ObjectiveTo investigate the efficacy and safety of cinobufagin tablets combined with thalidomide/dexamethasone （TD） regimen in the treatment of newly diagnosed multiple myeloma （NDMM） with phlegm and stasis obstruction. MethodsThe clinical data of 50 patients with NDMM of phlegm and stasis obstruction who were hospitalized at the Jiangsu Province Hospital of Chinese Medicine from June 1st， 2015 to July 31th， 2019 were retrospectively analyzed， and they were divided into a control group （bortezomib/dexamethasone-containing regimen， 27 cases） and an observation group （cinobufagin tablets combined with TD regimen， 23 cases）. The clinical efficacy and safety were compared between the two groups after two or three courses of treatment. The primary outcomes were clinical remission rate including overall response rate and deep remission rate， one-year and two-year overall survival rate， and adverse effects. The secondary outcomes were the proportion of plasma cells in bone marrow， hemoglobin， β2-microglobulin， lactate dehydrogenase， serum creatinine， blood urea nitrogen， bone pain score， and KPS functional status score （KPS score） before and after treatment. ResultsIn terms of clinical efficacy， there was no statistically significant difference （P＞0.05） in the overall response rate ［the observation group 69.57%（16/23） vs the control group 70.37% （19/27）］ and deep remission rate ［the observation group 56.52% （13/23） vs the control group 55.56% （15/27）］ between groups after the treatment. The one-year overall survival rates of the observation group and the control group were 90.9% and 92.4%， and the two-year overall survival rates were 81.8% and 80.9% respectively， with no statistically significant differences between groups （P＞0.05）. During the treatment， no renal function injury occurred in both groups. The incidence of peripheral nerve injury in the observation group was 8.70%， which was lower than 48.15% in the control group （P＜0.01）. After the treatment， the proportion of myeloma plasma cells， β2-microglobulin， serum creatinine level， and bone pain score decreased， while the hemoglobin level and KPS score increased in both groups （P＜0.05 or P＜0.01）. Compared between groups after treatment， the bone pain score of the observation group was lower than that of the control group， while the KPS score was higher than that of the control group （P＜0.05）. ConclusionThe clinical efficacy of cinobufagin tablets combined with TD in the treatment of NDMM is equivalent to bortezomib/dexamethasone-containing regimen， but the former is more helpful in relieving the pain and improving the quality of life， and has better safety.

Objective:To investigate the clinical phenotype and genetic characteristics of infantile epileptic spasm syndrome caused by BRWD3 gene mutation. Methods:Clinical data of a child with BRWD3 related infantile epileptic spasm syndrome who was admitted to Department of Pediatric Neurology of Linyi People′s Hospital on August 2, 2019 were collected and followed up, whole exome sequencing technology and Sanger sequencing were applied to verify the child and his parents, and the pathogenicity of mutation site was analyzed. The studies till June 2023 were searched with keywords of " BRWD3" in both English and Chinese databases of China National Knowledge Infrastructure, Wanfang, Online Mendelian Inheritance in Man, and PubMed. The clinical phenotype and genetic characteristics of patients with BRWD3 related epilepsy were summarized. Results:The patient was a 4 years and 4 months old boy, with a clinical phenotype including severe global development delay, focal seizures (the onset age was 4 months), epileptic spasm (the onset age was 6 months), autism, megacephaly, high forehead as well as hypsarrhythmia. The whole exome sequencing results showed a de novo and frameshift variation c.4318_4319del(p.Q1441Efs*20)(NM_153252) in the BRWD3 gene, and the variation was interpreted as pathogenic (PVS1+PS2+PM2) according to the American College of Medical Genetics and Genomics variant classification criteria and guidelines. A total of 7 English literature articles were retrieved reporting 16 cases of BRWD3 gene related epilepsy in children (including 1 case of infantile epileptic spasm syndrome), and there has been no report in China yet. Totally there were 17 cases of BRWD3 gene related epilepsy including this case. All the cases showed X chromosome dominant inheritance, of whom 15 cases showed minor variations, including 7 missense variations, 3 frameshift variations, 3 splicing variations, 2 nonsense variations, and the remaining 2 cases showed large segment deletions. A total of 15 different variants were found. The phenotypes of the 17 patients mainly included epileptic seizures (17/17), intellectual disability (10/17), motor development disorder (7/17), speech impairment (9/17), megacephaly (8/17), facial malformation (8/17), autism (4/17) and hypotonia (4/17). The common seizure types were found to be focal seizures, occasionally epileptic spasm seizures and tonic seizures. Conclusions:BRWD3 gene variation related epilepsy is an X chromosome dominant genetic disease with a wide clinical phenotype spectrum. BRWD3 gene mutation c.4318_4319del(p.Q1441Efs *20) could cause infantile epileptic spasm syndrome, manifested as severe global developmental delay, epileptic spasm, focal seizures, autism, craniofacial malformation and hypsarrhythmia. This research enriches BRWD3 gene mutation spectrum.

Objective:To report the clinical characteristics, diagnosis and treatment of a patient with linear scleroderma en coup de sabre (LSCS), and review the relevant literature in order to provide the basis for early diagnosis and timely treatment of the disease.Methods:The clinical data and treatment process of a patient with LSCS admitted to Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University on September 22, 2022 were summarized, and the case reports or case series studies related to LSCS with epilepsy or Coats-like response at home and abroad were systematically analyzed. The gender, age, onset time, clinical manifestations, treatment and prognosis of this type of patients were summarized.Results:The patient is a 22 years old female with a history of scalp patchy alopecia and ipsilofrontal en coup de sabre for over 10 years and was diagnosed as Coasts disease due to decreased vision in the right eye 5 years ago, and now she is blind. This visit was due to "episodic loss of consciousness for more than 2 hours" with epileptic seizures and Coats-like response of the left eye. Treatment with antiepileptic drugs, glucocorticoids and immunosuppressants showed satisfactory results. The clinical data of all 20 patients with LSCS reported in domestic and foreign literature were analyzed. The age of onset was 11.00 (6.75, 20.50) years, with a male to female ratio of 1∶1. The imaging findings of patients with LSCS with epilepsy were mainly manifested as multiple brain calcifications, soft tissue atrophy and skull thinning on the focal side. The results of fundus examination and fundus fluorescein angiography in patients with LSCS with Coats-like response were mainly exudative inflammation and retinal detachment, including 1 case with cerebral cerebrovascular inflammation. In terms of treatment, most of the patients with LSCS with epilepsy were treated with antiepileptic drugs, glucocorticoids combined with immunosuppressant, interleukin-6 inhibitor tozizumab, and the other 2 cases were treated with surgery. Patients with LSCS with Coats-like response were treated with intravitreal bevacizumab in combination with glucocorticoids and immunosuppressive therapy or retinal targeted photocoagulation or local laser therapy with triamcinolone. The above treatment can control the patient′s refractory epilepsy and improve the vision loss.Conclusions:The main manifestations of LSCS are en coup de sabre lesion with pigmentation on the forehead above the eyelid, accompanied by Coats-like response of the eye, epilepsy, and brain imaging abnormalities. The above clinical features may appear successively or simultaneously. In some patients, these symptoms may progress slowly, and can lead to blindness and refractory epilepsy severely. Glucocorticoids combined with immunosuppressive therapy should be given as early as possible, and intravitreal bevacizumab therapy can improve visual loss of LSCS patients.

OBJECTIVE To study the correlation between penetration enhancement effect and transepidermal water loss(TEWL)values of essential oils(EOs)from traditional Chinese medicine(TCM).METHODS The amount of 3 kinds of glycosides(geniposide,gentiopicroside,paeoniflorin)and their oil-water partition coefficient were determined by HPLC.The penetration enhancement effect of the five EOs from Gaoliangjiang(Alpiniae Officinarum Rhizoma,AOR),Ganjiang(Zingiberis Rhizoma,ZR),Bohe(Menthae Haploca-lycis Herba,MHH),Hujiao(Piperis Fructus,PF)and Wuzhuyu(Euodiae Fructus,EF)on geniposide,gentiopicroside,and paeoniflor-in were performed by the modified Franz diffusion cell method with the abdominal skin of rats.The TEWL values were measured to evalu-ate the effect of the five EOs on the skin barrier function of rats.The correlation between penetration enhancement effect of EOs and their effect on skin barrier function was investigated by correlation analysis.RESULTS AOR oil,ZR oil,MHH oil,and PF oil could im-prove the absorption of the three glycosides and reduce skin barrier function of rats.The results of correlation analysis showed that the penetration enhancement effect of EOs was significantly related to TEWL values following dermal administration of EOs.CONCLUSION TEWL measurement technology provides a more convenient method for the selection of penetration enhancers.

Serum and glucocorticoid-inducible kinases (SGKs) are serine threonine protein kinases involved in the regulation of multiple signal transduction pathways in vivo. SGKs include SGK1, SGK2 and SGK3. SGK1 plays a crucial role in the development of diseases such as digestive inflammation and tumors by regulating inflammatory and immune responses through phosphorylation. This article briefly introduces the structure and function of SGK1, and describes the research progress and clinical significance of SGK1 in digestive diseases.

Objective:To compare the efficacy and safety of red light and daylight photodynamic therapy in the treatment of facial common acne.Methods:From March 2019 to November 2019, 52 patients with facial common acne who received 5-aminolevulinic acid photodynamic therapy in the Department of Dermatology, Chongqing Hospital of Traditional Chinese Medicine were enrolled, including 34 males and 18 females, aged 18-35 years, with an average age of 23.2 years. A 5% concentration of 5-aminolevulinic acid was applied to the entire face, with the right side of the face being exposed to red light for 20 minutes and the left side to daylight for 2 hours. The treatment was administered once a week for a total of 4 sessions. After the treatment, the acne remission, adverse reactions, and patient satisfaction on both sides of the face were compared.Results:Compared with before treatment, the number of inflammatory and non-inflammatory lesions on both sides of the face in the enrolled patients decreased, and there was no significant difference in the clearance rate of skin lesions between the two sides [53.7% (28/52) vs 59.1% (31/52), χ 2=0.89, P>0.05]. The overall effective rate on the red light side was 88.5% (46/52), and 82.7% (43/52) on the daylight side, with no significant difference between the two (χ 2=0.38, P>0.05). In terms of adverse reactions, mild erythema was common, and it was less on the daylight side than on the red light side [34.6% (18/52) vs 19.2% (10/52), χ 2=5.98, P<0.05]. During the treatment period, the pain score on the daylight side decreased compared to the red light side [(7.6±2.3) vs (4.1±1.3), t=13.10, P<0.001]. Overall satisfaction with the daylight side was reported in 49 cases (94.2%), and with the red light side in 37 cases (71.2%), with the daylight side being higher than the red light side, and the difference was statistically significant (χ 2=9.60, P<0.05). Conclusion:Daylight photodynamic therapy is as effective as red light photodynamic therapy for common acne, but it produces fewer adverse reactions and higher patient satisfaction.

Using chemoproteomic techniques, we first identified EIF2AK2, eEF1A1, PRDX3 and VPS4B as direct targets of berberine (BBR) for its synergistically anti-inflammatory effects. Of them, BBR has the strongest affinity with EIF2AK2 via two ionic bonds, and regulates several key inflammatory pathways through EIF2AK2, indicating the dominant role of EIF2AK2. Also, BBR could subtly inhibit the dimerization of EIF2AK2, rather than its enzyme activity, to selectively modulate its downstream pathways including JNK, NF-κB, AKT and NLRP3, with an advantage of good safety profile. In EIF2AK2 gene knockdown mice, the inhibitory IL-1β, IL-6, IL-18 and TNF-α secretion of BBR was obviously attenuated, confirming an EIF2AK2-dependent anti-inflammatory efficacy. The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target, and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammation-related disorders.

Objective:To summarize the clinical and genetic characteristics of children with epilepsy associated with SCN2A gene variations. Methods:A retrospective study was performed. Eleven children with epilepsy admitted to Department of Pediatric Neurology, Linyi People's Hospital from January 2017 to December 2022 were included; all of them had pathogenic SCN2A gene mutation. Genetic results and clinical data as epileptic seizure type/frequency, intelligence and motor development of these 11 children were collected. Epilepsy-related variations and pathogenesis of SCN2A gene were analyzed, and their correlations with clinical phenotypes in these children were analyzed. Results:Among the 11 patients, 6 had self-limited epilepsy (4 with variation in the intracellular domain and 2 in the transmembrane domain), 1 had febrile convulsion accompanied by childhood absent epilepsy (with variation in the intracellular domain), and 4 had developmental epileptic encephalopathy (2 with variation in the extracellular domain and 2 with variation in the transmembrane domain). SCN2A gene was missense mutation in these 11 children, and the mutation site in 6 children was not reported before. Various forms of video EEG discharge were noted, and 1 child with self-limited epilepsy showed transient multifocal epileptic discharge during frequent seizures. Oxcarbazepine and topiramate were effective for self-limiting epilepsy, and lamotrigine was effective in 1 child with late-onset epileptic encephalopathy. Eleven patients were followed up for (66±32) months; the age ranged from 8 months to 11 years and 6 months at the last follow-up; 10 patients had seizure remission and 1 had uncontrolled seizure. Conclusions:Besides self-limited epilepsy and developmental epileptic encephalopathy, SCN2A gene mutations are also associated with febrile convulsion and childhood absent epilepsy. Phenotypic differences are highly correlated with mutation locations; developmental epileptic encephalopathy associated variants are mostly located in extracellular domains, while self-limited epileptic variants are mostly located in intracellular domains.

Objective:To investigate the safety and effectiveness of Willis covered stent in patients having carotid artery rupture during transnasal endoscopic pituitary tumor resection.Methods:A retrospective analysis was performed. Six patients having carotid artery rupture during transnasal endoscopic pituitary tumor resection admitted to the 3 hospitals from May 2016 to December 2019 were chosen; their clinical data were collected. The surgical processes and complications were concluded, and the prognoses were evaluated by modified Rankin scale (mRS).Results:One patient was treated with intraoperative simple tamponade compression for hemostasis, and died for massive intracranial hemorrhage 2 weeks after surgery. Five patients were occluded by Willis covered stents; the occluded success rate was 100% but ophthalmic arteries were blocked in all. During the perioperative period, diabetes insipidus occurred in one patient and incomplete oculomotor paralysis occurred in one patient; 5 patients were followed up for 3-12 months: MRI indicated subtotal resection of tumor in 4 patients and total resection in one patient, no new bleeding or ischemic stroke events occurred in these 5 patients, and the prognosis was good.Conclusion:Willis covered stent is safe and effective in patients having carotid artery rupture during transnasal endoscopic pituitary tumor resection.

Pneumonia caused by SARS-CoV-2 has seriously threatened human life and health worldwide and caused a large number of deaths. Viral infection and acute inflammation are important causes of death, so it is particularly important to combine antiviral therapy with anti-inflammatory therapy. Glycyrrhizic acid, the main component of the glycyrrhizic root extract, has a wide range of pharmacological effects as well as high efficiency and low toxicity, its preparation has been widely used in the treatment of chronic hepatitis and other diseases. Glycyrrhizic acid can regulate the expression and release of a variety of cytokines and play a significant anti-inflammatory effect. At the same time, glycyrrhizic acid also showed significant inhibition towards a variety types of viruses. Therefore, the potential application of glycyrrhizic acid as COVID-19 treatment should be explored.