Treatment persistence of bictegravir/emtricitabine/tenofovir alafenamide and efavirenz + lamivudine + tenofovir disoproxil among HIV-1 patients newly starting treatment in Hunan Province in China.

BACKGROUND: Though bictegravir/emtricitabine/tenofovir (BIC/FTC/TAF) have been regulatory approved and included in the National Reimbursement Drug List in China, due to the affordability concern, generic version of efavirenz + lamivudine + tenofovir (EFV + 3TC + TDF) is still recommended as the first-line therapy in the clinical guideline and widely used in clinical practice. The aim of the study is to assess the persistence with first-line BIC/TAF/TAF and EFV + 3TC + TDF in newly treated HIV-1 patients in the real-world setting in Hunan Province in China. METHODS: A retrospective analysis of the medical records of HIV patients initiating first-line antiretroviral therapy in the First Hospital of Changsha in January 1st, 2021-July 31st, 2022 was conducted. Persistence was assessed as the number of days on the therapy from the index until treatment discontinuation or end of data availability. Kaplan-Meier Curves and Cox Proportional Hazard models were used to evaluate the discontinuation rates. Subgroup analysis was performed excluding BIC/FTC/TAF patients with treatment discontinuation due to economic reason, and EFV + 3TC + TDF patients with a viral load > 500,000 copies/mL. RESULTS: A total of 310 eligible patients were included in the study, with 244 and 66 patients in the BIC/FTC/TAF group and EFV + 3TC + TDF group, respectively. Compared with EFV + 3TC + TDF patients, BIC/FTC/TAF patients were older, more living in the capital city currently, and had significantly higher total cholesterol and low-density level (all p < 0.05). No significant difference was shown in the time to discontinuation between BIC/FTC/TAF patients and EFV + 3TC + TDF patients. After excluding BIC/FTC/TAF patients with treatment discontinuation due to economic reason, EFV + 3TC + TDF group were shown to have a significantly higher risk of discontinuation than BIC/FTC/TAF group (hazard ratio [HR] = 11.1, 95% confidence interval [CI] = 1.3-93.2). After further removing the EFV + 3TC + TDF patients with a viral load > 500,000 copies/mL, the analysis showed similar results (HR = 10.1, 95% CI = 1.2-84.1). 79.4% of the EFV + 3TC + TDF patients discontinued treatment due to clinical reasons, while 83.3% of the BIC/FTC/TAF patients discontinued treatment due to economic reasons. CONCLUSIONS: Compared with BIC/FTC/TAF, EFV + TDF + 3TC patients were significantly more likely to discontinue the first-line treatment in Hunan Province in China.

A single-center randomized controlled trial of local methylcobalamin injection for subacute herpetic neuralgia.

OBJECTIVE: This study explored the efficacy of local methylcobalamin injection in relieving pain and improving the quality of life among subjects with subacute herpetic neuralgia. DESIGN: A single-center, randomized controlled trial of local methylcobalamin injection was performed. SUBJECTS: Ninety-eight subjects (age, ≥ 50 years) with unilateral, dermatomal pain ≥ 4 related to herpes zoster on the torso lasting for 30 days after onset of rash were enrolled. METHODS: Subjects were randomized to receive local methylcobalamin injection (N = 33), oral methylcobalamin (N = 33), or subcutaneous 1.0% lidocaine injection (N = 32) for 4 weeks. Worst pain severity, global impression of change, continuous spontaneous pain, paroxysmal pain, allodynia, paresthesia, interference with activities of daily living, and quality of life were assessed after 28-day treatment period. RESULTS: Time per group interaction and group difference on overall pain at each follow-up point were statistically significant (P < 0.001) among groups. In the injected methylcobalamin group, the overall pain (P < 0.001), continuous spontaneous pain (P < 0.05), paroxysmal pain (P < 0.05), and allodynia (P < 0.05) revealed a significant effect at each follow-up point as compared with the other groups. Twenty subjects achieved pain reduction ≥ 50%, 24 perceived worst pain ≤ 3, 24 stopped using analgesics at end point; activities of daily living and quality of life improved significantly as compared with the other groups (P < 0.001). Although both of the other groups showed a significant response after the 14-day treatment (P < 0.001) compared with the baseline, oral methylcobalamin did not provide any significantly pain relief (P > 0.05). CONCLUSIONS: Local methylcobalamin injection was not only efficacious in relieving pain, but also appears to be tolerable and a potential choice of treatment for subacute herpetic neuralgia.

Toll-like receptor 9-dependent activation of myeloid dendritic cells by Deoxynucleic acids from Candida albicans.

The innate immune system of humans recognizes the human pathogenic fungus Candida albicans via sugar polymers present in the cell wall, such as mannan and beta-glucan. Here, we examined whether nucleic acids from C. albicans activate dendritic cells. C. albicans DNA induced interleukin-12p40 (IL-12p40) production and CD40 expression by murine bone marrow-derived myeloid dendritic cells (BM-DCs) in a dose-dependent manner. BM-DCs that lacked Toll-like receptor 4 (TLR4), TLR2, and dectin-1, which are pattern recognition receptors for fungal cell wall components, produced IL-12p40 at levels comparable to the levels produced by BM-DCs from wild-type mice, and DNA from a C. albicans pmr1Delta null mutant, which has a gross defect in mannosylation, retained the ability to activate BM-DCs. This stimulatory effect disappeared completely after DNase treatment. In contrast, RNase treatment increased production of the cytokine. A similar reduction in cytokine production was observed when BM-DCs from TLR9(-/-) and MyD88(-/-) mice were used. In a luciferase reporter assay, NF-kappaB activation was detected in TLR9-expressing HEK293T cells stimulated with C. albicans DNA. Confocal microscopic analysis showed similar localization of C. albicans DNA and CpG-oligodeoxynucleotide (CpG-ODN) in BM-DCs. Treatment of C. albicans DNA with methylase did not affect its ability to induce IL-12p40 synthesis, whereas the same treatment completely eliminated the ability of CpG-ODN to induce IL-12p40 synthesis. Finally, impaired clearance of this fungal pathogen was not found in the kidneys of TLR9(-/-) mice. These results suggested that C. albicans DNA activated BM-DCs through a TLR9-mediated signaling pathway using a mechanism independent of the unmethylated CpG motif.

Medical waste management in China: a case study of Nanjing.

Medical waste management is of great importance due to its infectious and hazardous nature that can cause undesirable effects on humans and the environment. The objective of this study was to analyze and evaluate the present status of medical waste management in the light of medical waste control regulations in Nanjing. A comprehensive inspection survey was conducted for 15 hospitals, 3 disposal companies and 200 patients. Field visits and a questionnaire survey method were implemented to collect information regarding different medical waste management aspects, including medical waste generation, segregation and collection, storage, training and education, transportation, disposal, and public awareness. The results indicated that the medical waste generation rate ranges from 0.5 to 0.8 kg/bed day with a weighted average of 0.68 kg/bed day. The segregated collection of various types of medical waste has been conducted in 73% of the hospitals, but 20% of the hospitals still use unqualified staff for medical waste collection, and 93.3% of the hospitals have temporary storage areas. Additionally, 93.3% of the hospitals have provided training for staff; however, only 20% of the hospitals have ongoing training and education. It was found that the centralized disposal system has been constructed based on incineration technology, and the disposal cost of medical waste is about 580 US$/ton. The results also suggested that there is not sufficient public understanding of medical waste management, and 77% of respondents think medical waste management is an important factor in selecting hospital services. The problematic areas of medical waste management in Nanjing are addressed by proposing some recommendations that will ensure that potential health and environmental risks of medical waste are minimized.

Small cell lung cancer starting with diabetes mellitus: Two case reports and literature review.

BACKGROUND: Small-cell lung cancer (SCLC) is a type of fatal tumor that is increasing in prevalence. While these are unpleasant facts to consider, it is vitally important to be informed, and it is important to catch the disease early. Typically, lung cancer does not show severe clinical symptoms in the early stage. Once lung cancer has progressed, patients might present with classical symptoms of respiratory system dysfunction. Thus, the prognosis of SCLC is closely related to the early diagnosis of the disease. Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is related to cancer occurrence, especially for SCLC with the presence of Cushing's syndrome, which is dependent on markedly elevated ACTH and cortisol levels. CASE SUMMARY: In the current report, we describe two middle-age patients who were originally diagnosed with diabetes mellitus with no classical symptoms of lung cancer. The patients were eventually diagnosed with SCLC, which was confirmed by bronchoscopic biopsy and histopathology. SCLC-associated diabetes was related to EAS, which was an endogenous ACTH-dependent form of Cushing's syndrome with elevated ACTH and cortisol levels. Multiple organ metastases were found in Patient 1, while Patient 2 retained good health at 2 years follow-up. EAS symptoms including thyroid dysfunction, hypercortisolism and glucose intolerance were all resolved after anticancer treatment. CONCLUSION: In conclusion, SCLC might start with diabetes mellitus and increased cortisol and hypokalemia or other EAS symptoms. These complex clinical features were the most significant factors to deteriorate a patient's condition. Early diagnosis and treatment from clinicians were essential for the anti-cancer treatment for patients with SCLC.

[Study on using laser Doppler flowmetry to determine the pulpal blood flow of immature maxillary incisors].

OBJECTIVE: This study aimed to evaluate the influence of age on the pulpal blood flow (PBF) of immature maxillary incisors of maxillary incisors, which was detected by laser Doppler flowmetry (LDF). METHODS: LDF was used to detect the PBF value of maxillary central and lateral incisors of a child group (aged 7-13 years old) and a positive control group (aged 18-25 years old), as well as the central incisor of a negative control group (the central incisor had undergone endodontic treatment). We then compared the features of PBF in all groups with the influence of gender and position on PBF. The relation of maxillary central incisor and lateral incisor, age, and maxillary incisor were analyzed. RESULTS: The PBF value of the negative control group was (2.08±0.73) PU. The PBF values in the positive control group in central and lateral incisors were (8.49±1.88) and (7.52±1.82) PU. In the child group, PBF values in central incisors and lateral incisors were (11.31±2.21) and (12.18±2.65) PU. A significant difference was observed between different groups and between central and lateral incisors (P<0.01). Meanwhile, no significant difference was found in the PBF values between the right and the left parts in both males and females (P>0.05). Age had a linearity negative correlation with the PBF value of incisors in the child group. A linear negative correlation existed between the age and PBF of central and lateral incisors (r=-0.310 and r=-0.510, respectively) (P<
0.01). CONCLUSIONS: PBF value decreased with increased age in children aged 7-13 years old.

Prostate-specific IL-6 transgene autonomously induce prostate neoplasm through amplifying inflammation in the prostate and peri-prostatic adipose tissue.

BACKGROUND: The causative role of the pro-inflammatory cytokine IL-6 in prostate cancer progression has been well established at molecular level. However, whether and how IL-6 may play a role in prostate cancer risk and development is not well defined. One limitation factor to acquiring this knowledge is the lack of appropriate animal models. METHODS: We generated a novel line of prostate-specific IL-6 transgenic mouse model. We compared the prostate pathology, tumorigenic signaling components, and prostate tumor microenvironment of the IL-6 transgenic mice with wild type littermates. RESULTS: With this model, we demonstrate that IL-6 induces prostate neoplasm autonomously. We further demonstrate that transgenic expression of IL-6 in the prostate activates oncogenic pathways, induces autocrine IL-6 secretion and steadily-state of STAT3 activation in the prostate tissue, upregulates paracrine insulin-like growth factor (IGF) signaling axis, reprograms prostate oncogenic gene expression, and more intriguingly, amplifies inflammation in the prostate and peri-prostatic adipose tissue. CONCLUSIONS: The pro-inflammatory IL-6 is autonomous oncogene for the prostate. IL-6 induces prostate oncogenesis through amplifying local inflammation. We also presented a valuable animal model to study inflammation and prostate cancer development.

Thiamine, cobalamin, locally injected alone or combination for herpetic itching: a single-center randomized controlled trial.

OBJECTIVES: The present study was designed to explore the efficacy of locally injected thiamine or cobalamin in relieving itch or pain and improving the daily living activities among patients with herpetic itching. METHODS: Eighty eligible patients with herpetic itching with a worst itching score of ≥ 4 were randomized to receive locally injected thiamine (B1 group), cobalamin (B12 group), lidocaine (LD group), or combination of thiamine and cobalamin (COB group) for 4 weeks. The treatment efficacy was assessed based on the patients' pruritus and pain severity, global impression of change, and activities of daily living and quality of life. RESULTS: After 7 days, thiamine yielded a significant itch relief, cobalamin yielded a significant pain relief, and their combination significantly relieved both pain and itch; which all continued till the endpoint (all Ps<0.001). However, lidocaine did not provide significant itch or pain relief than the other groups. Sixteen patients in the thiamine group achieved ≥ 30% itch reduction; 18 patients in the cobalamin group obtained ≥ 30% pain reduction; and 18 patients achieved ≥ 30% itch reduction and 19 patients obtained ≥ 30% pain reduction in the combination group. The activities of daily living and quality of life data at the endpoint were consistent with a significant benefit in the thiamine (P<0.05), cobalamin, and combination groups (both Ps<0.001). DISCUSSION: Locally injected thiamine had a significant antipruritic effect, cobalamin had an analgesic effect, and their combination had the dual effect with no obvious synergies. This intervention was efficacious, tolerable, and safe for herpetic itching.

Adjuvant effect of CpG-oligodeoxynucleotide in anti-fungal chemotherapy against fatal infection with Cryptococcus neoformans in mice.

Cryptococcal meningoencephalitis is a life-threatening infectious disease in immunocompromised patients. Unmethylated CpG-oligodeoxynucleotides (CpG-ODN) protects hosts in a mouse model. In the present study, we tested the adjuvant effect of CpG-ODN in anti-fungal chemotherapy. Administration of either fluconazole (FLCZ) or CpG-ODN was effective in extending survival, accelerating clearance of fungi and preventing disseminated infection. Combination of both agents provided more beneficial effect than either agent alone. Cytokine balance in the infected lungs was biased to Th1-type response by CpGODN, while FLCZ did not further promote. These results suggest that CpG-ODN is a promising adjuvant in chemotherapy against this infection.