Bone grafting is a primary method for treating bone defects. Among various graft materials, xenogeneic bone substitutes are widely used in clinical practice due to their abundant sources, convenient processing and storage, and avoidance of secondary surgeries. With the advancement of domestic production and the limitations of imported products, an increasing number of bone filling or grafting substitute materials isentering clinical trials. Relevant experts have drafted this consensus to enhance the management of medical device clinical trials, protect the rights of participants, and ensure the scientific and effective execution of trials. It summarizes clinical experience in aspects, such as design principles, participant inclusion/exclusion criteria, observation periods, efficacy evaluation metrics, safety assessment indicators, and quality control, to provide guidance for professionals in the field.
Humans ; Bone Substitutes/therapeutic use* ; Randomized Controlled Trials as Topic/methods* ; Consensus ; Bone Transplantation ; Research Design

Objective: To determine the inhibitory effects of pachymic acid on lung adenocarcinoma (LUAD) cells and elucidate its underlying mechanism. Methods: CCK-8, wound healing, Transwell, Western blot, tube formation, and immunofluorescence assays were carried out to measure the effects of various concentrations of pachymic acid on LUAD cell proliferation, metastasis, angiogenesis as well as autophagy. Subsequently, molecular docking technology was used to detect the potential targeted binding association between pachymic acid and protein tyrosine phosphatase 1B (PTP1B). Moreover, PTP1B was overexpressed in A549 cells to detect the specific mechanisms of pachymic acid. Results: Pachymic acid suppressed LUAD cell viability, metastasis as well as angiogenesis while inducing cell autophagy. It also targeted PTP1B and lowered PTP1B expression. However, PTP1B overexpression reversed the effects of pachymic acid on metastasis, angiogenesis, and autophagy as well as the expression of Wnt3a and β-catenin in LUAD cells. Conclusions: Pachymic acid inhibits metastasis and angiogenesis, and promotes autophagy in LUAD cells by modulating the Wnt/ β-catenin signaling pathway via targeting PTP1B.

AIM To study the chemical constituents form the leaves of Castanopsis orthacantha Fance and their α-glucosidase inhibitory activities.METHODS The methanol extract form the leaves of C.orthacanth was isolated and purified by various column chromatography methods,such as MCI gel CHP 20P,Sephadex LH-20,Diaion HP20SS,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The α-glucosidase inhibitory activities were determined by PNPG method.RESULTS Eighteen compounds were isolated and identified as protocatechuic acid(1),gallic acid(2),3-O-α-L-arabininopyranosyl-4-hydroxybenzoic acid(3),3-O-galloyl shikimic acid(4),methyl 4-epi-shikimate-3-O-gallate(5),5-O-galloyl shikimic acid(6),5-O-caffeoylshikimic acid(7),6-O-galloyl-glucoside(8),1,6-di-O-galloyl-β-D-pyranogluloside(9),1,3-di-O-galloyl-α-D-glucoside(10),2,3-di-O-galloyl-D-glucoside(11),β-O-methylgluco-2,3-digalloyl esters(12),(3R,1'S)-[1'-(6"-O-galloyl-β-D-gluco-pyranosyl)oxyethyl]-3-hydroxy-dihydrofuran-2(3H)-one(13),4-O-D-(6'-O-galloyl)glucopyranyl-(E)-p-coumaryl acid(14),chestanin(15),1-desgalloyl eugeniin(16),picrorhiza acid(17),11-methyl chebulate(18).The IC50 values of compounds 2 and 16 were(0.12±0.059),(0.00089±0.00025)mmol/L,respectively.CONCLUSION All compounds are isolated from the leaves of C.orthacantha for the first time.Compounds 2 and 16 have strong α-glucosidase inhibitory activities.

Objective To explore the clinical efficacy and safety of Beimu Zhizhu Prescription(derived from the modification of Zhizhu Pills)in the treatment of GERC by retrospectively analyzing the clinical data of 297 patients with gastroesophageal reflux cough(GERC).Methods A retrospective cohort study was conducted in a total of 297 patients with GERC of rebellious stomach qi type who were admitted to the Outpatient Department of Wangjing Hospital of China Academy of Chinese Medical Sciences from July 2021 to July 2023.The patients were divided into an exposure group(136 cases)and a non-exposure group(161 cases)according to the medication of Beimu Zhizhu Prescription or not.The exposure group was treated with Beimu Zhizhu Decoction,and the non-exposure group was treated with proton pump inhibitor of Esomeprazole Magnesium Enteric-coated Tablets.A total of 119 pairs of cases were obtained after propensity score matching(PSM)at the ratio of 1 to 1.The changes of salivary pepsin level before and after treatment in the two groups were observed.After two weeks and eight weeks of treatment,the cough response rate and the remission rates for reflux-related symptoms of acid reflux,heartburn,belching and gastric distension were compared between the two groups,and the incidence of adverse reactions was recorded.Results(1)After two weeks of treatment,the comparison of symptom remission rate after PSM showed that the cough response rate and the remission rates for reflux-related symptoms of acid reflux,heartburn,belching and gastric distension in the exposure group were 84.87％(101/119),80.77％(84/104),82.61％(76/92),82.5％(66/80),84.42％(65/77),respectively,and those in the non-exposure group were 73.95％(88/119),72.90％(78/107),70.41％(69/98),65.38％(51/78),64.38％(47/73),respectively.The intergroup comparison showed that the remission rates for all of the symptoms except for acid reflux in the exposure group was significantly superior to that in the non-exposure group(P＜0.05 or P＜0.01).After eight weeks of treatment,the cough response rate and the remission rates for reflux-related symptoms of acid reflux,heartburn,belching,and gastric distension in the exposure group were 94.74％(36/38),91.67％(33/36),91.43％(32/35),93.75％(30/32),94.12％(32/34),respectively,and those in the non-exposure group were 77.78％(35/45),74.42％(32/43),71.43％(30/42),68.42％(26/38),66.67％(24/36),respectively.The intergroup comparison showed that the remission rate of all of the symptoms in the exposure group was significantly superior to that in the non-exposure group(P＜0.05 or P＜0.01).(2)After two weeks of treatment,the comparison of salivary pepsin level after PSM showed that the salivary pepsin level of the exposure group was significantly lower than that before treatment(P＜0.01),while that of the non-exposure group was not significantly decreased(P＞0.05).The decrease of salivary pepsin level in the exposure group was significantly superior to that in the non-exposure group.Statistically significant differences were presented in the post-treatment salivary pepsin level after two weeks of treatment and in the pre-and post-treatment difference of salivary pepsin level between the two groups(P＜0.05 or P＜0.01).(3)There were four cases(2.48％)of adverse reactions in the non-exposure group,while no related adverse reactions occurred in the exposure group.There was no significant difference in the incidence of adverse reactions between the two groups(x2=1.180,P=0.178).Conclusion Beimu Zhizhu Decoction can effectively relieve cough and reflux-related symptoms of acid reflux,heartburn,belching,and gastric distension in patients with GERC of rebellious stomach qi type,reduce the level of salivary pepsin,and has high safety.

OBJECTIVE To evaluate the clinical effectiveness and safety of domestic generic and imported original clopidogrel for antiplatelet therapy in patients with acute coronary syndrome （ACS）. METHODS The clinical data of ACS patients in Nanjing Drum Tower Hospital of China Pharmaceutical University from January 2020 to June 2021 were retrospectively collected by using electronic medical record system， and the patients were divided into original drug group （321 cases） and generic drug group （328 cases） according to the drug use. Both groups were given dual antiplatelet therapy with clopidogrel and aspirin. The effectiveness and safety outcomes of the two groups were followed up for 12 months and compared， the related influential factors were analyzed. RESULTS Major adverse cardiovascular events （MACE） occurred in 16 and 22 patients in original drug group and generic drug group respectively， including nonfatal myocardial infarction （4 and 5 cases）， stroke （2 and 4 cases）， revascularization （8 and 3 cases）， cardiovascular related death （2 and 4 cases）， and all-cause death （4 and 6 cases）. There were 12 and 7 patients with major bleeding events， 38 and 29 patients with minor bleeding events， and 33 and 21 patients with non-bleeding adverse events. There was no statistically significant difference in the cumulative incidence of related events （P values of Log-Rank tests were all greater than 0.05）. Cox regression analysis showed that the use of generic clopidogrel did not increase the risk of MACE and major bleeding events in ACS patients [hazard ratio of 1.305 and 0.416， 95% confidence interval of （0.678， 2.512） and （0.155， 1.117）， respectively， P＞0.05]， and the combination of proton pump inhibitors （PPI） could reduce the risk of major bleeding events [hazard ratio of 0.196， 95% confidence interval of （0.063， 0.611）， P＜0.05]. CONCLUSIONS Compared with imported original drug， domestic generic clopidogrel has similar clinical effectiveness and good safety. Combined use of PPI may be a beneficial factor to reduce the occurrence of major bleeding events in patients.

In recent years, continuous manufacturing technology has attracted considerable attention in the pharmaceutical industry. This technology is highly sought after for its significant advantages in cost reduction, increased efficiency, and improved productivity, making it a growing trend in the future of the pharmaceutical industry. Compared to traditional batch production methods, continuous manufacturing technology features real-time control and environmentally friendly intelligence, enabling pharmaceutical companies to produce drugs more efficiently. However, the adoption of continuous manufacturing technology has been slow in the field of traditional Chinese medicine(TCM) pharmaceuticals. On the one hand, there is insufficient research on continuous manufacturing equipment and technology that align with the characteristics of TCM preparations. On the other hand, the scarcity of talent with diverse expertise hampers its development. Therefore, in order to promote the modernization and upgrading of the TCM pharmaceutical industry, this article combined the current development status of the TCM industry to outline the development status and regulatory requirements of continuous manufacturing technology. At the same time, it analyzed the problems with existing TCM manufacturing models and explored the prospects and challenges of applying continuous manufacturing technology in the field of TCM pharmaceuticals. The analysis focused on continuous manufacturing control strategies, technical tools, and pharmaceutical equipment, aiming to provide targeted recommendations to drive the development of the TCM pharmaceutical industry.
Medicine, Chinese Traditional ; Quality Control ; Drug Industry ; Technology, Pharmaceutical/methods* ; Drugs, Chinese Herbal ; Pharmaceutical Preparations

Chuanxiong Rhizoma (CX, the dried rhizome of Ligusticum wallichii Franch.), a well-known traditional Chinese medicine, is clinically used for treating cardiovascular, cerebrovascular and hepatobiliary diseases. Cholestatic liver damage is one of the chronic liver diseases with limited effective therapeutic strategies. Currently, little is known about the mechanism links between CX-induced anti-cholestatic action and intercellular communication between cholangiocytes and hepatic stellate cells (HSCs). The study aimed to evaluate the hepatoprotective activity of different CX extracts including the aqueous, alkaloid, phenolic acid and phthalide extracts of CX (CX_AE, CX_AL, CX_PA and CX_PHL) and investigate the intercellular communication-related mechanisms by which the most effective extracts work on cholestatic liver injury. The active compounds of different CX extracts were identified by UPLC-MS/MS. A cholestatic liver injury mouse model induced by bile duct ligation (BDL), and transforming growth factor-β (TGF-β)-treated human intrahepatic biliary epithelial cholangiocytes (HIBECs) and HSC cell line (LX-2 cells) were used for in vivo and in vitro studies. Histological and other biological techniques were also applied. The results indicated that CX_AE, CX_AL and CX_PHL significantly reduced ductular reaction (DR) and improved liver fibrosis in the BDL mice. Meanwhile, both CX_AE and CX_PHL suppressed DR in injured HIBECs and reduced collagen contraction force and the expression of fibrosis biomarkers in LX-2 cells treated with TGF-β. CX_PHL suppressed the transcription and transfer of plasminogen activator inhibitor-1 (PAI-1) and fibronectin (FN) from the 'DR-like' cholangiocytes to activated HSCs. Mechanistically, the inhibition of PAI-1 and FN by CX_PHL was attributed to the untight combination of the acetyltransferase KAT2A and SMAD3, followdd by the suppression of histone 3 lysine 9 acetylation (H3K9ac)-mediated transcription in cholangiocytes. In conclusion, CX_PHL exerts stronger anti-cholestatic activity in vivo and in vitro than other CX extracts, and its protective effect on the intracellular communication between cholangiocytes and HSCs is achieved by reducing KAT2A/H3K9ac-mediated transcription and release of PAI-1 and FN.

AIM: To compare the efficacy of aflibercept and ranibizumab in the treatment of diabetic macular edema(DME).METHODS: Prospective randomized controlled trial. A total of 35 patients(60 eyes)with non-proliferative diabetic retinopathy complicated with DME confirmed in our hospital from June 2020 to September 2021 were included. Intravitreal injection was performed using the 3+PRN protocol in all cases, of which 17 cases(30 eyes)received aflibercept treatment(aflibercept group)and 18 cases(30 eyes)received ranibizumab(ranibizumab group). The two groups were followed up for 12mo, observing the central macular thickness(CMT)and the best corrected visual acuity(BCVA)of the two groups, and recording the number of intravitreal injections and the occurrence of complications.RESULTS: After treatment, CMT and BCVA in the aflibercept group were significantly better than that in the ranibizumab group at 1, 3, 6 and 12 mo(all P<0.001). During the follow-up period, the number of intravitreal injections in the aflibercept group was lower than that in the ranibizumab group(4.23±0.86 vs. 6.40±0.97, P<0.05), there were no serious complications such as drug-related adverse reactions, intraocular infection, and vascular embolism in either group.CONCLUSION: Both aflibercept and ranibizumab have clear efficacy and safety in the treatment of DME, and aflibercept may be a more effective and convenient treatment option than ranibizumab for DME patients.

Abstract: Objective　To understand the clinical manifestations, symptoms, treatment and recovery of neonates infected with Omicron variant (BA.5.1.3) of SARS-CoV-2, and provide a certain reference for subsequent diagnosis and treatment of related diseases. Methods　The clinical manifestations, epidemiology, auxiliary examinations, and treatment processes of the neonate aged 4-day-old who was community-acquired infection of variant BA.5.1.3 in Sanya was retrospectively analyzed. Results　The neonate's mother was identified as a close contact with patients with coronavirus disease 2019 (COVID-19) one hour before delivery, and tested positive for nucleic acid within 24 hours after delivery. But her breast milk, amniotic fluid, placenta, and umbilical cord were not detected for nucleic acid test after delivery. The nucleic acid test of the neonate was negative within 24 hours after birth. Then he was transferred to the hotel for isolation. Before the transfer, the mother and baby stayed in the same room and ate breast milk but the mother did not wear any mask. The neonate didn't have nucleic acid test on the second and third days of his life, and the nucleic acid test of the neonate was positive on the fourth day, negative on the fifth day, and positive on the sixth day. Then he was transferred to the designated hospital of COVID-19 for treatment. The neonate had no cough, no fever, yellow skin, abdominal distension, general breast feeding, and good reaction. On admission, the laboratory examination showed that blood routine examination and electrolyte were normal, and the myocardial enzyme and liver and kidney functions were normal. The bilirubin was significantly increased (449.3 μmol/L). The nucleic acid test of the neonate was positive and his chest imaging results were normal. The treatment measures were mainly isolation, feeding, blue light fading, close monitoring of vital signs, and antiviral drugs were administered. Jaundice subsided and abdominal distension was relieved after 6 d of treatment, and the treatment process was smooth without complications. Conclusions　The results suggest that the neonates are susceptible to Omicron variant BA.5.1.3 and prone to aggregation. The evidence of vertical transmission is insufficient and the clinical symptoms of neonates infected with Omicron variant BA.5.1.3 are mid, with no involvement of organ damage of the heart, liver, kidney, brain, and other organs.

Abstract: Objective　To explore the clinical characteristics of nucleic acid negative newborns delivered by pregnant women infected with SARS-CoV-2 (Omicron variant BA. 5.1.3) in Sanya area, and to provide evidence for understanding its clinical characteristics. Methods　A retrospective analysis was performed on 14 neonates with negative nucleic acid delivered by pregnant women who tested positive for SARS-CoV-2 (Omicron variant BA.5.1.3) in Sanya Central Hospital (the Third People's Hospital of Hainan Province) from June 2022 to September 2022 (observation group, n=14). The corresponding nucleic acid-negative newborns delivered by pregnant women detected negative with SARS-CoV-2 (Omicronon variant strain BA.5.1.3) were set as the control group (n=56), and the general data and clinical characteristics of neonates in the two groups were compared. Results　There was no significant difference between the observation group and the control group in pregnancy diabetes, pregnancy induced hypertension, gestational pre-eclampsia, fetal intrauterine distress, premature rupture of membranes (P>0.05); there was no significant difference between the observation group and the control group in terms of sex, gestational age, birth weight, age, mode of delivery, birth Apgar score, heart screening, pulmonary disease, glucose 6-phosphate dehydrogenase (G6PD) deficiency, thalassemia, breast milk jaundice, hemolytic jaundice (P>0.05). The bilirubin level, blue light irradiation cases and the duration of blue light irradiation of the newborns in the observation group at 7 days after birth were higher than those in the control group (P<0.05); the ratio of blood oxygen saturation ≥ 90% in the observation group was lower than that in the control group (21.43% vs 89.29%, P<0.05), and the ratio of blood oxygen saturation occasionally<90% was higher than that in the control group (57.14% vs 10.71%, P<0.05). The ratio of blood oxygen saturation<90% had no significant difference compared with that in the control group (7.14% vs 0, P>0.05), and the ratio of blood oxygen saturation reduced to the required oxygen uptake was higher than that in the control group (14.29% vs 0, P<0.05). Conclusions　The jaundice manifestation of the nucleic acid-negative newborns delivered by pregnant women infected with SARS-CoV-2 (Omicronon variant strain BA.5.1.3) in Sanya area is relatively obvious, with blood oxygen saturation easily lower than 90% and even requiring oxygen inhalation in severe cases.