To investigate the regulation of N6- methyladenosine ( m6A ) modification on L-type calcium channels in atrial myocytes under high hydrostatic pressure, mediated by methyltransferase-like protein 3 ( METTL3 ). Methods C57BL/6J mice were randomly assigned to the control group and the hypertension group ( treated with continuous administration of angiotensin for four weeks ). Masson staining was used to observe the fibrosis of mouse atrial tissue, while dot blot assay and Western blot were used to detect the levels of m6A, METTL3, and Cavi1 2 in the atrial tissue. A high hydrostatic pressure model was constructed using the HL-1 cell line cultured in vitro, and METTL3 was intervened to observe changes in m6A expression levels, METTL3 and Cavi1 2 levels in cells,and action potential duration ( APD ) and L-type calcium current ( I

The chemical constituents in the ethanol extract of Hypericum wightianum(Hypericaceae) were purified by column chromatography and identified via magnetic resonance imaging(NMR), high-resolution mass spectrum, and circular dichroism. A total of 22 compounds were identified, including eight polyprenylated phloroglucinols(1-8), three chromones(9-11), and three terpenoids(14-16) and so on. Among them, compounds 16 and 17 were first reported in the genus Hypericum, and compounds 1-11, 14, 15, and 19 were first isolated from H. wightianum. Compounds 1-4 were previously reported as two pairs of enantiomers. This study reported the chiral resolutions and absolute configurations of compounds 1-4 for the first time.
Phloroglucinol ; Hypericum/chemistry* ; Molecular Structure ; Magnetic Resonance Spectroscopy ; Drugs, Chinese Herbal/chemistry*

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

OBJECTIVE: To comprehensively evaluate the long-term efficacy and safety of coated metal stent implantation for ureteroscopic lithotripsy related refractory ureteral stricture (URL-rUS). METHODS: Electronic medical records of 30 patients (31 affected renal units) receiving coated metal stent implantation for URL-rUS from Sept. 2018 to Aug. 2021 at Peking University People' s Hospital were reviewed for analysis. Coated metal stents were implanted in retrograde approach via ureteroscope. Last outpatient follow-up was set as endpoint. Baseline information, stricture characteristics and decompression strategy before coated metal stent implantation were retrospectively collected. Serum creatinine (Scr) concentration and renal pelvis width (RPW) were used as renal function indicators. Peri-operative and long-term complications and according outcomes were recorded. For the patients who had double J tubes implanted for drainage before operation, Ureteral Stent Symptom Questionnaire (USSQ) was applied to evaluate the stent-related discomforts and quality of life (QoL) before and after surgery. Data analysis was conducted with SPSS (version 25.0; SPSS, Chicago, IL, USA). RESULTS: Totally 30 patients with 31 affected renal units were included. All the patients previously underwent unsuccessful traditional endoscopic balloon dilation or endoureterotomy before receiving coated metal stent implantation. The mean age was (45.5±9.3) years old. The median follow-up time were 14 (6-36) months. All coated metal stents were successfully placed with a median duration of 60 (30-195) min. No severe peri-operative complications occurred. At endpoint, 28 (90.3%) sides of coated metal stents remained unobstructed with a longest indwelling time of 36 months. Causes of failures included stent migration (1 case, 3.2%), encrustation (1 case, 3.2%) and repeated stent related urinary tract infection (1 case, 3.2%). When compared with the baseline, significant reductions were observed in both Scr concentration and RPW at endpoint [(90.7±19.5) mmol/L vs. (83.1±18.5) μmol/L, P < 0.01, for Scr; (2.5±1.3) cm vs. (1.9±0.8) cm, P < 0.01, for RPW], indicating good preservation of renal function and remission of hydronephrosis. For 26 patients with double J stents before operation, significant reduction of USSQ average score (100.4±6.6 vs. 82.1±4.9, P < 0.01) evidenced better life quality preserving ability of coated metal stent versus double J stent. CONCLUSION Coated metal stent implantation is a safe and minimally invasive management of ureteral stricture providing a satisfying long-term patency rate, after which the patients' quality of life and renal function could be both improved. This method could serve as a promising alternative long-term maintenance treatment option for patients with URL-US, especially when traditional endoscopic interventions failed.
Adult ; Constriction, Pathologic ; Humans ; Lithotripsy ; Metals ; Middle Aged ; Quality of Life ; Retrospective Studies ; Stents/adverse effects* ; Treatment Outcome ; Ureteral Obstruction/surgery* ; Ureteroscopy

Objective: Autologous peripheral blood stem cells (PBSC) derived from bone marrow can promote liver regeneration and improve the liver function of patients, but there are few studies on its effect on the long-term outcomes in patients with decompensated cirrhosis. Based on previous work, this study observed the clinical outcomes of PBSC treatment in patients with decompensated cirrhosis for 10 years, in order to provide more data support for the safety and efficacy of stem cells in clinical applications. Methods: Data of patients with decompensated liver cirrhosis who completed PBSC treatment in the Department of Gastroenterology of the First Affiliated Hospital of Air Force Military Medical University from August 2005 to February 2012 were included. The follow-up endpoint was death or liver transplantation, and patients who did not reach the follow-up endpoint were followed-up for at least 10 years. The patients with decompensated liver cirrhosis who met the conditions for PBSC treatment but did not receive PBSC treatment in our hospital during the same period were used as controls. Results: A total of 287 cases with decompensated liver cirrhosis had completed PBSC treatment, and 90 cases were lost to follow-up within 10 years after surgery. A total of 151 cases with complete survival follow-up data were included in the control group. There were no statistically significant differences in baseline information such as gender, age, etiological composition and liver function score between the two groups. The 10-year survival rate was higher in PBSC than control group (37.56% vs. 26.49%, P<0.05). Cholinesterase, albumin, international normalized ratio, Child-Turcotte-Pugh score, model for end-stage liver disease score, and other indicators were gradually recovered within 3 months to 1 year after PBSC treatment, and stabilized at a more desirable level in the long-term after follow-up for up to 10 years. There was no statistically significant difference in the incidence of liver cancer between the two groups (25.22% vs.31.85%, P=0.267). The age of onset of hepatocellular carcinoma was later in PBSC than control group [(56.66±7.21) years vs. (52.69±8.42) years, P<0.05]. Conclusions: This long-term observational follow-up study of more than ten years confirms that PBSC treatment can bring long-term benefits to patients with decompensated cirrhosis, with good long-term safety, thus providing more data support on the safety and efficacy of stem cells for clinical applications.
End Stage Liver Disease ; Follow-Up Studies ; Humans ; Liver Cirrhosis/drug therapy* ; Middle Aged ; Peripheral Blood Stem Cells ; Severity of Illness Index ; Treatment Outcome

Objective:To observe the effect of Zuoguiwan on bone metabolism and Wnt/β-catenin signaling pathway in ovariectomized osteoporotic rats model， and to explore the molecular biological mechanism of Zuoguiwan in the prevention and treatment of osteoporosis. Method:The rat model of postmenopausal osteoporosis was established by bilateral ovariectomy， 60 female SD rats were randomly divided into sham operation group， model group， positive group （estradiol valerate tablet 0.05 mg·kg^-1·d^-1） and low， middle and high dose groups of Zuoguiwan （5.5，11，22 g·kg^-1·d^-1）.After successful establishment of the model in the 13^th week， intragastric administration （ig） was given once a day for a total of 12 weeks. After administration， the histomorphological changes of femur in rats were observed by hematoxylin-eosin （HE） staining， the bone mineral density （BMD） and bone mineral content（BMC） of femur were measured by dual energy X-ray apparatus， and the biomechanical properties of bone were measured by MTS Acumen3 biomechanical testing system. The contents of bone alkaline phosphatase （BALP）， bone glaprotein（BGP），estradiol （E₂） ，and tartrate-resistant acid phosphatase （TRAP）， type Ⅰ procollagen N-terminal propeptide （PINP） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the protein level of Wnt2，β-catenin，low density lipoprotein related receptor protein 5 （LRP5） and the phosphorylation level of glycogen synthase kinase-3β（GSK-3β） in rat tibia. Result:Compared with sham operation group， the maximum load and stiffness of BMD，BMC， in the model group decreased significantly（P<0.01）， the contents of E₂ and PINP in serum decreased significantly（P<0.01）， the content of BALP，BGP，TRAP increased significantly（P<0.01）， the expression levels of Wnt2，p-GSK-3β Ser9，LRP5 and β-catenin protein in bone tissue decreased significantly（P<0.01）， the trabecula of femur became thinner and thinner， the number of bone trabeculae decreased. Compared with model group， the maximum load and stiffness of BMD，BMC， in estradiol group and Zuoguiwan group were significantly increased （P<0.05，P<0.01）， the contents of serum E₂ and PINP were significantly increased （P<0.05，P<0.01）， the content of BALP，BGP，TRAP was significantly decreased （P<0.01）， and the expression level of Wnt2，p-GSK-3β Ser9，LRP5， β-catenin protein in bone tissue was significantly increased （P<0.05，P<0.01） ， the trabeculae of femur became thicker， the number increased， the structure was basically clear. Conclusion:Zuoguiwan has a certain preventive and therapeutic effect on osteoporosis in ovariectomized rats， and its mechanism may be related to increasing the level of estrogen， activating Wnt/β-catenin signaling pathway， up-regulating the expression of Wnt2 and LRP5 protein， inhibiting the activity of GSK-3β， reducing the degradation of β-catenin， coordinating the dynamic coupling balance between bone formation and bone resorption， correcting the disorder of bone metabolism and improving bone morphology.

The ripe dried fruit of citron(Citrus medica) is one of the important sources of Chinese herb Citri Fructus. At the same time, it is also grown for edible and ornamental uses. There are many species and abundant genetic variation. To clarify the intraspecific variation and resource distribution of citron, this study investigated the variation in 11 citron fruits, basically covering the main species in China, including Xiaoguo citron(C. medica var. ethrog), Goucheng(C. medica var. yunnanensis), Muli citron(C.medica var. muliensis), Dehong citron(C.medica×Citrus spp.), Fuzhou citron(C.medica×C.grandis?), Mawu(C.medica×C.grandis?), Cangyuan citron, Binchuan citron, Sweet citron, Big citron, and Small citron. The natural communities of citron were proved to be mainly distributed in the southwestern and western Yunnan and southeastern Tibet of China, with Yunnan, Sichuan, Guangxi, Chongqing, Hubei, and Zhejiang identified as the main production areas. Citron has also been widely grown in India, the Mediterranean region, and the Caribbean coast countries. The field investigation revealed the large-scale intraspecific variation of citron fruits. Most of the fruits are oval-like or sphere-like in shape. The fruits are green when raw and yellow when ripe, with oil cell dots on the skin, stripe-likes running from top to bottom, and bulge at the top. Usually, in the smaller citron fruits, the pulp and juice vesicles are better developed and the central columella is tighter. By contrast, the juice vesicles and central columella in larger fruits became more vacant, with carpels visible, and the apex segregation and development of the carpels is one of the reasons for variation. These variations should be given top priority in the future variety selection and breeding, and the quality differences of different citron species and their mechanisms should be further studied. In particular, variety selection and classification management according to their medicinal or edible purposes will provide scientific and technological supports for the orderly, safe, and effective production of citron products consumed as food and medicine.
China ; Citrus ; Fruit ; Taste ; Tibet

OBJECTIVE: To investigate the clinical effectiveness of polytheretherketone (PEEK) cages assisted anterior cervical discetomy and fusion (ACDF) to treat cervical spondylosis with sympathetic symptoms. METHODS: Retrospective analysis was undertaken for 39 patients who were diagnosed as cervical spondylosis with sympathetic symptoms and underwent ACDF with PEEK cages. Radiographs obtained before surgery, after surgery, and at the final follow-up were assessed for quality of fusion. The following criteria were used for assessing radiographic success of fusion: (1) endplate obliterated with no lucent lines; (2) obliteration of disc space by bony trabeculae; (3) less than 2°of intervertebral motion or 2 mm of motion between the spinous processes at the operated segment on flexion-extension lateral radiographs. The sympathetic symptoms including vertigo, headache, tinnitus, nausea and vomiting, heart throb, hypomnesia and gastroenterological discomfort were scored by 20-point system preoperatively, 2 months postoperatively and at the final follow-up. The recovery rate and clinical satisfaction rate were also evaluated. Surgical complications were also assessed. RESULTS: They were followed up for at least one year. The mean follow-up was 15.6 months. Radiographs of the cervical spine at the last follow-up revealed a solid fusion with no signs of a pseudoarthrosis in 36 cases. In two patients delayed union and bony fusion were achieved at the end of 9 and 11 months. Pseudoarthosis was found in 1 case but the patient had no symptoms. The score of sympathetic symptoms before surgery, 2 months after surgery and at the final follow-up were 8.4±1.0,2.2±0.3,and 2.4±0.3, respectively. There were 22 excellent cases, 15 good cases, 1 fair case and 1 bad case in terms of RR. Good to excellent results were attained in 95% of theses patients. The sympathetic symptoms improved in all the patients and the score was significantly improved after surgery. There was one patient who had cerebral spinal fluid leakage but he recovered one week after surgery. Two patients felt a mild swallowing discomfort, but it disappeared within one month after surgery. Subcutaneous hematoma occurred in one patient due to obstructed drainage. It was cleared two days after surgery. CONCLUSION Cervical spondylosis patients with sympathetic symptoms may be managed successfully with ACDF using PEEK cages. Successful clinical results regarding symptom improvement and general satisfaction with the surgical procedure depend not only on obtaining successful decompression and radiographic fusion but also on patient selection.
Cervical Vertebrae/surgery* ; Decompression, Surgical ; Diskectomy ; Humans ; Male ; Nausea ; Neurosurgical Procedures ; Radiography ; Retrospective Studies ; Spinal Fusion ; Spondylosis/surgery* ; Treatment Outcome ; Vomiting

OBJECTIVETo investigate the adjuvant therapeutic effects of fermented red ginseng (FRG) extract on non-small cell lung cancer (NSCLC) patients treated with chemotherapy.

METHODSA total of 60 patients with advanced NSCLC were divided into two groups using a random number table, i.e., the gemcitabine plus cisplatin (GP) chemotherapy alone group (26 patients) and the FRG + GP chemotherapy group (34 patients), for 60-day treatment. Patients were then assessed according to the Fatigue Symptom Inventory, Chinese medicine symptoms score, Self-Rating Anxiety Scale, Self-Rating Depression Scale, Karnofsky Performance Status Scale, and Functional Assessment of Cancer Therapy-Lung. In addition, chemotherapy toxicity and tumor biomarkers were measured.

RESULTSFor NSCLC patients after chemotherapy, FRG extract significantly improved the FSI score, CM symptoms score, psychological status, physical conditions, and quality of life and reduced chemotherapy toxicity, but the expression levels of carcinoembryonic antigen, cytokeratin-19 fragments, and neuron-specific enolase were not significantly different between the chemotherapy alone and the FRG + chemotherapy groups or between pre- and post-treatments.

CONCLUSIONSThis study demonstrated that FRG extract had an adjuvant effect on advanced NSCLC patients treated with chemotherapy. Further studies with a larger sample size will verify the current findings.

To increase the permeation and retention of isopsoralen in skin, and improve its bioavailability.Isopsoralen loaded nanostructure liquid carrier (IPRN-NLC) was prepared by high pressure homogenization andoptimized by orthogonal experiment with the encapsulation efficiency, drug loading and average particle size as the evaluation indexes. The in vitro transdermal permeation of IPRN-NLC was evaluated by Franze diffusion cells.The results showed that solid-liquid lipid ratio of optimum IPRN-NLC formulation was 7∶3,drug-lipid ratio of 1∶30, 1% surfactant. Under these conditions, IPRN-NLC had an average encapsulation of （90.25±0.73）%,drug loading of （1.56±0.27）% and an average particle size of (305±1.57) nm.The in vitro transdermal permeation results showed that IPRN-NLC could increase the amount of IPRN permeated though skin, with 3 times of the epidermal retention as compared with IPRN solution. From the results we can know that the IPRN-NLC prepared by high pressure homogenization can improve the permeation andaccumulation of IPRN in the skin, with wide application prospects in the field of transdermal administration.