Objective By observing the effects of"three methods and three points"tuina technique on the expression of interleukin-17F(IL-17F),interleukin-17 receptor C(IL-17RC),activator 1 of nuclear transcription factor-κB(Act1),tumour necrosis factor receptor-associated factor 6(TRAF6)and M1 microglial cell expression in the spinal dorsal horn of rats with mild chronic compressive injury(minor CCI)model,we explored the immediate analgesic mechanism of tuina on peripheral neuropathic pain(pNP).Methods Thirty-six SD rats were divided into the sham group,the model group and the tuina group according to the random number method,twelve rats in each group,and the minor CCI model was replicated by ligating the right sciatic nerve.The rats in the tuina group were subjected to pointing,plucking and kneading at the BL37,BL57 and GB34 points on the affected side using a tuina simulator,while the sham group and the model group were only grasped and restrained,and were intervened for one time.The mechanical pain test and cold plate test were used to evaluate the response of rats to mechanical stimulation and cold stimulation after immediate intervention.The protein expression of IL-17F and TRAF6 in the spinal dorsal horn of rats in each group was detected by Western blotting.The mRNA expression of IL-17F,IL-17RC,Act1 and TRAF6 in the spinal dorsal horn of rats in each group was detected by real-time PCR.The average fluorescence intensity of M1 microglia in the spinal dorsal horn of rats in each group was detected by immunofluorescence.Results Behavioral results showed that before intervention,compared with the sham group,paw mechanical withdraw threshold(PMWT)decreased and cold sensitivity threshold(CST)increased in the model group and the tuina group;after tuina intervention,PMWT in the tuina group was increased,and CST was decreased compared with the model group;after intervention,PMWT in the tuina group was increased,while CST was decreased(P＜0.05).RT-PCR results showed that compared with the sham group,mRNA expression levels of IL-17F,IL-17RC,TRAF6 and Act1 in the spinal dorsal horn of the model group were increased;compared with model group,the mRNA expression levels of above indexes in the tuina group were decreased(P＜0.05).Western boltting results showed that compared with the sham group,the expression levels of IL-17F and TRAF6 protein in the spinal dorsal horn of the model group were increased;compared with the model group,the expression levels of IL-17F and TRAF6 protein in the tuina group decreased(P＜O.05).Immunofluorescence results showed that the mean fluorescence intensity of CD40 in the spinal dorsal horn of model group was enhanced compared with the sham group;compared with the model group,the mean fluorescence intensity of CD40 in the tuina group was decreased(P＜0.05).Conclusion The"three methods and three points"tuina technique can produce immediate analgesia by inhibiting the expression of IL-17F,IL-17RC,Act1,TRAF6 and the activation of M1 microglia in the dorsal horn of the spinal cord after one intervention.

Objective:To investigate the effect of tocilizumab (TCZ) on ventricular arrhythmias (VAs) after myocardial infarction (MI) in Sprague-Dawley rats and explore its potential mechanism.Methods:The random number table method was used to divide 32 adult male Sprague-Dawley rats into 4 groups: Sham group, TCZ group, MI group and MI+TCZ group, with 8 rats in each group. The MI model was established by ligation of the left anterior descending branch of the coronary artery in the MI and MI+TCZ groups, and only sutured without ligation in the Sham and TCZ groups. TCZ was injected into the left superior cervical ganglion (SCG) of rats in the TCZ and MI+TCZ groups after successful modeling or sham operation, and the same amount of normal saline was injected in the Sham and MI groups. 24 h after successful modeling, ECG of rats in each group was recorded, heart rate variability (HRV, including low frequency power (LF), high frequency power (HF), LF/HF ratio), QT interval, QTc interval were calculated, and left ventricular effective refractory period (ERP) and VA inducibility were measured. Myocardial infarct size and tissue changes were observed with triphenyl tetrazolium chloride staining and HE staining. Real-time PCR analysis was used to detect the messager RNA (mRNA) expression of interleukin-6 (IL-6) and signal transducer and activator of transcription (STAT) 3 in SCG and potassium voltage-gated channel subfamily D member 2 (Kcnd2) in myocardial infarction periphery. The expression of c-fos in SCG was detected by immunofluorescence staining.Results:Compared with Sham group and MI+TCZ group, rats in MI group had higher LF and LF/HF ratio, longer QT interval and QTc interval, more VAs induced, lower HF and shorter ERP ( P all<0.05). Triphenyl tetrazolium chloride staining and HE staining showed that rats in the Sham and TCZ groups had normal myocardial tissue structure, those in the MI group had severe myocardial injury, and those in the MI+TCZ group had less myocardial injury than those in the MI group. Real-ime PCR analysis showed that compared with Sham group and MI+TCZ group, mRNA expression levels of IL-6 and STAT3 in SCG of rats in MI group were higher, and mRNA expression level of myocardial Kcnd2 was lower ( P all<0.05). Immunofluorescence staining showed that the content of c-fos in SCG of rats in MI group was higher than that of Sham group and MI+TCZ group ( P all<0.05). Conclusions:TCZ may reduce neural activity of the SCG after MI by inhibiting the IL-6/STAT3 signaling pathway, thereby alleviating myocardial injury and inhibiting VAs.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

Objective To compare cortical inhibition(CI)function between patients with schizophrenia and depression,and to explore the correlation between CI function and clinical symptoms.Methods A total of 35 first episode schizophrenia(FES)patients,41 depression patients(21 with first episode depression,20 with recurrent depression),and 35 healthy controls(HC)were recruited.The positive and negative syndrome scale(PANSS)was used to assess symptoms in FES patients,while the 17-item Hamilton depression scale(HAMD-17)and Hamilton anxiety scale(HAMA)were used to assess symptoms in depression patients.All participants'cortical inhibition and excitation measures were examined using single or paired pulses transcranial magnetic stimulation.Analysis of covariance/generalized linear model was employed to compare cortical inhibition and excitation measures among groups including age,gender,and medication status as covariates.The correlations between cortical inhibition and excitation measures and clinical symptoms were analyzed.Results The cortical silent period(CSP)in FES group was longer than that in control group and depression group[(92.08±35.43)ms vs.(70.27±22.12)ms vs.(70.81±29.29)ms,P<0.05].Depression group was further divided into first episode depression(FED)and recurrent depression(RD)subgroups.The short-interval cortical inhibition(SICI)was weaker in FED group than in the RD group and the control group(0.76±0.44 vs.0.43±0.32 vs.0.45±0.20,P<0.05).In FED group,CSP was negatively correlated with the general symptom score of PANSS(r=-0.544,P<0.001),and SICI was negatively correlated with the negative symptom score of PANSS(r=-0.501,P=0.005).In the FED group,SICI was positively correlated with HAMD-17 score(r=0.605,P=0.028).Conclusion Both FES patients and FED patients exhibit abnormal CI.There are distinct characteristics between FES and FED.FES patients exhibit prolonged CSP,while FED patients exhibit decreased SICI.The abnormal CI in FES and FED are correlated with their clinical symptoms.

Articular cartilage (AC) injuries often lead to cartilage degeneration and may ultimately result in osteoarthritis (OA) due to the limited self-repair ability. To date, numerous intra-articular delivery systems carrying various therapeutic agents have been developed to improve therapeutic localization and retention, optimize controlled drug release profiles and target different pathological processes. Due to the complex and multifactorial characteristics of cartilage injury pathology and heterogeneity of the cartilage structure deposited within a dense matrix, delivery systems loaded with a single therapeutic agent are hindered from reaching multiple targets in a spatiotemporal matched manner and thus fail to mimic the natural processes of biosynthesis, compromising the goal of full cartilage regeneration. Emerging evidence highlights the importance of sequential delivery strategies targeting multiple pathological processes. In this review, we first summarize the current status and progress achieved in single-drug delivery strategies for the treatment of AC diseases. Subsequently, we focus mainly on advances in multiple drug delivery applications, including sequential release formulations targeting various pathological processes, synergistic targeting of the same pathological process, the spatial distribution in multiple tissues, and heterogeneous regeneration. We hope that this review will inspire the rational design of intra-articular drug delivery systems (DDSs) in the future.

Objective:To explore the long-term efficacy of a modified unilateral cutaneous ureterostomy in bladder cancer patients receiving radical cystectomy.Methods:The medical data of 104 bladder cancer patients who underwent ureterostomy in our hospital from Janurary 2013 to December 2020 were retrospectively analyzed. The patients were divided into unilateral and bilateral group. The unilateral group contained 66 cases, with 53 males and 13 females, average age (71.8±9.8) years, body mass index (BMI)(23.3±3.2)kg/m 2. The bilateral group contained 38 cases, with 33 males and 5 females, average age (75.1±10.8) years; BMI (22.7±3.0)kg/m 2. There was no significant difference in the above characteristics between the two groups ( P>0.05). The pathology, survival status, long-term complications between the two groups were compared. Quality of life was assessed during follow-up using the European Core Questionnaire for Quality of Life in Cancer Patients (EORTC QLQ-C30). Results:The unilateral group contained 46(69.7%) muscle invasive bladder cancer (MIBC) cases, 15 (22.7%) cases with lymph node metastasis, 7 (10.6%) cases with distant metastasis. The bilateral group contained 24(63.2%) muscle invasive bladder cancer(MIBC) cases, 6 (15.8%) cases with lymph node metastasis, 2 (5.3%) cases with distant metastasis. There was no significant difference in disease specific survival between the two groups ( P>0.05). During the follow-up, the incidence of overall complication rate in the unilateral group was significantly lower than that in the bilateral group [43.9% (29/66) vs. 63.2% (24/38), P<0.001]. The incidence of pyelonephritis in unilateral group was significantly lower than that in the bilateral group [16.6%(11/66) vs. 42.1%(16/38), P=0.006]. There was no statistical significance in terms of quality of life before operation in the two groups. After operation, both physical function score[(54.9±7.1) vs.(49.2±6.7)] and emotional function score [(63.1±6.4) vs.(59.9±6.7)] in unilateral group were higher than that in bilateral group ( P<0.05). Conclusions:The modified unilateral cutaneous ureterostomy could achieve relatively low complication rate, and improve the quality of life to some extent compared with bilateral ureterostomy.

Rats ; Animals ; Sciatic Neuropathy ; Muscle, Skeletal ; Sciatic Nerve/physiology* ; Sequence Analysis, RNA ; Nerve Regeneration/physiology*

Objective:To investigate the changes in the hypothalamic metabolites of lipopolysaccharide(LPS)febrile young rabbits after the treatment with pediatric tuina.Methods:A total of 30 young rabbits were randomly assigned into three groups:the normal group,the model group,and the tuina group.Both the model group and the tuina group were injected intrave-nously with LPS."Six antipyretic manipulations"(pushing Tianmen,pushing Kangong,kneading Taiyang,kneading Erhougaogu,clearing Tianheshui,and pushing Jizhu)were administered 1 h after the LPS in-jection in the tuina group.The rectal temperatures of the young rabbits were monitored during the experiment to explore the antipyretic effect.Three hours after the injection,the content of interleukin-1 β(IL-1β),tumor necrosis factor(TNF)-α,and prostaglandin E2(PGE2)in the serum was detected.In addition,liquid chromatography-mass spectrometry(LC-MS)was used for the hypothalamus metabolomics.Results:Compared with the model group,the rectal temperature of the tuina group was decreased at 2 h and 3 h after the LPS injection(P=.04,P=.03,respectively),and the content of IL-1β,TNF-α,and PGE2 was decreased(P=.03,P=.003,and P=.008,respectively).The metabolomics results showed that there were 23 potential biomarkers after the tuina intervention,enriching 27 pathways.Lipid metabolites,especially glycerophospholipids,were a majority of the altered metabolites.The primary metabolic pathways affected by tuina included the arachidonic acid metabolism,the GABAergic synapse,D-gluta-mine and D-glutamate metabolism,and the glutamatergic synapse.Conclusion:Pediatric tuina reduced the temperature of the febrile rabbits and downregulated the expression of IL-1β,TNF-α,and PGE2,and the antipyretic mechanism may be related to changes in metabolites and metabolic pathways in the hypothalamus.

Objective:To evaluate the effect of micro-implant assisted rapid palatal expansion (MARPE) in patients with different radiographic stages of midpalatal suture maturation.Methods:Twenty-eight patients [7 males and 21 females; age (15.5±5.5) years] with maxillary transverse deficiency were selected in the Department of Orthodontics, Hospital of Stomatology, Jilin University from February 2017 to October 2019. According to the fusion of the midpalatal suture, the patients were divided into two groups: 10 patients [3 males and 7 females; age (19.9±6.9) years] were in fusion group and 18 patients [4 males and 14 females; age (13.0±2.4) years] were in non-fusion group. Each patient had cone-beam CT (CBCT) images taken immediately after the placement of micro-implants (T1) and the completion of maxillary expansion (T2). The CBCT images were analyzed using the Dolphin Imaging software to evaluate the amount of midpalatal expansion and the percentages of bony expansion, etc. Statistical analysis was carried out to compare the two groups.Results:After MARPE treatment, the amount of sutural expansion in fusion group was (3.23±1.45) mm while that in non-fusion group was (4.97±1.47) mm ( P<0.05). There was a statistically significant difference in the percentages of bony expansion efficiency between the non-fusion group (71±20)% and the fusion group (46±18)% ( P<0.05). Conclusions:Bony expansion efficiency was affacted by the radiographic stages of midpalatal suture maturation.

Objective:To establish a sensitive and specific real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) method for rapid detection of Getah virus (GETV).Methods:All the gene sequences of GETV were downloaded from GenBank database. Clustal X was used for sequence alignment, and specific primers and probes were designed according to highly conserved regions; we established a standard curve using the nucleic acid of GETV as a standard, and the sensitivity, specificity and stability of this method were evaluated respectively.Results:This method could specifically detect GETV and has no cross-reactivity with multiple arboviruses; the sensitivity was 1.0×10 pfu/ml, and the intra-assay and inter-assay coefficients of variation were less than 1%. One case was GETV positive in 196 batches of mosquitoes collected from Hunan province, Hebei province, Fujian province and Chongqing city.Conclusions:We established a TaqMan probe real-time quantitative RT-PCR with high sensitivity and specificity which can be used for screening.