Objective To investigate whether Angelica Sinensis and Astragalus capsules(AAC)regulates myocardial autophagy in heart failure rats via the phosphatidylinositol 3 kinase(PI3K)/protein kinase(Akt)/mammalian target of sirolimus(mTOR)signaling pathway.Methods A rat model of heart failure was constructed by intraperitoneal 2.5 mg·kg-1 doxorubicin,and another 8 rats served as the control group.The modeling rats were randomly divided into model group,control group and experimental-L,-M,-H groups.Control group was given 30 mg·kg-1 3-methyladenine by intraperitoneal injection;experimental-L,-M,-H groups were given 150,300 and 450 mg·kg-1 AAC by gavage,respectively;blank and model groups were given the same quantity of sterile distilled water.Six groups were administered once daily for 6 weeks.The cardiac function was measured by ultrasound,and the expression levels of PI3K,Akt,mTOR,sequestosome 1(P62)and microtubule-associated light chain protein 3-Ⅱ/Ⅰ(LC3 Ⅱ/Ⅰ)in myocardial tissue were measured by Western blot.Results In the blank,model,control and experimental-H groups,the left ventricular ejection fraction values were(85.00±3.63)％,(56.75±4.83)％,(75.63±3.70)％and(72.75±4.23)％;the relative expression levels of PI3K were 1.00±0,0.28±0.05,0.64±0.08 and 0.74±0.16;phosphorylated Akt/Akt were 1.00±0,0.49±0.06,0.90±0.16 and 0.95±0.10;phosphorylated mTOR/mTOR values were 1.00±0,0.42±0.09,0.73±0.13 and 0.83±0.08;the relative expression levels of P62 proteins were 1.00±0,0.24±0.12,0.57±0.09 and 0.96±0.10;the relative expression levels of LC3 Ⅱ/Ⅰ proteins were 1.00±0,4.31±0.75,2.20±0.76 and 1.59±0.24,respectively.Compared to the model group,statistical significant were identified in the experimental-H and control groups(all P＜0.05).Conclusion AAC can regulate PI3K/Akt/mTOR pathway,inhibit myocardial autophagy and improve cardiac function in rats with heart failure.

Objective:To investigate the clinical effect of extraperitoneal robot-assisted laparoscopic modified Y-V plasty(LMYVP)in the treatment of refractory bladder neck contracture(BNC).Methods:We retrospectively analyzed the clinical data on 10 cases of refractory BNC after transurethral resection of the prostate between September 2020 and January 2023,all with a history of recurrent urethral dilatation and at least two failures in transurethral surgical treatment of scarring.After definite diagnosis and re-moval of some of the scar tissues to flatten the elevated bladder neck under the cystoscope,we performed robot-assisted LMYVP using the da Vinci Si robotic system and a four-port extraperitoneal approach.The surgical procedure involved an inverted T-shaped incision in the bladder neck and urethral stricture ring,an inverted V-shaped excision of the scar area at the 3-9 o'clock position on the ventral side of the prostatic urethra,continuous full-layer suturing of the bladder neck and inverted V-shaped urethra with 3-0 barbed thread,and indwelling of an F20 silicone catheter for 2 weeks.At 3 months after surgery,we performed cystoscopic examination,measured the maximum urinary flow rate(Qmax),and obtained the IPSS and quality of life(QOL)scores of the patients.Results:Operations were successfully completed in all the cases.At 3 months after surgery,the patients showed significantly increased Qmax([3.65±1.27]vs[20.3±1.77]ml/s,P＜0.05),IPSS(5.9±2.02 vs 30±1.15,P＜0.05)and QOL score(1.3±0.95 vs 5.2±0.79,P＜0.05)compared with the baseline.Cystoscopy revealed a wide and flat bladder neck with good survival and hemody-namics of the bladder flap.All the patients met the criteria for clinical cure at a median follow-up of 13.2 months.Conclusion:Extraper-itoneal robot-assisted LMYVP provides a new strategy for urinary tract reconstruction in the management of refractory BNC,with the ad-vantages of minimal invasiveness,high efficiency and high success rate.

Objective:This study aims to evaluate the clinical efficacy and safety of Dibai Yijing Formula(DYF)in the treat-ment of male infertility with essence deficiency in the kidney and damp-heat in the essence chamber(Abbreviation:kidney deficiency and damp-heat type).Methods:This study employed a randomized,controlled clinical trial design,recruiting 72 male patients with infertility due to kidney deficiency and damp-heat type.Patients were randomly assigned to an treatment group(36 patients)and a control group(36 patients)using a random number table.The control group received oral Clomiphene Citrate Capsules(50 mg,twice daily),while the treatment group received oral DYF(one dose daily,200 ml each time,30 minutes after breakfast and dinner).Both groups underwent a 12-week treatment period.After treatment,sperm concentration(SC),percentage of progressively motile sperms(PR),total sperm motility[PR+percentage of non-progressively motile sperms(NP)],and semen volume(SV)were compared between the two groups before and after treatment.Additionally,the total score of Traditional Chinese Medicine(TCM)syndrome score and sperm DNA fragmentation index(DFI)and pregnancy outcomes of the patients'spouses were compared between the two groups.Results:Three patients dropped out from the treatment group and four from the control group.There were no statistically sig-nificant differences in semen parameters between the two groups(P＞0.05).After treatment,the patients in the treatment group showed significant difference in the percentage of SC([19.42±5.30]x 106/ml vs[10.75±2.41]x 106/ml),PR([27.72±6.62]％vs[20.04±4.10]％),PR+NP([49.86±10.68]％vs(33.74±5.58)％],DFI([12.33±3.43]％vs[15.06±3.98]％)and TCM symtom score([7.45±1.82]vs[13.85±1.91]),and the difference was statistically significant(P＜0.05).The patients in the control group showed significant difference in the percentage of SC([19.56±5.24]× 106/ml vs[11.31±2.08]× 106/ml)and TCM symptom score([12.81±1.86]vs[14.06±1.64]).But no significant changes were observed in the PR([21.75±5.93]％vs[20.05±4.67]％),PR+NP([34.23±7.15]％vs[32.35±4.09]％),SV([3.19±1.08]ml vs[3.12±1.13]ml),and DFI([15.11±4.76]％vs[15.51±4.35]％)were not statistically significant(P＞0.05).Improve-ments in PR,PR+NP,TCM symptom score and DFI in the treatment group were better than those in the control group after treatment(P＜0.05);the differences in SC and SV and spousal pregnancy in the treatment group were not statistically significant compared with those in the control group(P＞0.05).No serious adverse events occurred in both groups during the treatment period.Conclusion:The treatment of male infertility with DYF is effective and safe.

OBJECTIVE: Physical exercise, a common non-drug intervention, is an important strategy in cancer treatment, including hepatocellular carcinoma (HCC). However, the mechanism remains largely unknown. Due to the importance of hypoxia and cancer stemness in the development of HCC, the present study investigated whether the anti-HCC effect of physical exercise is related to its suppression on hypoxia and cancer stemness. METHODS: A physical exercise intervention of swimming (30 min/d, 5 d/week, for 4 weeks) was administered to BALB/c nude mice bearing subcutaneous human HCC tumor. The anti-HCC effect of swimming was assessed in vivo by tumor weight monitoring, hematoxylin and eosin (HE) staining, and immunohistochemistry (IHC) detection of proliferating cell nuclear antigen (PCNA) and Ki67. The expression of stemness transcription factors, including Nanog homeobox (NANOG), octamer-binding transcription factor 4 (OCT-4), v-Myc avian myelocytomatosis viral oncogene homolog (C-MYC) and hypoxia-inducible factor-1α (HIF-1α), was detected using real-time reverse transcription polymerase chain reaction. A hypoxia probe was used to explore the intratumoral hypoxia status. Western blot was used to detect the expression of HIF-1α and proteins related to protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling pathway. The IHC analysis of platelet endothelial cell adhesion molecule-1 (CD31), and the immunofluorescence co-location of CD31 and desmin were used to analyze tumor blood perfusion. SMMC-7721 cells were treated with nude mice serum. The inhibition effect on cancer stemness in vitro was detected using suspension sphere experiments and the expression of stemness transcription factors. The hypoxia status was inferred by measuring the protein and mRNA levels of HIF-1α. Further, the expression of proteins related to Akt/GSK-3β/β-catenin signaling pathway was detected. RESULTS: Swimming significantly reduced the body weight and tumor weight in nude mice bearing HCC tumor. HE staining and IHC results showed a lower necrotic area ratio as well as fewer PCNA or Ki67 positive cells in mice receiving the swimming intervention. Swimming potently alleviated the intratumoral hypoxia, attenuated the cancer stemness, and inhibited the Akt/GSK-3β/β-catenin signaling pathway. Additionally, the desmin⁺/CD31⁺ ratio, rather than the number of CD31⁺ vessels, was significantly increased in swimming-treated mice. In vitro experiments showed that treating cells with the serum from the swimming intervention mice significantly reduced the formation of SMMC-7721 cell suspension sphere, as well as the mRNA expression level of stemness transcription factors. Consistent with the in vivo results, HIF-1α and Akt/GSK-3β/β-catenin signaling pathway were also inhibited in cells treated with serum from swimming group. CONCLUSION Swimming alleviated hypoxia and attenuated cancer stemness in HCC, through suppression of the Akt/GSK-3β/β-catenin signaling pathway. The alleviation of intratumoral hypoxia was related to the increase in blood perfusion in the tumor. Please cite this article as: Xiao CL, Zhong ZP, Lü C, Guo BJ, Chen JJ, Zhao T, Yin ZF, Li B. Physical exercise suppresses hepatocellular carcinoma progression by alleviating hypoxia and attenuating cancer stemness through the Akt/GSK-3β/β-catenin pathway. J Integr Med. 2023; 21(2): 184-193.
Humans ; Animals ; Mice ; Carcinoma, Hepatocellular/drug therapy* ; Proto-Oncogene Proteins c-akt/metabolism* ; Proliferating Cell Nuclear Antigen/therapeutic use* ; Mice, Nude ; Glycogen Synthase Kinase 3 beta/genetics* ; beta Catenin/therapeutic use* ; Liver Neoplasms/drug therapy* ; Desmin/therapeutic use* ; Ki-67 Antigen ; Cell Line, Tumor ; Hypoxia ; RNA, Messenger/therapeutic use* ; Cell Proliferation

Objective: To investigate the incidence and risk factors of systemic allergic reactions induced by subcutaneous immunotherapy (SCIT) in patients undergoing SCIT injections in Peking Union Medical College Hospital (PUMCH). Methods: This is a single center retrospective cohort study. Using the outpatient information system of PUMCH, the demographic information and injection-related reaction data of patients undergoing SCIT injection in Allergy Department of PUMCH from December 2018 to December 2022 were retrospectively analyzed to count the incidence and risk factors of systemic allergic reactions caused by SCIT. Mann-Whitney nonparametric test or chi-square test was used for single-factor analysis, and multiple logistic regression was used for multiple-factor analysis. Results: A total of 2 897 patients received 18 070 SCIT injections in Allergy Department during the four years, and 40 systemic allergic reactions occurred, with the overall incidence rate of 0.22%. The incidence of systemic allergic reaction was 0.37% when using imported dust mite preparation and 0.15% when using domestic multi-component allergen preparation. The risk factors significantly related with SCIT-induced systemic allergic reactions in patients using imported dust mite preparation were age less than 18 years old (OR=3.186,95%CI: 1.255-8.085), highest injection concentration (OR value could not be calculated because all patients with systemic reactions were injected with highest concentration), and large local reaction in previous injection (OR=22.264,95%CI: 8.205-60.411). The risk factors for SCIT-induced systemic allergic reactions in patients using domestic allergen preparation were 5 or more types of allergens (OR=3.455,95%CI: 1.147-10.402), highest injection concentration (OR=3.794,95%CI: 1.226-11.740) and large local reaction in previous injection (OR=63.577,95%CI: 22.248-181.683). However, SCIT injection in pollen allergic patients during the pollen season did not show a correlation with systemic allergic reaction. Conclusion: The incidence of SCIT-induced systemic allergic reactions was low in the Chinese patient population of this study. Patients with one or more risk factors, such as multiple allergen injection, highest injection concentration, large local reaction in previous injection, should be given high attention and vigilance against systemic allergic reactions.
Humans ; Allergens ; Asian People ; Desensitization, Immunologic/adverse effects* ; Hypersensitivity/epidemiology* ; Retrospective Studies

Objective: To investigate the incidence and risk factors of systemic allergic reactions induced by subcutaneous immunotherapy (SCIT) in patients undergoing SCIT injections in Peking Union Medical College Hospital (PUMCH). Methods: This is a single center retrospective cohort study. Using the outpatient information system of PUMCH, the demographic information and injection-related reaction data of patients undergoing SCIT injection in Allergy Department of PUMCH from December 2018 to December 2022 were retrospectively analyzed to count the incidence and risk factors of systemic allergic reactions caused by SCIT. Mann-Whitney nonparametric test or chi-square test was used for single-factor analysis, and multiple logistic regression was used for multiple-factor analysis. Results: A total of 2 897 patients received 18 070 SCIT injections in Allergy Department during the four years, and 40 systemic allergic reactions occurred, with the overall incidence rate of 0.22%. The incidence of systemic allergic reaction was 0.37% when using imported dust mite preparation and 0.15% when using domestic multi-component allergen preparation. The risk factors significantly related with SCIT-induced systemic allergic reactions in patients using imported dust mite preparation were age less than 18 years old (OR=3.186,95%CI: 1.255-8.085), highest injection concentration (OR value could not be calculated because all patients with systemic reactions were injected with highest concentration), and large local reaction in previous injection (OR=22.264,95%CI: 8.205-60.411). The risk factors for SCIT-induced systemic allergic reactions in patients using domestic allergen preparation were 5 or more types of allergens (OR=3.455,95%CI: 1.147-10.402), highest injection concentration (OR=3.794,95%CI: 1.226-11.740) and large local reaction in previous injection (OR=63.577,95%CI: 22.248-181.683). However, SCIT injection in pollen allergic patients during the pollen season did not show a correlation with systemic allergic reaction. Conclusion: The incidence of SCIT-induced systemic allergic reactions was low in the Chinese patient population of this study. Patients with one or more risk factors, such as multiple allergen injection, highest injection concentration, large local reaction in previous injection, should be given high attention and vigilance against systemic allergic reactions.
Humans ; Allergens ; Asian People ; Desensitization, Immunologic/adverse effects* ; Hypersensitivity/epidemiology* ; Retrospective Studies

Currently, the national schistosomiasis control program of China is moving from transmission interruption to elimination, and there are multiple challenges during the stage moving towards the progression of schistosomiasis elimination, including a high difficulty in shrinking snail-infested areas, unstable achievements for infectious source control, imperfect surveillance system and a reduction in schistosomiasis control and administration. Based on the core suggestions proposed in the 2022 WHO guideline on control and elimination of human schistosomiasis, recommendations on schistosomiasis surveillance system building, development of novel diagnostics, adjustment of the schistosomiasis control strategy and maintaining and improvements of the schistosomiasis control capability are proposed for the national schistosomiasis control program of China in the new era according to the actual status of schistosomiasis control in China. Formulation of the national schistosomiasis control strategy and goal from One Health perspective, verification of transmission interruption and elimination of schistosomiasis, precision implementation of schistosomiasis control interventions with adaptations to local circumstances, development and application of highly sensitive and specific diagnostics are recommended for elimination of schistosomiasis in China. In addition, the implementation of the 2022 WHO guideline on control and elimination of human schistosomiasis may guide the elimination of schistosomiasis in China.
Animals ; China/epidemiology* ; Goals ; Humans ; Schistosomiasis/prevention & control* ; Snails ; World Health Organization

Since 2015 when the transmission of schistosomiasis was controlled in China, the country has been moving towards elimination of schistosomiasis, with the surveillance-response as the main interventions for schistosomiasis control. During the period of the 13th Five-Year Plan, the transmission of schistosomiasis had been interrupted in four provinces of Sichuan, Jiangsu, Yunnan and Hubei and the prevalence of schistosomiasis has been at the historically lowest level in China. As a consequence, the goal set in The 13th Five-Year National Schistosomiasis Control Program in China is almost achieved. However, there are multiple challenges during the stage moving towards elimination of schistosomiasis in China, including the widespread distribution of intermediate host snails and complicated snail habitats, many types of sources of Schistosoma japonicum infections and difficulty in management of bovines and sheep, unmet requirements for the current schistosomiasis control program with the currently available tools, and vulnerable control achievements. During the 14th Five-Year period, it is crucial to consolidate the schistosomiasis control achievements and gradually solve the above difficulties, and critical to provide the basis for achieving the ultimate goal of elimination of schistosomiasis in China. Based on the past experiences from the national schistosomiasis control program and the challenges for schistosomiasis elimination in China, an expert consensus has been reached pertaining to the objectives, control strategy and measures for The 14th Five-Year National Schistosomiasis Control Program in China, so as to provide insights in to the development of The 14th Five-Year National Schistosomiasis Control Program in China.

OBJECTIVE: To explore the characteristics and influencing factors of high-risk factors and adverse outcomes of pregnancy in different occupational populations in a medical college community. METHODS: A total of 719 pregnant women in a medical college community were selected by convenient sampling method and divided into medical staff group(218 women) and non-medical staff group(501 women, including 138 teaching staff subgroup, 129 administrative service staff subgroup and 234 other occupation subgroup). The detection rate of high-risk factors and adverse outcomes of pregnancy were compared among these groups. RESULTS: Among the study subjects with the top five detection rates, high-risk factors of pregnancy were abnormal body mass index, advanced age, diabetes mellitus, scarred uterus and abnormal thyroid function, with the detection rate of 21.4%, 17.5%, 9.7%, 7.5% and 7.5%, respectively. The detection rates of pregnancy high-risk factors≥two, adverse pregnancy outcome, adverse fetal outcome, miscarriage and low birth weight in the medical group were significantly lower than those in the non-medical staff group(all P<0.05). The detection rates of pregnancy risk factors, primary screening risk factors, scarred uterus and pregnancy anemia in the teaching staff subgroup were significantly higher than those in the other occupation subgroups(all P<0.008). The detection rates of pregnancy high-risk factors ≥two and advanced age in the teaching staff subgroup were higher than those in medical staff group(all P<0.008). The detection rates of adverse pregnancy outcome and miscarriage in the administrative service staff subgroup were higher than those in medical staff group(all P<0.008). Multivariate logistic regression analysis results showed that occupation, advanced age, parity and scarred uterus were the main influencing factors of adverse pregnancy outcome(all P<0.05). CONCLUSION: There are differences in pregnancy high-risk factors and adverse pregnancy outcomes among different occupational groups. The teaching staff subgroup has a relatively higher detection rate of pregnancy high-risk factors, and the adverse pregnancy outcomes and miscarriage were relatively higher in the administrative service staff subgroup, compared with the medical staff group.

Objective: To explore the effect of moxibustion at Shenque (CV 8) on myocardial structure and function in exercise-induced fatigue rats. Methods: A 12-week treadmill running training was performed to create an exercise-induced fatigue rat model. Sixty eligible male specific-pathogen-free grade Sprague-Dawley rats were randomly divided into a blank group, a control group, a model group, a non-meridian non-acupoint group, a Zusanli (ST 36) group and a Shenque (CV 8) group, with 10 rats in each group. Rats in the blank group did not receive treadmill running training or moxibustion. Rats in the control group did not receive treadmill running training but received mild moxibustion at Shenque (CV 8). Rats in the model group received treadmill running training but no moxibustion. Rats in the non-meridian non-acupoint group, the Zusanli (ST 36) group and the Shenque (CV 8) group received moxibustion at the non-meridian non-acupoint points, Zusanli (ST 36) or Shenque (CV 8) immediately after each treadmill running training, 15 min each time, once a day for 5 consecutive days a week at a 2-day interval, 60 times of moxibustion in total. Left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic diameter (LVESd), left ventricular diastolic volume (LVDv), left ventricular systolic volume (LVSv), ejection fraction (EF), stroke volume (SV), early diastolic peak flow velocity of mitral valve (E) and late diastolic peak flow velocity of mitral valve (A) of each group before and after the last treadmill running training were measured. Blood was collected 6 h after the last treadmill running training, and serum C-reactive protein (CRP), myoglobin (Mb), creatine kinase-myocardial band (CK-MB), cardiac troponin I (cTnI) and cardiac troponin T (cTnT) levels were detected. Finally, the heart was separated, the heart mass (HM) was measured, the cTnT level of the myocardial tissue was detected, the ultrastructural changes of the left ventricular myocardium were observed by transmission electron microscope, the left ventricular fraction shortening (LVFS), E/A and heart mass index (HMI) were calculated. Results: Compared with the same group before treatment, the rat cardiac LVEDd, LVESd, LVDv, LVSv, SV, E and A were significantly increased (all P<0.01), and the rat LVFS, E/A and EF were significantly decreased (all P<0.01) in the model group and the non-meridian non-acupoint group after treatment; the rat cardiac SV, LVDv, LVSv, E and A were all increased (all P<0.01), while E/A and EF were decreased (all P<0.01) in the Zusanli (ST 36) group after treatment; the rat cardiac LVDv, E and A were significantly increased (P<0.01 or P<0.05), and E/A was significantly decreased (P<0.01) in the Shenque (CV 8) group after treatment. After treatment, compared with the blank group, the rat cardiac LVEDd, LVESd, SV, LVDv, LVSv, E, A, the serum CRP, Mb, CK-MB, cTnI, cTnT and HMI, and the myocardial cTnT were increased (all P<0.01), and the LVFS, E/A and EF were all reduced (all P<0.01) in the model group; compared with the model group and the non-meridian non-acupoint group, rats in the Zusanli (ST 36) group and the Shenque (CV 8) group showed decreased LVEDd, LVESd, SV, LVDv, LVSv, E, A, serum CRP, Mb, CK-MB, cTnI, cTnT and HMI, and myocardial cTnT (P<0.01 or P<0.05), along with increased LVFS, E/A and EF (all P<0.01); compared with the Zusanli (ST 36) group, Mb and A of the Shenque (CV 8) group were decreased (both P<0.01), while both E/A and EF were increased (P<0.01, P<0.05). Transmission electron microscopy examination showed that myofibrils in the blank group and the control group were neatly arranged with clear light and dark bands; the model group and the non-meridian non-acupoint group showed different degrees of myofibril disintegration and breakage, increased and aggregated mitochondria of different sizes, and increased electron density. The myofibrils in the Shenque (CV 8) group and Zusanli (ST 36) group were arranged neatly with clear light and dark bands, and compensatory hyperplasia of mitochondria. Conclusion: Moxibustion at Shenque (CV 8) and Zusanli (ST 36) both can effectively improve the occurrence of myocardial remodeling in exercise-induced fatigue rats, and the effect of moxibustion at Shenque (CV 8) is better in improving cardiac function.