months, significantly higher than 2.0 months in those with a KPS score of <70 (P<0.05). The median survival of patients with one or two brain metastases was 8.0 months, significantly higher than 4.0 months of those with >2 brain metastases (P<0.05). The median survival time after diagnosis of brain metastasis was 4.0 months for those who received monotherapy (only steroids, only chemotherapy or only radiotherapy), significantly shorter than 10.0 months of patients who received chemoradiotherapy, and 12.0 months of those who underwent surgery (P<0.05). Comparing each two differently treated groups, the survival time of surgery combined with chemotherapy or radiotherapy group was significantly different from that of all of other groups (P<0.05). The median survival time of chemoradiotherapy group was longer than that of monotherapy, but the difference was not significant (P>0.05). Multivariate analysis showed that brain metastases >2 and treatment modality type are independent prognostic factors for survival.

CONCLUSIONSPatients initially diagnosed with a Dukes D stage primary colorectal tumor and occurrence of extracranial metastasis (especially, pulmonary metastasis) within one year are associated to an increased risk of brain metastases and have a shorter survival time. Most brain metastases in patients with liver metastases are supratentorial, while many patients without liver metastasis have subtentorial metastasis. Brain metastases >2 and the type of treatment modality are independent prognostic factors for survival. The prognosis of patients who received chemoradiotherapy is better than those treated only with chemotherapy or radiotherapy. Some subsets of patients may benefit from surgery plus chemotherapy/radiotherapy.

Brain Neoplasms ; mortality ; secondary ; therapy ; Chemoradiotherapy ; Colorectal Neoplasms ; Humans ; Liver Neoplasms ; secondary ; Lung Neoplasms ; secondary ; Neoplasm Staging ; Prognosis ; Rectal Neoplasms ; pathology ; Retrospective Studies ; Survival Rate ; Time Factors

Objective To investigate the clinical efficacy of superficial needling therapy for nape myofascitis. Method Seventy patients were randomly allocated to superficial needling and Western medicine groups, 35 cases each. The superficial needling group received superficial needling therapy once every other day, three times a week, two weeks as a course. The Western medicine group took celecoxib (Celebrex) 200 mg twice daily, two weeks as a course. The Pain Visual Analogue Scale (VAS) score, the tenderness score and the Neck Disability Index (NDI) score were recorded in the two groups of patients before and after treatment. Result The VAS score, the tenderness score and the NDI score decreased in the two groups of patients after treatment compared with before (P<0.05, P<0.01) and decreased more in the superficial needling group than in the Western medicine group (P<0.05). The cure and marked efficacy rate and the total efficacy rate were 57.1%and 94.3%, respectively, in the superficial needling group, which were higher than 31.4%and 77.1%in the Western medicine group (P<0.05). Conclusion Superficial needling therapy can better relieve the symptoms and is more effective than oral celecoxib in treating nape myofascitis.

Objective To observe the analgesic effect of acupuncture at Guanyuan (CV4) and its effect on vasomotor substances in rats with dysmenorrhea due to coagulated cold syndrome. Method The coagulated-cold dysmenorrhea rat model was developed by Estrodiol benzoate and Oxytocin injectin plus physical freezing. The writhing response (writhing latency, writhing frequency, and writhing score) was observed, and the contents of TXB2 and 6-keto-PGF1a were detected by using enzyme-linked immunosorbent assay (ELISA). Result Compared with the saline water group, the writhing latency was significantly shortened, the writhing frequency was significantly increased, and the writhing score was more significantly increased in the model group (P<0.01);compared with the model group, the writhing latency was significantly prolonged, the writhing frequency was decreased, and the writhing score was significantly lower in the acupuncture group (P<0.05, P<0.01). Compared with saline water group, the content of plasma 6-keto-PGF1a was significantly lower (P<0.05) and the content of plasma TXB2 showed an increasing tendency (P>0.05) in the model group. Compared with the model group, the content of plasma 6-keto-PGF1a showed an increasing tendency (P>0.05) and the content of plasma TXB2 showed a decreasing tendency (P>0.05) in the acupuncture group. Conclusion The vasomotor substances are obviously disordered in the blood of cold-coagulated dysmenorrhea rat models. Acupuncture at Guanyuan can improve the writhing response and release pain, and meanwhile positively regulate the vasomotor substances such as TXB2 and 6-keto-PGF1a. The vasomotor substances are plausibly one of the major substances in the action of acupuncture in preventing and treating dysmenorrhea.

A sub-microsecond pulse generation applied for electroporation effects of tumor cell is presented in this paper. The principle of the generator is that the expected pulse waveform is intercepted from the RC discharge curve by controlling the on-off states of two IGBT modules with a synchronous controller. Experimental tests indicate that the generator can produce adjustable pulse waveform parameters with 0.5-3.5kV amplitude, 300-800 ns pulse duration, 1-400Hz repetition frequency rate, and it is suitable for the study of the electroporation effect experiments.
Animals ; Cell Line, Tumor ; Cell Membrane ; Electricity ; Electroporation ; instrumentation ; methods ; Equipment Design ; Microtechnology ; instrumentation ; Neoplasms ; ultrastructure