Objective: To explore the correlation between the expression levels of endoplasmic reticulum stress(ERS) and trophoblast apoptosis-related markers and severe preeclampsia(SPE) in placental tissues of pregnant women with early-and late-onset SPE and normal pregnancy. Methods: Placental tissues from 20 early and late haired severe preeclamptic singleton pregnant women who attended the Hospital were collected(early-onset group, late-onset group), and 20 cases pregnant women of normal blood pressure and no other pregnancy complications who delivered in our hospital during the same period were selected as the normal group. Transmission electron microscopy was used to observe the ultrastructure of the endoplasmic reticulum of trophoblast cells in placental tissues. Protein blotting assay was used to detect the expression levels of endoplasmic reticulum stress-related proteins, including Glucose-regulated protein 78(GRP78), C/EBP homologous protein(CHOP), Phosphorylated eukaryotic translation initiation factor 2α(p-eIF2α) and Phosphatidylinositol-requiring enzyme 1(p-IRE1)α. Immunohistochemistry assay was used to detect the expression of proliferating cell nuclear antigen(Ki67), a proliferation marker, in placental tissues, and TUNEL staining was used to detect placental tissue trophoblast apoptosis. Results: The endoplasmic reticulum of trophoblast cells in the placental tissues of the normal pregnant women group was normal in volume, with no dilatation or swelling. In contrast, the endoplasmic reticulum of placental tissues in the severe preeclampsia group showed obvious edema and significant dilatation, and the dilatation was more obvious in the early-onset group than in the late-onset group. The expression level of endoplasmic reticulum stress-related proteins GRP78(P<0.001,P<0.05) and CHOP(P<0.01,P<0.001), the phosphorylation levels of eIF2α(P<0.000 1,P<0.01) and IRE1α(P<0.000 1,P<0.001) increased in placental tissues of both early-onset and late-onset groups compared to those of the normal group. The p-eIF2α/eIF2α(P<0.001) to p-IRE1α/IRE1α ratio(P<0.05) and GRP78(P<0.01) protein expression levels were significantly higher in the early-onset group than in the late-onset group. Compared with the normal group, the number of Ki67-positive cells per field of view was significantly reduced in the early-onset and late-onset groups(P<0.000 1,P<0.05), and the number of Ki67-positive cells was significantly lower in the early-onset group than in the late-onset group(P<0.01). There were more positive apoptotic cells per field of view in the placental tissues of the early-onset group, and the apoptosis rate of trophoblast cells was significantly higher than that in the other two groups(P<0.001,P<0.01). Conclusion Increased trophoblast apoptosis and suppressed proliferation in placental tissues of patients with severe preeclampsia may be associated with endoplasmic reticulum stress overactivation, and the activation level is higher in placental tissues of early-onset severe preeclampsia than that of late-onset group.

AIM To investigate the clinical effects of Supplemented Jiao'ai Decoction combined with warm acupuncture and moxibustion on patients with endometriosis due to Congealing Cold with Blood Stasis.METHODS Eighty-six patients were randomly assigned into control group(43 cases)for 3-menstrual cycle intervention of warm acupuncture and moxibustion,and observation group(43 cases)for 3-menstrual cycle intervention of both Supplemented Jiao'ai Decoction and warm acupuncture and moxibustion.The changes in clinical effects,TCM syndrome scores,dysmenorrhea degree indices(VAS score,PGE2,PGF2α),hemodynamic indices(RI,PI),sexhormones(E2,FSH,LH),inflammatory factors(IL-1β,IL-6,TNF-α)and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,dysmenorrhea degree indices,hemodynamic indices,sexhormones and inflammatory factors(P＜0.05),especially for the observation group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with endometriosis due to Congealing Cold with Blood Stasis,Supplemented Jiao'ai Decoction combined with warm acupuncture and moxibustion can safely and effectively regulate sexhormone levels,endometrial hemodynamics,inhibit inflammatory responses,and alleviate dysmenorrhea symptoms.

Objective To evaluate the clinical efficacy of electroacupuncture at acupoints distributed on conception vessel(CV)and governor vessel(GV)in treating ischemic stroke(AIS)complicated with dysphagia and explore its potential mechanism.Methods A total of 120 patients diagnosed with AIS complicated with dysphagia at Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University from December 2020 to December 2023 were enrolled and randomly divided into an observation group and a control group,with 60 patients per group.The control group received conventional swallowing training,while the observation group received additional electroacupuncture at acupoints distributed on CV and GV.The treatment lasted for 4 weeks.After 1 month of treatment,clinical efficacy was assessed,and the changes in Standardized Swallowing Assessment(SSA)scores,National Institutes of Health Stroke Scale(NIHSS)scores,hyolaryngeal mobility(thyroid cartilage anterior/superior displacement,hyoid bone anterior/superior displacement),and KubotaWater Swallowing Test scores were observed.Cerebral microcirculation parameters and the Chinese version of the Eating/Drinking Quality of Life(EDQoL)questionnaire were also compared.Safety and adverse events were evaluated.Results(1)The total effective rate in the observation group was 95.00%(57/60),compared to 76.67%(46/60)in the control group,demonstrating statistically superior therapeutic efficacy in the observation group(P＜0.05).(2)After treatment,both groups showed significant improvements in SSA scores and NIHSS scores(P＜0.05),with the observation group exhibiting markedly better enhancement in both SSA and NIHSS scores compared to the control group,showing statistically significant differences(P＜0.05).(3)After intervention,significant improvements were observed in anterior displacement of thyroid cartilage,superior displacement of thyroid cartilage,anterior displacement of hyoid bone,and superior displacement of hyoid bone in both groups(P＜0.05).The observation group outperformed the control group in all these laryngeal kinematic parameters with statistically significant differences(P＜0.05).(4)Both groups demonstrated significant improvement in Kubota Water Swallowing Test scores after treatment(P＜0.05),with the observation group displaying statistically greater improvement than the control group(P＜0.05).(5)Cerebral arterial parameters including peak systolic velocity(Vs),mean velocity(Vm),and resistance index(RI)were significantly improved in both groups after treatment(P＜0.05).The observation group showed superior enhancement in these cerebrovascular hemodynamic indices compared to the control group(P＜0.05).(6)Significant improvements in EDQoL scores were observed in both groups after treatment(P＜0.05),with the observation group achieving statistically greater improvement than the control group(P＜0.05).(7)The total incidence of adverse reactions was 1.67%(1/60)in the observation group versus 11.67%(7/60)in the control group,indicating a statistically significant lower adverse event rate in the observation group(P＜0.05).Conclusion Electroacupuncture at acupoints distributed on CV and GV effectively alleviates dysphagia and neurological impairment,improves hyolaryngeal mobility and cerebral microcirculation,enhances quality of life,and reduces adverse events such as aspiration pneumonia in AIS patients complicated with dysphagia.

OBJECTIVE: To elucidate the effect of Huanglian-Renshen-Decoction (HRD) on ameliorating type 2 diabetes mellitus by maintaining islet β -cell identity through regulating paracrine and endocrine glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1R) in both islet and intestine. METHODS: The db/db mice were divided into the model (distilled water), low-dose HRD (LHRD, 3 g/kg), high-dose HRD (HHRD, 6 g/kg), and liraglutide (400 µ g/kg) groups using a random number table, 8 mice in each group. The db/m mice were used as the control group (n=8, distilled water). The entire treatment of mice lasted for 6 weeks. Blood insulin, glucose, and GLP-1 levels were quantified using enzyme-linked immunosorbent assay kits. The proliferation and apoptosis factors of islet cells were determined by immunohistochemistry (IHC) and immunofluorescence (IF) staining. Then, GLP-1, GLP-1R, prohormone convertase 1/3 (PC1/3), PC2, v-maf musculoaponeurotic fibrosarcoma oncogene homologue A (MafA), and pancreatic and duodenal homeobox 1 (PDX1) were detected by Western blot, IHC, IF, and real-time quantitative polymerase chain reaction, respectively. RESULTS: HRD reduced the weight and blood glucose of the db/db mice, and improved insulin sensitivity at the same time (P<0.05 or P<0.01). HRD also promoted mice to secrete more insulin and less glucagon (P<0.05 or P<0.01). Moreover, it also increased the number of islet β cell and decreased islet α cell mass (P<0.01). After HRD treatment, the levels of GLP-1, GLP-1R, PC1/3, PC2, MafA, and PDX1 in the pancreas and intestine significantly increased (P<0.05 or P<0.01). CONCLUSION HRD can maintain the normal function and identity of islet β cell, and the underlying mechanism is related to promoting the paracrine and endocrine activation of GLP-1 in pancreas and intestine.
Animals ; Glucagon-Like Peptide 1/metabolism* ; Diabetes Mellitus, Type 2/metabolism* ; Glucagon-Like Peptide-1 Receptor/metabolism* ; Insulin-Secreting Cells/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Male ; Blood Glucose/metabolism* ; Insulin/blood* ; Mice ; Intestinal Mucosa/pathology* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Islets of Langerhans/pathology*

OBJECTIVE: To investigate the effect of Tongmai Hypoglycemic Capsule (THC) on myocardium injury in diabetic cardiomyopathy (DCM) rats. METHODS: A total of 24 Sprague Dawley rats were fed for 4 weeks with high-fat and high-sugar food and then injected with streptozotocin intraperitoneally for the establishment of the DCM model. In addition, 6 rats with normal diets were used as the control group. After modeling, 24 DCM rats were randomly divided into the model, L-THC, M-THC, and H-THC groups by computer generated random numbers, and 0, 0.16, 0.32, 0.64 g/kg of THC were adopted respectively by gavage, with 6 rats in each group. After 12 weeks of THC administration, echocardiography, histopathological staining, biochemical analysis, and Western blot were used to detect the changes in myocardial structure, oxidative stress (OS), biochemical indexes, protein expressions of myocardial fibrosis, and nuclear factor erythroid 2-related faactor 2 (Nrf2) element, respectively. RESULTS: Treatment with THC significantly decreased cardiac markers such as creatine kinase, lactate dehydrogenase, and creatine kinase-MB, etc., (P<0.01); enhanced cardiac function indicators including heart rate, ejection fraction, cardiac output, interventricular septal thickness at diastole, and others (P<0.05 or P<0.01); decreased levels of biochemical indicators such as fasting blood glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, aspartate transaminase, (P<0.05 or P<0.01); and decreased the levels of myocardial fibrosis markers α-smooth muscle actin (α-SMA), and collagen I (Col-1) protein (P<0.01), improved myocardial morphology and the status of myocardial interstitial fibrosis. THC significantly reduced malondialdehyde levels in model rats (P<0.01), increased levels of catalase, superoxide dismutase, and glutathione (P<0.01), and significantly increased the expression of Nrf2, NAD(P)H:quinone oxidoreductase 1, heme oxygenase-1, and superoxide dismutase 2 proteins in the left ventricle of rats (P<0.01). CONCLUSION THC activates the Nrf2 signaling pathway and plays a protective role in reducing OS injury and cardiac fibrosis in DCM rats.
Animals ; Diabetic Cardiomyopathies/physiopathology* ; Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Rats, Sprague-Dawley ; Myocardium/metabolism* ; Fibrosis ; Male ; Capsules ; Hypoglycemic Agents/therapeutic use* ; NF-E2-Related Factor 2/metabolism* ; Rats ; Diabetes Mellitus, Experimental/drug therapy*

OBJECTIVES: To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). METHODS: Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. RESULTS: Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). CONCLUSIONS TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.
Humans ; Retrospective Studies ; Transplantation Conditioning/methods* ; Thiotepa/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child, Preschool ; Infant ; Child ; Transplantation, Homologous ; Graft vs Host Disease ; Adolescent

Objective: To determine the clinical efficacy of platelet-rich plasma (PRP) injection combined with warm acupuncture and moxibustion for treating patients with knee osteoarthritis and cold dampness obstruction syndrome. Methods: One hundred and twenty-eight patients with knee osteoarthritis and cold dampness obstruction syndrome who visited the Rehabilitation Department and Orthopedics Department of the Second Affiliated Hospital of Anhui University of Chinese Medicine from January 2023 to March 2024 and who met the inclusion and exclusion criteria were randomly divided into an experimental (n=64) and control group (n=64) using the random number table method. The experimental group was treated with PRP injection combined with warm acupuncture and moxibustion, whereas the control group was treated with normal saline injection combined with warm acupuncture and moxibustion treatment. PRP and normal saline injections were administered once every two weeks, a total of four times. Patients were treated with warm acupuncture and moxibustion once a day, six times a week, for four consecutive weeks. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Traditional Chinese Medicine (TCM) syndrome, visual analog scale (VAS), and Lysholm scores were determined before treatment, at week 4 and week 8 of treatment, and week 16 of follow-up. Serum interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), tumor necrosis factor-α (TNF-α), osteoprotegerin (OPG), bone gla protein(BGP), and cartilage oligomeric matrix protein (COMP) levels were compared between the two groups before and after 8 weeks of treatment. The clinical efficacy and safety indicators between the two groups were also compared. Results: There was no statistical difference in baseline data such as gender, age, disease duration, and body mass index between the two groups of patients. Compared with before treatment, both groups showed decreased WOMAC total and subscale, TCM syndrome total score and symptom scores, and VAS scores, and an increase in Lysholm scores at 4, 8, and 16 weeks after treatment. After treatment, serum IL-6, MMP-3, TNF-α, and COMP levels decreased, whereas serum OPG and BGP levels increased (P<0.05). Compared with the control group, patients in the experimental group showed decreased WOMAC total and subscale, TCM syndrome total score and symptom scores, and VAS scores, and an increase in Lysholm score at 4, 8, and 16 weeks after treatment. Compared with the control group, patients in the experimental group showed decreased serum IL-6, MMP-3, TNF-α, and COMP levels and an increase in serum OPG and BPG levels after treatment (P<0.05). The total effective rate of the experimental group was 91.94%, higher than that of the control group (81.97%; P<0.05). Conclusion PRP injection combined with warm acupuncture and moxibustion can improve various TCM symptoms, improve knee joint function and bone metabolism, and reduce inflammation in patients with knee osteoarthritis and cold dampness obstruction syndrome.