Objective To observe the clinical efficacy and safety of rituximab injection combined with leflunomide tablets in the treatment of patients with systemic lupus erythematosus(SLE).Methods The SLE patients were divided into control and treatment groups according to cohort method.The control group received leflunomide with 50 mg·d-1 after meal in the first 3 days of treatment and was adjusted to 20 mg·d-1 thereafter.On the basis of control group,the treatment group was combined with rituximab,375 mg·m-2 was given intravenously every 2 weeks in the first 3 times of treatment,and adjusted to once every 4 weeks from the 4th dose.Two groups were treated for 24 weeks.The clinical efficacy,systemic lupus erythematosus disease activity index(SLEDAI)scores,serological indicators,24-hour urinary protein and adverse drug reactions were compared between two groups.Results The treatment and control groups were enrolled 74 cases and 72 cases,respectively.After treatment,the total effective rates of treatment and control groups were 91.89％(68 cases/74 cases)and 79.17％(57 cases/72 cases)with significant difference(P＜0.05).After treatment,the SLEDAI scores of treatment and control groups were(7.21±1.67)and(9.03±1.35)points;the levels of anti-Smith/ribonucleoprotein antibodies were(81.43±18.25)and(59.38±14.61)U·mL-1;the levels of immunoglobulin G were(12.04±2.15)and(17.28±2.64)g·L-1;the levels of interleukin-10 were(33.39±7.13)and(39.87±9.02)pg·mL-1;24-hour urinary protein quantification were(1.46±0.32)and(2.67±0.54)g·24 h-1;all the differences were statistically significant(all P＜0.05).The drug adverse reactions of two groups were liver and kidney function injury and digestive tract reactions.The total incidences of drug adverse reactions in the treatment and control groups were 13.51％and 5.56％without significant difference(P＞0.05).Conclusion Rituximab injection combined with leflunomide tablets has a definitive clinical efficacy in the treatment of SLE patients,which can significantly reduce disease activity and inflammatory reactions,improve immune function,without increasing the incidence of drug adverse reactions.

Objective To observe the improvement of motor dysfunction and serum levels of C-reactive protein(CRP),blood glucose and blood lipid in post-stroke patients treated with scalp acupuncture at different needle retention time.Methods A total of 120 patients with motor dysfunction after stroke were randomly divided into control group,observation group 1 and observation group 2,with 40 cases in each group.The patients in the 3 groups were treated with scalp acupuncture,body acupuncture and routine rehabilitation exercise,once a day and 6 times a week,lasting for 2 weeks.The control group was given scalp acupuncture with retaining of needles for 30 minutes,the observation group 1 was given scalp acupuncture with retaining of needles for one hour,and the observation group 2 was given scalp acupuncture with retaining of needles for 2 hours.Before and after treatment,the 3 groups were observed in the changes of the scale scores of National Institutes of Health Stroke Scale(NIHSS),Fugl-Meyer Assessment(FM A),Berg Balance Scale(BBS)and modified Barthel Index(MBI),and the levels of laboratory indicators of peripheral blood CRP,fasting plasma glucose(FPG),total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C).After treatment,the clinical safety of the three groups was evaluated.Results(1)After treatment,the scale scores of NIHSS in the three groups were lower(P＜0.01)and the scale scores FMA,BBS and MBI were higher than those before treatment(P＜0.05 or P＜0.01).The comparison of post-treatment scale scores showed that the differences among the three groups were statistically significant(P＜0.01).The intergroup comparison showed that the decrease of NIHSS score and the increase of FMA,BBS and MBI scores in the observation group 2 were significantly superior to those in the control group and the observation group 1(P＜0.01);the improvement of FMA score in the observation group 1 was significantly superior to that in the control group(P＜0.01),while the improvement of NIHSS,BBS and MBI scores tended to be superior to that in the control group without statistically significant differences(P＞0.05).The results indicated that the curative effect of scalp acupuncture plus exercise regimen was positively correlated with the duration of needle retention for scalp acupuncture.(2)After treatment,the laboratory indicator levels of CRP and FPG in the peripheral blood of the three groups,the levels of TG and LDL-C in the two observation groups and the level of HDL-C in the observation group 2 were improved compared with those before treatment(P＜0.05 or P＜0.01).Statistically significant differences were presented in the post-treatment levels of CRP and TG in peripheral blood among the three groups(P＜0.05 or P＜0.01).The intergroup comparison showed that the improvement of CRP and TG levels in the observation group 2 was significantly superior to that in the control group,and the improvement of CRP level in the observation group 2 was significantly superior to that in the observation group 1,the differences being statistically significant(P＜0.05 or P＜0.01).The TC level in the three groups after treatment did not differ from that before treatment,and there was no significant difference in TC level after treatment among the three groups either(P＞0.05).(3)During the treatment,no adverse reactions such as fainting,needle breaking and hematoma occurred in the three groups,the vital signs of the patients were stable,and there were no obvious abnormal changes in pulse,blood pressure and respiratory rate.Conclusion Scalp acupuncture can effectively improve the motor function of post-stroke patients in a pasitive time-effect relationship with the needle retention,and better the curative effect can be achieved by retaining of the needle for 2 h.

Objective To investigate the effect of evodiamine on renal fibrosis in rats with chronic renal failure(CRF)by regulating sphingosine kinase 1(SphK1)/S1P signaling pathway.Methods CRF rat model was established by feeding 0.5％adenine diet.The rats after modeling were randomly divided into model group,evodiamine low-and high-dose groups,Niaoduqing Granules group and evodiamine high-dose+K6PC-5(SphK1 activator)group.At the end of intervention,the levels of 24-hour urinary protein(24 h-UTP),serum urea nitrogen(BUN)and serum creatinine(SCr)were detected.The levels of monocyte chemoattractant protein 1(MCP-1)and interleukin 6(IL-6)in serum of rats were detected by enzyme-linked immunosorbent assay(ELISA).The pathological changes of renal tissue and collagen volume fraction(CVF)were observed by hematoxylin-eosin(HE)and Masson staining.The mRNA expressions of transforming growth factor β1(TGF-β1)and type Ⅳcollagen(COL-Ⅳ)in renal tissue were detected by real-time quantitative polymerase chain reaction(qRT-PCR).The protein expressions of SphK1 and S1P in renal tissue were detected by Western Blot.Results Compared with the normal group,the model group showed obvious inflammatory infiltration and collagen fiber deposition,the number of glomeruli decreased in renal tissue,and the expression levels of SCr,BUN,24h-UTP,IL-6,MCP-1,CVF,mRNA expressions of TGF-β1 and COL-Ⅳ,protein expessions of SphK1 and S1P were significantly increased(P＜0.05).Compared with the model group,the histopathological changes of the low-dose and high-dose evodiamine groups and the Niaoduqing Granules group was improved,and the expression levels of SCr,BUN,24 h-UTP,IL-6,MCP-1,CVF,mRNA expressions of TGF-β1 and COL-Ⅳ,protein expessions of SphK1 and S1P were significantly decreased.For intergroup comparison of each index,there were differences between the low-dose evodiamine group and the high-dose evodiamine group(P＜0.05),but there was no significant difference between the high-dose evodiamine group and the Niaoduqing Granules group(P＞0.05).Compared with the high-dose evodiamine group,the histopathological changes of the high-dose evodiamine+K6PC-5 group was further aggravated,and the improvement effect of all indexes were reversed(P＜0.05).Conclusion Evodiamine improves renal fibrosis in CRF rats by inhibiting SphK1/S1P signaling pathway.

Objective To investigate the therapeutic effect and mechanism of astragaloside Ⅳ on systemic lupus erythematosus(SLE)mice.Methods A total of 40 female spontaneous MRL/lpr SLE model mice were randomly divided into five groups:model group,Prednisone group,astragaloside Ⅳ group,astragaloside Ⅳ+CHPG[nuclear factor KappaB(NF-κB)pathway activator]group and astragaloside Ⅳ+Nigerian[NOD-like receptor family pyrin domain containing protein 3(NLRP3)activator]group,with eight mice in each group.Eight female MRL/MpJ mice were used as normal group.During the administration,the body mass was weighted.After administration,the spleen,thymus and kidney were weighted,and the organ index was calculated.The 24-hour urinary protein level in urine samples,the biochemical indexes of creatinine(SCr),blood urea nitrogen(BUN),autoantibodies[antinuclear antibody(ANA),anti-double-stranded DNA(dsDNA)antibody,anti-snRNP/Sm antibody]and inflammatory mediators[interleukin(IL)-1β,IL-18]in blood samples were detected.The pathological damage of renal tissue was observed by hematoxylin-eosin(HE)staining,and the fibrosis of renal tissue was observed by Masson staining.The expressions of NF-κB/NLRP3 inflammasome pathway-related proteins in kidney and spleen tissues were detected by Western Blot.Results Compared with the model group,the body mass of mice in prednisone group and astragaloside Ⅳ group increased,the spleen index,thymus index and kidney index were decreased,the serum levels of ANA antibody,anti-dsDNA antibody and anti-snRNP/Sm antibody were decreased,the levels of SCr,BUN and 24-hour urine protein were decreased,the levels of IL-1 βand IL-18 wrere decreased,the ratios of p-p65/p65,p-IKBα/IKBα,cleaved caspase-1/pro caspase-1 and the relative expression of NLRP3 protein in kidney and spleen tissues were decreased(all P＜0.05),and the pathological damage and fibrosis of renal tissue in SLE mice were alleviated,there being no significant difference between the two administration groups(P＞0.05).NF-κB activator and NLRP3 inflammasome activator eliminated the improvement of astragaloside Ⅳ on the above indexes in SLE mice to a certain extent.Conclusion Astragaloside Ⅳ can improve the immune function of SLE mice,reduce renal injury and inflammatory response,and its mechanism may be related to its inhibition of the activation of NF-κB/NLRP3 inflammasome pathway.

Objective:To investigate the application value of fecal Syndecan-2 (SDC2) gene methylated SDC2 (m SDC2) detection in colorectal cancer (CRC) screening among urban residents in Guangzhou City. Methods:A cross-sectional study was conducted in Shitan Town, Zengcheng District, Guangzhou City from July to December 2022. A community-based screening program for CRC was conducted among residents aged 40-74 years old. m SDC2 detection was employed in the participants, and those with positive results should be recommended to receive colonoscopy examination. The positive rate of m SDC2 detection, colonoscopy compliance rate, detection rate of intestinal lesions and clinicopathological characteristics were observed. The relationship between cycle threshold (CT) value of m SDC2 and intestinal lesions was explored. Further, the cost-effectiveness of screening was evaluated. Results:A total of 8 189 fecal samples were collected from 8 877 participants with the recovery rate of 92.25%. 8 048 qualified samples were enrolled in this study, consisted of 3 182 males (39.54%) and 4 866 females (60.46%), with the average age of 56 years old (40-74 years). The positive rate of m SDC2 detection was 7.99% (643/8 048), and the compliance rate of colonoscopy was 73.10% (470/643). 20 cases (4.25%) of colorectal cancer, 109 cases (23.19%) of advanced adenoma, 145 cases (30.85%) of non-advanced adenoma, 79 cases (16.81%) of polyps were detected. The detection rate of intestinal lesions was 75.11% and indicated significant differences in gender and age. 20 CRCs included 15 of stage 0-I, 4 of stage Ⅱ-Ⅲ and 1 of unknown stage. The CT value of m SDC2 was negatively correlated with the proportion of advanced colorectal neoplasms ( χ2=16.063, P<0.001). The total cost of the screening was 4.339 5 million yuan, the screening benefit was 28.506 2 million yuan, and the benefit-cost ratio was 6.57. Conclusion:The CRC screening strategy of fecal m SDC2 detection combined with colonoscopy has high colonoscopy compliance and detection rate of intestinal lesions, which is conducive to the detection of early CRCs, and has good cost-effectiveness. This study suggests that this method may be applied to the general CRC screening in China and contribute to the prevention of CRC. The CT value of m SDC2 may have a certain suggestion on the malignant degree of intestinal tumors.

Objective:To investigate the application value of fecal Syndecan-2 (SDC2) gene methylated SDC2 (m SDC2) detection in colorectal cancer (CRC) screening among urban residents in Guangzhou City. Methods:A cross-sectional study was conducted in Shitan Town, Zengcheng District, Guangzhou City from July to December 2022. A community-based screening program for CRC was conducted among residents aged 40-74 years old. m SDC2 detection was employed in the participants, and those with positive results should be recommended to receive colonoscopy examination. The positive rate of m SDC2 detection, colonoscopy compliance rate, detection rate of intestinal lesions and clinicopathological characteristics were observed. The relationship between cycle threshold (CT) value of m SDC2 and intestinal lesions was explored. Further, the cost-effectiveness of screening was evaluated. Results:A total of 8 189 fecal samples were collected from 8 877 participants with the recovery rate of 92.25%. 8 048 qualified samples were enrolled in this study, consisted of 3 182 males (39.54%) and 4 866 females (60.46%), with the average age of 56 years old (40-74 years). The positive rate of m SDC2 detection was 7.99% (643/8 048), and the compliance rate of colonoscopy was 73.10% (470/643). 20 cases (4.25%) of colorectal cancer, 109 cases (23.19%) of advanced adenoma, 145 cases (30.85%) of non-advanced adenoma, 79 cases (16.81%) of polyps were detected. The detection rate of intestinal lesions was 75.11% and indicated significant differences in gender and age. 20 CRCs included 15 of stage 0-I, 4 of stage Ⅱ-Ⅲ and 1 of unknown stage. The CT value of m SDC2 was negatively correlated with the proportion of advanced colorectal neoplasms ( χ2=16.063, P<0.001). The total cost of the screening was 4.339 5 million yuan, the screening benefit was 28.506 2 million yuan, and the benefit-cost ratio was 6.57. Conclusion:The CRC screening strategy of fecal m SDC2 detection combined with colonoscopy has high colonoscopy compliance and detection rate of intestinal lesions, which is conducive to the detection of early CRCs, and has good cost-effectiveness. This study suggests that this method may be applied to the general CRC screening in China and contribute to the prevention of CRC. The CT value of m SDC2 may have a certain suggestion on the malignant degree of intestinal tumors.

Objective:To evaluate the efficacy and safety of intensity modulated radiotherapy (IMRT) and programmed death-1 (PD-1) immunotherapy combined with single-agent chemotherapy for patients with local failure of esophageal cancer after initial radical chemoradiotherapy.Methods:Clinical data of 80 patients with local failure of esophageal cancer after initial radical chemoradiotherapy treated with IMRT or PD-1 immunotherapy combined with single-agent chemotherapy in People's Hospital of Xinghua between June 2014 and June 2023 were retrospectively analyzed. IMRT was delivered at 1.8-2.0 Gy per fraction, 5 fractions per week, with a total dose of 45.0-60.0 Gy in 40 patients (IMRT group). The other 40 patients received PD-1 immunotherapy combined with single-agent chemotherapy (PD-1 immunotherapy combined with single-agent chemotherapy group). Kaplan-Meier method was used for univariate analysis and the cumulative survival probability. Log-rank test was used for survival significance test. Cox proportional hazards model was used for multivariate analysis of related factors affecting overall survival (OS), progression-free survival (PFS) and local control (LC).Results:By December 2023, the follow-up rate was 100%. The 1- and 2-year OS rates in the IMRT group were 66.1% and 18.9%, with a median OS time of 10.1 months. In the PD-1 immunotherapy combined with single-agent chemotherapy group, the 1- and 2-year OS rates were 72.3% and 36.9%, with a median OS time of 12.4 months. There was a significant difference in OS rates between two groups ( χ2=3.89, P=0.049). The 1- and 2-year PFS rates in the IMRT group were 47.4% and 31.6%, with a median PFS time of 8.5 months. In the PD-1 immunotherapy combined with single-agent chemotherapy group, the 1- and 2-year PFS rates were 70.0% and 64.2%, with a median PFS time of 11.9 months. There was no significant difference in the PFS rates between two groups ( χ2=2.66, P=0.103). The 1- and 2-year LC rates in the IMRT group were 68.6% and 62.3%, with a median LC time of 8.9 months. In the PD-1 immunotherapy combined with single-agent chemotherapy group, the 1- and 2-year LC rates were 72.8% and 66.7%, with a median LC time of 12.0 months. There was no significant difference in LC rates between two groups ( χ2=0.18, P=0.672). Grade 2 radiation esophagitis and radiation pneumonitis developed in 82.5% (33/40) and 32.5% (13/40) in the IMRT group, respectively. The incidence of grade 1-2 peripheral blood leukopenia was 40.0% (16/40), 50.0% (20/40) for grade 1-2 peripheral blood thrombocytopenia, 27.5% (11/40) for moderate to severe anemia, and 20.0% (8/40) for grade 1-2 thyroid dysfunction in the PD-1 immunotherapy combined with single-agent chemotherapy, respectively. Single- and multi-factor analysis showed that the failure site ( χ2=9.01, P=0.011) and short-term efficacy ( χ2=7.78, P=0.005) were the independent prognostic factors affecting OS. The short-term efficacy was the independent prognostic factor for PFS ( χ2=31.63, P<0.001). The short-term efficacy was the independent prognostic factors affecting LCS ( χ2=17.64, P=0.001) too. Conclusion:For the patients with local failure of esophageal cancer after initial radical chemoradiotherapy, the combination of PD-1 immunotherapy with single-agent chemotherapy yields better survival prognosis than re-irradiation alone, but it is still necessary to pay attention to the related drug toxicities.

Objective To construct and apply a management plan for microaspiration of oropharyngeal secretions in ICU intubated patients.Methods Based on evidence summaries and expert consultation,a management plan for microaspiration of oropharyngeal secretions in ICU intubated patients was constructed,consisting of 19 items covering 7 aspects including identification of risk factors,position management,tube and cuff selection,cuff management,mechanical ventilation management,pain and sedation management,removal of oropharyngeal and subglottic secretions,and oral care.Convenience sampling was used to select 141 ICU intubated patients from a tertiary A comprehensive hospital in Suzhou from June,2022 to September,2023.Patients were divided into an experimental group(n=72)and a control group(n=69)according to the wards.The experimental group received the management plan for microaspiration of oropharyngeal secretions in ICU intubated patients.The control group received the nursing bundle for ventilator associated pneumonia(VAP).The incidence and time from intubation to microaspiration and VAP,duration of mechanical ventilation,ICU length of stay,and disease outcome were compared between the 2 groups.Results The incidence of microaspiration of oropharyngeal secretions,the duration of mechanical ventilation,time from intubation to microaspiration showed significant differences between the 2 groups(P<0.05).There were no significant differences in the incidence of ventilator associated pneumonia,ICU length of stay,and disease outcome between the 2 groups(P>0.05).The time from intubation to VAP in the experimental group was 7.5 days,and that in the control group was 3.8 days.Conclusion The application of the management plan for microaspiration of orophaiyngeal secretions in ICU intubated patients is beneficial for reducing the incidence of microaspiration,delaying the time from intubation to microaspiration and VAP,and shortening the duration of mechanical ventilation.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common and non-lethal urological condition with painful symptoms. The complexity of CP/CPPS’s pathogenesis and lack of efficient etiological diagnosis results in incomplete treatment and recurrent episodes, causing long-term mental and psychological suffering in patients. Recent findings indicate that the autonomic nervous system involves in CP/CPPS, including sensory, sympathetic, parasympathetic, and central nervous systems. Neuro-inflammation and sensitization of sensory nerves lead to persistent inflammation and pain. Sympathetic and parasympathetic alterations affect the cardiovascular and reproductive systems and the development of prostatitis. Central sensitization lowers pain thresholds and increases pelvic pain perception in chronic prostatitis. Therefore, this review summarized the detailed processes and mechanisms of the critical role of the autonomic nervous system in developing CP/CPPS.Furthermore, it describes the neurologically relevant substances and channels or receptors involved in this process, which provides new perspectives for new therapeutic approaches to CP/CPPS.

Colorectal cancer (CRC) is a prevalent malignant tumor often leading to liver metastasis and mortality. Despite some success with PD-1/PD-L1 immunotherapy, the response rate for colon cancer patients remains relatively low. This is closely related to the immunosuppressive tumor microenvironment mediated by tumor-associated macrophages (TAMs). Our previous work identified that a phosphoglycerate mutase 1 (PGAM1) allosteric inhibitor, HKB99, exerts a range of anti-tumor activities in lung cancer. Here, we found that upregulation of PGAM1 correlates with increased levels of M2-like tumor-associated macrophages (TAMs) in human colon cancer samples, particularly in liver metastatic tissues. HKB99 suppressed tumor growth and metastasis in cell culture and syngeneic tumor models. M2-polarization, induced by colon cancer cell co-culture, was reversed by HKB99. Conversely, the increased migration of colon cancer cells by M2-TAMs was remarkably restrained by HKB99. Notably, a decrease in TAM infiltration was required for the HKB99-mediated anti-tumor effect, along with an increase in CD8⁺ T cell infiltration. Moreover, HKB99 improved the efficacy of anti-PD-1 treatment in syngeneic tumors. Overall, this study highlights HKB99's inhibitory activity in TAM-mediated colon cancer progression. Targeting PGAM1 could lead to novel therapeutic strategies and enhance the effectiveness of existing immunotherapies for colon cancer.