BACKGROUND:The extracellular-regulated protein kinase 5(ERK5)signaling protein is essential for the survival of organisms,and resveratrol can promote osteoblast proliferation through various pathways.However,whether resveratrol can regulate osteoblast function through the ERK5 signaling protein needs further verification. OBJECTIVE:To explore the regulatory effect of ERK5 on the proliferation of MC3T3-E1 cells and related secreted proteins,and to further verify whether resveratrol can complete the above process by activating ERK5. METHODS:Mouse MC3T3-E1 preosteoblasts were treated with complete culture medium,XMD8-92(an ERK5 inhibitor),epidermal growth factor(an ERK5 activator),resveratrol alone,XMD8-92+EGF,and resveratrol+XMD8-92,respectively.Western blot assay was used to detect the expression of ERK5 and p-ERK5 proteins,proliferation-related proteins Cyclin D1,CDK4 and PCNA,and osteoblast-secreted proteins osteoprotegerin and receptor activator of nuclear factor-κB ligand in MC3T3-E1 cells of each group.The fluorescence intensity of ERK5,osteoprotegerin and receptor activator of nuclear factor-κB ligand in each group was detected by cell immunofluorescence staining,and cell proliferation was detected by EdU staining,respectively.The appropriate concentration and time of resveratrol intervention in MC3T3-E1 cells were determined by cell morphology observation and cell counting kit-8 assay. RESULTS AND CONCLUSION:The activation of ERK5 signaling protein could effectively promote the proliferation of MC3T3-E1 cells,up-regulate the osteoprotegerin/receptor activator of nuclear factor-κB ligand ratio.The appropriate concentration and time for resveratrol intervention in MC3T3-E1 cells was 5 μmol/L and 24 hours,respectively.Resveratrol could activate ERK5 signaling protein,thereby promoting osteoblast proliferation and up-regulating the osteoprotegerin/RANKL ratio.All these results indicate that resveratrol can promote the proliferation of MC3T3-E1 cells and up-regulate the osteoprotegerin/RANKL ratio by activating the ERK5 signaling protein.

BACKGROUND:The imbalance between bone resorption and bone formation in microgravity environments leads to significant bone loss in astronauts.Current research indicates that bone loss under microgravity conditions is the result of the combined effects of various cells,tissues,and systems. OBJECTIVE:To review different biological effects of microgravity on various cells,tissues,or systems,and summarize the mechanisms by which microgravity leads to the development of osteoporosis. METHODS:Databases such as PubMed,Web of Science,and the Cochrane Database were searched for relevant literature from 2000 to 2023.The inclusion criteria were all articles related to tissue engineering studies and basic research on osteoporosis caused by microgravity.Ultimately,85 articles were included for review. RESULTS AND CONCLUSION:(1)In microgravity environment,bone marrow mesenchymal stem cells tend to differentiate more into adipocytes rather than osteoblasts,and hematopoietic stem cells in this environment are more inclined to differentiate into osteoclasts,reducing differentiation into the erythroid lineage.At the same time,microgravity inhibits the proliferation and differentiation of osteoblasts,promotes apoptosis of osteoblasts,alters cell morphology,and reduces the mineralization capacity of osteoblasts.Microgravity significantly increases the number and activity of osteoclasts.Microgravity also hinders the differentiation of osteoblasts into osteocytes and promotes the apoptosis of osteocytes.(2)In a microgravity environment,the body experiences changes such as skeletal muscle atrophy,microvascular remodeling,bone microcirculation disorders,and endocrine disruption.These changes lead to mechanical unloading in the bone microenvironment,insufficient blood perfusion,and calcium cycle disorders,which significantly impact the development of osteoporosis.(3)At present,the mechanism by which microgravity causes osteoporosis is relatively complex.A deeper study of these physiological mechanisms is crucial to ensuring the health of astronauts during long-term space missions,and provides a theoretical basis for the prevention and treatment of osteoporosis.

Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective:To investigate the clinical effect of the modified vertical rectus abdominis myocutaneous flap in repairing the skin and soft tissue defect after abdominoperineal resection for rectal cancer.Methods:This study was a retrospective observational study. From June 2019 to July 2022, five male patients with low rectal cancer who were conformed to the inclusion criteria were admitted to the Department of Basic Surgery of Xiangya Hospital of Central South University, with ages ranging from 65 to 70 years and the sizes of the perianal skin ulcers ranging from 5 cm×4 cm to 11 cm×9 cm, and all of them underwent abdominoperineal resection. The secondary skin and soft tissue defects in the perineum with an area of 8 cm×6 cm-14 cm×12 cm (with the depth of pelvic floor dead space being 10-15 cm) were repaired intraoperatively with transplantation of modified vertical rectus abdominis myocutaneous flaps with the skin area being 9 cm×7 cm-16 cm×12 cm, the volume of the muscle being 18 cm×10 cm×5 cm-20 cm×12 cm×5 cm, and the vessel pedicle being 18-20 cm in length. During the operation, most of the anterior sheath of the rectus abdominis muscle was retained, the flap was transferred to the recipient area through the abdominal cavity, the remaining anterior sheaths of the rectus abdominis muscle on both sides of the donor area were repeatedly folded and sutured, the free edge of the transverse fascia of the abdomen was sutured with the anterior sheath of the rectus abdominis muscle, and the donor area skin was directly sutured. After the operation, the survival of the transplanted myocutaneous flap was observed. The occurrence of complications in the perineal recipient area was recorded within 2 weeks after the operation. The recovery of the perineal recipient area and the abdominal donor area was observed during follow-up, and the occurrence of complications in the donor area of the abdomen as well as the recurrence of tumors and metastasis were recorded.Results:All transplanted myocutaneous flaps in 5 patients survived after surgery. One patient had dehiscence of the incision in the perineal recipient area 2 days after surgery, which healed after 7 d with intermittent dressing changes and routine vacuum sealing drainage treatment. In the other 4 patients, no complications such as incisional rupture, incisional infection, or fat liquefaction occurred in the perineal recipient area within 2 weeks after surgery. Follow-up for 6-12 months after discharge showed that the skin of the perineal recipient area had good color, texture, and elasticity, and was not bloated in appearance; linear scars were left in the perineal recipient area and the abdominal donor area without obvious scar hyperplasia or hyperpigmentation; no complications such as incisional rupture, incisional infection, intestinal adhesion, intestinal obstruction, or weakening of the abdominal wall strength occurred in the abdominal donor area, and the abdominal appearance was good with no localized bulge or formation of abdominal hernia; there was no local recurrence of tumor or metastasis in any patient.Conclusions:The surgical approach of using the modified vertical rectus abdominis myocutaneous flap to repair the skin and soft tissue defects after abdominoperineal resection for rectal cancer is relatively simple in operation, can achieve good postoperative appearances of the donor and recipient areas with few complications, and is worthy of clinical promotion.

Objective:To explore the methods and clinical effects of reconstructing facial and cervical scars with expanded flaps based on the "MLT" principle.Methods:The study was a retrospective observational study. From January 2019 to May 2022, 74 patients with facial and cervical scars after burn or trauma injuries who met the inclusion criteria were admitted to Xiangya Hospital of Central South University, including 38 males and 36 females, aged from 5 to 58 years, including 24 patients with simple facial involvement, 24 patients with simple cervical involvement, and 26 patients with both facial and cervical involvement, with scar area ranging from 12 to 145 cm2. By following the "MLT" principle (color and texture similar to the face; flap area large enough to reconstruct the entire defect; skin tissue thin enough to transmit the expression, so as to facilitate the shape of the face and five features); in the stage Ⅰ surgery, the skin and soft tissue expanders (hereinafter referred to as the expanders) were implanted, and in the stage Ⅱ surgery, the expander removal+scar resection+flap transplantation to repair the secondary wound was performed, and the wound in the donor area of flap was directly sutured. After operation, silicone gel preparation and laser therapy were used to prevent scar hyperplasia. The expansion ratio and time period of expanders, the occurrence of complications of skin and soft tissue expansion surgery, the type of flap used, and the survival of flap after the stage Ⅱ surgery were observed and recorded. The long-term effect of facial and cervical reconstruction and the recovery of donor area and recipient area of flap were evaluated during the postoperative follow-up after surgery.Results:The expansion ratio of 135 expanders ranged from 1.36 to 3.00 times, and the expansion time period ranged from 6 to 14 months. During skin and soft tissue expansion surgery, 8 patients had poor healing of incisions after expander placement, 7 patients had expander rupture, 5 patients had infection in incisions after expander placement, 3 patients had expander exposure, 2 patients had difficult filling the injection pot, and 1 patient had water leakage from the injection pot. Dorsal shoulder expanded flaps with double blood supply of transverse cervical artery and circumflex scapular artery were used in 8 patients, the expanded flaps of anterior transverse carotid artery perforator were used in 11 patients, the expanded flaps of internal thoracic artery perforator were used in 12 patients, tandem expanded flaps of upper chest and neck were used in 16 patients, dorsal thoracic artery perforator expanded flaps were used in 5 patients, and adjacent rotary propulsive expanded flaps were used in 22 patients. After the stage Ⅱ surgery, the flaps of 71 patients were completely survived. One patient had blood circulation disorder in the flap, and the flap survived after hyperbaric oxygen treatment. Necrosis occurred at the end of the flaps in 2 patients, which healed after dressing change. After the surgery, 42 patients were followed up for 3 to 24 months. The color, texture, and thickness of flaps were good and similar to the surrounding normal skin tissue in the recipient area, the appearance and function of the face and neck were significantly improved, and the wound location in the donor and recipient areas of flaps was concealed with slight scar formation.Conclusions:In the reconstruction of facial and neck scars, by following the "MLT" principle, the expanded flap was carefully designed before surgery, the local aesthetic features within the subunit are reconstructed during the stage Ⅱ surgery, and standard anti-scar treatment measures are actively adopted after surgery. After reconstruction, the color, texture, and thickness of flaps were close to the normal skin in face and neck, and the appearance and function of face and neck are significantly improved, with less linear scars left. It is beneficial to improve the therapeutic effect.

BACKGROUND:Fluid shear stress plays an important role in osteoblast proliferation and apoptosis.However,whether Caveolin-1 is involved in the process of fluid shear stress-induced proliferation and apoptosis in osteoblasts is unknown. OBJECTIVE:To explore the role of Caveolin-1 in fluid shear stress-regulated osteoblast proliferation and apoptosis. METHODS:The MC3T3-E1 osteoblasts in good growth status were selected and loaded with fluid shear stress at an intensity of 1.2 Pa for different times(0,30,60,90 minutes).The expression of Caveolin-1 protein was observed and conditions with a time of 60 minutes were screened for the experiment.MC3T3-E1 cells were divided into control group,fluid shear stress group,fluid shear stress+pcDNA 3.1 group(control),fluid shear stress+pcDNA Cav-1 group(plasmid overexpression),and intervened with fluid shear stress and overexpression of Cav-1,respectively.The expression of molecules related to proliferation and apoptosis in MC3T3-E1 cells was detected by qRT-PCR and western blot.In addition,the proliferative activity of MC3T3-E1 cells was detected by cell counting kit-8 and EdU assay;and cell apoptosis was detected by Hoechst 33258 and flow cytometry. RESULTS AND CONCLUSION:The expression of Caveolin-1 in MC3T3-E1 cells was significantly down-regulated after loading fluid shear stress,and the expression level was lowest after 60 minutes.Overexpression of Caveolin-1 attenuated the proliferation-promoting and apoptosis-suppressing effects of fluid shear stress in MC3T3-E1 cells.In conclusion,Caveolin-1 has a vital role in fluid shear stress-regulated osteoblast proliferation and apoptosis,which may offer a potential therapeutic strategy for osteoporosis.

The main function of anterior cruciate ligament (ACL) is to maintain stability of the knee joint and prevent anterior displacement of the tibial plateau. ACL injury accounts for more than 50% of the knee joint injuries. If not timely handled, it will increase the risk of secondary injuries to structures such as the meniscus and cartilage, causing chronic pain and degeneration of the knee joint. Although most ACL injuries can be determined by their direct signs on MRI, the identification of complex situations and partial tears of ACL are still not satisfactory, which subsequently affects treatment strategies. After ACL injury, changes in anatomical relationship of the knee joint can also lead to morphological changes in other structures such as the posterior cruciate ligament (PCL) on MRI, and these indirect signs can assist in the diagnosis of ACL injury. The authors reviewed the application of MRI-related indicators of PCL in diagnosing ACL injury, hoping to provide references and new ideas for clinical decision-making.

Objective:To explore the repair methods of complex facial defect wounds involving paranasal sinuses and their clinical effectiveness.Methods:A retrospective observational study was conducted. From January 2020 to May 2022, 5 patients admitted to the Department of Burns and Plastic Surgery of Xiangya Hospital of Central South University and 4 patients admitted to the Department of Burns and Plastic Surgery of Chenzhou First People's Hospital with complex facial defect wounds involving paranasal sinuses met the inclusion criteria, including 6 males and 3 females, aged 35-69 years, including 4 patients with titanium mesh exposure combined with paranasal sinuses injury and 5 patients with tumor involving paranasal sinuses. After an adequate assessment of the damage by a multiple discipline team, titanium mesh removal, paranasal sinus debridement, and paranasal sinus mucosa removal were performed in patients with exposed titanium mesh, and radical tumor resection was performed in patients with tumors, with postoperative skin and soft tissue defects areas of 5.0 cm×2.5 cm to 18.0 cm×7.0 cm, anterior paranasal sinus wall defects/absence areas of 3 cm×2 cm to 6 cm×4 cm, and sinus cavity depths of 1 to 4 cm. Depending on the perforator course of the descending branch of the lateral circumflex femoral artery, the anterolateral femoral chimeric flap or anterolateral femoral myocutaneous flap (with flap area of 9 cm×4 cm to 19 cm×8 cm, muscle size of 5 cm×3 cm×3 cm to 11 cm×6 cm×3 cm) was transplanted to repair the defect, and the donor site wound was sutured directly. The type of tissue flap transplanted, the blood vessel of the recipient area, and the vascular anastomosis way during the operation, the recovery of the donor and recipient areas and the occurrence of complications after operation were observed. The appearance and blood supply of the recipient area and the recurrence of ulcers and tumors were followed up.Results:The anterolateral femoral myocutaneous flap transplantation was performed in 6 patients, and the anterolateral femoral chimeric flap transplantation was performed in 3 patients. The blood vessels in recipient areas were facial arteries and veins in 3 cases and superficial temporal arteries and veins in 6 cases. The superficial temporal arteries and veins were bridged with blood vessels in tissue flaps by flow-through way in 2 patients, and end-to-end anastomosis of blood vessels in donor and recipient areas was performed in 7 patients. After operation, all the tissue flaps survived, and the facial defect wounds were well repaired without cerebrospinal fluid leakage or paranasal sinus secretion leakage, no intracranial infection occurred, and the wounds in donor areas were healed well. Follow-up of 6-35 months after operation showed that all the patients had good blood supply in the recipient area, and the shape was acceptable; 4 patients with exposed titanium mesh had no recurrence of ulceration, and 5 patients with tumor had no local tumor recurrence or metastasis.Conclusions:Based on an adequate assessment of the extent of paranasal sinuses involved in the facial wound and the nature of the defect, good clinical effects can be achieved by using the anterolateral femoral muscle flap or the anterolateral femoral chimeric flap transplantation to repair complex facial defect wounds with open paranasal sinuses.

Objective:To explore the clinical effects of axillary propeller flaps in reconstructing the axillary fold scar contracture.Methods:A retrospective cohort study was conducted. From July 2016 to January 2020, 11 patients with anterior axillary fold or anterior and posterior axillary fold scar contractures after burns were admitted to Xiangya Hospital of Central South University, including 7 males and 4 females, aged 8 to 48 years. The lesions involved unilateral axilla in 9 cases and bilateral axilla in 2 cases, with the joint abduction angle of the affected shoulder ranging from 25 to 100°. The axillary fold contracture scars were excised and released, resulting in wound of 8 cm×5 cm-24 cm×20 cm. According to the condition of the residual normal skin in axilla, 2, 3, and 4-leaf propeller flaps with area of 5 cm×3 cm-24 cm×10 cm were designed to repair the wounds after scar excision and release. The donor site wound was closed by suturing directly, and the residual wound that could not be completely sutured was transplanted with free full-thickness skin grafts from the inner thigh or abdomen. The application of 2, 3, and 4-leaf propeller flaps, the joint abduction angle of the affected shoulder immediately after operation, and the survival of the flaps and skin grafts after operation were recorded. The recurrence of scar contracture, the appearance of the flaps, the joint abduction angle of the affected shoulder, and the functional recovery of the affected shoulder joint and upper arm were observed through a follow-up.Results:Among the 13 axillary propeller flaps transplanted in the 11 patients in this group, there were 9 double-leaf propeller flaps, two 3-leaf propeller flaps, and two 4-leaf propeller flaps. The joint abduction angle of the affected shoulder reached 110-165° immediately after operation. All the flaps survived after operation. Nine flap donor sites were repaired with free skin grafts, with skin grafts survived in 7 flap donor sites after operation. Scar erosion in incision and small area of skin graft necrosis developed in 2 flap donor sites. One of the wounds was debrided and repaired by transplantation of split-thickness skin grafts from inner thigh, and the other wound was healed after dressing changes. A follow-up of 6 to 24 months was conducted after surgery, and all the patients had no recurrence of axillary scar contracture; the color of the flap matched the receiving area; the elasticity of flap was good; the joint abduction angle of the affected shoulder reached 120-165°, and the joint pronation and supination, upper arm lifting and circular rotation of the affected shoulder were all good.Conclusions:Reconstruction of the axillary fold scar contracture with axillary propeller flaps has good result, with better flap appearance and recovery of the shoulder joint activity and upper arm function after operation.