[Cdc37 Expression in Multiple Myeloma and Its Role in Cell Proliferation].

OBJECTIVE: To investigate the expression of cell division cycle protein 37 (Cdc37) in multiple myeloma (MM) and its effect on MM cell proliferation. METHODS: The expression of Cdc37 mRNA in CD138+ cells derived from 63 newly diagnosed MM patients and 8 healthy people were detected by real-time quantitative PCR (RT-qPCR). Cdc37 was down-regulated by lentivirus in MM cell line NCI-H929. CCK-8 assay and soft agar clone formation assay were conducted to explore the role of Cdc37 on MM proliferation in vitro. To further verify the effect of Cdc37 on MM cell proliferation in vivo, NOD/SCID mice subcutaneous tumorigenesis model was established. Flow cytometry was carried out to explore the role of Cdc37 on cell cycle. Cell cycle associated proteins and NF-κB pathway were detected by Western blot (WB). RESULTS: Cdc37 was highly expressed in newly diagnosed CD138+cells compared with healthy people. After Cdc37 suppression by shRNA lentivirus infection in NCI-H929 cells, the proliferation of MM cells were decreased in vitro and in vivo. Compared with the control group, the ratio of cells arrested in G0/G1 phase significantly increased in NCI-H929-Cdc37 shRNA cells, the expression of cyclin D1 decreased, while the expression of p21 and p53 was significantly up-regulated. Meanwhile, the activation of NF-κB signaling pathway was hampered in NCI-H929-Cdc37 shRNA cells. CONCLUSION: Cdc37 is highly expressed in newly diagnosed MM patients. Inhibition of Cdc37 results in decreased proliferation activity and G0/G1 arrest in NCI-H929 cells. The possible mechanism may be to inhibit the activation of NF-κB signaling pathway.

Majocchi's granuloma caused by Trichophyton rubrum after facial injection with hyaluronic acid: A case report.

BACKGROUND: Facial cosmetic procedures become popular for people with a desire to have a younger appearance, and cosmetic technology has developed rapidly over the past several decades. However, increasing complications related to cosmetic injections have been reported, and infection is one of the most serious problems and can cause anxiety and facial injury. We here report a case of Majocchi's granuloma (MG) caused by Trichophyton rubrum after facial injection of hyaluronic acid. CASE SUMMARY: A 37-year-old woman presented to our hospital with a history of red papules, nodules, and abscesses on her left zygomatic arch for 2 mo. She had received a cosmetic injection of hyaluronic acid on the left side of her face prior to the appearance of the lesions. MG caused by Trichophyton rubrum after facial injection of hyaluronic acid was diagnosed based on morphology and molecular biological identification. In vitro antifungal susceptibility testing was conducted according to the Clinical and Laboratory Standards Institute M38-A2 method. Minimal inhibitory concentrations were used to evaluate the antifungal susceptibility. The antifungal agents and their minimal inhibitory concentrations for the strain were terbinafine (< 0.5 µg/mL), itraconazole (0.06 µg/mL), amphotericin B (0.25 µg/mL), fluconazole (32 µg/mL), voriconazole (0.125 µg/mL), posaconazole (0.125 µg/mL), and isavuconazole (0.06 µg/mL). We initially administered 250 mg/d oral terbinafine for 2 mo, but the patient still had painful papules, nodules and abscesses on her face. Then, we adjusted the treatment to itraconazole 400 mg/d for 8 wk based on the in vitro antifungal susceptibility testing results. The skin lesions improved significantly, and there was no recurrence during follow-up. CONCLUSION: This case revealed that facial injection of hyaluronic acid may cause serious MG. Antifungal susceptibility testing should be considered in the treatment of MG caused by Trichophyton rubrum.

Secretory status of monoclonal immunoglobulin is related to the outcome of patients with myeloma: a retrospective study.

The treatment of multiple myeloma (MM) with proteasome inhibitor (PI) bortezomib has significantly improved the survival of patients with MM. The 26S proteasome inhibitor targets the unfolded protein response (UPR) by inhibiting proteasome degradation of ubiquitinated paraprotein, subsequently leading to the lethal accumulation of paraprotein within the endoplasmic reticulum. According to secretory status of monoclonal immunoglobulin, newly diagnosed MM (NDMM) is divided into measurable and unmeasurable disease, which includes oligosecretory, nonsecretory, and nonproducer myeloma. The present study analyzed the clinical characteristics of 822 patients with NDMM who had either measurable or unmeasurable diseases and received bortezomib- or thalidomide-based therapies. Our results showed that the median progression-free survival (PFS) and overall survival (OS) of patients with MM was significantly longer in patients with measurable disease than those in oligosecretory, nonsecretory, and nonproducer MM (PFS: 27, 18, 19, and 2.0 months, respectively [P < .001]; OS: 51, 30, 22, and 2.0 months, respectively [P < .001]). Within the unmeasurable group, patients with nonproducer myeloma showed the shortest PFS and OS. Importantly, compared with thalidomide treatment, bortezomib significantly improved the PFS and OS of patients with MM with measurable disease (PFS: 25 and 33 months [P = .022], respectively; OS: 41 and 58 months [P < .001], respectively), but not those with unmeasurable disease (PFS: 18 and 16 months [P = .617], respectively; OS: 22 and 27 months [P = .743], respectively). Our results indicate that bortezomib-based therapy performed no better than thalidomide-based treatment in patients with unmeasurable MM. The results need to be confirmed in other patient cohorts, preferably in the context of a prospective trial.

Extracavitary KSHV-associated large B-Cell lymphoma: a distinct entity or a subtype of primary effusion lymphoma? Study of 9 cases and review of an additional 43 cases.

Primary effusion lymphoma (PEL) is a rare form of aggressive B-cell lymphoma in HIV patients, which typically presents with lymphomatous effusions in the body cavities without forming mass lesions. PEL is associated with Kaposi sarcoma-associated herpesvirus (KSHV) (also called human herpesvirus-8) with distinct clinical and pathologic features. Rare cases of KSHV-associated large B-cell lymphoma (KSHV-LBL) have been observed in the lymph nodes or extranodal sites without lymphomatous effusions during the course of disease. KSHV-LBL is generally similar to classic PEL on the basis of the clinical presentation (HIV(+) male), morphology (immunoblastic, plasmablastic, or anaplastic), immunophenotype (CD45(+), CD20(-), CD79a(-), CD30(+), CD138(+), and EMA(+)), presence of Epstein-Barr virus infection, and clonal immunoglobulin gene rearrangements. However, it is not clear whether KSHV-LBL is a distinct entity or represents part of the spectrum of classic PEL; in particular, there is no consensus diagnostic term for KSHV-LBL. In this study, we investigated the clinicopathologic features of 9 cases of KSHV-LBL from our files. An additional 43 such cases and 84 cases of classic PEL from the English literature were reviewed and compared with each other. In contrast to the classic PEL, KSHV-LBL had a very significant lower expression of CD45 (74% vs. 94%, P=0.004) but significant higher expression of CD20 (17% vs. 5%, P=0.04) and CD138 (70% vs. 38%, P=0.05). KSHV-LBL also had slightly higher positivity of CD79a (23% vs. 5%, P=0.13) and immunoglobulin light chain expression, although the difference was not statistically significant [κ chain (12% vs. 0%) and λ chain (31% vs. 21%)]. The expressions of EMA and CD30 were slightly lower in KSHV-LBL compared with those observed in PEL (57% vs. 75% and 63% vs. 76%, respectively). Interestingly, 29% (10/34) of cases of KSHV-LBL revealed aberrant CD3 expression, which may mislead to a diagnosis of T-cell lymphoma, particularly anaplastic large cell lymphoma in combination with the anaplastic morphology and expression of CD30 and EMA. Although KSHV-LBL shows different clinical presentations and some variations in immunophenotype from classic PEL, it is still uncertain, on the basis of our findings, whether it is justifiable to separate them as 2 distinct entities. Nevertheless, we feel it is necessary to have a consensus diagnostic term, and we recommend a tentative one as "KSHV-associated large B-cell lymphoma (KSHV-LBL)" to replace many different names previously used.

[Quality control for ABO blood group typing of neonatal umbilical cord blood].

This study was aimed to investigate a quality control method for ABO typing of neonatal umbilical cord blood(UCB). The routine serology method was used to identify the ABO type of UCB samples. These samples with questions were further detected by sequence specific primer PCR (PCR-SSP). The results showed that among total of 76120 UCB samples identified by positive ABO typing, there were 78 samples (1 per thousand) which could not be determined. Of these 78 samples, 30 (56.92%) samples with a weak agglutination reaction were excluded by reverse ABO typing. Out of 260 samples in reverse ABO typing, 148 samples were consistent with positive ABO typing, 112 samples (43.08%) were inconsistent with the positive ABO typing. 58 undetermined samples were detected by PCR-SSP. Out of them the genotyping results of 45 samples confirmed the serological typing, the phenotyping results in 3 cases were inconsistent to that of genotyping. 10 cases showed the unconformity between positive and reverse typing, but the genotyping results were fully consistent with the positive typing. In conclusion, positive typing for red cell antigens combined with PCR-SSP is efficient and sensitive for quality control of ABO typing for neonatal UCB.

[Frequencies of high-resolution HLA-Cw* alleles in China Northern Han population].

This study was purposed to investigate the frequencies of HLA-Cw* loci in China Northern Han population at gene level and to analyze the population genetic characteristics of HLA-Cw* alleles and distribution difference of gene frequency in regions. The high resolution genotyping for HLA-Cw* loci of 420 cases in China Northern Han population was performed by using PCR-SSP typing technique and their distribution regularity was analyzed statistically. The results showed that 30 HLA-Cw* alleles were detected, among which the frequency of Cw* 0102 (0.1776), 0702 (0.1217), 0602 (0.1150) were highest; other alleles with higher frequency were as follow in proper order: Cw* 0304, 0801, 0303, 0302, 0401, 1402. The rare observed HLA-Cw* 0506, 0810, 1510, 1601 and 1701 were detected firstly in this population. The statistical analysis indicated that the genotype distribution of HLA-Cw* loci coincides with the Hardy-Weinberg test. In conclusion, application of high resolution allele typing can accurately understand the distribution regularity and characteristics of HLA-Cw* alleles in China Northern Han population which provides the basis for research related with HLA-Cw* loci.