Hongjing Wang's research while affiliated with Lanzhou University Second Hospital and other places

Primary angiosarcomas are a rare type of soft-tissue sarcomas that originate from endothelial cells. These sarcomas can develop in any part of the body and have a poor prognosis. However, they are commonly found in the skin of elderly white men, particularly on the scalp and head region. Primary angiosarcoma of the cervix is exceptionally rare. To date, only two cases of this disease have been reported worldwide. The diagnosis of the disease is difficult microscopically, requiring immunohistochemistry and genetic testing to distinguish. We report a recent case, in which the lesion was preoperatively considered a high-grade endometrial stromal sarcoma. A 35-year-old woman presented with vaginal bleeding and cervical erosions. A high-grade endometrial stromal sarcoma involving the cervix was considered and a modified radical hysterectomy was performed with bilateral salpingo-oophorectomy and sentinel lymph nodes resection. The gene diagnosis performed by fluorescence in situ hybridization for YWHAE translocation fusion was negative excluding a YWHAE-translocated high-grade endometrial stromal sarcoma. A primary angiosarcoma of the cervix was finally diagnosed. Primary angiosarcoma of the cervix is rare, and gynecologic pathologists do not know it well, so it is easy to be wrongly considered. Immunohistochemistry and genetic testing help confirm the diagnosis.

Background Male infertility is a global health issue. The more causative genes related to human male infertility should be further explored. The essential role of Zcwpw1 in male mouse fertility has been established and the role of ZCWPW1 in human reproduction needs further investigation to verify. Methods An infertile man with oligoasthenoteratozoospermia phenotype and his parents were recruited from West China Second University Hospital, Sichuan University. A total of 200 healthy Han Chinese volunteers without any evidence of infertility were recruited as normal controls, while an additional 150 infertile individuals were included to assess the prevalence of ZCWPW1 variants in a sporadic male sterile population. The causative gene variant was identified by Whole-exome sequencing and Sanger sequencing. The phenotype of the oligoasthenoteratozoospermia was determined by Papanicolaou staining, immunofluorescence staining and electron microscope. In-vitro experiments, western blot and in-silicon analysis were applied to assess the pathogenicity of the identified variant. Additionally, we examined the influence of the variant on the DNA fragmentation and DNA repair capability by Sperm Chromatin Dispersion and Neutral Comet Assay. Results The proband exhibits a phenotype of oligoasthenoteratozoospermia, his spermatozoa show head defects by semen examination, Papanicolaou staining and electron microscope assays. Whole-exome sequencing and Sanger sequencing found the proband carries a homozygous ZCWPW1 variant (c.1064C > T, p. P355L). Immunofluorescence analysis shows a significant decrease in ZCWPW1 expression in the proband’s sperm. By exogenous expression with ZCWPW1 mutant plasmid in vitro, the obvious declined expression of ZCWPW1 with the mutation is validated in HEK293T. After being treated by hydroxyurea, MUT-ZCWPW1 transfected cells and empty vector transfected cells have a higher level of γ-H2AX, increased tail DNA and reduced H3K9ac level than WT-ZCWPW1 transfected cells. Furthermore, the Sperm Chromatin Dispersion assay revealed the proband’s spermatozoa have high DNA fragmentation. Conclusions It is the first report that a novel homozygous missense mutation in ZCWPW1 caused human male infertility with sperm head defects and high DNA fragmentation. This finding enriches the gene variant spectrum and etiology of oligoasthenoteratozoospermia.

Background In about one-third of cases, the genetic causes of asthenozoospermia are unknown. The more causative genes related to human male infertility should be further explored. The essential role of ZCWPW1 in mouse male fertility has been established and the role of ZCWPW1 in human reproduction need further investigation to verify. Methods Whole-exome sequencing was conducted to identify causative genes in the infertile man. The phenotype of the asthenozoospermia was determined by Papanicolaou staining, immunofluorescence staining and electron microscope. In-vitro experiments, western blot and in-silicon analysis were applied to assess the pathogenicity of the identified variant. Additionally, we examined the influence of the variant on the DNA fragmentation and DNA repair capability by Sperm Chromatin Dispersion and Neutral Comet Assay. Results The spermatozoa of the proband exhibited low quantity, head defects in semen examination, papanicolaou staining and electron microscope. Whole-exome sequencing and sanger sequencing found the proband carried a homozygous ZCWPW1 variant (c.1064C > T, p. P355L). Immunofluorescence analysis showed that a significant decrease of ZCWPW1 expression in proband’s sperm. The obvious declined expression of ZCWPW1 with the mutation was validated in HEK293T. Furthermore, Sperm Chromatin Dispersion assay revealed the proband’s spermatozoa had high DNA fragmentation. After treated by hydroxyurea, MUT-ZCWPW1 transfected cells and empty vector transfected cells had higher level of γ-H2AX and tail DNA than WT-ZCWPW1 transfected cells. Conclusions It is the first report that a novel homozygous missense mutation in ZCWPW1 caused human male infertility with sperm head defect and high DNA fragmentation. This finding enriches the gene variant spectrum and etiology of asthenozoospermia.

Background: Mirvetuximab Soravtansine (MIRV) is a promising antibody‒drug conjugate (ADC) that targets folate receptor alpha (FRα), which is overexpressed in several types of solid tumors. In November 2022, MIRV was approved in the USA for the treatment of adult patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer who received 1-3 prior systemic treatment regimens. Therefore, high-quality evidence for its efficacy and safety in different cancers is urgently needed. Methods: A systematic search (e.g., PubMed, Embase, Web Of Science, Cochrane Library) was conducted to identify all relevant clinical trials of MIRV alone or in combination with chemo- and/or target-therapies in solid tumors. The primary end-point was median progression-free survival (mPFS). The secondary endpoints were the overall response rate (ORR) and adverse effects (AEs). A random-effects model was applied. Results: The study included nine research studies with a total of 682 patients. The pooled mPFS and pooled ORR were 6.70 months (95% CI 4.54–8.86,I2=96.21%) and 36% (95% CI: 28% to 44%, I2=76.79%), respectively. Significant differences were observed among intervention regimens and response to platinum. The pooled mPFS of MIRV monotherapy and MIRV+ BEV combined therapy was 4.28 (95% CI 3.90–4.65, I2=0.00%) and 7.78 (95% CI 6.62-8.95, I2=0.00%), respectively. The pooled ORRs of MIRV monotherapy and MIRV+BEV combined therapy were 25% (95% CI 21%–29%, I2=25.20%) and 43% (95% CI 36%–50%, I2=0.01%), respectively. The pooled ORRs of the platinum-sensitive, platinum-resistant groups were 59% (95% CI 36%–81%, I2=61.88%), 33% (95% CI 25%–40%, I2=69.73%), respectively. In addition, we conducted supplementary subgroup analyses to explore the influence of FRα receptor expression levels and the number of prior treatments on treatment outcomes. The most common adverse effects were blurred vision (45.20%), nausea (40.13%), diarrhea (39.52%), fatigue (33.84%) and keratopathy (31.20%). Conclusions: MIRV has significant therapeutic effects in solid tumors, especially when combined with BEV. In platinum-tolerant tumors, the efficacy of MIRV is also considerable. Overall, MIRV is relatively safe in solid tumors, and adverse reactions are relatively rare and mild.

Background Mirvetuximab Soravtansine (MIRV) is a promising antibody‒drug conjugate (ADC) that targets folate receptor alpha (FRα), which is overexpressed in several types of solid tumors. In November 2022, MIRV was approved in the USA for the treatment of adult patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer who received 1–3 prior systemic treatment regimens. Therefore, high-quality evidence for its efficacy and safety in different cancers is urgently needed. Methods A systematic search (e.g., PubMed, Embase, Web Of Science, Cochrane Library) was conducted to identify all relevant clinical trials of MIRV alone or in combination with chemo- and/or target-therapies in solid tumors. The primary end-point was median progression-free survival (mPFS). The secondary endpoints were the overall response rate (ORR) and adverse effects (AEs). A random-effects model was applied. Results The study included nine research studies with a total of 682 patients. The pooled mPFS and pooled ORR were 4.70 months (95% CI 4.35–5.05, I2 = 87.40%) and 31% (95% CI: 27–34%, I2 = 76.90%), respectively. Significant differences were observed among intervention regimens and response to platinum. The pooled mPFS of MIRV monotherapy and MIRV + BEV combined therapy was 4.28 (95% CI 3.90–4.65, I2 = 0.00%) and 7.78 (95% CI 6.62–8.95, I2 = 0.00%), respectively. The pooled ORRs of MIRV monotherapy and MIRV + BEV combined therapy were 25% (95% CI 21–29%, I2 = 25.20%) and 43% (95% CI 36–50%, I2 = 0.01%), respectively. The pooled ORRs of the platinum-sensitive, platinum-resistant, and not-known groups were 57% (95% CI 44–71%, I2 = 61.90%), 29% (95% CI 26–33%, I2 = 74.60%), and 27% (95% CI 14–40%, I2 = 10.01%), respectively. The most common adverse effects were blurred vision (45.20%), nausea (40.13%), diarrhea (39.52%), fatigue (33.84%) and keratopathy (31.20%). Conclusions MIRV has significant therapeutic effects in solid tumors, especially when combined with BEV. In platinum-tolerant tumors, the efficacy of MIRV is also considerable. Overall, MIRV is relatively safe in solid tumors, and adverse reactions are relatively rare and mild.

Malignant ovarian tumors bear the highest mortality rate among all gynecological cancers. Both late tumor diagnosis and tolerance to available chemotherapy increase patient mortality. Accumulating evidence demonstrates that histone modifications play a key role in cancerization and progression. Histone deacetylases is associated with chromatin condensed structure and transcriptional repression and play a role in chromatin remodeling and epigenetics. Histone deacetylases are promising targets for therapeutic interventions intended to reverse aberrant epigenetic associated with cancer. Therefore, histone deacetylases inhibitors could be used as anti-cancer drugs. Preclinical studies have shown promising outcomes of histone deacetylases inhibitors in ovarian cancer while clinical trials have had mixed results and limited success as monotherapy. Therefore, combination therapy with different anticancer drugs for synergistic effects and newly selective histone deacetylases inhibitors development for lower toxicity are hot issues now. In this review, we summarize the latest studies on the classification and mechanisms of action of histone deacetylase and the clinical application of their inhibitors as monotherapy or combination therapy in ovarian cancer.

Background Cyclosporine is widely used for immunosuppressive treatment of various systematic and local autoimmune diseases. Breastfeeding is conventionally contraindicated when treating with cyclosporine due to its excretion into breast milk, which may cause immune suppression of exposed infants and affect infants` growth. A few cases have tested cyclosporine levels in random breast milk samples and concluded the infants exposed to safe cyclosporine levels during breastfeeding. Since infants do not maintain a fixed feeding schedule, we monitored cyclosporine levels in breast milk at different times of the day to assess the safety of breast milk for infants throughout the day. Case presentation A 32-year-old dichorionic twin-pregnancy woman had nephrotic syndrome with renal biopsy confirmed type V lupus nephritis for over five years. She was treated only with prednisone 10 mg a day before pregnancy and during early pregnancy. Cyclosporine was added in her regimen from 22 weeks gestation and was adjusted to 225 mg a day from 28 weeks gestation. After parturition, she partially breastfed her twin infants while being treated with cyclosporine 3 mg/kg a day as well as prednisone and hydroxychloroquine sulfate. The cyclosporine level in maternal blood was determined, and several breast milk samples were collected for consecutive 48 h beginning on the ninth day after parturition. The concentration of cyclosporine in breast milk was measured and ranged from 0.443 to 5.307 mcg/L. Both infants grew and developed normally at the three-month follow-up, with no adverse effects observed. The study was conducted at West China Second University Hospital of Sichuan University, started in September 2021, with the consent of the participant and the approval of the ethics committee. Conclusion In this case, cyclosporine levels in breast milk were low at all times of the day. The growth and development of both infants were normal at three months postpartum. Thus, breastfeeding may still be an option for mothers with nephrotic syndrome who are treated with cyclosporine.