T cell-redirecting antibody for treatment of solid tumors via targeting mesothelin.

T cell engaging bispecific antibodies (TCBs) have recently become significant in cancer treatment. In this study we developed MSLN490, a novel TCB designed to target mesothelin (MSLN), a glycosylphosphatidylinositol (GPI)-linked glycoprotein highly expressed in various cancers, and evaluated its efficacy against solid tumors. CDR walking and phage display techniques were used to improve affinity of the parental antibody M912, resulting in a pool of antibodies with different affinities to MSLN. From this pool, various bispecific antibodies (BsAbs) were assembled. Notably, MSLN490 with its IgG-[L]-scFv structure displayed remarkable anti-tumor activity against MSLN-expressing tumors (EC50: 0.16 pM in HT-29-hMSLN cells). Furthermore, MSLN490 remained effective even in the presence of non-membrane-anchored MSLN (soluble MSLN). Moreover, the anti-tumor activity of MSLN490 was enhanced when combined with either Atezolizumab or TAA × CD28 BsAbs. Notably, a synergistic effect was observed between MSLN490 and paclitaxel, as paclitaxel disrupted the immunosuppressive microenvironment within solid tumors, enhancing immune cells infiltration and improved anti-tumor efficacy. Overall, MSLN490 exhibits robust anti-tumor activity, resilience to soluble MSLN interference, and enhanced anti-tumor effects when combined with other therapies, offering a promising future for the treatment of a variety of solid tumors. This study provides a strong foundation for further exploration of MSLN490's clinical potential.

Long-term passaging of pseudo-typed SARS-CoV-2 reveals the breadth of monoclonal and bispecific antibody cocktails.

The continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses challenges to the effectiveness of neutralizing antibodies. Rational design of antibody cocktails is a realizable approach addressing viral immune evasion. However, evaluating the breadth of antibody cocktails is essential for understanding the development potential. Here, based on a replication competent vesicular stomatitis virus model that incorporates the spike of SARS-CoV-2 (VSV-SARS-CoV-2), we evaluated the breadth of a number of antibody cocktails consisting of monoclonal antibodies and bispecific antibodies by long-term passaging the virus in the presence of the cocktails. Results from over two-month passaging of the virus showed that 9E12 + 10D4 + 2G1 and 7B9-9D11 + 2G1 from these cocktails were highly resistant to random mutation, and there was no breakthrough after 30 rounds of passaging. As a control, antibody REGN10933 was broken through in the third passage. Next generation sequencing was performed and several critical mutations related to viral evasion were identified. These mutations caused a decrease in neutralization efficiency, but the reduced replication rate and ACE2 susceptibility of the mutant virus suggested that they might not have the potential to become epidemic strains. The 9E12 + 10D4 + 2G1 and 7B9-9D11 + 2G1 cocktails that picked from the VSV-SARS-CoV-2 system efficiently neutralized all current variants of concern and variants of interest including the most recent variants Delta and Omicron, as well as SARS-CoV-1. Our results highlight the feasibility of using the VSV-SARS-CoV-2 system to develop SARS-CoV-2 antibody cocktails and provide a reference for the clinical selection of therapeutic strategies to address the mutational escape of SARS-CoV-2.

Immunoglobulin G4-related kidney disease involving the renal pelvis and perirenal fat: A case report.

BACKGROUND: Immunoglobulin (Ig) G4-related disease (IgG4-RD) is an autoimmune disease associated with chronic and progressive inflammation and fibrosis. It is difficult to differentiate IgG4-RD involving the kidney from infectious diseases and malignancy on imaging. CASE SUMMARY: We report the case of a 51-year-old Chinese man whose abdominal computed tomography scan showed diffuse bilateral enlargement of the kidneys and perirenal fat, thickening of the renal pelvic walls, and hydronephrosis of the right kidney. Relevant laboratory test results showed a serum creatinine level of 464 µmol/L. The patient was diagnosed with acute renal failure and was started on intermittent hemodialysis. Further tests revealed high serum IgG4 levels (20.8 g/L) and an enlarged right submaxillary lymph node. Biopsy and histopathological examination of the enlarged node led to the diagnosis of IgG4-RD. After corticosteroid therapy, his serum creatinine level quickly decreased to near normal levels. CONCLUSION: IgG4-RD affecting the renal pelvis or perirenal fat is rare, with atypical imaging features. Multidisciplinary consultation is critical for accurate diagnosis and treatment of this disease. Suspected cases should undergo biopsy to avoid misdiagnosis.

LncRNA PINK1-AS promotes Gαi1-driven gastric cancer tumorigenesis by sponging microRNA-200a.

Gastric cancer (GC) is one of the leading causes of human mortality around the world. We have previously shown that Gαi1 (the inhibitory subunit 1 of the heterotrimeric guanine nucleotide-binding protein) recruitment to ligand-activated receptor tyrosine kinases (RTKs) is essential for signaling. Testing its role in GC cancer-promoting functions, we found that Gαi1 is upregulated in human GC, correlating with poor overall survival. In established and primary human GC cells, Gαi1 shRNA (small hairpin RNA) or knockout produced significant anti-GC cell activity, proliferation and migration was inhibited, and apoptosis was activated. Conversely, ectopic Gαi1 overexpression promoted proliferation and migration of GC cells in vitro. By examining the tumor-suppressive miRNA microRNA-200a (miR-200a), we found that miR-200a directly silenced Gαi1 to induce anti-GC cell activity. The expression of miR-200a was downregulated in human GC, correlating with upregulation of a novel miR-200a-targeting long non-coding RNA (LncRNA), PINK1 (PTEN Induced Kinase 1)-AS. RNA immunoprecipitation, RNA-pull down, and RNA fluorescence in situ hybridization assays confirmed that PINK1-AS directly binds to miR-200a. Silencing PINK1-AS in GC cells led to miR-200a accumulation, Gαi1 downregulation, and inhibition of GC cell progression in vitro, whereas PINK1-AS upregulation produced the converse results. Significantly, anti-GC cell activity induced by PINK1-AS shRNA was ameliorated by the expression of miR-200a antisense or the 3'-UTR (untranslated region)-depleted Gαi1. In vivo, the growth of subcutaneous MGC-803 xenografts in nude mice was inhibited by PINK1-AS shRNA, but accelerated by PINK1-AS overexpression. Patient-derived GC xenograft growth in nude mice was largely inhibited after intratumoral injection of PINK1-AS shRNA lentivirus. In conclusion, PINK1-AS promotes Gαi1-driven GC progression by sponging miR-200a.

The therapeutic effect of the BRD4-degrading PROTAC A1874 in human colon cancer cells.

A1874 is a novel BRD4-degrading proteolysis targeting chimera (PROTAC). In primary colon cancer cells and established HCT116 cells, A1874 potently inhibited cell viability, proliferation, cell cycle progression, as well as cell migration and invasion. The BRD4-degrading PROTAC was able to induce caspase and apoptosis activation in colon cancer cells. Furthermore, A1874-induced degradation of BRD4 protein and downregulated BRD-dependent genes (c-Myc, Bcl-2, and cyclin D1) in colon cancer cells. Significantly, A1874-induced anti-colon cancer cell activity was more potent than the known BRD4 inhibitors (JQ1, CPI203, and I-BET151). In BRD4-knockout colon cancer cells A1874 remained cytotoxic, indicating the existence of BRD4-independent mechanisms. In addition to BRD4 degradation, A1874 cytotoxicity in colon cancer cells was also associated with p53 protein stabilization and reactive oxygen species production. Importantly, the antioxidant N-acetyl-cysteine and the p53 inhibitor pifithrin-α attenuated A1874-induced cell death and apoptosis in colon cancer cells. In vivo, A1874 oral administration potently inhibited colon cancer xenograft growth in severe combined immuno-deficient mice. BRD4 degradation and p53 protein elevation, as well as apoptosis induction and oxidative stress were detected in A1874-treated colon cancer tissues. Together, A1874 inhibits colon cancer cell growth through both BRD4-dependent and -independent mechanisms.

Colonization With Multidrug-Resistant Organisms Among Healthy Adults in the Community Setting: Prevalence, Risk Factors, and Composition of Gut Microbiome.

BACKGROUND: The prevalence of colonization with multidrug-resistant organisms (MDROs) among healthy adults in the community is largely unknown. This study investigated the colonization rate of multidrug-resistant Enterobacteriaceae, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE) in the community in Taiwan, and compared the gut microbiota between MDRO carriers and non-carriers. METHODS: This prospective cohort study was conducted from March 2017 to February 2018 at the Hsin-Chu and Jin-Shan branches of National Taiwan University Hospital. Nasal swabs and stool samples were obtained from healthy adults attending a health examination to screen for MDROs. Bacteria isolates of MDROs were tested for antibiotic susceptibility and resistant genes. Relevant data were collected using a standardized questionnaire to evaluate the risk factors for MDROs carriage, and 16S rRNA metagenomics sequencing was performed to analyze gut microbiota. RESULTS: Among 187 participants, 4.6% (8/174) carried MRSA and 41.4% (77/186) carried third-generation cephalosporin-resistant (3GC-R) Escherichia coli or Klebsiella pneumoniae. The carriage rate of AmpC beta-lactamases and ESBL-producing strains were 16.1 and 27.4%, respectively. No carbapenem-resistant Enterobacteriaceae (CRE) or VRE were detected. The dominant resistant gene of E. coli isolates was CTX-M-type (73%), while that of K. pneumoniae was AmpC beta-lactamases (80%). In the multivariate analysis, the significant risk factors for carrying 3GC-R E. coli or K. pneumoniae were being an employee of technology company A [adjusted odds ratio (aOR) 4.127; 95% confidence interval (CI) 1.824-9.336; p = 0.001], and traveling to Southeast Asia in the past year (aOR 6.545; 95% CI 1.071-40.001; p = 0.042). The gut microbiota analysis showed that the phylum Proteobacteria and the family Enterobacteriaceae were significantly more abundant in 3GC-R E. coli and K. pneumoniae carriers. CONCLUSION: A high rate of Taiwanese adults in the community carried 3GC-R Enterobacteriaceae, while no CRE or VRE colonization was noted. Compared with non-carriers, an expansion of Enterobacteriaceae in gut microbiota was found among 3GC-R Enterobacteriaceae carriers.

Upregulation of lncRNA-NONRATT021203.2 in the dorsal root ganglion contributes to cancer-induced pain via CXCL9 in rats.

Cancer-induced pain (CIP) is a kind of chronic pain that occurs during cancer progression over time. However, the mechanisms are largely unknown, and clinical treatment remains challenging. LncRNAs have been reported to play critical roles in various biological processes, including chronic pain. The aim of our study was to investigate whether lncRNAs participate in the development of CIP by regulating the expression levels of some molecules related to pain modulation. The CIP model was established by injecting Walker 256 mammary gland tumor cells into the tibial canal of rats. In this study, we found that lncRNA-NONRATT021203.2 was increased in the CIP rats and that lncRNA-NONRATT021203.2-siRNA could relieve hyperalgesia in these rats. For elucidation of the underlying mechanism, we showed that lncRNA-NONRATT021203.2 could target C-X-C motif chemokine ligand 9 (CXCL9), which was increased in the CIP rats, and that CXCL9-siRNA could relieve hyperalgesia. At the same time, silencing lncRNA-NONRATT021203.2 expression decreased the mRNA and protein levels of CXCL9. Immunofluorescence analysis showed that CXCL9 was mainly expressed in the CGRP-positive and IB4-positive DRG neurons. Further research showed that lncRNA-NONRATT021203.2 and CXCL9 were colocalized in the DRG neurons. Our data suggested that lncRNA-NONRATT021203.2 participated in the CIP in rats and likely mediates the upregulation of CXCL9. The present study provided us with a new potential target for the clinical treatment of cancer-induced pain.

[Small-cell carcinoma of the prostate: A report of 2 cases and review of the literature].

OBJECTIVE: To investigate the clinicopathological characteristics and improve the clinical treatment of prostatic small-cell carcinoma (PSCC). METHODS: We reported 2 cases of PSCC derived from prostate cancer after treated by androgen blockade and prostate electrotomy and reviewed the relevant literature. RESULTS: Two patients with PSA elevation were diagnosed with prostate cancer by prostatic puncture biopsy and treated by maximum androgen blockade, which reduced their total PSA to the normal level. Later, due to difficult urination, they both underwent prostate electrotomy, followed by chemotherapy or radiotherapy for PSCC confirmed by postoperative pathology. Nevertheless, they died at 8 to 9 months after the discovery of PSCC. CONCLUSIONS: PSCC can derive from prostate cancer after treatment, which may be attributed to the pathological mutation induced by long-term endocrine therapy. PSCC is more malignant than prostate cancer, and its prognosis is poor.

Triptonide inhibits human nasopharyngeal carcinoma cell growth via disrupting Lnc-RNA THOR-IGF2BP1 signaling.

Advanced stage nasopharyngeal carcinoma (NPC) has a poor prognosis. Triptonide ("TN") is a small molecule monomer extract from the ancient Chinese herb Tripterygium wilfordii Hook. We show that TN, at nanomolar concentrations, potently inhibited survival and proliferation of multiple established and primary human NPC cells. TN induced NPC cell cycle arrest and apoptosis activation. NPC cell migration and invasion were also inhibited by TN. Importantly, TN was non-cytotoxic to nasopharyngeal epithelial cells. TN treatment in NPC cells disrupted LncRNA THOR ("Lnc-THOR")-IGF2BP1 association, causing depletion of Lnc-THOR and downregulation of IGF2BP1 mRNA targets (Myc, IGF2 and Gli1). Lnc-THOR or IGF2BP1 knockout by CRISPR/Cas9 gene-editing methods mimicked and abolished TN's actions in NPC cells. Conversely, ectopic Lnc-THOR overexpression inhibited TN-induced cytotoxicity in NPC cells. Significantly, Lnc-THOR, IGF2BP1 and its mRNA targets are elevated in human NPC tissues and cells, but almost undetectable in nasopharyngeal epithelial tissues and cells. In vivo, intraperitoneal TN administration significantly inhibited subcutaneous NPC xenograft growth in mice. Similarly, Lnc-THOR-knockout HONE-1 xenografts grew significantly slower than control tumors. Thus, TN inhibits human NPC cell growth in vitro and in vivo via disrupting Lnc-THOR-IGF2BP1 signaling.

Serum C-peptide concentration and prostate cancer: A meta-analysis of observational studies.

BACKGROUND: The association between serum C-peptide concentration and prostate cancer remains unexplored. Therefore, we conducted a meta-analysis to assess whether C-peptide serum concentrations are associated with increased prostate cancer risk. METHODS: Several databases were searched to identify relevant original research articles published before November 2017. Random-effects models were used to summarize the overall estimate of the multivariable-adjusted odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Nine observational studies involving 11,796 participants were identified. The findings of the meta-analysis indicated that the association between serum C-peptide concentration and prostate cancer was not significant (OR: 1.15, 95% CI: 0.85-1.54; for highest versus lowest category C-peptide concentrations, P = .376). The associations were inconsistent, as indicated by subgroup analyses. CONCLUSION: Although our findings provided no support for the hypothesis that serum C-peptide concentration is associated with excess risk of prostate cancer, people must pay attention to this aspect and increase physical activity or modify dietary habits to constrain insulin secretion, which possibly lead to decreased incidence of prostate cancer. Hence, well-designed observational studies involving different ethnic populations are still needed.

Association between cadmium exposure and urolithiasis risk: A systematic review and meta-analysis.

BACKGROUND: We performed a meta-analysis to determine whether a consistent relationship exists between cadmium exposure and urolithiasis in humans. Accordingly, we summarized and reviewed previously published quantitative studies. METHODS: Eligible studies with reference lists published before June 1, 2017 were obtained from searching several databases. Random effects models were used to summary the overall estimate of the multivariate adjusted odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Six observational studies involving 88,045 participants were identified and stratified into the following categories according to cadmium assessment results: occupational (n = 4) and dietary (n = 2). The findings of the meta-analysis suggested that the risk of urolithiasis increases significantly by 1.32 times at higher cadmium exposure (OR = 1.32; 95% CI = 1.08-1.62; for highest vs lowest category urinary cadmium values). The summary OR in occupational exposure (OR = 1.56; 95% CI = 1.13-2.14) increased at the same condition. Meanwhile, no association was observed between cadmium exposure and urolithiasis risk in dietary exposure (OR = 1.13; 95% CI = 0.87-1.47). A significant association remained consistent, as indicated by subgroup analyses and sensitivity analyses. CONCLUSIONS: The meta-analysis indicated that increased risk of urolithiasis is associated with high cadmium exposure, and this association is higher in occupational exposure than in dietary exposure. Nevertheless, well-designed observational studies with different ethnic populations are still needed.

Triptorelin relieves lower urinary tract symptoms in Chinese advanced prostate cancer patients: a multicenter, non-interventional, prospective study.

BACKGROUND: Although triptorelin is increasingly used in China for biochemical castration, its effects on primary prostate cancer symptoms remain unclear. This study aimed to assess the prevalence of lower urinary tract symptoms (LUTS) in Chinese prostate cancer patients and the effectiveness of triptorelin on LUTS. METHODS: In this 48-week multicenter, non-interventional, prospective study, we enrolled patients with locally advanced or metastatic prostate cancer. Patients received triptorelin (15 mg) intramuscularly at baseline and at weeks 12, 24, and 36 with symptom assessment using the International Prostate Symptoms Score (IPSS). The primary endpoints were the prevalence of LUTS at baseline per IPSS categories and the percentage of patients with moderate to severe LUTS (IPSS > 7) at baseline, having at least a 3-point reduction of IPSS score at week 48. RESULTS: A total of 398 patients were included; 211 (53.0%) and 160 (40.2%) among them had severe and moderate LUTS, respectively. Of the patients with IPSS scores available at baseline and at week 48 (n = 213), 81.2% achieved a reduction in IPSS of at least 3 points. Of the patients with moderate to severe LUTS at baseline and IPSS scores available at baseline and at week 48 (n = 194), 86.6% achieved a total IPSS reduction of at least 3 points. CONCLUSIONS: The vast majority of Chinese patients with locally advanced or metastatic prostate cancer scheduled to receive triptorelin as part of their standard treatment have severe or moderate LUTS. Triptorelin therapy resulted in sustained improvement of LUTS in these patients.

Association between butchers and cancer mortality and incidence: A systematic review and meta-analysis.

BACKGROUND: In this study, we evaluated whether increased risks of mortality and cancer incidence exist among butchers worldwide. To achieve this goal, we conducted a systematic review and meta-analysis to investigate the correlations of the risks of cancer death and incidence with male and female butchers. METHODS: We obtained data by performing a comprehensive literature search in several databases for eligible studies published before March 2017. Multivariable-adjusted standardized mortality ratios (SMRs) and odds ratio (OR), as well as associated 95% confidence intervals (CIs) and those by subgroups, were extracted and pooled. RESULTS: A total of 17 observational studies comprising 397,726 participants were included in the meta-analysis. The butcher occupation was not associated with all-cancer mortality risk, with pooled overall SMRs of 1.07 (95% CI 0.96-1.20). However, the pooled ORs revealed that butchers hold an elevated risk of total cancer incidence (OR, 1.51; 95% CI, 1.33-1.73). No proof of publication bias was obtained, and the findings were consistent in the subgroup analyses. CONCLUSION: Our results suggest that working as butchers did not significantly influence all-cancer mortality risk but significantly contributed to elevated all-cancer incidence risk. Nevertheless, well-designed observational studies on this topic are necessary to confirm and update our findings.

Vasectomy and cardiovascular disease risk: A systematic review and meta-analysis.

BACKGROUND: Even though several studies comparing vasectomy and cardiovascular disease (CVD) risk have been reported, most are small series with conflicting results. However, the extent of the risk is still uncertain. We therefore explored whether an association exists between vasectomy and CVD incidence and mortality. METHODS: We searched PubMed, Embase, Web of Science, and Cochrane Library databases for relevant studies published before January 2017. Multivariate adjusted odds ratio (OR) and associated 95% confidence intervals (CIs) and those by subgroups were extracted and pooled using random-effects models. RESULTS: Overall, 12 observational studies (2 cross-sectional studies, 4 case-control studies, and 6 retrospective cohort studies) comprising 299,436 participants were identified. There was no statistically significant relationship between vasectomy and CVD risk (OR: 0.90, 95% CI: 0.81-1.00). Moreover, vasectomy was not associated with CVD mortality (OR: 0.90, 95% CI: 0.81-1.00), coronary heart disease (CHD) incidence (OR: 0.94, 95% CI: 0.88-1.01), stroke incidence (OR: 0.90, 95% CI: 0.72-1.13), and myocardial infarction (MI) incidence (OR: 0.95, 95% CI: 0.88-1.02), with no significant publication bias. In subgroup analyses, the findings on the association between vasectomy and CVD risk were consistent. CONCLUSION: Our findings suggest that vasectomy is not associated with the excess risk of CVD incidence and mortality. Nevertheless, large-volume, well-designed observational studies, with different ethnic populations, low risk of bias, and adjusted confounding factors, are awaited to confirm and update the findings of this analysis.

Sleep problems and injury risk among juveniles: A systematic review and meta-analysis of observational studies.

Recent studies have reported inconsistent results regarding the association between sleep problems and injury risk among juveniles. Moreover, the extent of this risk remains largely unexplored. Thus, a systematic review and meta-analysis was conducted by our team to determine whether sleep problems increase the incidence of injuries among juveniles. PubMed, PsycINFO, Embase, and Cochrane Library databases were searched for relevant studies that explored the association between sleep problems and injury risk and have been published before July 2016. Multivariate adjusted odds ratio (OR) and associated 95% confidence intervals (CIs) were extracted and pooled using random-effects models. A total of 10 observational studies involving 73,418 participants were identified. Meta-analysis findings suggested that juveniles with sleep problems held a 1.64 times higher risk of injury than that of juveniles without sleep problems (OR: 1.64, 95% CI: 1.44-1.85). This relationship was also supported by subgroup analyses, which were based on different countries and study designs. The current evidence indicates that sleep problems are significantly associated with injury risk among juveniles. Sleep problems are highly important for young people; hence, sleep researchers and occupational physicians should focus on this aspect. Nevertheless, high-quality and adequately powered observational studies are still needed.

[Zinner syndrome:A case report and review of the literature].

OBJECTIVE: To explore the clinical diagnosis and treatment of seminal vesicle cyst (SVC) associated with ipsilateral renal agenesis (Zinner syndrome) in order to promote the understanding of the disease. METHODS: We retrospectively analyzed the clinical data about 1 case ofZinner syndrome diagnosed and treated in our hospital and reviewed the literature related to this disease in domestic and foreign authoritative databases. RESULTS: The patient was a 23-year-old male, diagnosed with Zinner syndrome, treated bytransrectal aspiration of SVC, and discharged from hospital 3 days postoperatively. Follow-upat 6 months after discharge found that the patient no longer felt perineal discomfort in the endstage of urination, but transrectal ultrasonography of the prostate revealedthe samevolume of fluid in the left seminal vesicles as before,which indicated recurrence. CONCLUSIONS: SVC associated with ipsilateral renal agenesis can be considered asZinner syndrome. Transrectal aspiration of SVCcan relieve the local symptoms of the patient but relapse may easilyoccur. Therefore it is not recommended as the first-choice treatment of the disease.

[Staging Based Strategies and Practice for Prostate Cancer].

Authors raised that staging based strategies and practice of integrative medicine (IM) by combining syndrome typing and disease identification, and choosing suitable measures in accordance with different persons and seasonal conditions after more than ten years' clinical practice and researches. Radical operation as prior (as evil eliminating) and strengthening vital qi in perioerative period are best strategy for promoting rapid rehabilitation of early stage prostate cancer patients. Strengthening body resistance to eliminate evil was used in treating advanced prostate cancer patients. For example, a comprehensive treatment program for hormone-dependent patients was combined with endocrinotherapy and Chinese herbs for synergisic efficacy-enhancing actions. In this way, these patients' quality of life (QOL) were improved and time to castration resistant prostate cancer (CRPC) was delayed, even some patients were clinically cured. There are lack of effective medicines and methods for CRPC patients. Greatly tonifying original qi is mainly used for improving their clinical symptoms and prolonging survivals. Practice has proved staging based strategies and practice of IM has favorable advantages in treating prostate cancer, especially showing prospect in prolonging survival and postponing progression of advanced prostate cancer patients. Besides, it also could provide beneficial considerations and inspiration for combination of syndrome typing and disease identification.

[Shenfu injection induces the apoptosis of prostate cancer PC-3 cells].

OBJECTIVE: To study the effect of Shenfu Injection (SF) on the apoptosis of prostate cancer PC-3 cells and its possible mechanism. METHODS: We divided prostate cancer PC-3 cells into a blank control group and three experimental groups, the latter treated with SF at 50, 100, and 200 microl/ml, respectively, for 24, 48, and 72 hours. Then we determined the proliferation of the cells by MTT assay, measured their apoptosis by Annexin V/PI flow cytometry, and detected the expression of P53 mRNA by RT-qPCR. RESULTS: Compared with the blank control group, the survival rates of the prostate cancer PC-3 cells in the 50, 100, and 200 microl/ml SF groups were (93.76 +/- 2.63)%, (81.21 +/- 1.80)% and (18.01 +/- 3.84)% at 24 hours, (94.67 +/-1.11)%, (78.33 +/- 2.89)% and (10.34 +/- 1.44)% at48 hours, and (91.30 +/- 0.47)%, (36.67 +/- 1.56)% and (1.33 +/- 0.32)% at 72 hours, all significantly increased in a dose- and time-dependent manner (P < 0.05). The expression of p53 mRNA was also markedly increased in all the three experimental groups at 48 hours (P < 0. 05). CONCLUSION: SF can inhibit the proliferation and induce the apoptosis of PC-3 cells, which may due to its upregulation of the p53 mRNA expression.

[Short-course kidney-invigorating therapy improves near-term semen quality in asthenozoospermic men with kidney deficiency].

OBJECTIVE: To evaluate the effect of short-course kidney-invigorating therapy on near-term semen quality in asthenozoospermic men with kidney deficiency. METHODS: Based on the differential types in traditional Chinese medicine, 121 asthenozoospermia patients received at our clinic of andrology were divided into groups A (kidney-yin deficiency), B (kidney-yang deficiency) and C (spleen and kidney deficiency), and treated with Yougui Decoction plus Wuziyanzong Pills, Jinkuishenqi Pills plus Wuziyanzong Pills, and Shizi Decoction plus Liujunzi Decoction, respectively, all given once daily for 4 weeks. Sperm parameters of the patients were analyzed with the computer-assisted sperm analysis system before and after treatment and compared among the three groups. RESULTS: The baseline sperm concentrations in groups A, B and C ([70.4 +/- 38.6], [73.5 +/- 40.2] and [56.0 +/-34.4] x 10(6)/ml) showed no significant differences from those after medication ([74.4 +/- 32.6], [67.0 +/- 30.8] and [58.6 +/- 24.6] x 10(6)/ml) (P > 0.05). The percentages of grade a sperm in the three groups were (12.9 +/- 5.3)%, (13.7 +/- 7.7)% and (12.9 +/- 6.4)% respectively after treatment, significantly higher than (9.9 +/- 6.7)%, (9.3 +/- 5.4)% and (9.0 +/- 6.8)% before treatment (P < 0.05), and so were the percentages of grade a + b sperm ([37.4 +/- 10.2 ]%, [35.7 +/- 13.7]% and [35.9 +/- 12.3]% after treatment versus [29.6 +/- 13.2]%, [27.5 +/- 10.4]% and [28.3 +/- 12.1]% before treatment, P < 0.05). All the three groups showed significantly increased sperm motility after treatment ([53.8 +/- 10.5]%, [52.6 +/- 15.2]% and [51.1 +/- 13.1]%) as compared with the baseline levels ([44.3 +/- 14.0]%, [43.5 +/- 15.0]% and [42.4 +/- 14.9]%) (P < 0.05). The cure rate and total effectiveness rate were significantly higher in group B than in A (P < 0.05), but had no significant differences between either A and C or B and C (P > 0.05). CONCLUSION: Short-course kidney-invigorating therapy can significantly improve near-term semen quality in asthenozoospermic men with kidney asthenia, especially in those with kidney-yang deficiency, and it has no obvious adverse effects.