Osteoarthritis (OA) is one of the most common chronic diseases in the world. However, current treatment modalities mainly relieve pain and inhibit cartilage degradation, but do not promote cartilage regeneration. In this study, we show that G protein-coupled receptor class C group 5 member B (GPRC5B), an orphan G-protein-couple receptor, not only inhibits cartilage degradation, but also increases cartilage regeneration and thereby is protective against OA. We observed that Gprc5b deficient chondrocytes had an upregulation of cartilage catabolic gene expression, along with downregulation of anabolic genes in vitro. Furthermore, mice deficient in Gprc5b displayed a more severe OA phenotype in the destabilization of the medial meniscus (DMM) induced OA mouse model, with upregulation of cartilage catabolic factors and downregulation of anabolic factors, consistent with our in vitro findings. Overexpression of Gprc5b by lentiviral vectors alleviated the cartilage degeneration in DMM-induced OA mouse model by inhibiting cartilage degradation and promoting regeneration. We also assessed the molecular mechanisms downstream of Gprc5b that may mediate these observed effects and identify the role of protein kinase B (AKT)-mammalian target of rapamycin (mTOR)-autophagy signaling pathway. Thus, we demonstrate an integral role of GPRC5B in OA pathogenesis, and activation of GPRC5B has the potential in preventing the progression of OA.

ObjectiveTo explore the clinical efficacy and safety of the combination of Erchentang and Bixie Fenqingyin in the treatment of patients with acute cerebral infarction accompanied by hyperuricemia of phlegm and blood stasis blocking collaterals syndrome to provide a new method and evidence for the treatment of acute cerebral infarction with hyperuricemia. MethodA total of 132 eligible patients with acute cerebral infarction accompanied by hyperuricemia of phlegm and blood stasis blocking collaterals syndrome admitted to the Putuo Hospital of Shanghai University of Traditional Chinese Medicine（TCM） from May 2021 to May 2022 were randomly divided into a Chinese medicine group， a western medicine group， and a control group， with 44 cases in each group. All three groups received routine western medical treatment for acute cerebral infarction. Additionally， the Chinese medicine group received Erchentang combined with Bixie Fenqingyin， the western medicine group received Benzbromarone tablets， and the control group did not receive any uric acid-lowering treatment. The treatment duration was four weeks. The modified Rankin Scale （mRS） score after three months of onset， as well as the National Institutes of Health Stroke Scale （NIHSS） scores， TCM syndrome scores， serum uric acid （SUA） levels， serum C-reactive protein （CRP） and interleukin-6 （IL-6） levels， serum superoxide dismutase （SOD） and malondialdehyde （MDA） levels， and other safety indicators were observed before and after treatment. ResultA total of 129 cases completed the trial observation， with 43 cases in the Chinese medicine group， 42 cases in the western medicine group， and 44 cases in the control group. The rate of good prognosis in the Chinese medicine group （83.7%，36/43） was higher than that in the western medicine group （64.3%，27/42） and the control group （40.9%，18/44） （χ²=4.184，16.930，P<0.05）， and the western medicine group was superior to the control group （χ²=4.707，P<0.05）. After treatment， the NIHSS scores， TCM syndrome scores， SUA， CRP， IL-6， and MDA levels of the patients in all three groups decreased， while the SOD levels increased compared with those before treatment （P<0.05）. Among them， the improvement in NIHSS score was better in the Chinese medicine group and the western medicine group than in the control group （P<0.05）. The Chinese medicine group showed the greatest improvement in TCM syndrome （P<0.05）， while the western medicine group showed the greatest reduction in uric acid levels （P<0.05）. No significant abnormalities in safety indicators were observed before and after treatment in the three groups， and no serious adverse reactions were reported. ConclusionThe combination of Erchentang and Bixie Fenqingyin can significantly improve the prognosis， early neurological deficits， and TCM syndromes of patients acute cerebral infarction accompanied by hyperuricemia of phlegm and blood stasis blocking collaterals syndrome. It can also lower uric acid levels and inhibit inflammatory and oxidative stress reactions.

Objective:To investigate the effect and safety of rituximab, programmed death 1 (PD-1) monoclonal antibody, and Bruton tyrosine kinase (BTK) inhibitor on elderly refractory primary central nervous system lymphoma (PCNSL).Methods:The clinical data of an elderly patient with refractory PCNSL treated with the combination of rituximab, PD-1 monoclonal antibody and BTK inhibitor in the First Hospital of Jilin University in February 2020 were retrospectively analyzed. The relevant literature was reviewed.Results:The patient had primary central nervous system diffuse large B-cell lymphoma (high-risk group), and the Memorial Sloan Kettering Cancer Center (MSKCC) score was 2 (estimated overall survival time was 7 months). Disease progressed after 1 course of treatment. Complete remission was achieved after the therapy of rituximab, PD-1 monoclonal antibody combined with BTK inhibitor. PD-1 monoclonal antibody maintenance therapy was performed and patient was followed up until November 17, 2021. The patient's condition was stable. The second progression-free survival (PFS) time was 20 months, and the overall survival time was 21 months. The patient well tolerated the new drug treatment, and no adverse reactions of grade 3 or above occurred.Conclusions:The new targeted combination therapy can be used as a treatment option for elderly PCNSL patients, which can further improve the curative effect and significantly improve the prognosis.

Objective:To investigate the clinical characteristics and prognosis of acute myeloid leukemia (AML) patients with positive TLS-ERG fusion gene.Methods:The clinical data of 9 AML patients with positive TLS-ERG fusion gene in the First Hospital of Jilin University from June 2013 to August 2020 were retrospectively analyzed, and the relevant literature was reviewed.Results:Among 9 patients with positive TLS-ERG fusion gene, there were 5 males and 4 females, with a median age of 16 years old (6-40 years old). Five patients received chemotherapy alone, 3 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), and 1 patient did not receive systematic treatment. Among 8 patients with systematic treatment, 1 patient had complete remission after the first induction chemotherapy and 5 patients had complete remission after induction therapy. The median overall survival time of 5 patients with chemotherapy alone was 1.5 months (1-11 months), of which 3 patients did not respond to the first course of treatment and died of infection, and 2 patients died after relapse. The median overall survival time of 3 patients with allo-HSCT was 16 months (13-17 months), of which 2 patients died after relapse and 1 patient had sustained molecular complete remission by the end of follow-up.Conclusions:AML with positive TLS-ERG fusion gene has low incidence rate and poor induction efficacy. Hematopoietic stem cell transplantation may partially improve the survival prognosis of patients, but it cannot overcome the adverse effect of positive TLS-ERG fusion gene on prognosis.

Objective:To explore immune cell reconstitution after allogeneic hematopoietic stem cell transplantation(allo-HSCT)by using mathematical function models.Methods:From June 2011 to May 2015, 65 patients with malignant hematological disorders were retrospectively analyzed. Immune cell frequencies and absolute counts were detected at day 14/28/42 and month 2/3/6/9/12/18/24 post-allo-HSCT. The immune cells included CD3 + T, CD4 + helper T, CD8 + effector T, regulatory T, CD19 + B, CD3 -CD56 + NK and CD3 + CD56 + NKT. Kinetic curve models and mathematical equations were established by utilizing curve model estimation. Results:Cubic curve models were observed for the changes of immune cell frequencies. Except for CD3 + T, CD8 + T and NK cells, the changes of absolute counts of immune cells conformed to cubic curve models. The reconstructed kinetic models of CD8 + T and NK cells after allo-HSCT were associated with relapse. Conclusions:Immune cell reconstitution after allo-HSCT conforms to certain mathematical function curve models. It may provide a new strategy for in-depth studies of immune reconstitution after allo-HSCT.

Objective To analyze the dosimetric advantages of CT-guided interstitial brachytherapy for recurrent cervical cancer. Methods A total of 16 patients with recurrent cervical cancer after radical surgery and adjuvant external beam radiotherapy received interstitial brachytherapy with CT-guided implantation of metal needles. The high-risk clinical target volume (HR-CTV) was given 36 Gy in 6 fractions.D90for HR-CTV in the brachytherapy and the cumulative D2 cm3values for the bladder,rectum,and sigmoid colon in the previous external beam radiotherapy and the brachytherapy were analyzed.Results The mean D90value for HR-CTV was 52.5±3.3 Gy. The cumulative D2 cm3values for the bladder, rectum, and sigmoid colon were 85.6±5.8 Gy,71.6±6.4 Gy,and 69.6±5.9 Gy,respectively.The mean number of metal needles was 6.1±1.5 in each brachytherapy. The actual 1-year overall survival and local control were 81% and 69%, respectively. Conclusions CT-guided interstitial brachytherapy for recurrent cervical cancer shows good dose-volume histogram parameters and few complications, so it may be clinically feasible. However,its long-term clinical efficacy needs further observation.

Objective To discuss the dosimetric advantage of computed tomography-guided interstitial brachytherapy compared with the conventional intracavitary brachytherapy for locally advanced cervical cancer,offering a more advantageous clinical treatment approach. Methods Twenty-eight locally advanced cervical cancer patients with bulky tumors ( tumor size>5 cm) after external beam radiotherapy received computed tomography-guided interstitial brachytherapy. Dosimetric outcomes of the current study, including the total dose ( external beam radiotherapy+ brachytherapy ) D90 for the HR-CTV and D2cc for the bladder,rectum, and sigmoid, were compared with a former patient group consisting of 30 patients who received the conventional intracavitary brachytherapy ( uterine tandem+ ovoid pairs ) . Results The mean D90 value for HR-CTV in the intracavitary brachytherapy group and interstitial brachytherapy group were (76.9±5. 7) and ( 88.1± 3. 3) Gy, respectively. The D2cc for the bladder, rectum, and sigmoid in the intracavitary brachytherapy group and interstitial brachytherapy group were (84.7±6. 8) Gy,(69.2±4. 2) Gy,(67.8±4. 5) Gy and (81.8±6. 5) Gy,(6.8±4. 0) Gy,(64.8±4. 1) Gy,respectively.1-year local tumor control rate in the intracavitary brachytherapy group and interstitial brachytherapy group were 59. 3％ and 85. 2％, respectively. Conclusions CT-guided interstitial brachytherapy shows a significant dosimetric advantage compared with the conventional intracavitary brachytherapy, and is, thereby, clinically possible feasible. However,the long term curative effect and toxicity need to be further investigated.

Objective To examine the dosimetric advantages of three-dimensional (3D) computed tomography (CT)-guided interstitial brachytherapy (BT) for target volume and surrounding normal tissue in patients with locally advanced cervical cancer,and to provide a simple and effective clinical treatment approach.Methods A total of 52 patients who had poor tumor response to external beam radiotherapy (EBRT) with a residual tumor greater than 5 cm at the time of BT were included.The patients were treated by 3D CT-guided interstitial BT using a hybrid applicator comprised of uterine tandem and free metal needles.The high-risk clinical target volume (HR-CTV),intermediate-risk clinical target volume (IR-CTV),and organs at risk (OAR) were contoured.The total dose,including external beam radiotherapy and high dose-rate BT,was biologically normalized to conventional 2 Gy fractions (EQD2).D90and D100for both HR-CTV and IR-CTV,and D2 ccfor the bladder,rectum,and sigmoid were analyzed.Results The mean D90value for HR-CTV was 88.4±3.5 Gy.The D2 ccfor the bladder,rectum,and sigmoid were 81.1±5.6,65.7±5.1,and 63.1±5.4 Gy,respectively.D2 cc≤90 Gy for the bladder and D2 cc≤70 Gy for the sigmoid were observed in all the patients.D2 cc≤70 Gy for the rectum was observed in 89% of patients.Conclusions 3DCT-guided interstitial BT has a significant dosimetric advantage for target volume accompanied by few minor complications,and thereby may be clinically feasible for treating locally advanced cervical cancer.However,its long-term efficacy and possible toxicities will require further clinical observation.

Objective To study the immune re-constitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with hematological malignancies.Methods From June 2011 to May 2015,65 patients with hematological malignancies were analyzed retrospectively.Lymphocyte subsets were determined by flow cytometry (FCM),including total T lymphocytes (CD3+),helper T cells (CD3+ CD4+),cytotoxic T cells (CD3+ CD8+),CD4/CD8 ratio,nature killer (NK) cells (CD3-CD56+),NKT cells (CD3+ CD56+),B lymphocytes (CD19+),naive T cells (CD3+ HLA-DR+),static T cells (CD3+ HLA-DR-),and regulatory T cells (CD4+ CD25high Foxp3+) on the day 14,28 and 42,and on the month 2,3,6,9,12,15,18 and 24 after allo-HSCT.Results The percentage of CD3+ T cells located normal range after hematological recovery,and its absolute number recovered to normal range at + 15 months.The percentage of CD3+ CD4+ T cells recovered to normal range at + 24 months.However,the absolute number of CD3+ CD4+ T cells did not recover to normal range until 24 months after allo-HSCT.The percentage of CD3+ CD8+ T cells was higher than normal range at + 42 day,and its absolute number was greater than normal range at + 3 months.Hence,low CD4/CD8 ratio was observed for a long period.The re-constitution time points of the percentage and absolute number of CD3+ HLA-DR+ T cells were + 3 months and + 24 months respectively.The re-constitution time points of the percentage and absolute number of CD3 + HLA-DR-T cells were + 2 months and + 15 months respectively.The re-constitution time points of the percentage and absolute number of regulatory T cells were + 12 months and + 15 months respectively.The percentage of NKT cells located in normal range after hematological recovery,and its absolute number retumed to normal range at + 12 months.The re-constitution time points of the percentage and absolute number of B cells were + 9 months and + 18 months respectively.The percentage of NK cells located in normal range after hematological recovery,and its absolute number returned nearly to normal range at + 3 months.Conditioning regimen containing ATG,source of stem cells,CD34+ cell number,GVHD,and CMV reactivation were all associated with immune re-constitution after allo-HSCT.Conclusion Different immune cells showed different re-constitution models after allo-HSCT,and the percentage recovered faster than absolute number for a certain kind of immune cells.Studying immune re-constitution and its associated factors may offer beneficial information for insight into transplantation immunology and improve the management of allo-HSCT.