[Effect of mandibular third molar tooth germ extraction on mandibular development: a retrospective study].

Objective: To investigatethe effect of extraction of mandibular third molar (M3) tooth germon the development of the mandible in orthodontic patients, with a view to providing a reference for clinical M3 tooth germ extraction. Methods: One hundred and twenty-nine Angel class Ⅰ patients aged 10-16 years who attended the Department of Orthodontics Division 1, School & Hospital of Stomatology, Wuhan University from 1 January 2013 to 30 December 2021 and fulfilled the criteria for nativity were included. Those who had their M3 extracted in the Department of Oral and Maxillofacial Surgery were included in the study group, with a total of 66 cases; and those who did not have their M3 extracted were included in the control group, with a total of 63 cases. The average annual growth was calculated by tracing point measurements on cephalometric films before and after orthodontic treatment according to the Jarabak and McNamara methods, with measurements of the mandibular ramus height (Ar-Go'), mandibular body length (Go'-Me), and overall mandibular length (Co-Gn) values, respectively. The average annual growth of Ar-Go', Go'-Me, and Co-Gn were compared between the two groups for the overall sample of patients, patients of the same sex (male/female), patients of the same age group (A, B, and C), and patients of the same cervical vertebral maturation stage (stages Ⅱ, Ⅲ, and Ⅳ), respectively, to see if there was any difference in the average annual growth of Ar-Go', Go'-Me, and Co-Gn. Results: There was no statistically significant difference in the average annual growth of Ar-Go', Go'-Me, and Co-Gn between the study group [0.88 (0.40, 1.80), 0.67 (0.15, 1.18), and 0.86 (0.40, 1.90) mm, respectively] and the control group [1.08 (0.45, 1.60), 0.53 (0.25, 1.13), and 1.20 (0.46, 2.28) mm, respectively] (P>0.05). In addition, there was no significant difference in the average annual growth in the Ar-Go', Go'-Me, and Co-Gn between the groups for patients of the same sex group (male/female), patients of the same age group (A, B, and C), and patients of the same cervical vertebral maturation stage group (stages Ⅱ, Ⅲ, and Ⅳ) (P>0.05). Conclusions: Extraction of the mandibular third molar tooth germ has no significant effect on the development of the mandible in Angle class Ⅰ orthodontic patients.

[A phase I study of subcutaneous envafolimab (KN035) monotherapy in Chinese patients with advanced solid tumors].

Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.

[Chinese multidisciplinary expert consensus on the management of adverse drug reactions associated with savolitinib].

MET gene is a proto-oncogene, which encodes MET protein with tyrosine kinase activity. After binding to its ligand, hepatocyte growth factor, MET protein can induce MET dimerization and activate downstream signaling pathways, which plays a crucial role in tumor formation and metastasis. Savolitinib, as a specific tyrosine kinase inhibitor (TKI) targeting MET, selectively inhibits the phosphorylation of MET kinase with a significant inhibitory effect on tumors with MET abnormalities. Based on its significant efficacy shown in the registration studies, savolitinib was approved for marketing in China on June 22, 2021 for the treatment of advanced non-small cell lung cancer with MET 14 exon skipping mutations. In addition, many studies have shown that MET TKIs are equally effective in patients with advanced solid tumors with MET gene amplification or MET protein overexpression, and relevant registration clinical studies are ongoing. The most common adverse reactions during treatment with savolitinib include nausea, vomiting, peripheral edema, pyrexia, and hepatotoxicity. Based on two rounds of extensive nationwide investigations to guide clinicians, the consensus is compiled to use savolitinib rationally, prevent and treat various adverse reactions scientifically, and improve the clinical benefits and quality of life of patients. This consensus was prepared under the guidance of multidisciplinary experts, especially including the whole-process participation and valuable suggestions of experts in Traditional Chinese Medicine, thus reflecting the clinical treatment concept of integrated Chinese and western medicines.

[Risk factors for recurrence and survival analysis in locally advanced T4a papillary thyroid carcinoma after R0 resection].

Objective: To investigate the treatment outcomes and risk factors of postoperative recurrence in T4a papillary thyroid carcinoma (PTC). Methods: A total of 185 patients with locally advanced T4a PTC treated in Beijing Tongren Hospital, Capital Medical University from January 2006 to December 2019 were retrospectively analyzed, including 127 females and 58 males, aged between 18 and 80 years, with 74 patients aged over 55 years. According to AJCC thyroid tumor staging, 111 cases were stage I (T4aN0M0 26 cases, T4aN1aM0 35 cases, and T4aN1bM0 50 cases) and 74 cases were stage Ⅲ (T4aN0M0 29 cases, T4aN1aM0 19 cases, and T4aN1bM0 26 cases). Kaplan-Meier method was used to calculate the overall survival and the recurrence-free rate, and univariate and multivariate logistic regression analyses on the clinical data were performed. Results: Recurrent laryngeal nerve invasion was observed in 150 cases, trachea invasion in 61 cases, esophagus invasion in 30 cases, and laryngeal structure invasion in 10 cases. Postoperative follow-up periods were 24-144 months, with an average of 68.29 months. Of the 185 patients, 18 (9.73%) had recurrences or metastases, including 9 cases (4.86%) died of recurrences or metastases. The 5-year and 10-year overall survival rates were respectively 95.21% and 93.10%. The 5-year and 10-year disease-free survival rates were respectively 89.65% and 86.85%. Univariate analysis showed that age of onset, tumor diameter, preoperative recurrent laryngeal nerve palsy, esophageal invasion and cervical lymph node metastasis were the risk factors for postoperative recurrence of T4a PTC(all P<0.05). Multivariate analysis showed that preoperative recurrent laryngeal nerve palsy (OR=3.27, 95%CI: 1.11-9.61, P=0.032) and lateral cervical lymph node metastasis (OR=4.71, 95%CI: 1.19-18.71, P=0.027) were independent risk factors for T4a PTC recurrence. Survival rate of patients with T4a PTC involving only the recurrent laryngeal nerve or the outer tracheal membrane was significantly better than that of patients with tracheal invasion (P<0.05). Conclusions: T4a PTC patients with R0 resection can still achieve good efficacy. Preoperative recurrent laryngeal nerve palsy and lateral cervical lymph node metastasis are independent risk factor for postoperative recurrence in the patients.

Therapeutic effect of Pleurotus eryngii cellulose on experimental fatty liver in rats.

The aim of this study was to explore the therapeutic effect of Pleurotus eryngii cellulose on experimental fatty liver in rats. Rats were fed high-fat fodder to establish a rat fatty liver model, and were then fed different concentrations of Pleurotus eryngii cellulose for six weeks. Lipitor was used as a positive control. Measured levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and total triglyceride (TG); the activity of malondialdehyde (MDA), superoxide dismutase (SOD), hepatic lipase (HL), and lipoprotein lipase; and liver histopathological changes. Successfully established rat fatty liver model after feeding high-fat fodder for one week. A diet of P. eryngii cellulose for six weeks significantly reduced ALT, AST, TC, and TG levels in rat serum (P < 0.01); TC and AST levels in P. eryngii cellulose high-dose group and Lipitor group were not significantly different from those of the control (P > 0.05). SOD activity increased significantly, while MDA and HL activity decreased (P < 0.05); fatty degeneration and fat accumulation both decreased in hepatic tissue. Hepatic protection of P. eryngii cellulose showed dose-related effect. P. eryngii cellulose can affect lipid metabolism, having therapeutic effects on fatty liver in rats.

YiQi ChuTan Recipe Inhibits Epithelial Mesenchymal Transition of A549 Cells under Hypoxia.

This study aims to investigate mechanism of YiQi ChuTan Recipe (YCR) for inhibiting epithelial mesenchymal transition (EMT) of A549 cells under hypoxia. Flow cytometry was used to optimize YCR dosage by measuring A549 apoptosis, which were subjected to different treatments, including normal condition, hypoxia, hypoxia+YCR. Cell morphology and expression of EMT were measured with differential interference contrast microscopy, real-time PCR and western blot. Optimized condition of 4 mg/ml YCR and 2% O2 for 72 h was used to establish hypoxia. Under hypoxic condition, morphology of A549 cells changed from oblate fusi-form to elongated spindle. E-cadherin expression decreased while vimentin and fibronectin increased. EMT-related genes expression were significantly increased in hypoxia group compared to control group (P<0.05). After treatment with YCR, mesenchymal cells obviously decreased and EMT-related genes expression was significantly decreased (P<0.05). Changes of E-cadherin, vimentin and fibronection were significantly attenuated by YCR when compared to hypoxia group. Expression of proteins GRP78, SRC, MAPK, smad2/3 were significantly increased in hypoxia group compared to control group, but was significantly inhibited by YCR treatment. In conclusion, A549 cells underwent EMT under hypoxia while YCR reversed the EMT through GRP78, smad2/3 and SRC/MAPK signal pathway.

[The effect of hypoxic preconditioning on myocardium energy metabolism].

AIM AND METHODS: To evaluate the protective effects of hypoxic preconditioning (HPC) on myocardial energy metabolism, Langendorff-perfused hearts, exposed to HPC, were subjected to hypoxia/reoxygenation (5/10 min). 31P NMR was used to sequentially follow the time courses of high energy phosphates (HEP) contents and intracellular pH (pHi) of the rat myocardium. RESULTS: The Contents of Phosphocreatine (PCr), Adenosine Triphosphate (ATP) and the PCr/Pi (inorganic phosphate) ratios decreased during 30 min hypoxia, but the reduction was slower for the HPC group compared with Control. Reoxygenation induced recovery of myocardial HEP in both groups, HPC enhanced t he recovery especially in initial stage o f reoxygenation. However, pHi change was not significant for HPC group in this experiment. CONCLUSION: HPC improves the myocardial energy metabolism level during prolonged hypoxia and subsequent reoxygenation and protects myocardium against hypoxia/reoxygenation injury.

Liquid chromatography-electrospray ionization mass spectrometry study of the flavonoids of the roots of Astragalus mongholicus and A. membranaceus.

High-performance liquid chromatography-electrospray ionization mass spectrometry has been applied to analyze the flavonoids of Huangqi, the roots of Astragalus mongholicus and A. membranaceus. Eight flavonoids were identified as calycosin-7-O-beta-D-glucoside, calycosin-7-O-beta-D-glucoside-6"-O-malonate (2), ononin, (6aR,11aR)-3-hydroxy-9,10-dimethoxypterocarpan-3-O-bet a-D-glucoside, calycosin, (3R)-7,2'-dihydroxy-3',4'-dimethoxyisoflavan-7-O-beta-D-glucoside, formononetin-7-O-beta-D-glucoside-6"-O-malonate and formononetin by direct comparison with the isolated standards from Huangqi. The existence of (6aR,11aR)-3-hydroxy-9,10-dimethoxypterocarpan, (3R)-7,2'-dihydroxy-3',4'-dimethoxyisoflavan, astrapterocarpanglucoside-6'-O-malonate and astraisoflavanglucoside-6'-O-malonate was detected. This is the first report of flavonoid glycoside malonates in these two Astragalus species, and malonate 2 is a structurally completely identified new compound.

LC-ESI-MS study of the flavonoid glycoside malonates of red clover (Trifolium pratense).

High-performance liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) was applied to the analysis of the flavonoids and their glycoside malonates of the flowers and leaves of red clover (Trifolium pratense). Through LC-MS comparative studies on the plant extracts and their malonate-free extracts, approximately 20 flavonoid glycoside malonates were detected in the flower extract. Eight were identified as genistin 6' '-O-malonate (39), formononetin 7-O-beta-D-glucoside 6' '-O-malonate (40), biochanin A 7-O-beta-D-glucoside 6' '-O-malonate (41), trifoside 6' '-O-malonate (42), irilone 4'-O-beta-D-glucoside 6' '-O-malonate (43), pratensein 7-O-beta-D-glucoside 6' '-O-malonate (44), isoquercitrin 6' '-O-malonate (45), and 3-methylquercetin 7-O-beta-D-glucoside 6' '-O-malonate (46). About 15 other flavonoids and clovamides were proved to be present in this extract. The study also found that the flowers contained flavones as the major flavonoids, whereas the leaves had isoflavones as the major flavonoids. This is the first detection of the six malonates (39 and 42-46) in the extracts of red clover, and among them, 42, 43, and 46 are new compounds.

[The studies on protective effects of SM against myocardial hypoxia/reoxygenation injury].

AIM AND METHODS: To assess the myocardial effects of Salvia Miltiorrhiza (SM) injection against hypoxia-reoxygenation injury, 31P NMR was used to trace the time courses of high energy phosphates (HEP) content and intracellular pH (pHi) of the isolated perfused rat hearts under hypoxia (30 min) and subsequent reoxygenation (40 min). RESULTS: It was discovered that SM significantly preven-ted the decrease in the myocardial HEP content during hypoxia, enhanced the recovery of myocardial phosphocreatine (PCr), adenosine triphosphate (ATP) and the PCr/Pi (inorganic phosphate) ratios during reoxygenation, and lightened the decrease of the myocardial pHi value caused by hypoxia. CONCLUSION: SM improves the myocardial energy metabolism level during prolonged hypoxia and subsequent reoxygenation and protects myocardium against hypoxia/reoxygenation injury. SM significantly attenuates acidosis during hypoxia and prevents the appearance of very acidic areas of the myocardium after reoxygenation.

Phenolic aporphine-benzylisoquinoline alkaloids from Thalictrum faberi.

From the roots of Thalictrum faberi, six new phenolic aporphine-benzylisoquinoline alkaloids, 3-hydroxy-6'-desmethyl-9-O-methylthalifaboramine (1), 3-hydroxythalifaboramine (2), 6'-desmethylthalifaboramine (3); 3,5'-dihydroxythalifaboramine (4), 5'-hydroxythalifaboramine (5) and 3-hydroxy-6'-desmethylthalifaboramine (6) were isolated. Their structures were established through the use of one- and two-dimensional NMR techniques. All of the tested alkaloids showed potent cytotoxic and antimalarial activities.

Acylated C-21 steroidal bisdesmosidic glycosides from Caraluma umbellata.

From the whole plant of Caraluma umbellata, three new C-21 steroidal glycosides, named as carumbellosides III-V, were isolated and their structures elucidated by extensive spectroscopic experiments, devoid of any derivatisation, as caralumagenin 3-O-beta-D-glucopyranosyl(1-->4)-beta-D-digitalopyranoside-20-O-be ta- D-glucopyranoside, caralumagenin 3-O-beta-D-glucopyranosy(1-->4)- beta-D-digitalopyranoside-20-O-(2-O- benzoyl)-beta-D-glucopyranoside and caralumagenin 3-O-[6-O-benzoyl-beta-D-glucopyranosyl(1-->4)]-beta-D- digitalopyranoside-20-O-(2-O-benzoyl)-beta-D-glucopyranoside. The determination of the absolute configuration of the aglycone as (20 R), the conformations of the sugars and the unambiguous assignments of their NMR spectroscopic signals were achieved by a combination of 2D-NMR techniques. The isolates were devoid of significant cytotoxity in the UIC human cancer cell panel.

(+)-Angchibangkine, a new type of bisbenzylisoquinoline alkaloid, and other dimers from Pachygone dasycarpa.

Analysis of the alkaloidal fraction of the stem bark extract of Pachygone dasycarpa (Menispermaceae) resulted in the isolation of 10 known bisbenzylisoquinolines, (+)-tetrandrine, (+)-penduline, (+)-fangchinoline, (+)-atherospermoline, (+)-N-methyl-7-O-demethylpeinamine, (+)-daphnoline, (4-)-isotrilobine (1), (+)-cocsuline (2), (+)-tricordatine (3), (+)-2'-norcocsuline, and the new alkaloid (+)-12-O-methyltricordatine (4). The last bisbenzylisoquinoline alkaloid isolated, (+)-angchibangkine (5), is the first member of this alkaloid class found to possess three diphenyl ether bridges in the 7-6',8-7', and 11-12' positions. Structure elucidation of these alkaloids and of (+)-O-methylangchibangkine (6) was achieved by analysis of spectral data. Compounds 4-6 show antiplasmodial activity against Plasmodium falciparum.

Electrospray high performance liquid chromatography-mass spectrometry in phytochemical analysis of kava (Piper methysticum) extract.

HPLC coupled with electrospray (ES) MS was used to study a chloroform extract from kava roots ( PIPER METHYSTICUM). A total of thirteen kavalactones and flavokavains were identified. Seven major kavalactones, methysticin, dihydromethysticin, kavain, 7,8-dihydrokavain, 5,6-dehydrokavain, 5,6-dehydromethysticin and yangonin, were easily recognized in the extract by their [M + H] (+) or [M + Na] (+) ions, UV spectra, and retention times, compared with those of standard compounds. Six minor constituents were isolated as our own reference compounds. These constituents were identified by their [M + H] (+) or [M + Na] (+) ions, UV spectra and NMR data as 11 -hydroxy-12-methoxydihydrokavain, 7,8-dihydro-5-hydroxy-kavain, 11,12-dimethoxydihydrokavain, and flavokavains A, B and C. HPLC-ES-MS appears to be a suitable technique for identification of kavalactones and kavachalcones in the kava extract. The method also provides direct guidance for identification of other trace constituents from kava extracts.

Nigranoic acid, a triterpenoid from Schisandra sphaerandra that inhibits HIV-1 reverse transcriptase.

An A ring-secocycloartene triterpenoid, nigranoic acid (3,4-secocycloarta-4(28),24-(Z)-diene-3,-26-dioic acid, (1) was isolated from the stems of Schisandra sphaerandra, a Chinese traditional medicinal plant. Its structure elucidation and unambiguous NMR spectral assignment were achieved by the combination of 1D- and 2D-NMR techniques with the aid of computer modeling. Nigranoic acid showed activity in several anti-HIV reverse transcriptase and polymerase assays.

Aleppicatines A and B from Euphorbia aleppica.

Two new pentacyclic diterpene polyesters, aleppicatine A and B, have been isolated from the acetone extract of the whole plant of Euphorbia aleppica, in addition to five known cycloartane-type triterpenes (24-methylenecycloartanol, cyclolaudenol cycloart-25-en-3 beta-ol-24-one, cycloart-22-en-3 beta,25-diol and cycloart-25-en-3 beta,24-diol), scopoletin, kaempferol and 4-hydroxybenzoic acid and its methyl ether. The structures of the new compounds and their hydrolysis products have been extensively characterized by high-field NMR spectroscopic methods, including 2D NMR techniques.

Cytotoxicity and NMR spectral assignments of ergolide and bigelovin.

Two potent cytotoxic sesquiterpene lactones, ergolide (1) and bigelovin (2) were isolated from Inula hupehensis I. helianthus-aquatica and their structures and NMR data were assignment unambiguously by using a combination of one-and two-dimensional NMR techniques and computer modeling calculations.

Further polyoxypregnanes from Marsdenia tenacissima.

Two new polyoxypregnanes, designated marstenacigenins A and B, along with a known compound, dresgenin, were isolated from the mild acid hydrolysate of the ethanol extract of the stems of Marsdenia tenacissima. Their structures were deduced by a combination of 1D and 2D NMR spectroscopic techniques as 12 beta-cinnamoyl-dihydrosarcostin and 12 beta,20-dibenzoyldihydrosarcostin, respectively.