AIM:To investigate the impact of platycodin D(PD)on the viability,migration,invasion,apop-tosis and cell cycle of osteosarcoma cells in vitro,along with its underlying mechanisms.METHODS:Human osteosarco-ma cells MG63 and U2OS were divided into control group(0 μmol/L)and PD treatment group(6.25,12.5,25,50 and 100 μmol/L,respectively).Human osteosarcoma cells MG63 and U2OS were categorized into control groups(0 μmol/L PD)and PD treatment groups(6.25,12.5,25,50 and 100 μmol/L).The CCK-8 assay determined cell viability and identified effective treatment concentrations.MG63(15 μmol/L PD)and U2OS(25 μmol/L PD)were specifically ana-lyzed.Cell scratch and Transwell assays assessed migration and invasion.Hoechst 33342 staining examined nuclear mor-phological changes.Flow cytometry analyzed cell cycle distribution and apoptosis rate.Western blot measured protein ex-pression levels:cleaved caspase-3,cleaved PARP,c-Jun N-terminal kinase(JNK),p-JNK,B-cell lymphoma-2(Bcl-2),Bcl-2-ssociated X protein(BAX),matrix metalloproteinase 2(MMP-2),MMP-9,cyclin-dependent kinase 4(CDK4),cyclin D1,CDK1,cyclin B1,extracellular signal-regulated kinase(ERK)and p-ERK.Proteome sequencing of MG63 cells was performed.RESULTS:PD treatment significantly decreased cell survival,scratch healing rate,and invasive cell numbers,while increasing apoptosis rates(P<0.05).Morphological changes such as nuclear hyperchroma-tism and fragmentation were observed in PD-treated cells.PD induced G2/M phase arrest in MG63 and G0/G1 phase arrest in U2OS cells.PD treatment upregulated BAX,cleaved caspase-3,cleaved PARP,and p-JNK/JNK,while downregulat-ing Bcl-2,MMP-2,MMP-9,CDK4,cyclin D1,CDK1,cyclin B1,and p-ERK/ERK(P<0.05).Proteome sequencing re-vealed PD's involvement in cell division,cell cycle regulation,focal adhesion,apoptosis,and the MAPK signaling path-way.CONCLUSION:PD inhibits cell viability,migration,and invasion of osteosarcoma cells in vitro,while promoting apoptosis and inducing cell cycle arrest.These effects are likely mediated through modulation of the MAPK signaling path-way.

Objective:To analyze the clinical manifestations, genetic and hematological test results of patients with sitosteronism (STSL) complicated with cardiovascular and cerebrovascular events.Methods:Clinical data were collected from 11 STSL patients at the outpatient department of Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine between November 2020 to June 2023. The whole exome sequencing technology was used to detect gene mutations associated with lipid metabolism, the serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were tested by the enzyme endpoint method; serum phytosterol levels by high-performance liquid chromatography; serum concentration of C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) by enzyme-linked immunosorbent assay, concentration of fibrinogen, the activity of protein C and coagulation factor Ⅷ (FⅧ) by the coagulation method; the antigen and activity of von Willebrand factor (vWF) by immunoturbidimetric assay; and the activity of antithrombin Ⅲ (ATⅢ) by chromogenic substrate assay.Results:There were 3 cases of coronary heart disease, 6 cases of cerebral infarction, 2 cases of coronary heart disease combined with cerebral infarction, 4 cases of eyelid melasma, and 2 cases of arthritis. Gene mutation was as follows: ABCG5 gene mutation including exon9: c G1166A: p R389H, exon9: c T1195C: p F399L, exon12: c.1762+1G>A, and ABCG8 gene mutation including exon 11 c.1720G>A: p.Gly574Arg, exon4:c.445_453del:p.A149_V151del, exon13 c.1949T>G: p.Leu650Arg. The percent of stomatocytes in the peripheral blood swears was (11.3±8.6)%. The concentrations of TC, LDL-C and sitosterol was (6.8±2.4), (4.4±2.0) mmol/L and 40.0 (22.0, 203.7) μmol/L. The level of CRP, interleukin IL-6, and TNF-α was 15.5 (7.2, 29.6)mg/L, (4.2±2.0) pg/ml and (6.7±1.5) pg/ml, respectively.The activity of PC, FⅧ and ATⅢ was (114±51)%, (110±41)% and (83±33)%. The values of FIB was (3.2±1.4)g/L.vWF antigen and vWF activity was (305±168)% and (275±112)%.Conclusions:STSL patients combined with cardiovascular and cerebrovascular events not only had complex dysfunctional lipid metabolism related gene defects, but also had significantly increased hematological indicators such as inflammatory mediator CRP, coagulation parameter vWF.

BACKGROUND: This study aimed to determine the reasons for conversion and elucidate the safety and efficacy of transition to tenofovir alafenamide/emtricitabine/bictegravir sodium (TAF/FTC/BIC) in highly active antiretroviral therapy (HAART)-experienced HIV-infected patients in real-world settings. METHODS: We conducted a retrospective cohort study. The treatment conversion rationales, safety, and effectiveness in 1684 HIV-infected patients with previous HAART experience who switched to TAF/FTC/BIC were evaluated at Beijing Ditan Hospital from September 2021 to Auguest 2022. RESULTS: Regimen simplification (990/1684, 58.79%) was the most common reason for switching, followed by osteoporosis or osteopenia (375/1684, 22.27%), liver dysfunction (231/1684, 13.72%), decline in tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (TAF/FTC/EVG/c) with food restriction (215/1684, 12.77%), virological failure (116/1684, 6.89%), and renal dysfunction (90/1684, 5.34%). In patients receiving non-nucleotide reverse transcriptase inhibitors (NNRTI)-containing regimens, lipid panel changes 1 year after switching indicated a difference of 3.27 ± 1.10 mmol/L vs . 3.40 ± 1.59 mmol/L in triglyceride ( P  = 0.014), 4.82 ± 0.74 mmol/L vs . 4.88 ± 0.72 mmol/L in total cholesterol ( P  = 0.038), 3.09 ± 0.70 mmol/L vs . 3.18 ± 0.66 mmol/L in low-density lipoprotein ( P  <0.001), and 0.99 ± 0.11 mmol/L vs . 0.95 ± 0.10 mmol/L in high-density lipoprotein ( P  <0.001). Conversely, among patients receiving booster-containing regimens, including TAF/FTC/EVG/c and lopinavir/ritonavir (LPV/r), lipid panel changes presented decreased trends. We also observed an improved trend in viral load suppression, and alanine transaminase (ALT), aspartate transaminase (AST), estimated glomerular filtration rate (eGFR), and serum creatinine levels after the transition ( P  <0.001). CONCLUSION The transition to TAF/FTC/BIC demonstrated good treatment potency. Furthermore, this study elucidates the motivations behind the adoption of TAF/FTC/BIC in real-world scenarios, providing clinical evidence supporting the stable conversion to TAF/FTC/BIC for HAART-experienced patients.
Humans ; Antiretroviral Therapy, Highly Active/adverse effects* ; Anti-HIV Agents/adverse effects* ; HIV Infections/drug therapy* ; Tenofovir/therapeutic use* ; Retrospective Studies ; Emtricitabine/pharmacology* ; Adenine/therapeutic use* ; Lipids

Objective:To explore the ethical issues arising from stem cell research in China and propose countermeasures to regulate stem cell research.Methods:This article analyzed the ethical issues arising from stem cells in terms of regulatory systems, source channels, production processes, storage industries, and translational applications.Results:Combining the current ethical situation of stem cell research and the practical exploration of the authors' unit, we proposed countermeasures to address the ethical issues of stem cell research in five aspects, including forming a scientific and effective stem cell ethical regulatory system, building an open and transparent stem cell traceability mechanism, creating a GMP-compliant stem cell production platform, selecting a legal and compliant stem cell storage institution, and conducting ethical stem cell clinical research.Conclusions:It is of great practical significance to strengthen the ethical construction of stem cell research and regulate stem cell transformation research to promote the healthy development of the stem cell industry.

Objective : To explore the main points of clinical treatment of fourth branchial cleft deformity in special positions and to provide a reference for clinical practice. Methods: The clinical data of one case of a fourth branchial cleft deformity that occurred in the left anterior chest wall with a fistula below the clavicle are summarized and combined with a literature review. Results: The patient complained of repeated swelling and pain under the left anterior chest wall for 2 months. A 10 mm×10 mm fistula with yellow clear liquid exudate from the fistula was observed on the left side below the clavicle. A 20 mm×20 mm×10 mm swelling was immediately adjacent at the superficial cervicothoracic junction of the upper sternoclavicular joint, with no fluctuation and poor activity; this swelling produced slight pain upon pressing. Imaging examinations pointed to cystic lesions. The primary diagnosis was a fourth branchial deformity. A small amount of methylene blue was injected into the patient's subclavian fistula, and a supraclavicular T-shaped incision was made where the cyst contacted the fistula. By turning the flap, all the methylene blue-stained areas and adjacent submucosal tissues were exposed. During the operation, a mass was found on the sternum. The platysma was found deep in the notch, which was incised before excising the surrounding area. The pathological result is the fourth branchial cleft deformity. After 1 week and 3 months of follow-up, the patients had no discomfort and no recurrence. A review of the relevant literature shows that the fourth branchial cleft deformity is a congenital developmental abnormality that occurs in 1% of all branchial cleft deformity. It often presents as a fistula, cyst, or sinus tract and is anatomically located at the neck root and supravicular region. The fistula is close to the medial lower boundary of the sternocleidomastoid muscle. The diagnosis is often made based on its anatomical location, imaging examinations and, ultimately, pathology. The differential diagnoses include other cervical swellings, such as hemangioma and a thyroglossal duct cyst. Surgical resection is a commonly used treatment method. In recent years, endoscopic positioning and internal fistula burning have had good curative effects for recurrent fourth branchial cleft deformity, with a small chance of recurrence or cancer. Conclusion Given its unique position, clinicians should make full use of imaging methods to determine the size, anatomical location and course of the lesion when treating the fourth branchial cleft deformity to ensure the complete and safe surgical resection of the lesion and prevent recurrence.

Objective:To explore the clinical efficacy of the double eyelid plasty with incision in eyelids margin position and internal fixation.Methods:A retrospective analysis was carried out in 47 patients who underwent double eyelid surgery in the outpatient department of our hospital from September 2015 to June 2017. There were 5 males and 42 females, aged from 17 to 32 (25±4) years. The skin was incised above the eyelid margin of 1-2 mm after anesthesia, orbicularis oculi muscle under the eyelid line, loose organization, and orbital septum fat were stripped and removed. The dermis and the tarsus were sutured under the double eyelid line, and the skin was sutured without any tension.Results:After collecting and analyzing 47 cases from September 2015 to June 2017 in our hospital with this method, we found that all 47 patients achievedⅠincision healing, which showed slight swell, natural and smooth radian of double eyelid, and without complications such as infection, hematoma and ptosis. And this method showed no obvious scar hyperplasia around incision line and thus possessed high patient satisfaction.Conclusions:With the advantage of less trauma, quick recovery, unobvious scar, natural and beartiful double eyelids, this method can be used as a supplementary method for the reconstruction of the blepharoplasty, which is worth promoting.

Objective : investigate the correlation between the ossification of the styloid hyoid ligament and Bell’s facial paralysis and provide a reference for clinical diagnosis and treatment. Methods: A case of ossification of the bilateral stylohyoid ligament with Bell's facial palsy caused by ossification of the bilateral stylohyoid ligament was diagnosed by clinical manifestations, differential diagnosis and imaging examination. The surgical plan was determined, and combined surgical resection of the ossified area of the styloid hyoid ligament and the greater horn of the hyoid was performed. Postoperative cefoxitin sodium anti-inflammatory treatment, methylprednisolone hormone treatment, acyclovir antiviral treatment, mecobalamin nutritional neurotherapy, and the relevant literature were analyzed. Results: The patient experienced pain when swallowing before surgery, disappearance of right frontal ridges, incomplete eyelid closure, and ptosis of mouth corners. An MRI scan of the brain excluded intracranial space-occupying lesions and resulted in the diagnosis of Bell’s facial paralysis. High-resolution CT of the styloid process confirmed ossification of the styloid hyoid ligament. Styloid process shortening and partial hyoid resection were performed under general anesthesia. Half a month after discharge, the symptoms of sore throat and pain in swallowing disappeared, facial nerve function recovered well, right eyelid closure function recovered well, and right mouth droop improved. The facial nerve function basically returned to normal after 1 month of follow-up. A review of the relevant literature showed that ossification of the stylohyoid ligament to form pseudojoint dilation can locally stimulate the peripheral facial nerve and lead to facial paralysis symptoms. Conclusion Ossification of the styloid hyoid ligament is usually characterized by pharyngeal pain, which can be confirmed by imaging examination. Ossification of the styloid hyoid ligament with facial paralysis is rare in the clinic, so it is necessary to make a clear diagnosis and treat the symptoms.

ObjectiveTo investigate the mechanism of Chaihu Qinggantang （CHQGT） in the treatment of granulomatous lobular mastitis （GLM） in the rat model. MethodSixty female rats were divided into a normal group， a model group， a prednisolone group （0.001 8 g·kg^-1）， and three CHQGT low-dose， medium-dose， and high-dose groups （4.5， 8.9， 17.8 g·kg^-1）. The tissue homogenates mixed with GLM lesion tissue and Fritner's reagent were used for modeling. After modeling， the treatment groups were given corresponding treatment factors， and the normal group and the model group were given the equal volume of normal saline. The changes in mammary gland of rats were observed after 14 d. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes in breast samples. The mRNA expressions of NOD-like receptor thermal protein domain associated protein 3 （NLRP3） inflammasome， Caspase-1， and interleukin-1β （IL-1β） were detected by real-time quantitative fluorescence polymerase chain reaction （Real-time PCR）. The protein expressions of NLRP3， Caspase-1， IL-1β， and IL-18 were detected by Western bolt. ResultAs compared with the normal group， the breasts of rats in the model group were obviously swelling， and mammary gland inflammation index was significantly increased （P<0.01）. Pathological changes included the formation of granuloma centered on the lobule of mammary gland with a large number of inflammatory cells such as lymphocytes and plasma cells. The mRNA expressions of NLRP3， Caspase-1， and IL-1β， and the protein expressions of NLRP3， Caspase-1， IL-1β， and IL18 in the model group were significantly increased （P<0.01）. Compared with the model group， the treatment groups improved breast swelling， and the CHQGT medium and high-dose groups and the prednisolone group reduced inflammation index to some extent after treatment （P<0.05， P<0.01）. The inflammation degree of mammary gland was significantly improved， and inflammatory cells such as macrophages， lymphocytes， and plasma cells were reduced to varying degrees in pathological aspects. The mRNA expressions of NLRP3， Caspase-1， and IL-1β， and the protein expressions of NLRP3， Caspase-1， IL-1β， and IL-18 in the CHQGT high-dose group and the prednisolone group were significantly down-regulated （P<0.05， P<0.01）. ConclusionCHQGT inhibits inflammation and treats GLM in rats. The mechanism is possibly related to the inhibition of NLRP3/IL-1β signaling pathway， which provides a new target for the prevention and treatment of GLM by Qingxiao method.

A new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has recently been proposed. We aim to examine the associations of MAFLD, particularly its discordance from non-alcoholic fatty liver disease (NAFLD), with the progression of elevated brachial-ankle pulse wave velocity (baPWV) and albuminuria in a community-based study sample in Shanghai, China. After 4.3 years of follow-up, 778 participants developed elevated baPWV and 499 developed albuminuria. In comparison with the non-MAFLD group, the multivariable adjusted odds ratio (OR) of MAFLD group for new-onset elevated baPWV was 1.25 (95% confidence interval (CI) 1.01-1.55) and 1.35 (95% CI 1.07-1.70) for albuminuria. Participants without NAFLD but diagnosed according to MAFLD definition were associated with higher risk of incident albuminuria (OR 1.77; 95% CI 1.07-2.94). Patients with MAFLD with high value of hepamet fibrosis score or poor-controlled diabetes had higher risk of elevated baPWV or albuminuria. In conclusion, MAFLD was associated with new-onset elevated baPWV and albuminuria independently of body mass index, waist circumference, and hip circumference. Individuals without NAFLD but diagnosed as MAFLD had high risk of albuminuria, supporting that MAFLD criteria would be practical for the evaluation of long-term risk of subclinical atherosclerosis among fatty liver patients.
Humans ; Pulse Wave Analysis ; Albuminuria ; Ankle Brachial Index ; Non-alcoholic Fatty Liver Disease/diagnosis* ; Vascular Stiffness ; Prospective Studies ; Risk Factors ; China/epidemiology*

Objective:To study and analyze the problems and challenges of stem cell clinical research quality control, and explore possible strategies to strengthen the quality control of stem cell clinical research.Methods:Analyze the problems of the stem cell clinical research quality control system, and summarize the factors that affect the quality control of stem cell clinical research.Results:In view of the current status analysis of stem cell clinical research quality control, it is recommended to promote stem cells from following five aspects: strengthening and improving the capacity building of clinical research institutions, establishing stem cell clinical quality control system, strengthening the quality control of stem cell preparations, strengthening the team-building of stem cell clinical research investigators, and establishing a stem cell clinical research data platform.Conclusions:Strengthening the quality control of stem cell clinical research is of great significance for accelerating the clinical research and transformational application of stem cells.