ZBTB24 regulates the apoptosis of human T cells via CDCA7/TRAIL-receptor axis.

Mutations in ZBTB24 and CDCA7 cause the Immunodeficiency, Centromeric Instability and Facial Anomalies syndrome type 2 and 3 (ICF2/3), respectively. Most ICF2 patients carry ZBTB24 nonsense mutations and are thus ZBTB24-deficient. Although the immune deficiency in ICF2 patients is primarily regarded as a B-cell defect due to the greatly reduced serum antibodies and circulating memory B cells, the reduced expansions of PBMCs stimulated by mitogens or recall antigens suggest a T-cell defect in these patients as well. However, the molecular mechanisms behind this T-cell dysfunction remain unknown. In the present study, we demonstrated that ZBTB24-deficiency significantly represses the proliferation of human T cells by promoting TRAIL-induced cell death. Downregulation of ZBTB24 in both Jurkat and human primary T cells upregulates the expression of TRAIL and/or its death receptors (TRAIL-R1/2), and induces significant amount of cells to undergo apoptosis. The profound survival defects of ZBTB24-deficient cells are largely reversed by blocking TRAIL/TRAIL-R interactions with exogenous recombinant TRAIL-R2. Moreover, ZBTB24-downregulation reduces the expression of CDCA7, and knockdown of the latter in human T cells results in a phenotype resembling that caused by ZBTB24-depletion. Functionally, overexpression of CDCA7 abrogates the increased apoptosis in ZBTB24-depleted Jurkat T cells. Together, these data indicated that ZBTB24 regulates human T-cell apoptosis via CDCA7/TRAIL-R axis. Our study thus not only provides a molecular explanation for the T-cell defects in ZBTB24-deficient ICF2 patients, but also highlights a convergence between ZBTB24 and CDCA7, the two ICF genes, in modulating the functions of T cells.

The diagnostic dilemma of tumor induced osteomalacia: a retrospective analysis of 144 cases.

Diagnostic delay of tumor induced osteomalacia (TIO) is common in clinic practice. To investigate the diagnostic condition of TIO in China and raise clinicians' awareness of TIO, we retrospectively analyzed clinical manifestations, biochemical features, and specially evaluated missed diagnoses and misdiagnoses among 144 TIO patients from Peking Union Medical College Hospital during December 1982 to December 2014. Clinical presentations of TIO mainly included bone pain, difficulty in walking, pathological fractures, muscle weakness, and height loss. TIO patients demonstrated hypophosphatemia (0.48±0.13 mmol/L), elevated serum alkaline phosphatase (277.9±152.6 U/L), reduced tubular maximum for phosphorus/glomerular filtration rate (0.39±0.14) and markedly elevated serum fibroblast growth factor 23 (FGF23) (median level 302.9 pg/mL). The average time from onset to a correct diagnosis was 2.9±2.3 years while the mean duration from onset to tumor resection was 5.4±4.2 years. The initial misdiagnosis rate was 95.1% (137/144) and 240 case-times of misdiagnoses occurred among the 144 cases. The most frequent misdiagnoses were intervertebral disc herniation, spondyloarthritis (including ankylosing spondylitis) and osteoporosis. A total of 43.1% (62/144) cases with hypophosphatemia presented on their laboratory sheets were neglected and missed diagnosed. Our study showed that TIO was frequently misdiagnosed and missed diagnosed due to its rarity, insidious onset, nonspecific clinical manifestations and clinicians' poor recognition. It is necessary to test serum phosphorus in patients with musculoskeletal symptoms and difficulty in walking. The measurement of serum FGF23 is rather valuable. Once hypophosphatemia is discovered, TIO should be suspected and it is highly recommended to search for tumors and perform curative surgery.

Association between nonalcoholic fatty liver disease and erectile dysfunction among American Adults from the National Health and Nutrition Examination Survey: a cross-sectional study.

Nonalcoholic fatty liver disease (NAFLD) is a pressing public health concern. NAFLD is recognized as a disease with systemic involvement. Erectile dysfunction is a prevalent condition among men. The study examined the relationship between NAFLD, assessed via U.S. Fatty Liver Index (USFLI), and erectile dysfunction. The study used cross-sectional data from the National Health and Nutrition Examination Survey conducted between 2001 and 2004 to examine the health of those over 20 years of age, collecting details on their erectile dysfunction, USFLI, and several other essential variables. A USFLI score equal to or exceeding 30 was chosen to diagnose NAFLD, while a USFLI score below 10 was utilized to exclude the presence of fatty liver. There were 3763 participants, with 29.1% (1095/3763) who experienced erectile dysfunction. After accounting for all potential covariates, USFLI was positively associated with erectile dysfunction (OR, 1.02; 95% CI, 1.02 ~ 1.03; P < 0.001). Compared with individuals with Q1 (USFLI < 10), the adjusted odds ratio values for USFLI and erectile dysfunction in Q2 (10 ≤ USFLI < 30) and Q3 (USFLI ≥ 30, NAFLD) were 1.84 (95% CI: 1.46 ~ 2.32, p < 0.001) and 2.18 (95% CI: 1.66 ~ 2.87, p < 0.001), respectively. The association USFLI and erectile dysfunction exhibited an L-shaped curve (nonlinear, P = 0.014). The odds ratio value of developing erectile dysfunction was 1.03 (95% CI: 1.021 ~ 1.04, P < 0.001) in participants with USFLI < 50.18. This study identified a positive correlation between USFLI and erectile dysfunction within the adult American population. Our findings imply that NAFLD might constitute an independent risk factor for erectile dysfunction.

Global burden of lung cancer in women of childbearing age attributable to ambient particulate matter pollution: 1990-2021.

BACKGROUND: This study aimed to evaluate the global burden of lung cancer due to ambient particulate matter (PM) pollution in women of childbearing age from 1990 to 2021. METHODS: This was a secondary analysis utilizing data from the Global Burden of Disease (GBD) 2021, with a focus on the temporal trends of the lung cancer burden attributable to ambient PM2.5 among women of childbearing age. RESULTS: In 2021, the global mortality and disability-adjusted life years (DALYs) number of lung cancer burden attributable to ambient PM2.5 among women of childbearing age were approximately 5205 and 247,211, respectively. The rate of lung cancer attributable to ambient PM2.5 among women of childbearing age increased between 1990 and 2021, with the age-standardized mortality rate (ASMR) increasing from 0.22 (95% uncertainty interval [UI]; 0.13 to 0.33) to 0.25 (95% UI; 0.14 to 0.37; average annual percent change [AAPC] = 0.40) and the age-standardized DALYs rate (ASDR) increasing from 10.39 (95% UI; 5.96 to 15.72) to 12.06 (95% UI; 6.83 to 17.51; AAPC = 0.41). The middle sociodemographic index (SDI) region, East Asia, and China had the heaviest burden, while the high SDI region showed the highest decrease. ASMR and ASDR exhibited an inverted U-shaped relationship with the SDI. CONCLUSIONS: From 1990 to 2021, the lung cancer burden attributable to ambient PM2.5 among women of childbearing age exhibited an increasing trend. Furthermore, increasing attention should be paid to the middle SDI region, East Asia, and China, as ambient PM pollution remains a critical target for intervention.

Perforated gastric ulcer causing mediastinal emphysema: A case report.

BACKGROUND: Mediastinal emphysema is a condition in which air enters the mediastinum between the connective tissue spaces within the pleura for a variety of reasons. It can be spontaneous or secondary to chest trauma, esophageal perforation, medically induced factors, etc. Its common symptoms are chest pain, tightness in the chest, and respiratory distress. Most mediastinal emphysema patients have mild symptoms, but severe mediastinal emphysema can cause respiratory and circulatory failure, resulting in serious consequences. CASE SUMMARY: A 75-year-old man, living alone, presented with sudden onset of severe epigastric pain with chest tightness after drinking alcohol. Due to the remoteness of his residence and lack of neighbors, the patient was found by his nephew and brought to the hospital the next morning after the disease onset. Computed tomography (CT) showed free gas in the abdominal cavity, mediastinal emphysema, and subcutaneous pneumothorax. Upper gastrointestinal angiography showed that the esophageal mucosa was intact and the gastric antrum was perforated. Therefore, we chose to perform open gastric perforation repair on the patient under thoracic epidural anesthesia combined with intravenous anesthesia. An operative incision of the muscle layer of the patient's abdominal wall was made, and a large amount of subperitoneal gas was revealed. And a continued incision of the peritoneum revealed the presence of a perforation of approximately 0.5 cm in the gastric antrum, which we repaired after pathological examination. Postoperatively, the patient received high-flow oxygen and cough exercises. Chest CT was performed on the first and sixth postoperative days, and the mediastinal and subcutaneous gas was gradually reduced. CONCLUSION: After gastric perforation, a large amount of free gas in the abdominal cavity can reach the mediastinum through the loose connective tissue at the esophageal hiatus of the diaphragm, and upper gastrointestinal angiography can clarify the site of perforation. In patients with mediastinal emphysema, open surgery avoids the elevation of the diaphragm caused by pneumoperitoneum compared to laparoscopic surgery and avoids increasing the mediastinal pressure. In addition, thoracic epidural anesthesia combined with intravenous anesthesia also avoids pressure on the mediastinum from mechanical ventilation.

[CDC73 gene mutation and parafibromin expression status of parathyroid carcinoma in Chinese].

OBJECTIVE: To explore the clinico-genetic characteristics and protein status of parathyroid carcinoma (PC) diagnosed at Peking Union Medical College Hospital from January 1980 to December 2012. METHODS: Genomic DNA was extracted from peripheral blood lymphocytes and paraffin-embedded tissue for analysis. The mutations of CDC73 gene were detected by direct sequencing. And the expression of parafibromin in tumor tissues was evaluated by immunohistochemical analysis. RESULTS: Twenty-four PC patients were recruited. The mean ages at the diagnosis of PHPT and PC were 42.2 and 42.6 years respectively. The serum calcium at the diagnosis of PHPT was 3.78 mmol/L, serum phosphorus 0.65 mmol/L and the median increment of serum parathyroid hormone (PTH) level 20.0. The recurrent rate was 76.2% during a 5-year follow-up.Genetic analysis identified 11 mutations of CDC73 gene (45.8%), among which c.34_35 insCT, c.626_629 delAACA, c.260_261 delGA, c.570 delG, c.40 C>T and IVS3+1 G>A were novel mutation first identified in our cohort. Nine of them had germline mutations. All tissue samples from normal parathyroid displayed strong positive immunostaining of parafibromin. Complete (55%, 11/20) or partial (45%, 9/20) loss of parafibromin expression was observed in PC tissues. The age at the diagnosis of PHPT, serum calcium, serum phosphorus, PTH, alkaline phosphatase (ALP), bone involvement rate, kidney stone/calcification rate, recurrent rate, metastatic rate and immunostaining level showed no significant difference between the patients with and without CDC73 mutation. CONCLUSION: In Chinese population, CDC73 mutation and complete/partial loss of immunohistochemical staining for parafibromin occur frequently in PC. Therefore it may be useful in the subset of tumors with equivocal histological examination.

The pro-tumorigenic activity of p38γ overexpression in nasopharyngeal carcinoma.

It is urgent to identify and validate biomarkers for early diagnosis and efficient treatment of nasopharyngeal carcinoma (NPC). Recent studies have proposed p38 gamma (p38γ) as a cyclin-dependent kinase (CDK)-like kinase that phosphorylates retinoblastoma (Rb) to promote cyclins expression and tumorigenesis. Here the Gene Expression Profiling Interactive Analysis (GEPIA) database and results from the local NPC tissues demonstrate that p38γ is significantly upregulated in NPC tissues, correlating with poor overall survival. Furthermore, p38γ mRNA and protein expression is elevated in established NPC cell lines (CNE-1 HONE-1 and CNE-2) and primary human NPC cells, but low expression detected in human nasal epithelial cells. In established and primary NPC cells, p38γ depletion, using the shRNA strategy or the CRISPR/Cas9 gene-editing method, largely inhibited cell growth, proliferation and migration, and induced significant apoptosis activation. Contrarily, ectopic p38γ overexpression exerted opposite activity and promoted NPC cell proliferation and migration. Retinoblastoma (Rb) phosphorylation and cyclin E1/A expression were decreased in NPC cells with p38γ silencing or knockout, but increased after p38γ overexpression. Moreover, mitochondrial subcellular p38γ localization was detected in NPC cells. Significantly, p38γ depletion disrupted mitochondrial functions, causing mitochondrial depolarization, reactive oxygen species production, oxidative injury and ATP depletion in NPC cells. In vivo, intratumoral injection of adeno-associated virus-packed p38γ shRNA potently inhibited primary human NPC xenograft growth in nude mice. In p38γ shRNA virus-injected NPC xenograft tissues, p38γ expression, Rb phosphorylation, cyclin E1/A expression and ATP levels were dramatically decreased. Taken together, we conclude that p38γ overexpression is required for NPC cell growth, acting as a promising therapeutic target of NPC.

[A case of adefovir dipivoxil induced hypophosphataemic osteomalacia and literature review].

OBJECTIVE: To investigate the clinical features and treatment protocol and prognosis for the hypophosphataemic osteomalacia related to adefovir dipivoxil. METHODS: Analysis was made upon a case of patient with chronic hepatitis B developed hypophosphataemic osteomalacia after administration of adefovir dipivoxil. Literature review was carried out to survey the global prevalence of hypophosphataemic osteomalacia after administration of adefovir dipivoxil among patients with chronic hepatitis B. RESULTS: The clinical symptoms started paralleling to the time taking adefovir dipivoxil, and alleviated after the patient withdrawn adefovir dipivoxil 10 weeks and was given phosphorus. Meanwhile, serum inorganic phosphorus recovered to normal (0.98 mmol/L), which lowest level was 0.77 mmol/L. Systematic review of the literature showed that hyperphosphaturia related to adefovir dipivoxil was dose-dependent, time-dependent and reversible. All reported cases of hypophosphataemic osteomalacia secondary to adefovir dipivoxil (10 mg/d) were from Asian population. CONCLUSIONS: Adefovir dipivoxil induced hypophosphataemic osteomalacia is rarely seen in clinical practice. Those patients with chronic hepatitis B who take adefovir dipivoxil, no matter dosages, should take periodical examinations including blood calcium and serum inorganic phosphorus to monitor whether hypophosphataemic osteomalacia occurs. Other anti-virus drugs could be used when it happens.

Infusion of ibandronate once every 3 months effectively decreases bone resorption markers and increases bone mineral density in Chinese postmenopausal osteoporotic women: a 1-year study.

The efficacy and safety of intravenous ibandronate were evaluated in postmenopausal osteoporosis women in China. In this multicenter, positive drug-controlled study, 158 postmenopausal osteoporotic women were randomized to receive 2 mg ibandronate given intravenously once every 3 months or 70 mg alendronate given orally once per week. All women also received supplemental calcium (500 mg) and vitamin D (200 IU) daily. One hundred fifty-one patients completed the 1-year study. Ibandronate produced mean increases in bone mineral density (BMD) by 4.27% at the lumbar spine, 3.48% at the femoral neck, and 2.03% at the trochanter. Mean increases in BMD by 4.24% at the lumbar spine, 2.72% at the femoral neck, and 2.99% at the trochanter were observed in the alendronate group. No significant difference was found between the two groups in BMD in all sites measured. Significant decreases in serum c-telopeptide of type I collagen (CTX) and alkaline phosphatase (ALP) were found in the two groups after 1 and 3 months of treatment, respectively; these serum CTX and ALP levels were then maintained at the decreased levels throughout the study period (12 months). No changes of stature were found in the patients of the two groups. Adverse events were similar in the two groups, except more mild muscle pain was observed in the first month after infusion of ibandronate than with oral alendronate (P < 0.001). The results observed in Chinese patients may support the observation that intravenous ibandronate significantly reduced bone resorption and increased BMD with good tolerance in Chinese postmenopausal osteoporotic women. Use of intravenous ibandronate possibly could potentially improve compliance as compared with other oral bisphosphonates because it may avoid the peptic side effects of oral bisphosphonate.

[Clinical and molecular genetic analyses for a sporadic parathyroid carcinoma].

OBJECTIVE: To analyze the clinical and molecular genetic characteristics of one patient with sporadic parathyroid carcinoma (s-PC). METHODS: The clinical profile, laboratory data and paraffin-embedded tissue sample of a s-PC patient were collected at our hospital. Genomic DNA was extracted from the leukocytes of peripheral blood and paraffin-embedded tissue of this patient. All 17 exons of HRPT2 gene including the flanking regions of introns were amplified by PCR. The mutations of HRPT2 gene were analyzed by directly sequencing the amplified DNA fragments. Parafibromin encoded by HRPT2 gene was analyzed by immunohistochemistry. RESULTS: The patient was diagnosed as s-PC by the clinical presentations, laboratory examinations and typical pathologic characteristics. HRPT2 germline mutation was identified as a base mutation at codon 222 (CGA > TGA) and caused a nonsense mutation at the codon (R222X) resulting in a truncated protein. Parafibromin was completely lost while comparing the normal parathyroid tissues by immunohistochemistry. CONCLUSION: The altered expression of parafibromin caused by HRPT2 gene mutation is one of the molecular mechanisms for explaining the clinical manifestations of this patient.

LncRNA miR143HG suppresses miR-21 through methylation to inhibit cell invasion and migration.

OBJECTIVE: This study aimed to investigate the role of lncRNA miR143HG in laryngeal squamous cell carcinoma (LSCC). METHODS: Quantitative polymerase chain reaction (PCR) and paired t test were used to measure and compare expression levels of miR143HG and miR-21 in LSCC and nontumor tissues. To analyze the interactions between miR143HG and miR-21, UM-SCC-17A cells were transfected miR143HG expression vector or miR-21 mimic. The effects of miR143HG and miR-21 overexpression on UM-SCC-17A cell invasion and migration were analyzed by transwell assays. RESULTS: We found that miR143HG was downregulated in LSCC and inversely correlated with miR-21. In LSCC cells, miR143HG overexpression led to the downregulated expression of miR-21, whereas miR-21 overexpression failed to affect miR143HG. Methylation-specific PCR results showed that miR143HG overexpression led to increased methylation of miR-21. Low expression levels of miR143HG were correlated with poor survival. Overexpression of miR143HG led to decreased, whereas miR-21 overexpression resulted in increased rate of LSCC cell migration and invasion. In addition, miR-21 overexpression led to reduced effects of miR143HG on cell invasion and migration. CONCLUSION: Therefore, miR143HG suppresses miR-21 via methylation to regulate cell behaviors in LSCC. LEVEL OF EVIDENCE: NA Laryngoscope, 130:E640-E645, 2020.

The efficacy and safety of calcitriol and/or Caltrate D in elderly Chinese women with low bone mass.

AIM: To observe the efficacy and safety of Rocaltrol (calcitriol) and/or Caltrate D (calicum carbonate plus vitamin D) in elderly Chinese women with osteopenia or osteoporosis. METHODS: One hundred fifty Chinese women aged over 65 years with osteopenia or osteoporosis from three centers were randomly divided into two groups. Seventy-six participants received Caltrate D as one pill daily; the other 74 participants received 0.25 mug Caltrate D plus Rocaltrol daily. The changes in bone mineral density (BMD) served as primary end-points. Height changes, the presence of new vertebral fractures, muscle strength and balance were evaluated. RESULTS: The following are the mean percentage changes (and SD) in BMD over 12 months: at L2-L4, 0.83+/-3.88 in the Caltrate D group and 2.84+/-4.04 in the Rocaltrol+Caltrate D group (P=0.003, by ANCOVA); at the femoral neck, 0.04+/-3.94 in the Caltrate D group and 2.01+/-5.45 in the Rocaltrol+Caltrate D group (P=0.085, by ANCOVA); and in the trochanter, 1.59+/-4.57 in the Caltrate D group and 3.76+/-6.25 in the Rocaltrol+Caltrate D group (P=0.053, by ANCOVA). The stand and maximal forward reach test (SMFRT) was significantly enhanced in both groups during the 12 months of treatment, but no significant differences were found between these two groups. No severe adverse event related to these medications occurred throughout the study. CONCLUSION: Treatment with Rocaltrol plus Caltrate D or Caltrate D for 12 months in elderly Chinese postmenopausal women effectively increased BMD at the lumbar spine. Rocaltrol plus Caltrate D was more effective at the lumbar spine than Caltrate D alone.

[The efficacy and safety of intravenous bisphosphonates in the treatment of primary hyperparathyroidism complicated by hypercalcemia crisis].

OBJECTIVE: To study the efficacy and adverse events of intravenous bisphosphonates in the treatment of patients of primary hyperparathyroidism (PHPT) complicated by hypercalcemia crisis. METHODS: From October 2003 to December 2007, 14 patients admitted into our hospital were diagnosed as PHPT complicated by hypercalcemia crisis, which was defined as a serum calcium concentration greater than 3.50 mmol/L. Of them, 6 cases had parathyroid adenoma, 1 had hyperplasia and 7 had parathyroid carcinoma. One of the intravenous bisphosphonates including pamidronate, ibandronate and zoledronic acid was given for 29 times in all the 14 cases. Serum calcium, parathyroid hormone, hematology, and other biochemical markers were monitored. Adverse events were recorded. RESULTS: After intravenous bisphosphonates, the serum total calcium (Ca) levels decreased from (3.85 +/- 0.50) mmol/L to (2.86 +/- 0.39) mmol/L in (1.4 +/- 0.6) days, and were kept below 3.50 mmol/L for (10.14 +/- 8.54) days. There was no significant difference of the magnitude of decrease in serum Ca levels among the patients using pamidronate, ibandronate or zoledronic acid. The change of serum Ca level was associated with the serum Ca level before treatment. The response to intravenous bisphosphonates evaluated by the decrease of serum total calcium levels was more significant in patients with parathyroid adenoma or hyperplasia than those with parathyroid carcinoma. The most common adverse event was pyrexia, which occurred 15 times (51.7%) and 75% of the pyrexia events occurred after the first infusion. Other manifestations included fatigue, flu-like symptom, myalgia, arthralgia and diarrhea with an incidence of 3.4% each (one event in the 29 times of treatment). There were 2 events (6.7%) with mild increase of serum creatinine concentration. CONCLUSION: Bisphosphonates can decrease serum total calcium levels in hypercalcemia crisis caused by PHPT effectively with mild adverse events.

Assessment of the clinical efficacy of surgical treatment for cervical lymph node tuberculosis / 中华老年医学杂志

Objective:To assess the effectiveness and practical value of surgery in clinical treatment of cervical lymph node tuberculosis.Methods:110 patients receiving surgical treatment for tuberculosis at Hunan Provincial Chest Hospital between January 2020 and December 2022 were selected, all of whom were diagnosed with cervical lymph node tuberculosis.According to patient preferences, they were divided into two groups, a drug treatment group consisted of 60 patients receiving conventional Western medicine treatment and a surgical treatment group of 50 patients receiving surgical treatment.Statistical analysis was made to compare the clinical efficacy, recurrence rate, complications, quality of life, and patient satisfaction between the two groups.Results:The overall clinical effectiveness rate was higher in the surgical treatment group than in the drug treatment group(94.00% vs.70.00%, χ2=10.170, P=0.001), with the rate higher in the surgical treatment group than in the drug treatment group for patients under 60 years of age(64.29% vs.40.00%, χ2=-6.996, P=0.035), but there was no difference in therapeutic efficacy between the two groups for patients aged 60 and above(54.55% vs.40.00%, Z=3.842, P=0.146). Compared with the drug treatment group, the surgical treatment group had a lower recurrence rate(8.00% vs.46.67%, χ2=19.767, P<0.001)and a lower rate of complications(8.00% vs.21.67%, χ2=3.899, P=0.048), but higher scores of quality of life in all four domains(physical function: 64.02±4.49 vs.76.11±4.47, t=14.090, P<0.001; material life: 66.50±2.39 vs.81.03±2.28, t=32.417, P<0.001; psychological function: 62.98±2.51 vs.79.24±2.50, t=33.892, P<0.001; social function: 63.12±3.39 vs.76.08±3.51, t=19.645, P<0.001)and a higher level overall patient satisfaction(90.00% vs.66.67%, χ2=8.455, P=0.004). Conclusions:Surgical treatment for cervical lymph node tuberculosis patients has better efficacy, fewer complications and better prognosis and is clinically practical and highly valuable.

Preliminarily study of arthrocentesis combined with liquid phase concentrated growth factor injection in the treatment of unilateral temporomandibular joint osteoarthritis / 北京大学学报(医学版)

Objective:To observe the clinical effect of arthrocentesis combined with liquid phase con-centrated growth factor(CGF)injection in the treatment of unilateral temporomandibular joint osteoarthri-tis(TMJOA),in order to provide a new treatment option for TMJOA patients.Methods:In this non-randomized controlled study,patients diagnosed with unilateral TMJOA who visited the center for tem-poromandibular joint disorder and orofacial pain of Peking University School and Hospital of Stomatology from June 2021 to January 2023 were selected as research objects.The patients were divided into experi-mental group and control group,which were selected by patients themselves.The experimental group re-ceived arthrocentesis combined with liquid phase CGF injection and the control group received arthrocen-tesis combined with HA injection.Both groups were treated 3 times,once every two weeks.The clinical effect was evaluated by the maximum mouth opening,pain value and the degree of mandibular function limitation 6 months after treatment.The change of condylar bone was evaluated by cone beam CT(CBCT)image fusion technology before and after treatment.Results:A total of 20 patients were included in the experimental group,including 3 males and 17 females,with an average age of(34.40± 8.41)years.A total of 15 patients were included in the control group,including 1 male and 14 females,with an average age of(32.20±12.00)years.There was no statistical difference in general information between the two groups(P＞0.05).There were no statistical differences in the mouth opening,pain value and the degree of jaw function limitation between the two groups before treatment(P＞0.05),and all of them improved 6 months after treatment compared with before treatment(P＜0.05).However,the mouth opening of experimental group was significantly higher than that of control group 6 months after treatment(P＜0.05),and the degree of jaw function limitation was significantly lower than that of con-trol group(P＜0.05).CBCT 2D images showed that the condylar bone of both groups was smoother after treatment than before treatment,and image fusion results showed that 10 patients(50.0％)in the experimental group and 5 patients(33.3％)in the control group had reparative remodeling area of con-dylar bone,and there was no statistical difference between them(P＞0.05).Except for one CGF pa-tient,the other patients in both groups had some absorption areas of condylar bone.Conclusion:The ar-throcentesis combined with liquid phase CGF injection can improve the clinical symptoms and signs of unilateral TMJOA patients in short term,and is better than HA in increasing mouth opening and impro-ving jaw function.CBCT fusion images of both patient groups show some cases of condylar bone repara-tive remodeling and its relevance to treatment plans still requires further study.

Overexpressed miR-145 inhibits osteoclastogenesis in RANKL-induced bone marrow-derived macrophages and ovariectomized mice by regulation of Smad3.

BACKGROUND: MicroRNAs (miRs) play an important role in osteoclastogenesis. However, no study has investigated the underlying molecular mechanisms of miR-145 in this process. The purpose of the present study was to investigate the role of miR-145 and its post-transcriptional mechanism in the progression of osteoclast differentiation. METHODS: Macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-kB ligand (RANKL) were used to induce osteoclastogenesis originated from bone marrow-derived macrophages (BMMs). Female C57BL/6J mice were divided into sham, OVX, OVX + NC-agomir and OVX + miR-145-agomir groups. Tartrate-resistant acid phosphatase (TRAP) staining was performed to identify osteoclasts in-vitro and in-vivo. The mRNA and protein levels in osteoclast and tibia were assayed by qRT-PCR and western blotting, respectively. RESULTS: miR-145 expression was inhibited in RANKL-induced osteoclastogenesis, whereas overexpression of miR-145 attenuated it. We further found that Smad3 is a direct target gene of miR-145 by binding with its 3'-UTR. Overexpression of miR-145 significantly suppressed Smad3 mRNA and protein expression. In-vivo, miR-145 agomir treatment inhibited osteoclast activity in OVX mice by inhibiting Smad3 expression. CONCLUSION: We provide the evidence that over-expression of miR-145 could inhibit osteoclast differentiation, at least partially, by decreasing Smad3 expression.

TNF­α increases inflammatory factor expression in synovial fibroblasts through the toll­like receptor­3­mediated ERK/AKT signaling pathway in a mouse model of rheumatoid arthritis.

Osteoarthritis is a type of joint disease that may lead to other joint diseases. Previous research has demonstrated that tumor necrosis factor (TNF)­α is associated with osteoarthritis activity and pathology. The possible mechanisms of the TNF­α­mediated signaling pathway have not been clearly elaborated in synovial fibroblasts. The present study aimed to investigate the potential mechanisms of TNF­α in a mouse model of iodoacetate­induced osteoarthritis. Reverse transcription­quantitative polymerase chain reaction, ELISA, western blotting and immunohistochemistry were performed to evaluate the role of TNF­α in the progression of osteoarthritis. The results revealed that the serum levels of TNF­α, interleukin (IL)­1ß, IL­4 and IL­6 were significantly upregulated in a mouse model of iodoacetate­induced osteoarthritis compared with healthy mice (P<0.01). TNF­α, IL­1ß, IL­4 and IL­6 mRNA and protein levels were also significantly upregulated in synovial fibroblasts in the experimental mice (P<0.01). It was demonstrated that TNF­α increased pro­inflammation factors matrix metalloproteinase (MMP)­3, MMP­9, nuclear factor (NF)­κB and receptor activator of NF­κB ligand (RANKL) in synovial fibroblasts. It was also observed that the toll­like receptor (TLR)­3 was significantly upregulated and extracellular signal­regulated kinase (ERK) and protein kinase B (AKT) were significantly downregulated in synovial fibroblasts in osteoarthritis mice (P<0.01). An in vitro assay demonstrated that TNF­α inhibitor decreased mRNA and protein levels of IL­1ß, IL­4 and IL­6 in synovial fibroblasts. The knockdown of TLR­3 abolished the TNF­α upregulated mRNA and protein levels of IL­1ß, IL­4 and IL­6 in synovial fibroblasts. In addition, the knockdown of TLR­3 also reversed TNF­α­upregulated ERK and AKT expression in synovial fibroblasts. In vivo assays demonstrated that TNF­α inhibitor significantly decreased the deposition of IL­1ß, IL­4 and IL­6 as well as bone destruction and significantly increased the body weight and osteoarthritis score for osteoarthritic mice (P<0.01). TNF­α inhibitor decreased TLR­3 and significantly increased the expression and phosphorylation of ERK and AKT in articular cartilage (P<0.01). In conclusion the results of the present study indicate that TNF­α serves an essential role in synovial fibroblasts in osteoarthritis, suggesting that inhibition of TNF­α may decrease inflammation via the TLR­3­mediated ERK/AKT signaling pathway in a mouse model of monosodium iodoacetate­induced osteoarthritis.

Protection of side-branch ostium by the jailed balloon technique validated by three-dimensional optical coherence tomography / 中华心血管病杂志

Objective: To evaluate the protective effect of jailed balloon technique on side branch (SB) ostium using three-dimensional optical coherence tomography(OCT). Methods: This is a retrospective study. Consecutive coronary disease patients with coronary artery bifurcation lesions who underwent percutaneous coronary intervention (PCI) and completed pre-and post-procedural OCT examinations at the Chinese People's Liberation Army General Hospital from September 2019 to March 2022 were enrolled. Patients were divided into the jailed balloon technique group and the unprotected group according to the options applied for the SB. The SB ostium area difference was calculated from OCT images (SB ostium area difference=post-PCI SB ostium area-pre-PCI SB ostium area). The SB ostium area differences were compared between the two groups and compared further in the subgroup of true bifurcation lesions and non-true bifurcation lesions. In the jailed balloon group, the SB ostium area difference was compared between the active jailed balloon technique and the conventional jailed balloon technique, between the jailed balloon>2.0 mm diameter and the jailed balloon≤2.0 mm diameter, and between the higher balloon pressure (>4 atm, 1 atm=101.325 kPa) and the lower balloon pressure (≤4 atm). Multivariate linear regression analysis was used to explore the correlation between the technical parameters of the jailed balloon technique and the SB protection effect. Results: A total of 176 patients with 236 bifurcation lesions were enrolled, aged (60.7±9.3) years, and there were 128 male patients (72.7%). There were 67 patients in the jailed balloon technique group with 71 bifurcation lesions and 123 patients in the unprotected group with 165 bifurcation lesions. Fourteen patients had 2 to 3 lesions, which were treated in different ways, so they appeared in the unprotected group and the jailed balloon technique group at the same time. The area difference in SB ostium was greater in the jailed balloon group than in the unprotected group (0.07 (-0.43, 1.05)mm2 vs.-0.33 (-0.83, 0.26)mm2, P<0.001), and the results were consistent in the true bifurcation lesion subgroup (0.29 (-0.35, 0.96)mm2 vs.-0.26 (-0.64, 0.29)mm2, P=0.004), while the difference between the two groups in the non-true bifurcation lesion subgroup was not statistically significant (P=0.136). In the jailed balloon technique group, the SB ostium area difference was greater in patients treated with the active jailed balloon technique than in those treated with the conventional jailed balloon technique ((0.43±1.36)mm2 vs. (-0.22±0.52)mm2, P=0.013). The difference in SB ostium area was greater in those using>2.0 mm diameter jailed balloons than in those using≤2.0 mm diameter jailed balloons (0.25 (-0.51, 1.31) mm2 vs.-0.01 (-0.45, 0.63) mm2, P=0.020), while SB ostium area difference was similar between those endowed with higher balloon pressure (>4 atm) compared to those with lower balloon pressure (≤4 atm) (P=0.731). Multivariate linear regression analysis showed that there was a positive correlation between jailed balloon diameter and SB ostium area difference (r=0.344, P=0.019). Conclusions: The jailed balloon technique significantly protects SB ostium, especially in patients with true bifurcation lesions. The active jailed balloon technique and larger diameter balloons may provide more protection to the SB.

A preliminary study to evaluate the efficacy and safety of CT-guided localization of pulmonary nodules with soft wire hook-wire by trailing technique / 中国医师进修杂志

Objective:The purpose of this study was to investigate the clinical value of CT-guided localization of pulmonary nodules with soft wire hook-wire by trailing technique.Methods:The clinical data of 211 pulmonary nodules of 185 patients from November 2020 to March 2022 in Beijing Aerospace General Hospital were retrospectively analyzed. The pulmonary nodules were localized with soft wire hook-wire by trailing technique before video-assisted thoracic surgery (VATS). The success rate, complications, pathological results and localization operations related data were statistically analyzed.Results:The success rate of localization was 97.63% (206/211), and the success rate of VATS removal was 99.53% (210/211). The average operation time was (7.19 ± 2.62) min, and the average time required for resection of lesions was 27 min (10 to 126 min). During the surgery, the soft wire hook-wire of two patient was found to be dislocated and retracted into the chest wall. The pulmonary nodules were successfully located and removed according traces left by puncture points on the lung surface. It was found that the hook-wire was located in the interlobar fissure in 3 patients. The pulmonary nodules were successfully removed by the hook-wire position and appropriately expanding the resection range. A minor pneumothorax occurred in 49 patients, but no closed drainage was needed; 12 patients developed intrapulmonary hematoma; 15 patients with chest pain were treated with analgesia.Conclusions:For small pulmonary nodules requiring thoracoscopic surgery, the computed tomography-guided pulmonary nodule localization with soft wire hook-wire by trailing technique is more convenient, safe and effective, and is worthy of promotion to use.

MiR-92a inhibits fibroblast-like synoviocyte proliferation and migration in rheumatoid arthritis by targeting AKT2.

Growing data have indicated that the miR-17-92 cluster is implicated in inflammatory response and rheumatoid arthritis (RA). This study was aimed to investigate the effects of miR-92a on the proliferation and migration of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs). Our results showed that miR-92a was significantly down-regulated in RA synovial tissue and RA-FLSs, whereas the protein level of AKT2 is increased. Restoration of miR-92a suppressed the proliferation and migration of RA-FLSs. Down-regulation of miR-92a promotes proliferation and migration of normal human FLSs. Dual luciferase reporter gene assay showed that miR-92a could specifically bind with the 30UTR of AKT2 and significantly repressed the luciferase activity. Down-regulation or up-regulation of miR-92a significantly increased or decreased the protein and phosphorylation levels of AKT2. siRNA-mediated down-regulation of AKT2 significantly prevented cell proliferation and migration of RA-FLSs, which were similar to the effects induced by overexpression of miR-92a. Moreover, AKT2 overexpression rescued miR-92a-mediated suppressive effect on proliferation and migration of RA-FLS. Thus, miR-92a could inhibit the proliferation and migration of RA-FLSs through regulation of AKT2 expression.