OBJECTIVE: To observe the effect of moxibustion on small intestinal mucosal immune barrier in rats with diarrhea-predominant irritable bowel syndrome (IBS-D) and explore its underlying mechanisms. METHODS: Of 38 newborn rats from 4 healthy SPF pregnant rats, 12 neonatal rats were randomly selected in a normal group. IBS-D model was prepared by the combined measures for the rest rats, including neonatal maternal separation, acetic acid enema and chronic restraint stress. Twenty-four successfully-modeled rats were randomized into a model group and a moxibustion group, 12 rats in each one. In the moxibustion group, suspending moxibustion was delivered at bilateral "Tianshu" (ST25) and "Shangjuxu" (ST37), 20 min each time, once daily and for 7 consecutive days. Separately, before acetic acid enema (aged 35 days), after modeling (aged 45 days) and after intervention (aged 53 days), the body mass, loose stool rate (LSR) and and the minimum volume threshold when abdominal withdrawal reflex (AWR) scored 3 were observed in the rats of each group. After intervention (aged 53 days), using HE and PAS staining, the morphology of duodenum was observed, the length of villus and the depth of crypt were measured, the ratio of the length of villus to the depth of crypt was calculated; and the numbers of mucosal intraepithelial lymphocytes (IELs) and goblet cells were counted. With ELISA adopted, the contents of γ-interferon (IFN-γ), interleukin-4 (IL-4) and secretory immunoglobulin A (sIgA) in duodenal mucosa of rats were detected. The proportion of T cell subsets in duodenal mucosa was detected using flow cytometry. The microvilli and tight junctions of duodenal mucosal epithelial cells were observed by transmission electron microscopy, and the integrity of duodenal mucosa observed by scanning electron microscopy. RESULTS: Compared with the normal group, for the rats in the model group, the body mass, the minimum volume threshold when AWR scored 3, the length of duodenal villus and the the ratio of the length of villus to the depth of crypt, as well as the proportion of CD₈⁺ T subset were all reduced (P<0.01, P<0.05), the counts of goblet cells in duodenal mucosa decreased (P<0.01); LRS, the proportion of CD₄⁺ T subset and CD₄⁺/CD₈⁺, as well as the contents of IFN-γ, IL-4 and sIgA in duodenal mucosa and IFN-γ/IL-4 were all elevated (P<0.01); and the numbers of IELs rose (P<0.01). The morphology of duodenal mucosa was irregular, the villi got shorter, sparse and scattered, with uneven density. The morphology of epithelial cells was destroyed and the tight junctions damaged, with larger spaces. When compared with the model group, in the moxibustion group, the body mass, the minimum volume threshold when AWR scored 3, the length of duodenal villus and the ratio of the length of villus to the depth of crypt, as well as the counts of goblet cells in duodenal mucosa increased (P<0.01); LRS, the proportion of CD₄⁺ T subset, and CD₄⁺/CD₈⁺, as well as the contents of IFN-γ, IL-4 and sIgA in duodenal mucosa and IFN-γ/IL-4 were reduced (P<0.01); and the numbers of IELs was dropped (P<0.01). The morphology of duodenal mucosa was more regular, the villi were grew, got longer and arranged regularly, with even density. The morphology of epithelial cells was slightly destroyed, and the tight junctions partially damaged. CONCLUSION Moxibustion at "Tianshu" (ST25) and "Shangjuxu" (ST37) can reduce visceral hypersensitivity in IBS-D rats and relieve abdominal pain, diarrhea and other symptoms. Its effect mechanism may be related to the repair of small intestinal mucosal immune barrier and the improvement in the immune function in IBS-D.
Animals ; Irritable Bowel Syndrome/immunology* ; Rats ; Moxibustion ; Intestinal Mucosa/immunology* ; Female ; Diarrhea/therapy* ; Intestine, Small/immunology* ; Male ; Humans ; Rats, Sprague-Dawley ; Disease Models, Animal

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

The application of platelet-rich plasma (PRP) in wound repair is progressively garnering attention. However, certain patients, owing to relative or absolute contraindications, encounter impediments in the acquisition or application of autologous PRP. The utilization of homologous allogeneic PRP, sourced through rigorous donor selection and standardized preparation methodologies, as a substitute for autologous PRP, may hold favorable implications for such individuals. This article endeavors to succinctly delineate and forecast the mechanisms, advantages, limitations, efficacy and safety of allogeneic PRP in the context of wound healing, furnishing a foundation for its implementation in wound repair.

Objective:To study the safety and efficacy of endoscopic submucosal dissection (ESD) for early gastric cardia cancer (EGCC) in elderly patients.Methods:A retrospective analysis was performed on data of 499 EGCC patients who underwent ESD from January 2011 to June 2018 in Nanjing Drum Tower Hospital. The patients were divided into two groups by age, the young/middle-aged group (<65 years old) and the elderly group (≥65 years old). The baseline data, lesion features, postoperative complications, short-term efficacy and long-term efficacy of the two groups were compared.Results:The elderly group included 272 patients (283 lesions) and the young/middle-aged group included 227 patients (229 lesions). Except that there were significant differences in the age ( P<0.001) and body mass index ( P=0.002) between the elderly group and the young/middle-aged group, there were no significant differences in the baseline data or pathological features between the two groups. The rate of curative resection in the elderly group was 77.0%, lower than that in the young/middle-aged group (84.3%, P=0.045). No significant differences were found in en bloc resection rate (100.0% VS 99.6%, P=1.000), complete resection rate (94.7% VS 93.9%, P=0.705), postoperative complications incidence (6.4% VS 5.7%, P=0.747), operation time (64.02±39.24 min VS 66.16±44.62 min, P=0.566) or hospitalization time (6.76±2.06 d VS 6.47±1.74 d, P=0.092]. After the median follow-up of 47.9 months, 13.4% patients in the elderly group received additional surgery, which was slightly lower than that in the young/middle-aged group ( P=0.891). There were no significant differences in postoperative recurrence, lymph node metastasis, distant metastasis, overall mortality and disease-related mortality between the two groups. The survival analysis showed that five-year overall survival rates were 94.41% and 96.34% in the elderly group and the young/middle-aged group respectively ( P=0.156), and five-year disease-specific survival rate were 99.18% and 99.03% in the two groups respectively ( P=0.858). Conclusion:ESD is safe and effective for EGCC in elderly patients with satisfactory short-term and long-term efficacy.

Objective:To investigate the clinicopathological characteristics and cost-effectiveness of endoscopic resection and surgical resection for gastric schwannomas arising from the muscularis propria layer.Methods:Thirty-eight consecutive cases of gastric schwannomas diagnosed by histopathology between October 2011 and July 2016 were divided into the endoscopy group(including endoscopic submucosal excavation and endoscopic full-thickness resection) and the surgery group. Complications, complete resection rate and cost-effectiveness were analyzed.Results:The age was 52±10 years (range, 41-63 years) with 11(28.9%) males and 27(71.1%) females. The most common site of gastric schwannomas was the body (71.1%) and the antrum (21.1%). All 38(100%) lesions were protruded. The maximum diameter of the lesions was 2.5±1.2 cm (range 0.6-4.5 cm). Under endoscopic ultrasonography (EUS), 60.5% lesions were heterogeneous hypoechoic, and 15 (39.5%) hypoechoic. The complete resection rate of endoscopy group was 100.0% (17/17). The median operation time of the endoscopy group was 54 minutes. Perforations occurred in 11 patients (64.7%, 11/17), and metal clips or the nylon rope combined with metallic clips were used to close the defect in the endoscopy group. Compared with the surgery group, the length of hospital stay was significantly shorter (4.6±0.6 d VS 9.6±4.4 d, P<0.001); the time to the first fluid diet was significantly shorter (1.2±0.4 d VS 2.7±0.7 d, P<0.001), and the costs were significantly lower (21 965.0±9 342.4 yuan VS 34 253.3±10 520.9 yuan, P<0.001) in the endoscopy group. S100 immunoreactivity was present in all tumors. Local recurrence and distant metastasis did not occur during the median 34 months of follow-up. Conclusions:Endoscopic resection appears to be safe and effective for diagnosis and treatment of gastric schwannomas from the muscularis propria layer. The cost-effectiveness of endoscopic resection is significantly higher than surgical resection.

OBJECTIVE: To explore the effect of vinyl chloride on the blood sex hormones and liver function of male workers. METHODS: A total of 129 male vinyl chloride workers(exposure group) and 128 male office workers who were not exposed to occupational hazards(control group) were selected as study subjects by judgment sampling method. The time weighted average concentration(C_(TWA)) of vinyl chloride in the workplace air was measured. The level of urine thiodiglycolic acid(TDGA), blood routine, electrocardiogram and liver B-ultrasound were performed on the subjects. The serum levels of liver function and sex hormones were measured. RESULTS: The median of C_(TWA) of vinyl chloride in the workplace was 0.90 mg/m~3, and the geometric mean was 1.40 mg/m~3. The level of urine TDGA in the exposed group was higher than that of the control group(median: 0.68 vs 0.02 mg/g Cr, P<0.01). The abnormal rate of hemoglobin level, erythrocyte count, leukocyte count, hematocrit, mean platelet volume, aspartate transaminase, total bilirubin, indirect bilirubin and liver B-ultrasound increased in the exposure group than that of the control group(P<0.05). The levels of serum prolactin, leuteinizing hormone(LH), follicle-stimulating hormone and estradiol in the exposure group increased, the abnormal rates of prolactin, LH and estradiol increased, and the level of testosterone decreased compared with the control group(P<0.05). The levels of prolactin in the low-, medium-and high-TDGA subgroups in the exposure group increased(P<0.05), and the abnormal rates increased compared with the control group(P<0.017). CONCLUSION: Vinyl chloride can cause liver function damage in male workers and have reproductive toxicity. Prolactin can be used as a biomarker of reproductive toxicity of vinyl chloride.

Objective To investigate the roles of Pipeline embolization device ( PED) in combination with coils in the treatment of large and giant unruptured internal carotid artery aneurysms. Methods From January 2014 to December 2016,51 patients with large (diameter 10-25 mm) and giant (diameter >25 mm) internal carotid artery aneurysms treated at the Department of Neurosurgery,Xuanwu Hospital,Capital Medical University were analyzed retrospectively. Among them,35 were females and 16 were males, the average age was 53 ±13 years (range 15-71). They were divided into a PED group (n=31) and a PED combined with coil group (n=20) according to whether using coils for packing aneurysm cavity or not. The treatment of two groups of patients and ≥6 months of imaging follow-up effect were analyzed. The embolic rate was evaluated by Raymond grade. Results Thirty-one patients with 32 aneurysms ( mean diameter 15 ± 3 mm) in the PED group were treated with 33 PEDs,including 15 with cavernous sinus aneurysm and 17 with supraclinoid aneurysm;20 patients with 21 aneurysms ( mean diameter 17 ± 4 mm) were treated with 22 PEDs in the PED combined with coil group,including 10 cavernous sinus aneurysms and 11 supraclinoid carotid aneurysms. Six months after procedure,imaging follow-up revealed that the incidence of residual aneurysm ( Raymond grade Ⅱ-Ⅲ) in the PED group was significantly higher that that in the PED combined with coil group (9. 7% [n =3] and 0％,respectively). The incidence of thrombosis in PED combined with coil group was significantly higher than that in the PED group,there was significant difference between two groups (P<0. 05). Conclusions When using PED to treat large and giant internal carotid artery aneurysms,packing aneurysm cavity in combination with coils can reduce the incidence of residual aneurysm,but it may have a higher risk of thrombotic events. A prospective randomized controlled trial of large samples is still needed to prove it.

Objective To investigate the roles of high-resolution magnetic resonance imaging (HR-MRI) in the diagnosis and treatment of vertebrobasilar dissecting aneurysms (VBDA).Methods From January 2016 to December 2016,62 patients with VBDA admitted to Xuanwu Hospital,Capital Medical University using 3.0 T HR-MRI (3D-TOF-MRA,3D-T1WI,and 3D-T1WI+C sequence) and diagnosed by DSA were analyzed retrospectively.They were divided into either an asymptomatic group (n=18) or a symptomatic group (n=44) according to their medical histories.Their clinical features,imaging features,and the relationship with prognosis were analyzed.Results HR-MRI revealed that the double lumen sign/intimal flap accounted for 27.8% (n=5) and 54.5% (n=24) respectively in the asymptomatic group and symptomatic group.The intramural hematoma accounted for 22.2% (n=4) and 43.2% (n=19) respectively in both groups.The enhancement of aneurysmal wall accounted for 33.3% (n=6) and 77.3% (n=34) in the asymptomatic group and symptomatic group.There were significant differences in the above features between the two groups (all P<0.05).In the symptomatic group,18.2% (n=8) of patients had aneurysm recurrence,which was significantly higher than the asymptomatic group (5.6%,n=1).The difference between the two groups was statistically significant (P<0.05).Conclusions HR-MRI can better reveal the lesion characteristics of VBDA.The rates of aneurysmal wall enhancement and recurrence in symptomatic VBDAs are higher,which indicates that HR-MRI can assess the stability of the aneurysmal wall and identify the prognosis to a certain extent.

OBJECTIVETo evaluate the feasibility of monitoring clopidogrel resistance with flow cytometric analysis of platelet vasodilator stimulated phosphoprotein (VASP) phosphorylation.

METHODSTwenty patients with coronary heart disease (CHD) and 17 healthy volunteers were examined for platelet aggregation rate and phosphorylation of VASP (calculated as platelet reactivity index, PRI) using traditional optical nephelometry and flow cytometry before and after concurrent therapy of clopidogrel and aspirin.

RESULTSNo significant differences were found in PRI between CHD group and healthy control group [(89.45∓5.22)% vs (86.58∓4.35)%] before treatment. The PRI in CHD group was significantly lowered after treatment to (67.66∓19.77)% (P<0.05). Clopidogrel resistance was found in 6 (30%) cases in CHD group by flow cytometric analysis, which showed a higher sensitivity than optical nephelometry (10%).

CONCLUSIONFlow cytometric analysis of VASP phosphorylation is a more reliable test to specifically evaluate clopidogrel resistance.

Aged ; Aged, 80 and over ; Case-Control Studies ; Cell Adhesion Molecules ; chemistry ; Drug Resistance ; Female ; Flow Cytometry ; Humans ; Male ; Microfilament Proteins ; chemistry ; Middle Aged ; Phosphoproteins ; chemistry ; Phosphorylation ; Platelet Function Tests ; Ticlopidine ; analogs & derivatives ; pharmacology