Abstract Glutamate receptors are widely distributed in the central nervous system(CNS) and participate in the delivery of excitatory neurotransmitters, including ionotropic glutamate receptors and metabotropic glutamate receptors. Metabotropic glutamate receptors(mGluRs) regulate neuronal excitability and synaptic plasticity, and are classified into group Ⅰ, Ⅱ and Ⅲ. The roles of group Ⅰ mGluRs in psychiatric and neurodegenerative diseases have been extensively studied, especially in the pathological progression of acute brain injury. Several studies have shown that group Ⅰ mGluRs can be involved in eliminating inflammatory damage, suppressing cell apoptosis, regulating neural network disorders, and promoting brain function recovery after acute brain injury. Therefore, group Ⅰ mGluRs have the potential to be effective targets for the treatment of acute brain injury. This paper reviews the distribution and function of group Ⅰ mGluRs in CNS, the pathological role in acute brain injury, and explore the potential of the development of drugs targeting group Ⅰ mGluRs.

Infectious bone defect is bone defect with infection or as a result of treatment of bone infection. It requires surgical intervention, and the treatment processes are complex and long, which include bone infection control,bone defect repair and even complex soft tissue reconstructions in some cases. Failure to achieve the goals in any step may lead to the failure of the overall treatment. Therefore, infectious bone defect has been a worldwide challenge in the field of orthopedics. Conventionally, sequestrectomy, bone grafting, bone transport, and systemic/local antibiotic treatment are standard therapies. Radical debridement remains one of the cornerstones for the management of bone infection. However, the scale of debridement and the timing and method of bone defect reconstruction remain controversial. With the clinical application of induced membrane technique, effective infection control and rapid bone reconstruction have been achieved in the management of infectious bone defect. The induced membrane technique has attracted more interests and attention, but the lack of understanding the basic principles of infection control and technical details may hamper the clinical outcomes of induced membrane technique and complications can possibly occur. Therefore, the Chinese Orthopedic Association organized domestic orthopedic experts to formulate An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique ( version 2023) according to the evidence-based method and put forward recommendations on infectious bone defect from the aspects of precise diagnosis, preoperative evaluation, operation procedure, postoperative management and rehabilitation, so as to provide useful references for the treatment of infectious bone defect with induced membrane technique.

OBJECTIVE: To investigate the chemical constituents from the leaves of Jatropha curcas and evaluate their inhibition on lipopolysaccharide (LPS)-activated BV-2 microglia cells. METHODS: The n-BuOH extract of the leaves of J. curcas was isolated by macroporous adsorption resin, silica gel, ODS, column chromatography and semi-preparative HPLC. The structures of the compounds were identified by MS, NMR, ECD, and other spectroscopic methods. In addition, anti-neuroinflammatory effects of isolated compounds were evaluated by measuring the production of nitric oxide (NO) in over-activated BV-2 cells. RESULTS: Seventeen compounds, including (7R,8S)-crataegifin A-4-O-β-D-glucopyranoside ( 1), (8R,8'R)-arctigenin ( 2), arctigenin-4'-O-β-D-glucopyranoside ( 3), (-)-syringaresinol ( 4), syringaresinol-4'-O-β-D-glucopyranoside ( 5), (-)-pinoresinol ( 6), pinoresinol-4'-O-β-D-glucopyranoside ( 7), buddlenol D ( 8), (2R,3R)-dihydroquercetin ( 9), (2S,3S)-epicatechin ( 10), (2R,3S)-catechin ( 11), isovitexin ( 12), naringenin-7-O-β-D-glucopyranoside ( 13), chamaejasmin ( 14), neochamaejasmin B ( 15), isoneochamaejasmin A ( 16), and tomentin-5-O-β-D-glucopyranoside ( 17) were isolated and identified. Compounds 2, 4 and 8 significantly inhibited the release of NO in BV-2 microglia activated by LPS, with IC₅₀ values of 18.34, 29.33 and 26.30 μmol/L, respectively. CONCLUSION Compound 1 is a novel compound, and compounds 2, 3, 8, 14- 17 are isolated from Jatropha genus for the first time. In addition, the lignans significantly inhibited NO release and the inhibitory activity was decreased after glycosylation.

Objective:To analyze the expression and clinical significance of serum microRNA (miR)-622 and miR-944 in patients with epithelial ovarian cancer.Methods:Seventy patients with ovarian epithelial cancer admitted in Yuyao People′s Hospital from January 2018 to June 2021 were selected as the study group, and 50 patients with benign ovarian tumors were selected as the control group. The expression of serum miR-622, miR-944 and the expression of tumor tissue protein E cadherin, mitogen-activated protein kinase-1(MAPK1), extracellular regulated protein kinases (ERK) were detected in both groups, and the correlation between miR-622, miR-944 and tumor tissue protein were analyzed. The receiver operating characteristic (ROC) curve was drawn to analyze the efficacy of miR-622 and miR-944 in the diagnosis of ovarian epithelial cancer.Results:The levels of serum miR-622, miR-944 and the expression of E-cadherin, MAPK1 and ERK in the study group were higher than those in the control group: 14.72 ± 1.87 vs. 5.94 ± 1.26, 13.02 ± 1.65 vs. 4.15 ± 0.62, (5.12 ± 0.77) scores vs. (2.37 ± 0.34) scores, (6.47 ± 1.09) scores vs. (2.56 ± 0.45) scores, (5.58 ± 0.86) scores vs. (1.87 ± 0.28) scores, there were statistical differences ( P<0.05). The serum levels of miR-622, miR-924 were positively correlated with the expression of E-cadherin, MAPK1 and ERK ( P<0.05). The area under the curve of miR-622, miR-944 and combined diagnosis of ovarian epithelial cancer were 0.763, 0.797, 0.808, respectively. Conclusions:The serum level of miR-622 and miR-944 were up-regulated in the patients with ovarian epithelial cancer, which was positively correlated with the expression of E-cadherin, MAPK1 and ERK protein in tumor tissues.

Neurological impairment in the form of stroke,cognitive dysfunction and delirium is a common complication after cardiac surgery and a major cause of postoperative death and long-term disability in patients undergoing cardiac surgery.There have been many studies attempting to identify intervention and treatment strategies,but no standardized protocols for neurological protection have been developed.The purpose of this article is to discuss the risk factors,mechanisms and neuroprotective measures to improve patient prognosis of neurological injury after cardiac surgery,and to review the recent research progress from three aspects:preoperative assessment and intervention,intraoperative management and monitoring,and postoperative diagnosis and treatment,emphasizing that the focus of perioperative prevention and treatment should be on the prevention of ischemic-hypoxic injury.Future research directions should focus on translational research of preclinical experiments and the development of novel imaging techniques to reduce the incidence of neurological complications and improve clinical outcome.

Curcuma kwangsiensis root tuber is a widely used genuine medicinal material in Guangxi, with the main active components of terpenoids and curcumins. It has the effects of promoting blood circulation to relieve pain, moving Qi to relieve depression, clearing heart and cooling blood, promoting gallbladder function and anti-icterus. Modern research has proved its functions in liver protection, anti-tumor, anti-oxidation, blood lipid reduction and immunosuppression. Considering the research progress of C. kwangsiensis root tubers and the core concept of quality marker(Q-marker), we predicted the Q-markers of C. kwangsiensis root tubers from plant phylogeny, chemical component specificity, traditional pharmacodynamic properties, new pharmacodynamic uses, chemical component measurability, processing methods, compatibility, and components migrating to blood. Curcumin, curcumol, curcumadiol, curcumenol, curdione, germacrone, and β-elemene may be the possible Q-markers. Based on the predicted Q-markers, the mechanisms of the liver-protecting and anti-tumor activities of C. kwangsiensis root tubers were analyzed. AKT1, IL6, EGFR, and STAT3 were identified as the key targets, and neuroactive ligand-receptor interaction signaling pathway, nitrogen metabolism pathway, cancer pathway, and hepatitis B pathway were the major involved pathways. This review provides a basis for the quality evaluation and product development of C. kwangsiensis root tubers and gives insights into the research on Chinese medicinal materials.
China ; Curcuma/chemistry* ; Humans ; Liver ; Neoplasms ; Terpenes/pharmacology*

ObjectiveTo reveal the medication rules of the clinical prescriptions containing Citri Sarcodactylis Fructus， and to provide a basis for the modern clinical application of Citri Sarcodactylis Fructus， the development of health products and the research and development of new drugs. MethodThe clinical prescriptions containing Citri Sarcodactylis Fructus were retrieved from CNKI， Wanfang Data， and VIP， and then a basic database of prescriptions was established via the traditional Chinese medicine inheritance auxiliary platform （V2.5）， IBM SPSS V20， and Excel （Microsoft Office 2016）. The frequency and association rules of the medicines in prescriptions （compatible medicines） and the corresponding syndromes were then mined. ResultThe prescriptions were screened according to the inclusion and exclusion criteria. A total of 458 clinical prescriptions containing Citri Sarcodactylis Fructus were collected， involving 388 Chinese medicines， and the total frequency of medicines reached 6 199. The core compatible medicines （frequency > 130） of Citri Sarcodactylis Fructus included Poria （frequency of 222）， Atractylodis Macrocephalae Rhizoma （217）， Paeoniae Radix Alba （196）， Bupleuri Radix （159）， and Citri Reticulatae Pericarpium （142）. The Citri Sarcodactylis Fructus-compatible medicines with frequency > 49 were selected for further analysis， which included 34 medicines with the cumulative frequency of 3 131 （50.51% of the total frequency）. These medicines mainly have the functions of tonifying Qi， invigorating Qi， tonifying blood， alleviating edema and promoting urination， promoting digestion， and activating blood and relieving pain. They are mainly warm， cold， or mild-natured， taste bitter， sweet， or acrid， and have the tropism in the spleen， liver， stomach， or lung meridians. The association rule analysis demonstrated that 14 medicine combinations were commonly used， and the core combinations were Poria-Citri Sarcodactylis Fructus， Atractylodis Macrocephalae Rhizoma-Citri Sarcodactylis Fructus， Paeoniae Radix Alba-Citri Sarcodactylis Fructus， Bupleuri Radix-Citri Sarcodactylis Fructus， Atractylodis Macrocephalae Rhizoma-Poria-Citri Sarcodactylis Fructus， and Citri Reticulatae Pericarpium-Citri Sarcodactylis Fructus. The clinical prescriptions containing Citri Sarcodactylis Fructus were mainly used to treat 52 diseases corresponding to 11 types of traditional Chinese medicine （TCM） syndromes. Three representative syndrome types， including spleen and stomach syndromes， Qi-blood-body fluid syndromes， and gynecological syndromes were selected for further association rule analysis. In the treatment of spleen and stomach syndromes， the core compatible drugs were Atractylodis Macrocephalae Rhizoma， Poria， Paeoniae Radix Alba， Bupleuri Radix， Citri Reticulatae Pericarpium， and Pinelliae Ehizoma， which， together with Citri Sarcodactylis Fructus， formed 25 commonly used medicine combinations （16 combinations composed of 2 medicines and 9 combinations composed of 3 medicines）. In the treatment of Qi-blood-body fluid syndromes， the core compatible drugs were Poria， Paeoniae Radix Alba， Atractylodis Macrocephalae Rhizoma， Astragali Radix， Hordei Fructus Germinatus， and Bupleuri Radix， which， together with Citri Sarcodactylis Fructus， formed 23 common medicine combinations （17 combinations composed of 2 medicines， 5 combinations composed of 3 medicines， and 1 combination composed of 4 medicines）. In the treatment of gynecological syndromes， the core compatible medicines were Atractylodis Macrocephalae Rhizoma， Paeoniae Radix Alba， Angelicae Sinensis Radix， Astragali Radix， Cyperi Rhizoma， and Poria， which constituted 25 common medicine combinations （15 combinations composed of 2 medicines and 10 combinations composed of 3 medicines）. ConclusionWe employed the traditional Chinese medicine（TCM） inheritance auxiliary platform to explore the compatibility of Citri Sarcodactylis Fructus-containing clinical prescriptions and the corresponding TCM syndromes， which intuitively showcased the medication rules of Citri Sarcodactylis Fructus. Specifically， Citri Sarcodactylis Fructus was mainly combined with the medicines for tonifying Qi， invigorating Qi， tonifying blood， alleviating edema and promoting urination， promoting digestion， and activating blood and relieving pain to treat different TCM syndromes. While soothing liver， regulating Qi， harmonizing stomach， and relieving pain， the combinations tonify and activate blood， invigorate spleen， and resolve dampness. The findings are of great significance to the rational application of Citri Sarcodactylis Fructus， the development of health food， and the research of new drugs and will bolster the development of Chinese medicine industry.

Objective:To investigate the efficacy and safety of thulium laser enucleation of the prostate-pre-transection urethral mucosa at the apex of prostate and traditional three lobe enucleation of the prostate for the treatment of benign prostatic hyperplasia patients.Methods:The data of 270 patients with benign prostatic hyperplasia who were underwent ThuLEP-PAM or ThuLEP in our hospital from May 2020 to September 2021 were analyzed retrospectively. According to the operation methods, the patients were divided into two groups: ThuLEP-PAM group (120 cases) and ThuLEP group (150 cases). There was no significant difference comparing the age [(69.8±7.7) years vs. (71.4±8.0) years], prostate volume [55.5(41.0, 71.0)ml vs. 58.5(45.0, 80.3)ml], the serum PSA [3.0(1.8, 4.6) ng/ml vs. 3.3(2.1, 5.5)ng/ml], international prostate symptom scores (IPSS) [22(17, 28) vs. 22(17, 27)], the quality of life score (QOL)[5(4, 6) vs. 5(4, 6)], the maximum urinary flow rate (Q max)[5.6(3.5, 7.3)ml/s vs. 5.5(4.0, 7.1)ml/s], the residual urine volume [ 31(0, 81)ml vs. 31(0, 102)ml] between the ThuLEP-PAM group and the ThuLEP group. No significant difference was found between the two groups( P>0.05). In the ThuLEP-PAM group, the external sphincter ring was located firstly, and urethral mucosa at the apex of prostate was circumferentially incised at 5 mm proximal of the sphincter ring by laser. Then the urethral mucosa was incised at the left sulcus beside the verumontanum and the prostate surgical capsule gap was exposed. After the middle lobe was removed, the left and right lobes were removed along the urethral mucosa pre-incision line at the prostatic apex. The ThuLEP group was enucleated by traditional three lobes enucleation. Perioperative indicators and postoperative complications during short-term follow-up were compared between the two groups. Results:All patients successfully completed the operation and the symptoms of the lower urinary tract were significantly improved. Comparison the perioperative factors between ThuLEP-PAM group and ThuLEP group included the following: operative time 90(70, 103)min vs. 83(61, 102)min; enucleated tissue weight 27.0(19.3, 36.5)g vs. 27.0(19.0, 39.0)g; decrease of the hemoglobin 9.9(7.4, 12.4)g/L vs. 9.5(7.1, 12.7)g/L; catheterization time 3.5(3.0, 4.0)d vs. 3.5(3.0, 5.0)d; hospital stay 6.0(5.0, 6.0)d vs. 5.0(4.0, 6.0)d. NO significant difference in these parameters was found between the two groups( P>0.05). There also was no significant difference in PSA[1.1(0.8, 1.5) ng/ml vs. 1.0(0.8, 1.6) ng/ml], IPSS score [5(4, 6) min vs. 5(4, 6)min], QOL score [2(1, 3) vs. 2(1, 3)], Q max [20.9(17.5, 22.5) ml/s vs. 20.4(17.8, 22.7) ml/s] and PVR [0 ml vs. 0(0, 6)ml] between the two groups ( P>0.05) after more than 3 months of follow-up. The incidence of incontinence for ThuLEP-PAM(2 cases)were lower than that for ThuLEP(11 cases)( P=0.031), but there was no significant between the two groups in other complications such as blood transfusion, haematuria, post-voidalurinary retention and urethral stricture. Conclusions:ThuLEP-PAM and ThuLEP have similar effect on the improvement of lower urinary tract symptoms in patients with benign prostatic hyperplasia, both of which have good efficacy and high safety. The biggest advantage of ThuLEP-PAM over ThuLEP is that it reduces the incidence of early postoperative stress urinary incontinence.

Objective Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9％) were men. Among them, nearly two-thirds (62.5％) of the survivors were moderate, three (9.4％) were severe, and more than half (59.4％) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6％ at 3 months to 15.8％ at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1％) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

Objective: To analyze the medication rules of traditional Chinese medicine (TCM) preventive oral prescriptions for COVID-19. Methods: The preventive oral prescriptions for COVID-19 published by national and provincial health and wellness committees, administrations of TCM, medical institutions at all levels, medical masters and Chinese medicine experts were collected to establish a database, manual screening was carried out according to the inclusion and exclusion criteria, and frequency statistics, association rule analysis. The mutual information method, entropy hierarchical clustering and other methods were improved through Excel and the TCM inheritance auxiliary platform V2.5 to mine the rules and characteristics of medication. Results: The selected 157 prescriptions contained a total of 130 TCMs. The top five TCMs with the highest use frequency were Glycyrrhizae Radix et Rhizoma (86), Astragali Radix (80), Lonicerea Japonicae Flos (70), Atractylodis Macrocephalae Rhizoma (62), Saposhnikoviae Radix (60). In accordance with TCM efficacy classification, most of them were medicines for qi-tonifying (279), followed by medicines for clearing heat and drying dampness (163), dispelling pathogenic wind-cold (126), resolving dampness (111), as well as dispelling pathogenic wind-heat (99). The characteristics of four-natures of the selected medicines are as follows: most of them were cold (59), followed by warm (38) and mild (21). In terms of five-taste, most of them were sweet (26) and acrid-and-bitter (24), followed by sweet-and-bitter (20), bitter (20) and acrid (15). For the meridian attribution, the five-zang organs and six-fu organs were all involved, most of them attributed to lung meridian (80), followed by stomach meridian (57) and spleen meridian (40). Based on association rule analysis, 12 commonly used medicine combinations with two or three TCMs were found. The commonly used medicinal pairs included Astragali Radix and Saposhnikoviae Radix (51), Astragali Radix and Atractylodis Macrocephalae Rhizoma (46), Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix (43), Astragali Radix and Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix (38), Forsythiae Fructus and Astragali Radix (37), and so on. In addition, 14 core combinations of medicines were obtained by complex system entropy cluster analysis, on this basis, six new prescriptions were screened out based on unsupervised entropy hierarchical clustering analysis. According to The Catalogue of Edible Traditional Chinese Medicinal Materials, Traditional Chinese Medicinal Materials for Health Food, and New Resources of Food published by National Health Commission of the People's Republic of China, there are 35 species belonging to the group of edible traditional Chinese medicinal materials, 20 species belonging to the group of new resources of food, 31 species belonging to the group of traditional Chinese medicinal materials for health food, 19.11% of the preventive oral prescriptions for COVID-19 were composed of the medicines belonging to the above three groups. Besides, there are 11 toxic species, and 24.84% of the preventive oral prescriptions for COVID-19 contained toxic TCMs. Conclusion: We found that invigorating qi and resolving dampness were the main treatment used to prevent for COVID-19, combined with the methods for strengthening vital energy and eliminating pathogenic factors. Most of the preventive oral prescriptions for COVID-19 were treated in lung, spleen and stomach meridians. In the process of selecting prescriptions and using TCMs to prevent for COVID-19, the safety of preventive medicines was also emphasized. And the theory of “Preventive Treatment of Disease” was embodied in these preventive oral prescriptions for COVID-19. For the prescriptions containing toxic TCMs, special attention should be paid to their safety in clinical application.