Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Sesquiterpenes are natural terpenes containing 15 carbon atoms. They are widely used in the perfume, pharmaceutical, and biofuel industries due to their remarkable biological activities. The traditional production of sesquiterpenes relies on chemical synthesis or plant extraction, which has the disadvantages of low yields and waste of resources. The construction of microbial cell factories for the efficient synthesis of sesquiterpenes by means of synthetic biology provides a new option. In recent years, with the development of metabolic engineering and synthetic biology, the heterologous synthesis of a variety of sesquiterpenes has been successfully achieved by metabolic engineering of the oleaginous yeast, Yarrowia lipolytica. In this paper, we review the research progress in the heterologous synthesis of different sesquiterpenes by Y. lipolytica, discuss the synthetic biology strategies commonly used in this field, and make an outlook on the research directions and engineering approaches to further enhance the sesquiterpene yield in this host. This paper provides a reference for strategies such as synergistic optimization of synthetic biology and metabolic engineering, enhanced precursors, and opens up new directions for the application of synthetic biology in green chemistry and sustainable production.
Yarrowia/genetics* ; Sesquiterpenes/metabolism* ; Metabolic Engineering/methods* ; Synthetic Biology/methods*

Objective:To explore the application value of blue laser endoscopic linkage color imaging (LCI) in the diagnosis of benign and malignant lesions in colonic laterally spreading tumor (LST).Methods:A retrospective case series study was conducted. The clinical data of 62 patients with colonic LST diagnosed and treated in the Second People's Hospital of Kunshan from June 2019 to June 2022 were retrospectively analyzed. All patients underwent 2 modes of blue laser endoscopic LCI and white light imaging (WLE) combined with indigo blush staining for colonoscopy to determine the benign and malignant LST lesions, and the lesion tissues were taken under the endoscope for pathological diagnosis. Kappa test was used to evaluate the consistency of the diagnostic results of LCI and WLE with pathological diagnosis. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of LCI and WLE for LST. Results:A total of 92 LST lesions were detected in 62 patients. Pathological findings showed that among the 92 lesions, there were 2 inflammatory lesions, 4 proliferative lesions, 46 low-grade intraepithelial neoplasia, 37 high-grade intraepithelial neoplasia and 3 infiltrating cancer in mucosa or under mask. The results of LCI of 92 lesions showed that 4 lesions were type Ⅰ, 39 lesions were type Ⅱ, 45 lesions were type Ⅲ, 2 lesions were inflammatory and 2 lesions were hyperplastic; the diagnosis results of WLE showed that 6 lesions were type Ⅰ, 40 lesions were type Ⅱ, 37 lesions were type Ⅲ, 4 lesions were inflammatory and 5 lesions were proliferative. Among LCI results, 82 neoplastic lesions were consistent with pathological diagnosis, and 4 non-neoplastic lesions were consistent with pathological diagnosis, with a total coincidence rate of 93.48% (86/92); LCI was consistent with pathological diagnosis ( Kappa = 0.586, P < 0.05). Among WLE results, 74 neoplastic lesions were consistent with pathological diagnosis, and 3 non-neoplastic lesions were consistent with pathological diagnosis, with a total coincidence rate of 83.70% (77/92); WLE was consistent with pathological diagnosis ( Kappa =0.447, P < 0.05). The consistency of pathological diagnosis with LCI was higher than that with WLE. ROC analysis showed that the area under the curve of LCI and WLE for the diagnosis of benign and malignant lesions in colonic LST was 0.810 (95% CI: 0.715-0.884) and 0.681 (95% CI: 0.575-0.774), respectively. Conclusions:Blue laser endoscopic LCI has a high consistency with pathological diagnosis in the diagnosis of benign and malignant lesions in colonic LST. It has a high diagnostic value for colonic LST.

【Objective】 To explore pain and collapse mechanisms in fosteonecrosis of the femoral head (ONFH) with bone marrow edema (BME). 【Methods】 ONFH patients at ARCO Ⅲ stage who underwent total hip arthroplasty in the First Affiliated Hospital of Guangzhou University of Chinese Medicine were enrolled; the femoral head samples, clinical and imaging data were collected. These patients were divided into BME group and non-BME group according to the MR data in one week preoperative. Hematoxylin-eosin and Sirius red staining were performed to observe the morphological changes in bone tissue of femoral head specimens. Western blotting and qPCR were used to semi-quantitatively analyze the expression levels of CTSK, RANKL, and Netrin-1 proteins and mRNA in different regions of the bone tissue. 【Results】 Clinical and imaging data showed that ONFH patients with BME had significantly higher scores of VAS than ONFH patients without BME. Hematoxylin-eosin staining showed that bone structure disorder and a large number of empty bone lacunae were found in the necrotic areas in both groups, but there exited significant granulation tissue in the BME group, and spindle-shaped fibroblastic cells and inflammatory cells aggregated in the repaired region. Sirius red staining revealed the necrotic and sclerotic areas were accumulated with many collagenous fiber in the BME group. The results of Western blotting and qPCR showed that Netrin-1 expressions in the necrotic, sclerotic and health areas in the BME group were higher than those in the non-BME group (P<0.05), while osteoclast related proteins and mRNA expressions of the necrotic and sclerotic areas in the BME group was higher than those in the non-BME group (P<0.05). 【Conclusion】 All these findings indicated that hip pain was positively correlated with femoral head necrosis with BME, hyperactive osteoclasts participated in the femoral head collapse with BME, and the upregulated expression of Netrin-1 mediated the pain mechanism.

Objective:To explore the clinical effects of pre-expanded anterior perforator flap of transverse cervical artery in extensive facial and cervical scar reconstruction and contralateral pre-expanded thoracic random flap in relay in donor site repair.Methods:A retrospective cohort study was conducted. From May 2008 to December 2018, 10 patients with extensive facial and cervical scar after burns were treated in the Fourth Medical Center of PLA General Hospital, including 8 males and 2 females, aged 10-55 years. In the first stage of operation, two skin and soft tissue expanders of the same volume (with rated capacity of 250-600 mL) were respectively placed in the right side and left side of the chest according to the size of scar, and then the skin was expanded. The total amount of normal saline injected was 2 to 4 times of the rated capacity of the expander. In the second stage, the defect with area of 12 cm×8 cm-23 cm×15 cm caused by scar resection and release was repaired with unilateral pre-expanded anterior perforator flap of transverse cervical artery with area of 12 cm×9 cm-24 cm×16 cm. The contralateral pre-expanded thoracic random flap with the same area as that of the above-mentioned perforator flap was extended to repair the secondary defect with area of 8 cm×6 cm-17 cm×14 cm formed after transfer of the above-mentioned perforator flap. The exploration of perforating branch of transverse cervical artery, flap transfer and survival, injury repair, and complications were observed. The appearance and related function of donor and recipient sites and satisfaction of patients were followed up.Results:The perforating branches of transverse cervical artery appeared stably in the 10 patients. All the flaps were transferred to the recipient area without tension and survived. Both facial and cervical injuries were repaired successfully with no common complications. During the follow-up of 6 months-8 years, the color and texture of the pre-expanded anterior perforator flap of transverse cervical artery matched with the surrounding tissue, the functions of head raising and neck rotation of patients were significantly improved compared with those before operation, the color and texture of the flap transplanted in the first donor site matched with the original skin, linear scar left at the surgical incision, and 9 patients were satisfied with the restoration of the appearance and function of donor and recipient sites.Conclusions:The color and texture of the pre-expanded anterior perforator flap of transverse cervical artery match well with the face and neck, and the repairable area is large. After the perforator flap is removed, the secondary wound can be repaired with the pre-expanded thoracic random flap at the same time, and the injury of the chest donor site is alleviated. This relay repair method is a good choice for reconstructing extensive facial and cervical scar.

Objective:To compare the clinical efficacy between the pressing tendon suture with a lateral anchor and the knotted suture with a lateral anchor in the treatment of severe rotator cuff tear under shoulder arthroscopy.Methods:A retrospective study was conducted of the 42 patients who had been treated at Department of Orthopedic Sports Medicine, Affiliated Hospital to Qingdao University from December 2018 to December 2019 for severe rotator cuff tear. They were 13 males and 29 females, with an age of (58.3±10.1) years (from 32 to 74 years). The injury was on the right side in 26 cases and on the left side in 16 cases. Of them, 22 received pressing tendon suture with a lateral anchor under shoulder arthroscopy and 20 knotted suture with a lateral anchor under shoulder arthroscopy. The flexion, abduction and external rotation of the shoulder, Visual Analog Scale (VAS) pain score, University of California-Los Angeles (UCLA) score, Constant-Murley shoulder score, American Shoulder and Elbow Surgeons (ASES) score and imaging MRI Sugaya grading were compared between the 2 groups 12 months after operation.Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability between them ( P>0.05). At 12 months after operation, the pressing tendon suture group had better abduction and flexion of the shoulder, a lower VAS pain score and a higher ASES score than the knotted suture group, but the differences were insignificant ( P>0.05). At 12 months after operation, the pressing tendon suture group achieved significantly better external rotation (39.2°±11.7°) and significantly higher UCLA score (28.1±4.7) and Constant-Murley shoulder score (77.0±9.3) than the knotted suture group (29.8°±14.6°, 22.1±5.7 and 66.4±11.0) ( P<0.05). At 12 months after operation, the imaging MRI Sugaya grading was significantly lower for the pressing tendon suture group than that for the knotted suture group ( P<0.05). Conclusion:In the treatment of patients with severe rotator cuff tear under shoulder arthroscopy, the pressing tendon suture with a lateral anchor may lead to better clinical prognosis than the knotted suture with a lateral anchor.

Objective:To compare the clinical efficacies of Da Vinci robotic and laparoscopic total mesorectal excision (TME) for low rectal cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 64 patients with low rectal cancer who were admitted to the Third Xiangya Hospital of Central South University from October 2015 to January 2019 were collected. There were 42 males and 22 females, aged from 40 to 84 years, with a median age of 59 years. Of the 64 patients, 31 undergoing Da Vinci robotic TME and 33 undergoing laparoscopic TME were allocated into robotic group and laparoscopic group, respectively. Observation indicators: (1) surgical situations and postoperative recovery; (2) postoperative pathological examination; (3) follow-up. Follow-up using outpatient examination and telephone interview was conducted to detect long-term complications and pelvic autonomic nerve injury up to January 2020. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M ( P25, P75), and comparison between groups was analyzed using the rank sum test. Count data were represented as absolute numbers, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ordinal data between groups was analyzed using the Mann-Whitney U test. Results:(1) Surgical situations and postoperative recovery: cases with anus preservation, cases with defunctioning stoma, cases with intraoperative conversion to laparotomy, cases with intraoperative blood transfusion, operation time, volume of intraoperative blood loss, time to postoperative first out-of-bed activities, time to postoperative first flatus, time to postoperative diet resumption, duration of hospital stay, cases with incision infection, cases with postoperative hemorrhage, cases with anastomotic fistula, cases with pulmonary infection, cases with urinary retention, comprehensive complication index for the whole group, comprehensive complication index for patients with complications, and treatment expenses of the robotic group were 30, 23, 0, 1, (285±73)minutes, (147±112)mL, (1.6±0.8)days, (3.6±1.1)days, (3.2±1.5)days, (9.8±2.8)days, 1, 4, 3, 1, 4, 15.0±12.0, 22.6(20.9, 27.3), (11.7±1.2)×10 4 yuan, respectively. The above indicators of the laparoscopic group were 22, 13, 2, 2, (253±57)minutes, (211±123) mL, (1.8±0.8) days, (3.9±1.6)days, (4.1±1.9)days, (11.8±4.3)days, 2, 5, 3, 3, 2, 20.0±12.0, 24.2(10.5, 30.8), (7.7±1.3)×10 4 yuan, respectively. There were significant differences in the cases with anus preservation, volume of intraoperative blood loss, duration of hospital stay, and treatment expenses between the two groups ( χ2=8.581, t=-2.065, -2.133, 12.700, P<0.05). There was no significant difference in the cases with defunctioning stoma, operation time, time to postoperative first out-of-bed activities, time to postoperative first flatus, time to postoperative diet resumption, comprehensive complication index for the whole group, or comprehensive complication index for patients with complications between the two groups ( χ2=2.425, t=1.957, -0.679, -0.846, -1.941, -1.867, Z=-0.850, P>0.05). There was no significant difference in the cases with intraoperative conversion to laparotomy, cases with intraoperative blood transfusion, cases with incision infection, cases with postoperative hemorrhage, cases with anastomotic fistula, cases with pulmonary infection, or cases with urinary retention between the two groups( P>0.05). One patient with anastomotic fistula in the robotic group was clipped under endoscopy, and the other patients with complications were cured after symptomatic treatment. (2) Postoperative pathological examination: distance from tumor to surgical margin, tumor diameter, case with positive or negative surgical margin, cases with highly, highly-moderately, moderately, moderately-poorly, poorly differentiated tumor (tumor differentiation degree), cases in stage Ⅰ, Ⅱ, Ⅲa+ b, Ⅲc+ Ⅳ (tumor pathological stage), the number of lymph node dissected were 1.0 cm(0.3 cm, 2.0 cm), (3.5±1.1)cm, 2, 29, 3, 7, 14, 5, 2, 5, 18, 4, 4, 16.0±2.8 of the robotic group, respectively, versus 1.3 cm(0.5 cm, 3.0 cm), (4.2±1.4)cm, 2, 30, 1, 7, 16, 6, 3, 1, 19, 7, 6, 13.9±3.8 of the laparoscopic group. There was a significant difference in the number of lymph node dissected between the two groups ( t=2.420, P<0.05) . There was no significant difference in the distance from tumor to surgical margin, tumor diameter, tumor differentiation degree, or tumor pathological stage between the two groups ( Z=-0.980, t=-1.912, Z=-0.809, -1.595, P>0.05). There was no significant difference in the surgical margin between the two groups ( P>0.05). (3) Follow-up: of the 31 patients in the robotic group, 29 were followed up for 3-24 months, with a median follow-up time of 12 months. Of the 33 patients in the laparoscopic group, 30 were followed up for 3-36 months, with a median follow-up time of 15 months. Cases with intestinal obstruction, cases with timely stoma closure, cases with local recurrence, cases with distant metastasis, cases with death, Wexner score at postoperative 12 months, international prostate symptom score at postoperative 12 months, times of nocturia at postoperative 12 months, international index of erectile function of the robotic group were 2, 20, 3, 2, 2, 0.0(0.0, 0.0), 4.5(1.3, 8.8), 1.5(1.0, 2.0), 2.0(1.3, 10.8), respectively. The above indicators were 4, 7, 3, 2, 3, 1.0(0.0, 3.0), 8.0(2.0, 14.3), 2.0(1.0, 4.0), 3.0(1.0, 11.8) of the laparoscopic group. There was no significant difference in the cases with intestinal obstruction, cases with timely stoma closure, cases with local recurrence, cases with distant metastasis, or cases with death between the two groups ( P>0.05). There were significant difference in the Wexner score and times of nocturia at postoperative 12 months between the two groups ( Z=-2.202, -1.986, P<0.05). There was no significant difference in the international prostate symptom score and international index of erectile function at postoperative 12 months between the two groups ( Z=-0.885, 0.094, P>0.05). Conclusion:Both Da Vinci robotic and laparoscopic TME for low rectal cancer are safe and effective, of which the former can improve the anal sphincter retention rate, reduce the nocturia frequency and enhance the protection of defecation function under the premise of radical resection of tumor.

Objective: To summarize the measures and experience of treatment in mass extremely severe burn patients. Methods: The clinical data and treatment of 8 extremely severe burn patients in August 2 Kunshan factory aluminum dust explosion accident who were admitted in the 100th Hospital of PLA on August 2nd, 2014, were retrospectively analyzed. There were 4 males and 4 females, aging 22-45 (34±7) years, with total burn area of 55%-98% [(89±15)%] total body surface area (TBSA) and full-thickness burn area of 45%-97% [(80±21)%] TBSA. All the 8 patients were accompanied with severe shock, inhalation injury, and blast injury. According to the requirements of former PLA General Logistics Department and Nanjing Military Command, a treatment team was set up including a special medical unit and a special care unit, with Chai Jiake from the First Affiliated Hospital of PLA General Hospital as the team leader, Zheng Qingyi from the 175th Hospital of PLA (the Affiliated Dongnan Hospital of Xiamen University) as the deputy leader, the 100th Hospital of PLA as the treatment base, and burn care, respiratory, nephrology, nursing specialists from the First Affiliated Hospital of PLA General Hospital, and the burn care experts and nursing staff from the 180th Hospital of PLA, 118th Hospital of PLA, 98th Hospital of PLA, and 175th Hospital of PLA, and nurses from the 85th Hospital of PLA, 455th Hospital of PLA, 101th Hospital of PLA, 113th Hospital of PLA as team members. Treatment strategies were adopted as unified coordination by the superior, unified responsibility of team leader, division of labor and cooperation between team members, and multidisciplinary cooperation led by department of burns. With exception of one patient who received deep vein catheterization before admission, the other 7 patients were treated with deep vein catheterization 0.5 to 3.0 hours after admission to correct hypovolemic shock as soon as possible. Eight patients received tracheotomy, and 7 patients were treated with mechanical ventilation by ventilator in protective ventilation strategy with low tide volume and low volume pressure to assist breathing. Fiberoptic bronchoscopy was done one to three times for all the 8 patients to confirm airway injuries and healing status. Escharectomy and Meek dermatoplasty in the extremities of all the 8 patients were performed 3 to 6 days after injury for the first time. Escharectomy, microskin grafting, and covering of large pieces of allogeneic skin on the trunks of 4 patients were performed 11 to 16 days after injury for the second time. The broad-spectrum antibiotics were uniformly used at first time of anti-infective therapy, and then the antibiotics species were adjusted in time. The balance of internal environment was maintained and the visceral functions were protected. One special care unit was on responsibility of only one patient. Psychological intervention was performed on admission. The rehabilitative treatment was started at early stage and in company with the whole treatment. Results: Acute renal injury occurred in 5 patients within 36 hours after injury and their renal function was restored to normal 4 days after injury due to active adjustment of fluid resuscitation program. No pulmonary complications, such as severe pulmonary infection and ventilator-associated pneumonia, occurred in the survived patients. One of the 8 patients died, and the other 7 patients were cured successfully. The wounds were basically healed in 2 patients in 26 or 27 days by 2 or 3 times of operation, and in 5 patients by 4 or 5 times of operation. The basic wound healing time was 26-64 (48±15) days for all the 7 patients. Conclusions Treatment strategies of unified coordination by the superior, unified responsibility of team leader, division of labor and cooperation between team members, and multidisciplinary cooperation led by department of burns are the bases to successful treatment. Correcting shock as soon as possible is the prerequisite and closing wound as soon as possible is the key to successful treatment. Comprehensive treatment measures, such as maintaining and regulating the function of viscera, improving the body immunity, and preventing and treating the complications, are the important components to successful treatment. It is emphasized that in the treatment of mass extremely severe burn patients, specialist burn treatment should always be in the dominant position, and other related disciplines may play a part in auxiliary function.

BACKGROUNDOsteoporosis (OP) is a common bone disease, which adversely affects life quality. Effective treatments are necessary to combat both the loss and fracture of bone. Recent studies indicated that caffeic acid phenethyl ester (CAPE) is a natural chemical compound from honeybee propolis which is capable of attenuating osteoclastogenesis and bone resorption. Therefore, this study aimed to investigate the effect of CAPE on bone loss in OP mice using micro-computed tomography (CT) and histology.

METHODSEighteen mice were prepared and evenly divided into three groups. The six mice in the sham+PBS group did not undergo ovariectomy and were intraperitoneally injected with PBS during the curing period. Twelve mice were ovariectomized (OVX) to induce OP. Six of them in the OVX+CAPE group were intraperitoneally injected with 0.5 mg/kg CAPE twice per week for 4 weeks after ovariectomy. The other six OVX mice in OVX+PBS group were treated with PBS. All the mice were sacrificed 4 weeks after ovariectomy. The tibias were bilaterally excised for micro-CT scan and histological analysis. The Mann-Whitney U test was used to test the statistical differences among groups.

RESULTSBone loss occurred in OVX mice. Compared with the sham+PBS group, mice in the OVX+PBS group exhibited a significant decrease in bone mineral density (BMD, P < 0.05), bone volume fraction (BV/TV, P < 0.01), trabecular thickness (Tb.Th, P < 0.05), and trabecular number (Tb.N, P < 0.01), as well as a non-insignificant increase in the number of osteoclasts (N.Oc/B.Pm). With CAPE treatment, the microarchitecture of the tibial metaphyses was significantly improved with a reduction of osteoclast formation. Compared with the OVX+PBS group, BV/TV in the OVX+CAPE group was significantly increased by 33.9% (P < 0.05).

CONCLUSIONCAPE therapy results in the protection of bone loss induced by OVX.

Animals ; Bone Density ; drug effects ; Caffeic Acids ; pharmacology ; Female ; Metabolism ; drug effects ; Mice ; Mice, Inbred C57BL ; Ovariectomy ; Phenylethyl Alcohol ; analogs & derivatives ; pharmacology ; Propolis ; chemistry ; Tomography, X-Ray Computed

Objective To explore a method of large cranial bone defect reconstructed by titanium implant with computer aided design(CAD)/computer aided manufacture(CAM)technique.Methods From April 2006 to June 2008,7 cases of cranial bone defect due to tumor and trauma were admitted.The data of skull bone defects were obtained by CT.The resin model was designed and manufactured with rapid prototyping technique.Results The CT data could be used by image software directly.The resin model was manufactured accurately by RP technique.The titanium implant design could be completed by CAD/CAM.7 patients achieved one stage healing.After a follow-up of 6 months to 1 year,cranial bone defect was reconstructed satisfactorily.Conclusion Individual design and repair of large cranial bone defect with CAD/CAM technique is worth extending application clinically.It is a quite ideal and very simple method for the surgical treatment of the cranial bone defect.