Composite Interventions on Outcomes of Severely and Critically Ill Patients with COVID-19 in Shanghai, China.

Background: The sixty-day effects of initial composite interventions for the treatment of severely and critically ill patients with COVID-19 are not fully assessed. Methods: Using a Bayesian piecewise exponential model, we analyzed the 60-day mortality, health-related quality of life (HRQoL), and disability in 1082 severely and critically ill patients with COVID-19 between 8 December 2022 and 9 February 2023 in Shanghai, China. The final 60-day follow-up was completed on 10 April 2023. Results: Among 1082 patients (mean age, 78.0 years, 421 [38.9%] women), 139 patients (12.9%) died within 60 days. Azvudine had a 99.8% probability of improving 2-month survival (adjusted HR, 0.44 [95% credible interval, 0.24-0.79]), and Paxlovid had a 91.9% probability of improving 2-month survival (adjusted HR, 0.71 [95% credible interval, 0.44-1.14]) compared with the control. IL-6 receptor antagonist, baricitinib and a-thymosin each had a high probability of benefit (99.5%, 99.4%, and 97.5%, respectively) compared to their controls, while the probability of trail-defined statistical futility (HR > 0.83) was high for therapeutic anticoagulation (99.8%; HR, 1.64 [95% CrI, 1.06-2.50]) and glucocorticoid (91.4%; HR, 1.20 [95% CrI, 0.71-2.16]). Paxlovid, Azvudine, and therapeutic anticoagulation showed a significant reduction in disability (p < 0.05) Conclusions: Among severely and critically ill patients with COVID-19 who received 1 or more therapeutic interventions, treatment with Azvudine had a high probability of improved 60-day mortality compared with the control, indicating its potential in a resource-limited scenario. Treatment with an IL-6 receptor antagonist, baricitinib, and a-thymosin also had high probabilities of benefit in improving 2-month survival, among which a-thymosin could improve HRQoL. Treatment with Paxlovid, Azvudine, and therapeutic anticoagulation could significantly reduce disability at day 60.

Clinical Progression and Outcome of Hospitalized Patients Infected with SARS-CoV-2 Omicron Variant in Shanghai, China.

BACKGROUND: Studies on the Omicron variant infection have generally been restricted to descriptions of its initial clinical and epidemiological characteristics. We investigated the timeline-related progression and clinical outcome in hospitalized individuals with the Omicron variant. METHODS: We conducted a retrospective, single-centered study including 226 laboratory-confirmed cases with the Omicron variant between 6 April and 11 May 2022 in Shanghai, China. The final date of follow-up was 30 May 2022. RESULTS: Among 226 enrolled patients, the median age was 52 years, and 118 (52.2%) were female. The duration from onset of symptoms to hospitalization was 3 days (interquartile range (IQR): 2-4 days) for symptomatic patients. Cough occurred in 168 patients (74.3%). The median interval to negative reverse-transcriptase PCR tests of nasopharynx swab was 10 days ((IQR): 8-13 days). No radiographic progressions were found in 196 patients on the 7th day after onset of symptoms. The median duration of fever in all participants was 5 days (IQR: 4-6 days). The median PCR conversion time of Paxlovid-treated patients was 8 days (IQR: 7-10 days) compared with that of a traditional Chinese herb medicine lianhuaqingwen (10 days, IQR: 8-13 days) (p = 0.00056). Booster vaccination can significantly decrease the severity of Omicron infection when compared with unvaccinated patients (p = 0.009). In multivariate logistic analysis, erythrocyte sedimentation rate (ESR) (OR = 1.05) was independently related to the severity of the infection. CONCLUSIONS: The majority of clinical symptoms of Omicron infection were not severe. Early and aggressive administration of Paxlovid can significantly reduce the PCR conversion time. Booster vaccination should also be highly recommended in the population over 14 years old.

CD45: a critical regulator in immune cells to predict severe and non-severe COVID-19 patients.

The ongoing outbreak of COVID-19 has been announced by the World Health Organization as a worldwide public health emergency. The aim of this study was to distinguish between severe and non-severe patients in early diagnosis. The results showed that the mortality of COVID-19 patients increased accompanied by age. Host factors CRP, IL-1ß, hs-CRP, IL-8, and IL-6 levels in severe pneumonia patients were higher than in non-severe patients. CD3, CD8, and CD45 counts were decreased in COVID-19 patients. The results of this study suggest that the K-values of CD45 might be useful in distinguishing between severe and non-severe cases. The cut-off value for CD45 was -94.33. The K-values for CD45 in non-severe case were above the cut-off values, indicating a 100% prediction success rate for severe and non-severe cases following SARS-CoV-2 infection. The results confirmed that immune system dysfunction is a potential cause of mortality following COVID-19 infection, particularly for the elderly. CD45 deficiency dysfunction the naïve and memory T lymphocytes which may affects the long-term effectiveness of COVID-19 vaccines. K-values of CD45 might be useful in distinguishing between severe and non-severe cases in the early infection. May be CD45 could increase the diagnostic sensitivity.

Activation of Notch pathway is linked with epithelial-mesenchymal transition in prostate cancer cells.

Notch signaling has been reported to play an essential role in tumorigenesis. Several studies have suggested that Notch receptors could be oncoproteins or tumor suppressors in different types of human cancers. Emerging evidence has suggested that Notch pathway regulates cell growth, apoptosis, cell cycle, and metastasis. In the current study, we explore whether Notch-1 could regulate the cell invasion and migration as well as EMT (epithelial-mesenchymal transition) in prostate cancer cells. We found that overexpression of Notch-1 enhanced cell migration and invasion in PC-3 cells. However, downregulation of Notch-1 retarded cell migration and invasion in prostate cancer cells. Importantly, we observed that overexpression of Notch-1 led to EMT in PC-3 cells. Notably, we found that EMT-type cells are associated with EMT markers change and cancer stem cell phenotype. Taken together, we concluded that downregulation of Notch-1 could be a promising approach for inhibition of invasion in prostate cancer cells, which could be useful for the treatment of metastatic prostate cancer.

[Desmoplastic small round-cell tumor of the paratesticular region: a case report and review of the literature].

OBJECTIVE: To investigate the clinical and pathological features of paratesticular desmoplastic small round cell tumor (DSRCT), and to improve the diagnosis and treatment of the disease. METHODS: One case of paratesticular DSRCT was studied retrospectively and a considerable amount of related literature from Medline and Chinese journals reviewed. The patient was a 27-year-old man presenting with a painless testicular mass in the left hemiscrotum. On physical examination, a cystic mass was palpable while the testis was not in the left hemiscrotum. RESULTS: During the operation the paratesticular area was found full of multiple nodular tumor masses of various sizes ranging from 0.5 cm to 1.5 cm in diameter. Pathological examination showed the characteristic histological pattern of nests of small undifferentiated cells embedded in a dense fibrous stroma. The tumor presented an immunohistochemical feature of epithelial, mesenchymal as well as neural multidirectional differentiation. Following testicular tumor orchiectomy, chemotherapy was performed with DDP, VP16, ifosfamide and EPI. Three years follow-up found no tumor recurrence. CONCLUSION: Desmoplastic small round cell tumor has a specific clinicopathologic stigmata, usually occurring in young males, for which surgical resection with chemotherapy is the treatment of choice. DSRCT located in the paratesticular region may have a better prognosis than its more frequently abdominal counterpart.

[IIEF-5 cannot be used as a tool for differential diagnosis of vasculogenic erectile dysfunction].

OBJECTIVE: To evaluate the 5-item version of the international index of erectile function (IIEF-5) as a method to differentiate the causes of vasculogenic erectile dysfunction (ED). METHODS: In all, 103 ED patients (mean age 46.8 +/- 18.7) were reviewed by IIEF-5. Penile blood flow was also assessed in each patient after an intracavernosal injection (ICI) and audio-visual sex stimulation by duplex Doppler ultrasonography. The 99mTc-(113m)In dual radioisotope test was performed to confirm specific vascular causes in the vasculogenic ED cases. Kruskal-Wallis TEST was employed to compare the scores of IIEF-5 with the results of ICI, duplex Doppler ultrasonography and the 99mTC-(113m)In dual radioisotope test. RESULTS: Of the total number of ED cases, 37 (37/103, 35.9%) were nonvasculogenic, 18 (18/103, 17.5%) arteriogenic, 35 (35/103, 34.0%) venogenic and 13 (13/103, 12.6%) combined vasculogenic. There was no significant difference in the IIEF-5 scores either between the vasculogenic group and the non-vasculogenic one (P = 0.253) or among different groups of the vasculogenic ED patients. CONCLUSION: IIEF-5 cannot be used as a tool for differential diagnosis of vasculogenic ED, or to compare its specific vascular causes, nor can the scores of IIEF-5 reflect penile vascular conditions.

[Survey on reproductive health status of Shanghai college students].

OBJECTIVE: To explore reproductive health condition of college students in Shanghai and provide scientific basis for reproductive health education. METHODS: From July 2004 to March 2005, 1192 college students (majors including medicine, science and engineering, arts and culture; 618 medical students and 549 non-medical; 555 male and 612 female) from seven time-day colleges in Shanghai were investigated with a reproductive health questionnaire involving sex. The questionnaire was constituted by 72 topics, involving the need of education, sex attitude, sex videos, sex hygiene knowledge and sexually transmitted diseases (STDs), etc. RESULTS: 39.33% (459/1167) students thought they had accepted formal sex education; 49.19% (574/1167) students chose lecture as the favorite way; 41.90% (489/1167) students thought the reproductive health education would not increase the incidence of premarital sexual behavior; 64.10% (748/1167) students thought it was necessary to give college students reproductive health instructions and knowledge. On the other hand, we found 45.05% (250/555) boys and 27.45% (168/612) girls could accept the premarital sexual behaviors; 35.32% (196/555) boys and 39.38% (241/612) girls could accept premarital pregnancy; 44.39% (518/1167) students could calculate the safe period accurately; 71.38% (833/1167) students knew emergency contraception measures; 57.67% (673/1167) students knew how to and when to use condoms; To our surprise, only 2.19% (12/549) non-medical students and 12.14% (75/618) medical students knew exactly the whole 4 sexually transmitted diseases that needed to be essentially prevented in China. CONCLUSION: At present, the reproductive health condition of college students in Shanghai is sophisticated. Much more education on sex safety, self-protection skills and acquired immunodeficiency syndrome (AIDS) knowledge, etc should be reinforced.

[Comparison between sildenafil plus sertraline and sertraline alone in the treatment of premature ejaculation].

OBJECTIVE: To compare the efficacy and safety of sildenafil plus sertraline with those of sertraline alone in the treatment of premature ejaculation (PE). METHODS: Seventy-two patients with PE but without any obvious organic cause were enrolled in this study. They were randomly divided into Groups A and B of equal number. Group A received 50 mg sertraline daily 4 to 6 hours before planned sexual activity for 12 weeks, and Group B were given 50 mg sertraline daily plus 50 mg sildenafil as needed, 1 hour before planned sexual activity, for 12 weeks. Before and after the treatment, the mean intravaginal ejaculation latency time, the intercourse satisfaction, the mean number of coituses per week and the drug-related side effects were evaluated. RESULTS: The mean intravaginal ejaculatory latency time was (0.59 +/- 0.12), (3.9 +/- 0.15) minutes (P < 0.001) at baseline and post-treatment in Group A, and (0.56 +/- 0.11), (5.6 +/- 0.12) minutes (P < 0.001) in Group B, improved in both of the 2 groups, but more significantly in Group B (P < 0.05). Before and after the treatment, the mean intercourse satisfaction domain values of the IIEF were (8.9 +/- 1.2), (10.8 +/- 1.1) (P < 0.05) and (8.8 +/- 1.1), (13.8 +/- 1.3) (P < 0.001) in Groups A and B, respectively, significantly greater in Group B than in Group A (P < 0.05) after the treatment; the mean numbers of coituses per week in Groups A and B were (0.9 +/- 0.2), (1.9 +/- 0.3) (P < 0.05) and (1.0 +/- 0.2), (2.7 +/- 0.2) (P <0.001) respectively, significantly larger in Group B (P<0.05) after the treatment. As for the side effects, there was a higher rate of headaches (P < 0.01) and flushing episodes (P < 0.001) in Group B than in Group A. CONCLUSION: Sertraline combined with sildenafil can produce significantly better results than sertraline alone in patients with premature ejaculation. However, the combined treatment is associated with a slight increase in the drug-related side effects.

[Effects of growth hormone supplementation on erectile function and expression of nNOS in aging rats].

OBJECTIVE: To explore the effects of growth hormone( GH) supplementation on erectile function and expression of nNOS in the intracavernosal nerves in aging rats. METHODS: Twenty male Sprague-Dawley rats aged 18 months were randomly divided into Groups A and B, and ten 2-month-old male Sprague-Dawley rats included in Group C. 1 U/(kg x d) GH was given to Group A, and the same volume of saline to Groups B and C. After 8 weeks of treatment, evaluation was made of the erections induced by apomorphine (APO), maximal intracavernous pressure (ICP) induced by intracavernous papaverine injection and expression of nNOS in the intracavernosal nerves by streptavidin-peroxidase immunohistochemical techniques. RESULTS: After 8 weeks of treatment, the erection frequency, maximal ICP and expression of nNOS in the intracavernosal nerves of the rats in Groups A and C were significantly higher than those in Group B (P < 0.05 or P < 0.01). CONCLUSION: Growth hormone supplementation can improve the erectile function of aging rats, which may be attributed to the increase in the expression of nNOS in the intracavernosal nerves.

[Applied study on small-dose growth hormone supplement for aging-related symptom complex].

OBJECTIVE: To assess the response of aging-related symptom complex to small-dose supplement of growth hormone. METHODS: Thirty patients, aged 42 to 77, with aging-related symptom complex and normal serum testosterone were studied. Each subject received growth hormone at the dosage of 0.04 U/kg, 3 times/week for six months. Before and after treatment, body weight, grip strength, abdomen circumference, IPSS, uroflow rate, prostate volume, serum testosterone, cholesterol, triglyceride, PSA, IGF-1, glucose and side effects were determined in every case. Self Rating Scale used by Bosphorus university was adopted. RESULTS: After the treatment, the rating scores were significantly improved, grip strength and serum level of IGF-1 increased, and abdomen circumference and serum cholesterol decreased. Whereas, IPSS, uroflow rate, prostate volume, serum testosterone, triglyceride, PSA, glucose and body weight were not significantly changed. CONCLUSION: Six months treatment with small-dose growth hormone can improve aging-related symptom complex with little adverse effect.

[The effect of endothelin receptor in androgen-independent prostate cancer].

OBJECTIVE: To study the expression of ET receptor and the apoptosis after intervened with ET receptor antagonist in androgen-independent prostate cancer. METHODS: PC3, an androgen-independent prostate cancer cell line, was used. The expression of ETA and ETB receptor in PC3 was measured through RT-PCR. After intervened with selective ETA and ETB receptor antagonist, the apoptosis in PC3 was studied through flow cytometry and electron microscope. RESULTS: Clear signal was obtained in PC3 for ETA receptor mRNA transcript, while the signal for ETB receptor mRNA transcript was very weak. The expression of ETA receptor mRNA was obviously reduced and the apoptosis of PC3 cell was observed after intervened with selective ETA receptor antagonist. There was no change after intervened with selective ETB receptor antagonist. CONCLUSION: ET-1 exerts its effects through the ETA receptor subtype and ETB receptor is silenced in PC3. The expression of ETA was reduced and the apoptosis was observed in PC3 when ETA receptor was blocked. It was dose-dependent.

[Culture and identification of human and rabbit corpus cavernosum smooth muscle cells].

OBJECTIVE: To investigate an effective method to produce large numbers of pure corporal smooth muscle cells in vitro according to the requirement of study. METHODS: In this study, we used the primary tissue culture technique to isolate and culture the corpus cavernosum smooth muscle cells (CCSM) from human males with normal erectile function and New Zealand white rabbits. The cells were identified in regard to morphological and growing characteristics via immunohistochemical methods (including alpha-smooth muscle actin, desmin, myocin and factor VIII related antigen), special dye techniques (including Masson and Van Gieson) and transmission electron microscope. RESULTS: CCSM were isolated and cultured successfully with high purity. Morphologically, the cells were spindle shaped and grow on top of each other, resembling a "hill and valley" in appearance. When characterized in immunohistochemistry, the cells were stained with alpha-smooth muscle actin, desmin and myocin, but not with anti-factor VIII, an endothelial marker. CONCLUSION: The CCSM, which can be isolated and cultured successfully, may be used for further studying their biological function. The CCSM cultured in vitro was proved to be useful to evaluate and investigate the effect of some new medicine for penile erection. There is also a clinical and theoretical significance in further studying the experimental mechanisms of erectile dysfunction.