BACKGROUND:The extracellular-regulated protein kinase 5(ERK5)signaling protein is essential for the survival of organisms,and resveratrol can promote osteoblast proliferation through various pathways.However,whether resveratrol can regulate osteoblast function through the ERK5 signaling protein needs further verification. OBJECTIVE:To explore the regulatory effect of ERK5 on the proliferation of MC3T3-E1 cells and related secreted proteins,and to further verify whether resveratrol can complete the above process by activating ERK5. METHODS:Mouse MC3T3-E1 preosteoblasts were treated with complete culture medium,XMD8-92(an ERK5 inhibitor),epidermal growth factor(an ERK5 activator),resveratrol alone,XMD8-92+EGF,and resveratrol+XMD8-92,respectively.Western blot assay was used to detect the expression of ERK5 and p-ERK5 proteins,proliferation-related proteins Cyclin D1,CDK4 and PCNA,and osteoblast-secreted proteins osteoprotegerin and receptor activator of nuclear factor-κB ligand in MC3T3-E1 cells of each group.The fluorescence intensity of ERK5,osteoprotegerin and receptor activator of nuclear factor-κB ligand in each group was detected by cell immunofluorescence staining,and cell proliferation was detected by EdU staining,respectively.The appropriate concentration and time of resveratrol intervention in MC3T3-E1 cells were determined by cell morphology observation and cell counting kit-8 assay. RESULTS AND CONCLUSION:The activation of ERK5 signaling protein could effectively promote the proliferation of MC3T3-E1 cells,up-regulate the osteoprotegerin/receptor activator of nuclear factor-κB ligand ratio.The appropriate concentration and time for resveratrol intervention in MC3T3-E1 cells was 5 μmol/L and 24 hours,respectively.Resveratrol could activate ERK5 signaling protein,thereby promoting osteoblast proliferation and up-regulating the osteoprotegerin/RANKL ratio.All these results indicate that resveratrol can promote the proliferation of MC3T3-E1 cells and up-regulate the osteoprotegerin/RANKL ratio by activating the ERK5 signaling protein.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

BACKGROUND:Fluid shear stress plays an important role in osteoblast proliferation and apoptosis.However,whether Caveolin-1 is involved in the process of fluid shear stress-induced proliferation and apoptosis in osteoblasts is unknown. OBJECTIVE:To explore the role of Caveolin-1 in fluid shear stress-regulated osteoblast proliferation and apoptosis. METHODS:The MC3T3-E1 osteoblasts in good growth status were selected and loaded with fluid shear stress at an intensity of 1.2 Pa for different times(0,30,60,90 minutes).The expression of Caveolin-1 protein was observed and conditions with a time of 60 minutes were screened for the experiment.MC3T3-E1 cells were divided into control group,fluid shear stress group,fluid shear stress+pcDNA 3.1 group(control),fluid shear stress+pcDNA Cav-1 group(plasmid overexpression),and intervened with fluid shear stress and overexpression of Cav-1,respectively.The expression of molecules related to proliferation and apoptosis in MC3T3-E1 cells was detected by qRT-PCR and western blot.In addition,the proliferative activity of MC3T3-E1 cells was detected by cell counting kit-8 and EdU assay;and cell apoptosis was detected by Hoechst 33258 and flow cytometry. RESULTS AND CONCLUSION:The expression of Caveolin-1 in MC3T3-E1 cells was significantly down-regulated after loading fluid shear stress,and the expression level was lowest after 60 minutes.Overexpression of Caveolin-1 attenuated the proliferation-promoting and apoptosis-suppressing effects of fluid shear stress in MC3T3-E1 cells.In conclusion,Caveolin-1 has a vital role in fluid shear stress-regulated osteoblast proliferation and apoptosis,which may offer a potential therapeutic strategy for osteoporosis.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

OBJECTIVE: To observe the clinical effect of acupuncture on coronavirus disease 2019 (COVID-19) based on the conventional treatment. METHODS: A total of 35 patients with COVID-19 of mild or ordinary type were involved (3 cases dropped off). Acupuncture was applied on the basis of western medicine and Chinese materia medica treatment. Dazhui (GV 14), Fengchi (GB 20), Kongzui (LU 6), Hegu (LI 4), etc. were selected as the main acupoints, the supplementary acupoints and the reinforcing and reducing manipulations were selected according to syndrome differentiation. Acupuncture treatment was given once a day, 5 times a week. On day 3 and day 7 of acupuncture, relief condition of the main symptoms was observed. Before acupuncture and on day 3 and day 7 of acupuncture, efficacy evaluation scale of TCM on COVID-19 (efficacy evaluation scale) score was recorded. The effects of different intervention time of acupuncture on patients' hospitalization time were compared, the understanding of acupuncture treatment of patients discharged from hospital was recorded, the clinical efficacy and safety of acupuncture treatment were evaluated. RESULTS: On day 3 and day 7 of acupuncture, the symptoms of lung system and non lung system were both relieved; the scores of efficacy evaluation scale were both decreased compared before acupuncture (P<0.05), and the efficacy evaluation scale score of day 7 of acupuncture were lower than day 3 of acupuncture (P<0.05). The average hospitalization time of patients received early acupuncture was shorter than late acupuncture (P<0.05). The total effective rate was 84.4% (27/32) on day 7 of acupuncture, which was higher than 34.4% (11/32) on day 3 of acupuncture (P<0.05). During the acupuncture treatment, there were neither adverse reactions in patients nor occupational exposures in doctors. The patients generally believed that acupuncture could promote the recovery of COVID-19 and recommended acupuncture treatment. CONCLUSION On the basis of the conventional treatment, acupuncture can effectively relieve the clinical symptoms in patients with COVID-19, early intervention of acupuncture can accelerate the recovery process. Acupuncture has good safety, clinical compliance and recognition of patients.
Acupuncture Points ; Acupuncture Therapy ; COVID-19/therapy* ; Combined Modality Therapy ; Humans ; Treatment Outcome

The name， origin， place of origin， medicinal parts， harvesting and processing of lotus are verified by consulting ancient Chinese herbal medicines and medical books， combined with modern literature， providing a basis for the development of famous classical formulas containing lotus. According to textual research， the original base of lotus is Nelumbo nucifera since ancient times， rhizome （Nelumbinis Rhizomatis Nodus）， leaf （Nelumbinis Folium）， seed （Nelumbinis Semen）， embryo （Nelumbinis Plumula）， receptacle （Nelumbinis Receptaculum）， stamen （Nelumbinis Stamen） and other medicinal parts of N. nucifera can be used as medicine and have different clinical effects. Nelumbinis Semen was originally produced in Henan， and then gradually expanded to Jiangnan. Today， it can be cultivated and planted throughout the country， with Fujian， Hunan， and Jiangxi as the authentic production areas. After combing the medicinal parts of N. nucifera and the historical evolution of its processing， it is suggested that the dried and mature fruits of N. nucifera taking in autumn and removing the shell and Nelumbinis Plumula should be used in Qingxin Lianziyin. Nelumbinis Folium in Erdongtang should be harvested in summer and autumn， and the raw products was used as medicine and processed in accordance with the provision of the 2020 edition of Chinese Pharmacopoeia.

Based on the ancient literature of all dynasties， this article makes a systematic textual research on the name， origin， producing area， quality， harvesting and processing of Zisu （Perillae） in the famous classical formulas， so as to clarify the information of the drug in different historical periods and provide a reference for the development and utilization of the related formulas. The main origin of Perillae in the ancient literature was Perilla frutescens var. frutescens （purple leaf type）， followed by P. frutescens var. acuta （purple leaf type）， but not Baisu. Modern chemical composition studies also show that there are obvious differences between Perillae and Baisu， which provides a scientific basis for distinguishing them. Although they are often treated as a species in plant classification， P. frutescens var. frutescens （purple leaf type） is recommended in the development of famous classical formulas， and Baisu should be avoided. Perillae is widely distributed， but its producing area did not record in most of the literature in the past dynasties， or the producing area is described as everywhere today. In the period of the Southern and Northern dynasties， the medicinal parts of Perillae included stems， leaves and seeds， and doctors in the Ming dynasty began to pay attention to the differentiation of different medicinal parts. The harvesting and processing methods of Perillae in the past dynasties are close to that of today. Perillae Fructus is mostly stir-fried and ground into medicine， Perillae Folium and Perillae Caulis are mainly simple cleansing. In production， we can refer to the 2020 edition of Chinese Pharmacopoeia.

In this paper， the name， origin， quality evaluation， producing area and processing methods of Platycodonis Radix used in the famous classical formulas are researched by consulting related materia medicas， prescription books and medical books of the past dynasties. It was found that Platycodonis Radix was the correct name in the materia medicas of the past dynasties， which was named for its "roots are strong but the stems are straight". Its dominant base of the past dynasties was Platycodon grandiflorus， and since the Ming and Qing dynasties， Hexian county of Anhui has been respected as the representative authentic producing area. In modern times， it has been concluded that the quality of Platycodonis Radix is best if the body is dry， thick and uniform， solid， white in color， and bitter in taste. In ancient times， the processing methods of Platycodonis Radix were mainly removing the reed head and floating skin， rice simmering and drying， and slicing and micro-frying. In modern times， its processing methods have been mainly simplified to peeling and cutting into thick slices. Therefore， it is recommended to use the dry roots of P. grandiflorus and its raw products in the famous classical formulas.

Based on various ancient documents such as materia medica， prescription books， classics and history， combined with relevant research materials in modern times， this paper made a textual research on the name， origin， geoherbalism， harvesting time， processing methods of Chuanxiong Rhizoma， which provides a basis for the development of famous classical formulas containing this herb. According to the textual research， the original name of Chuanxiong is Xiongqiong （芎䓖）， which was first recorded in Shennong Bencaojing ， there are many aliases and trade names in the past dynasties. Since the Song dynasty， doctors all take Xiongqiong produced in Sichuan as the best medicine， so they take Chuanxiong as the rectification of name. In the early stage， the origin of Chuanxiong Rhizoma was relatively complicated， and the main origin was Ligusticum chuanxiong， which was a cultivated and domesticated species of Ligusticum. However， wild related plants of Ligusticum are still used as medicine. After the Ming dynasty， new cultivated varieties appeared in various places， such as Jiangxi L. sinense cv. Fuxiong， which gradually turned to self-production and self-marketing after the Republic of China. After several changes in the authentic producing area of Chuanxiong Rhizoma， Tianshui in Gansu province was highly praised in the Tang dynasty， and Dujiangyan in Sichuan province was the best place in the Song dynasty and later dynasties. Chuanxiong Rhizoma has been widely used in the past dynasties as raw products， and it has also been processed with excipients. For example， wine-processed products can enhance the effect of promoting blood circulation， promoting Qi circulation and relieving pain. There are other processing methods such as stir-frying and vinegar processing. Chuanxiong Rhizoma in the famous classical formulas can be selected according to this research conclusion.