Objective:To explore the external treatment methods of hemorrhoids based on ancient books and documents; To guide clinical medication.Methods:The relevant articles on external treatment of hemorrhoids using Chinese materia medica included in Zhong Hua Yi Dian (5th edition) were retrieved. Excel 2021 was used to analyze the properties, tastes, meridian tropism, external treatment methods and drug efficacy of Chinese materia medica included in the prescriptions, and the relevant discussion contents were sorted out according to the classification of external treatment methods of hemorrhoids. Results:A total of 255 articles in ancient books were included, involving 165 prescriptions. 146 kinds of Chinese materia medica for external treatment of hemorrhoids were selected. The medicinal properties were mainly cold and warm, the main tastes were pungent, bitter and sweet, and the meridian tropism mainly involved the liver, spleen, stomach, heart, lung and large intestine meridians. Fumigation, application and application are the most widely used external treatment methods. Chinese materia medica efficacy mainly includes heat clearing drugs, surface relieving drugs, resuscitation drugs, astringent drugs, anti venom, anti insect and anti itching drugs, and tonic drugs.Conclusions:Ancient physicians treated hemorrhoids with both cold and heat, and paid equal attention to clearing heat and reducing fire, warming and activating blood circulation. They paid attention to the combination of local medication of lesions and the overall treatment of multiple meridians and multiple viscera, so as to achieve the simultaneous treatment of specimens. The treatment methods were rich, including fumigation and washing method to improve local microcirculation, application method using natural adhesive, coating method focusing on precise administration and ligation method of minimally invasive, forming a unique external treatment system, which can be used for modern clinical reference.

AIM:To explore the therapeutic effects of Liuwei-Dihuang decoction(LD)on ovarian function in pre-mature ovarian failure(POF)mice,and to uncover the role of the Notch signaling pathway in its mechanism.METHODS:A mouse model of POF was constructed through intraperitoneal injection of cyclophosphamide/busulfan.Subsequently,the mice were randomly divided into six groups(n=12 per group):control,POF model,low-dose LD(LD-L),medium-dose LD(LD-M),high-dose LD(LD-H),and positive drug(0.7 mg/kg diethylstilbestrol)groups.The ovarian histopathologi-cal alterations were assessed by hematoxylin-eosin(HE)staining.Serum levels of follicle-stimulating hormone(FSH),anti-Müllerian hormone(AMH),and estradiol(E2)were quantified via ELISA assays.Immunohistochemistry(IHC)was conducted to compare the expression level of cell proliferation marker Ki-67 in mouse ovarian tissues among the groups.The expression of proteins involved in the Notch pathway components[Notch1,Notch2,Jagged1(JAG-1),and hairy and enhancer of split 1(Hes1)]was determined via IHC and Western blot,while the corresponding mRNA levels of Notch1,Notch2,JAG-1,JAG-2,Hes1,and Hes5 were quantified through the qPCR analysis.RESULTS:Ovarian weight was significantly higher,and the number of atretic follicles was significantly lower in the LD-H and positive drug groups com-pared to the model group(P<0.05).However,serum FSH levels were decreased(P<0.01),whereas those of E2 and AMH were elevated in both treatment groups compared with the model group(P<0.01).In the LD-H group,the expres-sion of key molecules of the Notch pathway components was increased at the protein and mRNA level compared with the model group(P<0.01).CONCLUSION:LD ameliorates ovarian dysfunction in POF mice via activating the Notch sig-naling pathway.

AIM:To explore the therapeutic effects of Liuwei-Dihuang decoction(LD)on ovarian function in pre-mature ovarian failure(POF)mice,and to uncover the role of the Notch signaling pathway in its mechanism.METHODS:A mouse model of POF was constructed through intraperitoneal injection of cyclophosphamide/busulfan.Subsequently,the mice were randomly divided into six groups(n=12 per group):control,POF model,low-dose LD(LD-L),medium-dose LD(LD-M),high-dose LD(LD-H),and positive drug(0.7 mg/kg diethylstilbestrol)groups.The ovarian histopathologi-cal alterations were assessed by hematoxylin-eosin(HE)staining.Serum levels of follicle-stimulating hormone(FSH),anti-Müllerian hormone(AMH),and estradiol(E2)were quantified via ELISA assays.Immunohistochemistry(IHC)was conducted to compare the expression level of cell proliferation marker Ki-67 in mouse ovarian tissues among the groups.The expression of proteins involved in the Notch pathway components[Notch1,Notch2,Jagged1(JAG-1),and hairy and enhancer of split 1(Hes1)]was determined via IHC and Western blot,while the corresponding mRNA levels of Notch1,Notch2,JAG-1,JAG-2,Hes1,and Hes5 were quantified through the qPCR analysis.RESULTS:Ovarian weight was significantly higher,and the number of atretic follicles was significantly lower in the LD-H and positive drug groups com-pared to the model group(P<0.05).However,serum FSH levels were decreased(P<0.01),whereas those of E2 and AMH were elevated in both treatment groups compared with the model group(P<0.01).In the LD-H group,the expres-sion of key molecules of the Notch pathway components was increased at the protein and mRNA level compared with the model group(P<0.01).CONCLUSION:LD ameliorates ovarian dysfunction in POF mice via activating the Notch sig-naling pathway.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

OBJECTIVE To investigate the pharmacokinetics and bioavailability of naproxen choline ionic liquid in rats after intragastric administration. METHODS Naproxen choline ionic liquid was given to rats by intragastric administration. Blood samples were collected at different time points after administration. The blood samples were precipitated by methanol and then centrifuged, and then an Extend-C18 column(4.6 mm×250 mm, 5 μm) was used. Methanol(A)-0.3% phosphoric acid aqueous solution(B) (74:26) was used as the mobile phase, the flow rate was 0.8 mL·min-1, and the detection wavelength was 230 nm. Indomethacin and naproxen were used as internal standard and tested object in determination of naproxen choline ionic liquid in rat plasma. Pharmacokinetic parameters were calculated using DAS 2.0 software. RESULTS After intragastric administration of naproxen suspension to rats, its t1/2α was 5.12 h, t1/2β was 10.13 h, Tmaxwas 2 h, Cmax was 112.92 mg·L-1, and AUC(0-t) was 1 091.01 mg·L-1·h. After intragastric administration of naproxen choline, its t1/2α was 5.64 h, t1/2β was 69.32 h, Tmax was 1 h, Cmax was 135.97 mg·L-1, AUC(0-t) was 1 305.79 mg·L-1·h, and the relative bioavailability was 119.686%. CONCLUSION After intragastric administration of naproxen choline to rats, the peak concentration and bioavailability of the naproxen in vivo are higher than those of the common suspension, and the peak time is earlier.

Objective:To investigate the protective effect of hyperbaric oxygen therapy(HBOT)on myocardial fibrosis and oxidative stress induced by D-galactose(D-gal)in senescent model mice and its possible mechanism.Methods:Three-month-old male Kunming mice(n=27)were randomized into control, D-gal, and D-gal + HBOT groups.The control group received subcutaneous sterilized saline(5 ml · kg -1· d -1)for 8 weeks; the remaining 2 groups received subcutaneous D-gal(200 mg · kg -1· d -1)for 8 weeks. The D-gal + HBOT group underwent HBOT intervention at week 7~8.At the end of the experiment, the histopathological changes were analyzed by hematoxylin-eosin(HE)staining, and the fibrosis changes were analyzed by Masson staining and Sirius red staining.Oxidative stress kit was used to detect catalase(CAT), total superoxide dismutase(T-SOD)activity and malon-di-aldehyde(MDA)content in serum of mice.Western blotting was used to detect the expression levels of the aging-related proteins p53 and p16 in mouse heart tissue, the heart-function-related proteins atrial natriuretic peptide(ANP)and brain natriuretic peptide(BNP), and the oxidative stress-related protein superoxide dismutase 1(SOD1), superoxide dismutase 2(SOD2)and catalase(CAT). Results:Cardiac morphologic staining indicated that as compared with the control group, mice of D-gal group exhibited features of senescence and the increased fibrosis area, and senescence and fibrosis were obviously improved after HBOT intervention as compared with the D-gal group.The findings of the oxidative stress kit measurement indicated that as compared with the control group, the D-gal group had markedly decreased activities of CAT and T-SOD, significantly increased MDA content in the serum.After HBOT treatment, as compared with d-gal group, serum CAT and T-SOD activities were increased, while MDA content was decreased( F=126.85, 32.89, 157.50, all P<0.05).Furthermore, as compared with the control group, the D-gal group had obviously increased contents of p53, p16, ANP and BNP, while the content of CAT, SOD1 and SOD2 were obviously decreased.After HBOT intervention, as compared with the D-gal group, the contents of p53, p16, ANP、BNP were reduced, while the content of CAT, SOD1 and SOD2 were increased( F=36.37, 14.81, 23.28, 58.41, 12.79, 80.08, 6.63, all P<0.05). Conclusions:HBOT intervention could protects against cardiac injury in aging mice, which may be related to attenuating myocardial fibrosis, inducing the expression of antioxidant enzymes, and reducing oxidative stress.

OBJECTIVES: Idiopathic intracranial hypertension (IIH) is a syndrome that excludes secondary causes such as intracranial space-occupying lesion, hydrocephalus, cerebrovascular disease, and hypoxic ischemic encephalopathy. If not be treated promptly and effectively, IIH can cause severe, permanent vision disability and intractable, disabling headache. This study aims to explore the clinical and image features for IIH, to help clinicians to understand this disease, increase the diagnose rate, and improve the outcomes of patients. METHODS: We retrospectively analyzed 15 cases of IIH that were admitted to Xiangya Hospital, Central South University, during January 2015 to September 2020. The diagnosis of IIH was based on the updated modified Dandy criteria. We analyzed clinical data of patients and did statistical analysis, including age, gender, height, weight, medical history, physical examination, auxiliary examination, treatment and outcome. RESULTS: There were 10 females and 5 males. Female patients were 22 to 42 years old with median age of 39.5. Male patients were 27 to 52 years old with the median age of 44.0. The BMI was 24.14-34.17 (28.71±2.97) kg/m CONCLUSIONS IIH primarily affects women of childbearing age who are overweight. The major hazard of IIH is the severe and permanent visual loss. Typical image signs have high specificity in IIH diagnosis. Prompt diagnosis and effective treatment are significantly important to improve the outcomes of patients.
Adult ; Anemia, Iron-Deficiency ; Female ; Humans ; Intracranial Hypertension ; Male ; Middle Aged ; Pseudotumor Cerebri/diagnostic imaging* ; Retrospective Studies ; Ventriculoperitoneal Shunt ; Young Adult

Objective:To explore a new method for correcting the senile blepharochalasis and depression of the upper eyelid.Methods:Fourteen female patients with blepharochalasis and depression of upper eyelid were treated with subcutaneous tissue flap filling during eyebrow lifting. The under-eyebrow incision was used to remove the loose skin and lift the eyebrow, and a subcutaneous tissue flap was made to fill up the upper eyelid depression.Results:All the incisions were healed in one stage without complications such as infection and subcutaneous hematoma. 12 patients were followed up for more than 6 months. In the 3rd month after operation, 1 patient had obvious scar under the eyebrow, 1 patient had skin traction wrinkles at the eyebrow. After 6 months, the incision scar was not obvious in all patients, the appearance of eyebrow ptosis was eliminated, the upper eyelid was smooth and flat, and no absorption and further depression of the upper filler were observed; the effect was satisfactory.Conclusions:The eyebrow lifting combined with the subcutaneous tissue flap filling to correct the senile upper eyelid chalasis and depression is significantly effective with less trauma and complications, and it is worthy to be promoted.

Psoriasis is characterized by abnormal proliferation of keratinocytes, as well as infiltration of immune cells into the dermis and epidermis, causing itchy, scaly and erythematous plaques of skin. The understanding of this chronic inflammatory skin disease remains unclear and all available treatments have their limitations currently. Here, we showed that IMMH002, a novel orally active S1P modulator, desensitized peripheral pathogenic lymphocytes to egress signal from secondary lymphoid organs and thymus. Using different psoriasis animal models, we demonstrated that IMMH002 could significantly relieve skin damage as revealed by PASI score and pathological injure evaluation. Mechanistically, IMMH002 regulated CD3 T lymphocytes re-distribution by inducing lymphocytes' homing, thus decreased T lymphocytes allocation in the peripheral blood and skin but increased in the thymus. Our results suggest that the novel S1P agonist, IMMH002, exert extraordinary capacity to rapidly modulate T lymphocytes distribution, representing a promising drug candidate for psoriasis treatment.

Objective To investigate the association between sarcopenia and nutritional status among inpatients aged 80 years and over.Methods A total of 120 patients aged ≥80 years admitted into geriatrics department of a third-grade first-class hospital in Shandong province who met inclusion and exclusion criteria were enrolled from March 2017 to March 2018 in this cross-sectional study.According to diagnostic criteria of Asian Working Group for Sarcopenia,patients were divided into the sarcopenia group and the non-sarcopenia group.General clinical data were collected.Nutritional assessment was validated by using Mini Nutritional Assessment(MNA)and the determined nutritional indexes of serum levels of hemoglobin and albumin.Univariate and multivariate analysis were used to analyze the association between sarcopenia and nutritional status.Results Of 120 inpatients aged ≥ 80,28 cases(23.3％)had sarcopenia,including 20 men(71.4％)and 8 women(28.6％).The incidences of sarcomenia were 1.4％ (1 case)in patients with normal nutritional status and 100％ (6 cases)in patients with malnutrition.Compared with the non-sarcopenia group,the sarcopenia group had lower levels of body mass index,serum hemoglobin,serum albumin and MNA scores[(20.0 ± 2.2) kg/m2 vs.(25.4±3.0)kg/m2,(34.5±3.4)g/L vs.(38.6±3.5)g/L,(114.4± 14.0)g/L vs.(127.3± 14.8) g/L,(8.8 ± 1.9) score vs.(12.7 ± 1.4) score,P ＜ 0.05].After adjustment for all covariates,multivariate Logistic regression analysis showed that MNA score was an independent risk factor for sarcopenia(OR =0.118,95％CI:0.026-0.530).Conclusions The incidence of sarcopenia is high in hospitalized patients aged 80 years and older.MNA score is an independent risk factor for sarcopenia.