Coronary microvascular dysfunction （CMD） is one of the important causes of myocardial ischemia and non-obstructive coronary artery ischemic symptoms. However， effective diagnostic methods and targeted treatment strategies for CMD are currently lacking. According to traditional Chinese medicine （TCM）， the comorbidity theory of "blood-vessel-cardiac collaterals" plays a central role throughout the entire development process of CMD. It suggests that in the clinical diagnosis and treatment of CMD， the treatment of blood， vessels， and cardiac collaterals should not be neglected. In light of this， insect medicines， known for their efficacy in promoting blood circulation， resolving stasis， and alleviating spasms， hold promise as a potential treatment for CMD. However， there is currently no research or summary on the use of insect medicines for the treatment of CMD. Therefore， this article took the comorbidity theory of "blood-vessel-cardiac collaterals" as the starting point and divided the pathogenesis of CMD into five evolution stages： Beginning in the blood （changes in blood components and hemorheology）， progressing in the vessels （atheromatous plaque formation and unstable plaques）， occurring in the cardiac collaterals （microvascular endothelial damage and microvascular constriction and spasms）， ending in the cardiac collaterals （microvascular remodeling）， and resulting in energy metabolism disorders throughout the process， so as to explore the pathogenesis and evolution of CMD. In addition， based on the modern pharmacological research on insect medicines， this article discussed the clinical application of insect medicines in the treatment of CMD from four aspects： Promoting blood circulation and removing blood stasis to relieve vessels' obstruction， relieving spasms to alleviate pain， combating poison with poison to disperse stagnation， and tonifying cardiac collaterals to nourish the heart， which aims to provide a theoretical basis for the use of TCM in treating CMD， broaden the scope of medication， and improve clinical efficacy.

ObjectiveThe purpose of this study was to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) on cognitive function of vascular dementia (VD) rats and its mechanism. MethodsVD rat model was established by modified two-vessel occlusion (2-VO). After modeling, TEAS and electroacupuncture (EA) were used to stimulate Baihui and Zusanli points of rats respectively for 14 d. After treatment, novel object recognition test, Morris water maze test, and Y maze test were used to evaluate the spatial memory and learning ability of rats. Hematoxylin and eosin staining was used to observe the morphology of hippocampal neurons. Transmission electron microscopy was used to observe the ultrastructure of hippocampal mitochondria. Enzyme-linked immunosorbent assay kits were used to detected the levels of SOD, CAT, GSH-Px, MDA and ROS in serum of rats. Western blot was used to detect the expression of PGC-1α, TFAM, HO-1, NQO1 proteins in the hippocampus, Keap1 protein in the cytoplasm and Nrf2, NRF1 proteins in the nucleus. ResultsAfter treatment for 14 d, compared to the model group, the escape latency of VD rats decreased, while the discrimination index, the times of rats crossing the original platform area, the residence time in the original platform quadrant, and the percentage of alternation increased. TEAS can improve the structure of hippocampal neurons and mitochondria of VD rats, showing that neurons were arranged more regularly and distributed more evenly, nuclear membrane and nucleoli were clearer, and mitochondrial swelling were reduced, mitochondrial matrix density were increased, and mitochondrial cristae were more obvious. The levels of SOD, GSH-Px and CAT in serum increased significantly, while the concentration of MDA and ROS decreased. TEAS also up-regulated the expression levels of PGC-1α TFAM, NQO1 and HO-1 proteins in the hippocampus and Nrf2, NRF1 proteins in the nucleus, but down-regulated the Keap1 protein in the cytoplasm. ConclusionTEAS can improve cognition, hippocampal neurons and mitochondrial structure of VD rats, and the effect is better than EA. The mechanism may be the activation of PGC-1α mediated mitochondrial biogenesis and antioxidant stress, which also provides a potential therapeutic technology and experimental basis for the treatment of VD.

R-spondin2 (Rspo2) is a member of protein family RSPOs, which can be coupled to receptor 4/5 (leucine-rich repeat-containing g protein-coupled receptor 4/5, LGR4/5), cell surface transmembrane E3 ubiquitin ligase ZNRF3/RNF43 (zinc and ring finger 3/ring finger protein 43), heparan sulfate proteoglycan (heparan sulfate proteoglycans, HSPGs) and the IQ motif (IQ gap 1) containing GTP enzyme activating protein 1, regulating the Wnt/β-catenin signaling pathway, which is the most widely studied signaling pathway and directly related to basic bone biology. Any problem in this pathway may have an impact on bone regulation. In recent years, it has been found that Rspo2 can act on osteoblast, osteoclast and chondrocytes through Wnt/β-catenin, and take part in occureace and development of some bone diseases such as ossification of the posterior longitudinal ligament (OPLL), osteoarthritis (OA) and rheumatoid arthritis (RA), so the study of Rspo2 may become a new therapeutic direction for bone-related diseases. Based on the latest research progress, this paper reviews the structure and main functions of Rspo2, the mechanism of Rspo2 regulating Wnt/β-catenin signaling pathway and its influence on skeletal system, in order to provide new ideas and ways for the prevention and treatment of bone-related diseases.

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.

Objective To study the pharmacokinetic characteristics of lamotrigine tablets in Chinese healthy subjects under fasting and fed conditions,and to evaluate the bioequivalence and safety profiles between the domestic test preparation and the original reference preparation.Methods Twenty-four Chinese healthy male and female subjects were enrolled under fasting and fed conditions,18 male and 6 female subjects under fasting conditions,17 male and 7 female subjects under fed conditions.A random,open,single-dose,two preparations,two sequences and double-crossover design was used.Plasma samples were collected over a 72-hour period after give the test or reference preparations 50 mg under fasting and fed conditions.The concentration of lamotrigine in plasma was detected by liquid chromatography-tandem mass spectrometry,and the main pharmacokinetic parameters were calculated to evaluate the bioequivalence by WinNonLin 8.1 program.Results The main pharmacokinetic parameters of single-dose the tested and reference preparations were as follows:The fasting condition Cmax were(910.93±248.02)and(855.87±214.36)ng·mL-1;tmax were 0.50(0.25,4.00)and 1.00(0.25,3.50)h;t1/2 were(36.1±9.2)and(36.0±8.2)h;AUC0_72h were(27 402.40±4 752.00)and(26 933.90±4 085.80)h·ng·mL-1.The fed condition Cmax were(701.62±120.67)and(718.95±94.81)ng·mL-1;tmax were 4.00(1.00,5.00)and 4.00(0.50,5.00)h;t1/2 were(44.2±12.4)and(44.0±12.0)h;AUC0-72h were(30 253.20±7 018.00)and(30 324.60±6 147.70)h·ng·mL-1.The 90％confidence intervals of the geometric mean ratios of Cmax and AUC0-72 hfor the test preparation and reference preparation were all between 80.00％and 125.00％under fasting and fed conditions.Conclusion Two kinds of lamotrigine tablets are bioequivalent,and have similar safety in Chinese healthy male and female subjects under fasting and fed conditions.

Celastrol and wilforlide A are the main active triterpenoids of the traditional Chinese medicine Lei Gong Teng, which have anti-tumour, anti-inflammatory and immunosuppressive activities, and are the material basis for the clinical efficacy of Lei Gong Teng-related Chinese medicinal preparations. By analysing the biosynthetic pathway of active ingredients, optimizing genetic elements and utilizing "cell factory" to produce triterpenoids heterologously will be an effective way to obtain from Tripterygium wilfordii in the future in a "low-cost and high-efficient" manner. CYP712Ks are the first cytochrome P450s involved in the skeleton modification of friedelane-type and oleanane-type triterpenoids in T. wilfordii, and they can catalyse the generation of polpunonic acid from friedelin and 3-epi-katonic acid from β-amyrin by carboxylation at C-29 position. In this study, four multifunctional TwCYP712K1/2/3/5 were used to clarify the catalytic function and substrate selection preference using in vivo functional characterization in Saccharomyces cerevisiae. The spatial structure of the protein-substrate binding was clarified through homology modeling and molecular docking, and then the differential amino acids in the active pocket of the protein were mutated to clarify the crucial amino acids determining the catalytic function and the selection of substrate structure. A total of 63 mutant elements were constructed, and the amino acid sites affecting the carboxylation function of TwCYP712Ks were analyzed. In particular, the key amino acids affecting the substrate selectivity of TwCYP712K2 towards oleanane-type and friedelane-type triterpenoids were revealed and the TwCYP712K2^F127I and TwCYP712K2^A227T mutants would result in a reversal of the product ratio. In conclusion, four proteins of TwCYP712Ks were semi-rationally designed by homologous protein alignment and mutual mutation to elucidate multiple amino acid sites determining the catalytic function of the proteins, and a series of activity-enhancing or altering mutants were obtained, which provide abundant catalytic elements for the biosynthesis of active triterpenoids from T. wilfordii, and the mechanism of carboxylation in the C-29 position was initially elucidated.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To investigate the clinical efficacy of total laparoscopic technique in the treatment of pelvic and acetabular fractures.Methods:A total of 7 patients with pelvic and acetabular fractures admitted to the First Affiliated Hospital of Nanjing Medical University from April 2017 to August 2023 were retrospectively analyzed. There were 5 males and 2 females, aged 43.9±9.9 years (range, 27-56 years). There was 1 pelvic fracture (Tile B3) and 6 acetabular fractures, Letournel typing transverse in 2 cases, double column in 1 case, transverse combined anterior column in 1 case, anterior column in 1 case, and "T" shape in 1 case. The causes of injury included traffic accident in 4 cases, falling from height in 1 case, falling in 1 case, and heavy object injury in 1 case. The operation time, intraoperative blood loss, iatrogenic injuries of blood vessels, nerves, bladder and rectum, and incidence of postoperative complications were recorded. Matta imaging criteria was used to evaluate the quality of fracture reduction, and the hip function was evaluated by modified Merle d'Aubigné-Postel score.Results:All 7 patients were successfully operated and followed up for 12.0 (7.0, 72.0) months (range, 7-77 months). The operation time was 251.1±80.2 min (range, 150.0-370.0 min), and the intraoperative blood loss was 100.0 (50.0, 300.0) ml (range, 50-350 ml). There was no nerve, blood vessel, bladder or rectum injury during operation. Postoperative pelvic X-ray and CT showed no internal fixation into the joint. Anatomic reduction was achieved in 5 cases and satisfactory reduction in 2 cases. One patient with a transverse acetabular fracture had a slight separation and displacement of the posterior column, but the acetabular articular surface was flat as a whole without obvious steps and was not fixed. One patient with pelvic fracture had a comminuted anterior pelvic ring with severe displacement and did not achieve anatomical repositioning intraoperatively, but the anterior pelvic ring was a non-intra-articular fracture, and the fracture ends were immobilized with bilateral plates, and the morphology and stability of the anterior pelvic ring recovered well after the operation. The Merle d'Aubigné - Postel score at the final follow-up was 18.0 (17.0, 18.0) points (range, 17.0-18.0 points), with 4 excellent and 3 good cases. All 7 patients achieved clinical healing with a healing time of 2.5 (2.5, 3.0) months (range, 1.0-3.0 months). No delayed union or nonunion occurred. At the last follow-up, there were no complications such as internal fixation fracture, incision and internal fixation infection, and deep vein thrombosis.Conclusion:Total laparoscopic technique for the treatment of pelvic and acetabular fractures has less intraoperative blood loss, less surgical trauma, and satisfactory clinical efficacy. It can be used as a new choice of minimally invasive treatment of pelvic and acetabular fractures.

Objective To explore clinical effect of the fifth metatarsal head excision and non-excision in rheumatoid arthritis(RA)forefoot deformity reconstruction.Methods Retrospective analysis was performed on 50 patients(76 feet)with moderate to severe forefoot deformity caused by RA treated from May 2015 to January 2019.According to degeneration of the fifth metatarsophalangeal joint,the fifth metatarsal head was retained or excised by wind-like forefoot reconstruction,and divid-ed into the fifth metatarsal head preservation group(preservation group)and the fifth metatarsal head resection group(resec-tion group).Twenty-four female patients in preservation group,aged from 47 to 81 years old with an average of(60.37±8.60)years old;the course of disease ranged from 13 to 22 years with an average of(19.00±3.06)years;body mass index(BMI)ranged from 21 to 28 kg·m-2 with an average of(23.53±2.47)kg·m-2;six patients(6 feet)with moderate hallux valgus defor-mity and 18 patients(30 feet)with severe hallux valgus deformity;treated with the first metatarsophalangeal joint fusion com-bined with the second th the fourth metatarsophalangeal joint arthroplasty and the fifth metatarsophalangeal joint cleanup.Twenty-six female patients in resection group were female,aged from 30 to 80 years old with an average of(58.53±13.70)years old;the course of disease ranged from 8 to 25 years with an average of(17.94±3.92)years;BMI raged from 20 to 28 kg·m-2 with an average of(24.60±2.03)kg·m-2;4 patients(4 feet)with moderate bunion valgus deformity and 22 patients(36 feet)with severe bunion valgus deformity;treated by the first metatarsophalangeal joint fusion combined with the second th the fifth metatarsophalangeal joint resection of the metatarsophalangeal head.Operation time and postoperative complications between two groups were observed,hallux valgus angle(HVA),intermetatarsal angles between the first and the second metatarsals(I-MAFS),intermetatarsal angles between the first and fifth metatarsals(IMAFF),Japanese Society for Surgery of Foot(JSSF)score before surgery and at the latest follow-up were compared.Results Fifty patients were followed-up from 14 to 46(25.30± 8.83)months in resection group and 12 to 48 with an average of(24.30±1 1.12)months in preservation group,while no signifi-cant difference between two groups(P＞0.05).There were no significant difference in operation time and postoperative compli-cations between two groups(P＞0.05).JSSF scores,HVA,IMAFS and IMAFF in fesection group were improved from(45.09± 3.35)points,(38.90±13.67)°,(12.88±1.72)°,(32.50±2.99)° before operation to(81.60±3.27)points,(15.40±0.90),(9.06±2.27)°,(22.20±1.98)° at the latest follow-up(P＜0.05);preservation group were improved from(47.09±3.96)points,(43.30±12.65)°,(13.99±3.13)°,(33.20±6.14)° to(83.10±3.66)points,(15.20±1.54)°,(8.99±1.02)°,(24.70±1.88)°,respectively.There were no significant difference in JSSF score,HVA,IMAFS and IMAFF between two groups before opera-tion and the latest follow-up(P＞0.05).At the latest follow-up,there were statistically significant differences in pain and defor-mity in JSSF scores between two groups(P＜0.05).Conclusion Both rheumatoid anterior foot reconstruction and anterior foot reconstruction fifth metatarsophalangeal joint debridement showed significant improvement in clinical efficacy and imaging re-sults.Compared with rheumatoid prefoot reconstruction,the fifth metatarsophalangeal joint reconstruction for the treatment of moderate and severe deformity of rheumatoid prefoot showed better improvement in pain,but worse improvement in deformity.For the moderate to severe deformity of the forefoot caused by rheumatoid disease,patients with mild to moderate degenerative deformity of the articular surface of the fifth metatarsal phalanges may be considered for use.

Objective To investigate the high-frequency ultrasonic anatomical features of the adjacent C7 transverse process and its clinical value in stellate ganglion block(SGB).Methods High-frequency ultrasound was applied to obtain ultrasonographic anatomical sonogram features in the plane of bilateral C7 transverse processes in 52 cases(104 sides in total)of healthy adults and then stored for the operator to learn and correctly label each tissue structure.Fifty patients who underwent ultrasound-guided SGB were selected and divided into the BC7 group(25 cases before study)and AC7 group(25 cases after study).The operation time,SGB success rate,number of adjusted needle tips,dosage of anaesthetic and adverse reaction of patients in both group were recorded.Results The main muscles observed in the C7 plane were the longissimus and anterior scalene muscles,the ultrasonographic anatomical relationships of the vagus nerve located in the carotid sheath,the pleura located posterior to the subclavian artery,and the recurrent laryngeal nerve located in the vicinity of the branches of the inferior thyroid artery are described,and the stellate ganglion was illustrated as a flattened hypoechogenic structure visible on the deep surface of the prevertebral fascia in the region of the external cervical longissimus muscle,vertebral artery and vein,and the medial aspect of the anterior oblique muscle,and emanated the sonographic features of several hypoechoic nerve bundles.Ultrasound guided SGB was completed uneventfully in patients of both groups,and all patients developed Horner syndrome,with the SGB success rate of 100%.The operation time[(5.36±1.11)minutes]of patients in the BC7 group was longer than that in the AC7 group[(3.08±0.86)minutes],the number of adjusted needle tips[(4.20±1.00)times]of patients in the BC7 group was more than that in the AC7 group[(2.24±0.87)times],and the dosage of anaesthetic[(1.82±0.28)mL]of patients in the BC7 group was more than that in the AC7 group[(1.64±0.22)mL],all the differences were statistically significant(P<0.05).There was no significant difference in the incidence of adverse reaction between the two groups(P>0.05).Conclusion After ultrasonic learning of adjacent structures through C7 transverse process,SGB is safe and easy to perform.