Short-term Therapeutic Effects Research Articles

Pathogenesis or a response to lithium? A novel perspective for mitochondrial mass fluctuation of naïve T cells in patients with bipolar disorder

BackgroundImmune imbalances are associated with the pathogenesis and pharmacological efficacy of bipolar disorder (BD). The underlying mechanisms remain largely obscure but may involve immunometabolic dysfunctions of T-lymphocytes. MethodsWe investigated if inflammatory cytokines and the immunometabolic function of T-lymphocytes, including frequencies of subsets, mitochondrial mass (MM), and low mitochondrial membrane potential (MMPLow) differed between BD patients (n = 47) and healthy controls (HC, n = 43). During lithium treatment of hospitalized patients (n = 33), the association between weekly T-lymphocyte immune metabolism and clinical symptoms was analyzed, and preliminary explorations on possible mechanisms were conducted. ResultsIn comparison to HC, BD patients predominantly showed a trend toward CD4+ naïve T (Tn) activation and exhibited mitochondrial metabolic disturbances such as decreased MM and increased MMPLow. Lower CD4+ Tn-MM correlated with elevated IL-6, IL-8, and decreased IL-17 A in BD patients. With lithium treatment effective, MM of CD4+ T/Tn was negatively correlated with depression score HAMD. When lithium intolerance was present, MM of CD4+ T/Tn was positively correlated with depression score HAMD and mania score BRMS. Lithium does not mediate through the inositol depletion hypothesis, but the mRNA level of IMPA2 in peripheral blood is associated with mitochondrial function in CD8+ T cells. LimitationsThe cross-sectional design and short-term follow-up meant that we could not directly examine the causality of BD and immune dysregulation. ConclusionThe altered metabolism of CD4+ Tn was strongly associated with remodeling of the inflammatory landscape in BD patients and can also be used to reflect the short-term therapeutic effects of lithium.

Comparing the short-term clinical outcomes and therapeutic effects of different colectomies in patients with refractory slow-transit constipation in eastern countries: a network meta-analysis.

Surgical treatment has been widely used in patients with refractory slow transit constipation (RSTC). The aim of this network meta-analysis (NMA) was to compare the effects of different colectomies on short-term postoperative complications and quality of life in patients with RSTC. Electronic literature searches were performed in the PubMed, Web of Science, EMBASE, WANFANG DATA, and Cochrane Central Register of controlled trials databases and were searched up to December 2022. Selected to compare the short-term clinical outcomes and quality of life of the treatment of RSTC. A random-effects Bayesian NMA was conducted to assess and rank the effectiveness of different surgical modalities. This study included a total of six non-randomized controlled trials involving 336 subjects. It was found that subtotal colectomy with cecorectal anastomosis (CRA) demonstrated superior effectiveness in several aspects, including reduced hospital stay (MD 0.06; 95% CI [0.02, 1.96]), shorter operative time (MD 4.75; 95% CI [0.28, 14.07]), lower constipation index (MD 0.61; 95% CI [0.04, 1.71]), improved quality of life (MD 4.42; 95% CI [0.48, 4.42]). Additionally, in terms of short-term clinical outcomes, subtotal colectomy with ileosigmoidal anastomosis (SC-ISA) procedure ranked the highest in reducing small bowel obstruction (OR 0.24; 95% CI [0.02, 0.49]), alleviating abdominal pain (OR 0.53; 95% CI [0.05, 1.14]), minimizing abdominal distension (OR 0.33; 95% CI [0.02, 0.65]), and reducing incision infection rates (OR 0.17; 95% CI [0.01, 0.33]). Furthermore, SC-ISA ranked as the best approach in terms of patient satisfaction (OR 0.66; 95% CI [0.02, 1.46]). Based on our research findings, we recommend that CRA be considered as the preferred treatment approach for patients diagnosed with RSTC.

The mitochondrial genome-encoded peptide MOTS-c interacts with Bcl-2 to alleviate nonalcoholic steatohepatitis progression

Nonalcoholic steatohepatitis (NASH) is a metabolism-associated fatty liver disease with accumulated mitochondrial stress, and targeting mitochondrial function is a potential therapy. The mitochondrial genome-encoded bioactive peptide MOTS-c plays broad physiological roles, but its effectiveness and direct targets in NASH treatment are still unclear. Here, we show that long-term preventive and short-term therapeutic effects of MOTS-c treatments alleviate NASH-diet-induced liver steatosis, cellular apoptosis, inflammation, and fibrosis. Mitochondrial oxidative capacity and metabolites profiling analysis show that MOTS-c significantly reverses NASH-induced mitochondrial metabolic deficiency. Moreover, we identify that MOTS-c directly interacts with the BH3 domain of antiapoptotic B cell lymphoma-2 (Bcl-2), increases Bcl-2 protein stability, and suppresses Bcl-2 ubiquitination. By using a Bcl-2 inhibitor or adeno-associated virus (AAV)-mediated Bcl-2 knockdown, we further confirm that MOTS-c improves NASH-induced mitochondrial dysfunction, inflammation, and fibrosis, which are dependent on Bcl-2 function. Therefore, our findings show that MOTS-c is a potential therapeutic agent to inhibit the progression of NASH.

Short-term and long-term efficacy in robot-assisted treatment for mid and low rectal cancer: a systematic review and meta-analysis

ObjectiveThis study aims to conduct a meta-analysis to evaluate the short-term and long-term therapeutic effects of robot-assisted laparoscopic treatment in patients with mid and low rectal cancer.MethodsA comprehensive search strategy was employed to retrieve relevant literature from PubMed, NCBI, Medline, and Springer databases, spanning the database inception until August 2023. The focus of this systematic review was on controlled studies that compared the treatment outcomes of robot-assisted (Rob) and conventional laparoscopy (Lap) in the context of mid and low rectal cancer. Data extraction and literature review were meticulously conducted by two independent researchers (HMW and RKG). The synthesized data underwent rigorous analysis utilizing RevMan 5.4 software, adhering to established methodological standards in systematic reviews. The primary outcomes encompass perioperative outcomes and oncological outcomes. Secondary outcomes include long-term outcomes.ResultA total of 11 studies involving 2239 patients with mid and low rectal cancer were included (3 RCTs and 8 NRCTs); the Rob group consisted of 1111 cases, while the Lap group included 1128 cases. The Rob group exhibited less intraoperative bleeding (MD = −40.01, 95% CI: −57.61 to −22.42, P < 0.00001), a lower conversion rate to open surgery (OR = 0.27, 95% CI: 0.09 to 0.82, P = 0.02), a higher number of harvested lymph nodes (MD = 1.97, 95% CI: 0.77 to 3.18, P = 0.001), and a lower CRM positive rate (OR = 0.46, 95% CI: 0.23 to 0.95, P = 0.04). Additionally, the Rob group had lower postoperative morbidity rate (OR = 0.66, 95% CI: 0.53 to 0.82, P < 0.0001) and a lower occurrence rate of complications with Clavien–Dindo grade ≥ 3 (OR = 0.60, 95% CI: 0.39 to 0.90, P = 0.02). Further subgroup analysis revealed a lower anastomotic leakage rate (OR = 0.66, 95% CI: 0.45 to 0.97, P = 0.04). No significant differences were observed between the two groups in the analysis of operation time (P = 0.42), occurrence rates of protective stoma (P = 0.81), PRM (P = 0.92), and DRM (P = 0.23), time to flatus (P = 0.18), time to liquid diet (P = 0.65), total hospital stay (P = 0.35), 3-year overall survival rate (P = 0.67), and 3-year disease-free survival rate (P = 0.42).ConclusionRobot-assisted laparoscopic treatment for mid and low rectal cancer yields favorable outcomes, demonstrating both efficacy and safety. In comparison to conventional laparoscopy, patients experience reduced intraoperative bleeding and a lower incidence of complications. Notably, the method achieves comparable short-term and long-term treatment results to those of conventional laparoscopic surgery, thus justifying its consideration for widespread clinical application.

Therapeutic efficacy of rare earth carbonate with chemoradiotherapy in late-stage non-small cell lung cancer: a cohort prospective study.

To compare the therapeutic effects and adverse reactions of sterilizing rare earth carbonate combined with concurrent chemoradiotherapy and simple concurrent chemoradiotherapy in the treatment of late-stage non-small cell lung cancer (NSCLC), and to analyze the reasons for the differences. A total of 817 patients with pathologically diagnosed late-stage NSCLC from June 1, 2021 to December 30, 2022, in the affiliated hospital of Kunming University of Science and Technology, were selected. They were randomly divided into a control group of 394 people and an experimental group of 423 people. The control group was given concurrent chemoradiotherapy (cisplatin + etoposide), while the experimental group simultaneously took a low dose of sterilized rare earth carbonate (0.05mg/Kg). The χ² test and Fisher's test were used to compare the clinical pathological features, objective response rate (ORR), ECOG score, and adverse reactions of the two groups of patients, while survival analysis was used to compare the progression-free survival (PFS) of the two groups. Cox regression analysis was used to test factors related to prognosis. The differences in clinical pathological features between the two groups of patients were not statistically significant, with all P>0.05. The ORR of the control group was 45.18% (178/394), and the experimental group was 89.83% (380/423), with a statistically significant difference (P=0.001). After treatment, the ECOG score of the experimental group was lower than that of the control group, P<0.001. The adverse reaction grading of patients in both groups was below level 3 after treatment, and no treatment-related fatalities occurred. The risk of pulmonary infection and bone marrow suppression in the experimental group was lower than that in the control group. In late-stage NSCLC patients, compared with simple concurrent chemoradiotherapy, the combination of concurrent chemoradiotherapy and sterilizing rare earth carbonate can significantly improve the short-term therapeutic effect and prognosis of patients, with good safety.

Ceria-vesicle nanohybrid therapeutic for modulation of innate and adaptive immunity in a collagen-induced arthritis model.

Commencing with the breakdown of immune tolerance, multiple pathogenic factors, including synovial inflammation and harmful cytokines, are conjointly involved in the progression of rheumatoid arthritis. Intervening to mitigate some of these factors can bring a short-term therapeutic effect, but other unresolved factors will continue to aggravate the disease. Here we developed a ceria nanoparticle-immobilized mesenchymal stem cell nanovesicle hybrid system to address multiple factors in rheumatoid arthritis. Each component of this nanohybrid works individually and also synergistically, resulting in comprehensive treatment. Alleviation of inflammation and modulation of the tissue environment into an immunotolerant-favourable state are combined to recover the immune system by bridging innate and adaptive immunity. The therapy is shown to successfully treat and prevent rheumatoid arthritis by relieving the main symptoms and also by restoring the immune system through the induction of regulatory T cells in a mouse model of collagen-induced arthritis.

Short-term beneficial effects of human dental pulp stem cells and their secretome in a rat model of mild ischemic stroke

Although cell therapy has been applied in regenerative medicine for decades, recent years have seen greatly increased attention being given to the use of stem cell-based derivatives such as cell-free secretome. Dental pulp stem cells (DPSCs) are widely available, easily accessible, and have high neuroprotective and angiogenic properties. In addition, DPSC-derived secretome contains a rich mixture of trophic factors. The current investigation evaluated the short-term therapeutic effects of human DPSCs and their secretome in a rat model of mild ischemic stroke.Mild ischemic stroke was induced by 30 min middle cerebral artery occlusion, and hDPSCs or their secretome was administered intra-arterially and intranasally. Neurological function, infarct size, spatial working memory, and relative expression of seven target genes in two categories of neurotrophic and angiogenic factors were assessed three days after stroke. In the short-term, all treatments reduced the severity of neurological and histological deficits caused by ischemic stroke. Moreover, transient middle cerebral artery occlusion led to the striatal and cortical over-expression of BDNF, NT-3, and angiogenin, while NGF and VEGF expression was reduced. Almost all interventions were able to modulate the expression of target genes after stroke. The obtained data revealed that single intra-arterial administration of hDPSCs or their secretome, single intranasal transplantation of hDPSCs, or repeated intranasal administration of hDPSC-derived secretome was able to ameliorate the devastating effects of a mild stroke, at least in the short-term.

Short-Term Efficacy and Safety of the Direct Triamcinolone Application Using Absorbable Nasal Packing in Anosmic Patients

Background and Objectives The most common treatment for olfactory dysfunction is the use of glucocorticoids. However, using systemic glucocorticoids is limited due to systemic side effects, and topical glucocorticoids are less effective than systemic glucocorticoids. The aim of this study is to evaluate short-term therapeutic effects of direct triamcinolone (TA) application using absorbable nasal packing material on anosmia patients.Subjects and Method This was a retrospective study that evaluated patients who were diagnosed with anosmia and treated with oral prednisolone (PD) pulse therapy or 2 times of a 20 mg dose of TA impregnated absorbable nasal packing in both olfactory clefts. Information of the demographic features, the self-reporting olfaction scores (visual analogue scale [VAS], 0-10), and the threshold, discrimination, identification (TDI) scores of Korean version of the Sniffin’ stick test II were collected and analyzed.Results The data of 72 patients were analyzed in this study: 30 patients were treated with TA nasal packing, and 42 patients with oral PD. In both group, VAS and TDI scores were significantly improved 2 weeks after treatment. The rate of significant olfactory improvement of TA nasal packing group was higher than oral PD group (60.0% vs. 47.6%), but there was no statistically significant difference (&lt;i&gt;p&lt;/i&gt;=0.300). There was no significant systemic adverse effect after TA nasal packing treatments.Conclusion Direct TA application using absorbable nasal packing is a possible treatment option in anosmic patients.

Active surveillance versus immediate surgery: A comparison of clinical and quality of life outcomes among patients with highly suspicious thyroid nodules 1 cm or smaller in China

IntroductionActive surveillance (AS) is considered an alternative to immediate surgery (IS) for low-risk papillary thyroid microcarcinoma (PTMC) patients. However, it is difficult to decide between AS and IS due to limited evidence regarding risks and benefits for patients in China. MethodsThis study prospectively enrolled 485 patients with highly suspicious thyroid nodules </= 1 cm who chose AS and 331 patients who underwent IS during the same period. The oncological outcomes, adverse events and quality of life, were compared between the two groups. ResultsThe oncological outcomes of the IS and AS groups were similarly excellent. The IS group had significantly higher rates of temporary vocal cord paralysis (VCP) and temporary hypoparathyroidism than the AS group (2.7% vs. 0.2%, p = 0.002; 13.6% vs.1.9%, p < 0.001, respectively). The IS group had significantly more patients on hormone replacement therapy (98.4% vs. 10.9%, p < 0.001) and a significantly higher incidence of neck scarring (94.3% vs. 9.1%, p < 0.001) compared to the AS group. In the early stages, the quality of life questionnaire showed significant differences with respect to three items: voice, throat/mouth, and surgical scarring, with more complaints in the IS group. However, one year or more after surgery, the main complaint was surgical scarring. ConclusionIn China, AS can achieve similar short-term therapeutic effects as IS. As this approach can reduce the occurrence of unfavorable events, achieve better quality of life, it is a feasible option for patients with highly suspicious thyroid nodules.

Protective effect of anti-idiopathic pulmonary fibrosis drug Pirfenidone and Sufenidone (SC1011) on pulmonary injury induced by tuberculosis in a mouse tuberculosis model

Objective: To evaluate the protective effect of anti-idiopathic pulmonary fibrosis (IPF) marketed drug Pirfenidone and its clinical drug Sufenidone (SC1011) against lung injury in a mouse tuberculosis model. Methods: C57BL/6 mouse model of tuberculosis was established. A total of 75 C57BL/6 mice were infected with 1×107 CFU/ml H37Rv suspension by aerosol and randomly divided into untreated (n=9) group, isoniazid+rifampicin+pyrazinamide (HRZ) group (n=22), PFD+HRZ group (n=22), and SC1011+HRZ group (n=22). C57BL/6 mice were infected with H37Rv by aerosol for 6 weeks and then treated. Seven mice in each treatment group were weighed, sacrificed, dissected and observed for lung and spleen lesions at 4 and 8 weeks of treatment. HE staining and Masson staining were used to assess degree of lung injury and fibrosis, respectively. ELISA was used to assess the IFN-γ/TNF-α content in the serum of mice in each treatment group after 4 weeks of treatment. Hydroxyproline (HYP) content in lung tissue was measured by alkaline hydrolysis; meanwhile, CFU counts were used to assess the bacterial load in the lung and spleen of mice in each treatment group and the recurrence of spleen and lung tissue after 12 weeks of drug withdrawal. Results: At 8 weeks, the HYP content in the lung tissue was (630±58), (635±17), and (840±70) μg/mg in the PFD+HRZ, SC1011+HRZ, and HRZ treatment group, respectively (P<0.05).At 8 weeks, the proportion of Masson staining blue-stained area, that was, positive area, in lung tissue was 16.65%±1.82%, 10.01%±2.16%, and 21.36%±3.21%, respectively (F=27.11, P<0.001).The lung injury scores by HE staining at 8 weeks were (5.00±0.50), (5.00±0.47), and (6.89±0.99) points, respectively (F=19.81, P<0.001).The results of 4-week ELISA showed that the levels of TNF-α and IFN-γ in the serum of the SC1011+HRZ-treated group were lower than those of the HRZ-treated group (all P<0.05).The degree of lung injury and fibrosis in PFD+HRZ and SC1011+HRZ treatment groups were lower than those in HRZ treatment group (all P<0.001). The number of viable bacteria in the lung tissue of mice treated with PFD+HRZ, SC1011+HRZ, and HRZ for 4 weeks was lower than that of mice untreated [(1.82±0.10), (1.91±0.05), (1.79±0.17) vs. (5.27±0.07) lg(CFU+1)/ml, all P<0.05)]. And the aseptic transformation of the spleen of mice was achieved in each treatment group at 8 weeks of administration. After 12 weeks of drug withdrawal, the recurrence of lung infection in the SC1011+HRZ treatment group was 3/7 lower than 5/7 in the HRZ treatment group (P>0.05); the recurrence of spleen infection in the SC1011+HRZ treatment group was 1/7 lower than 5/7 in the HRZ treatment group (P>0.05).Pulmonary infection recurred more frequently in PFD+HRZ 6/7 versus HRZ 5/7 (P>0.05). Conclusions: PFD/SC1011, when combined with HRZ, reduced lung injury and reduced secondary fibrosis in pulmonary tuberculosis in C57BL/6 mice. SC1011 combined with HRZ has no significant short-term therapeutic effect on MTB, but may reduce its recurrence rate in long-term treatment, especially in reducing the recurrence rate of mouse spleen.

Paclitaxel combined with platinum (PTX) versus fluorouracil combined with cisplatin (PF) in the treatment of unresectable esophageal cancer: a systematic review and meta-analysis of the efficacy and toxicity of two different regimens.

Chemotherapy plays an important role in definitive chemoradiotherapy strategies. However, the most optimal concurrent chemotherapy scheme is still controversial. This study aimed to systematically evaluate the efficacy and toxicity of paclitaxel/docetaxel combined with platinum (PTX) and fluorouracil combined with cisplatin (PF) in the concurrent chemoradiotherapy (CCRT) of unresectable esophageal cancer. The PubMed, China National Knowledge Infrastructure (CNKI), Google Scholar and Embase databases were searched by combining subject words and free words through December 31, 2021. The inclusion criteria were pathologically confirmed esophageal cancer studies using CCRT, where the chemotherapy regimen only compared PTX and PF. Quality evaluation and data extraction of studies that met the inclusion criteria were carried out independently. Stata 11.1 software was used to perform the meta-analysis. The begger analysis and egger analysis were used to assess publication bias, and the robustness of the pooled results further assessed by the Trim and Fill analysis. After screening, 13 randomized controlled trials (RCTs) were included. A total of 962 cases were enrolled, including 480 (49.9%) in the PTX group and 482 (50.1%) in the PF group. The gastrointestinal reaction to the PF regimen was the most serious [relative risk (RR) =0.54, 95% confidence interval (CI): 0.36-0.80, P=0.003]. The complete remission (CR) rate, objective response rate (ORR), and disease control rate (DCR) of the PTX group were higher than those of the PF group (RR =1.35, 95% CI: 1.03-1.76, P=0.030; RR =1.12, 95% CI: 1.03-1.22, P=0.006; RR =1.05, 95% CI: 1.01-1.09, P=0.022). In terms of the overall survival (OS) rate, the 2-year survival rates of the PTX group were higher than those of the PF group (P=0.005). There was no significant difference in the 1-, 3-, and 5-year survival rates between the two regimens (P=0.064, 0.144, and 0.341, respectively). There may be publication bias for ORR and DCR, and the results are reversed after applying the Trim and Fill method, so the combined results are not robust. PTX may be the preferred regimen for CCRT of esophageal squamous cell carcinoma, with better short-term therapeutic effect and 2-year OS rate and lower gastrointestinal toxicity.

Efficacy of brexanolone in postpartum depression

Introduction Depression whose onset in the peripartum period is commonly referred to as Postpartum Depression.Postpartum Depression affects 11.5% of women during pregnancy or postpartum.Brexanolone has been developed for the treatment of Postpartum Depression, it is a formulation of Allopregnanolone, which is administered parenterally. Several studies have found that a single Brexanolone infusion had rapid antidepressant effects for severe Postpartum Depression, with good safety.ObjectivesThe objective of this review is to evaluate the effectiveness of treatment with Brexanolone in Postpartum Depression.MethodsA systematic search was performed through Pubmed, including randomized controlled trials (RCTs).Results2 articles were selected that included three RCTs, in which participated 156 women diagnosed with Postpartum Depression who received an infusion of Brexanolone and 111 women with Postpartum Depression who received placebo .Compared to placebo, women who received Brexanolone had a significant clinical response, starting 24 hours after administration (RR: 1.34; 95% CI: 1.03–1.73). ), reaching its maximum action peak at 36 hours ( RR: 1.50; 95% CI 1.06–2.13; P = 0.02 ), and with a duration of effect up to the seventh day ( RR = 1.32, 95% CI: 1.01–1.73). Likewise, women with Postpartum Depression, treated with Brexanolone, had a significantly greater remission, starting at 24 hours of treatment (RR: 1.86; 95% CI: 1.03–3.34), reaching its peak maximum action at 60 hours ( RR: 2.20; 95% CI 1.31–3.70 ), and with a duration of effect up to 72 hours ( RR = 1.96; 95% CI: 1 .41–2.72).ConclusionsThe administration of a dose of Brexanolone seems to have an ultra-rapid antidepressant effect for the treatment of Postpartum Depression. The short-term and long-term therapeutic effect of brexanolone needs to be examined with large-scale randomized controlled studies.Disclosure of InterestNone Declared

Human Umbilical Cord Blood-Derived Mesenchymal Stem Cell Transplantation for Patients with Decompensated Liver Cirrhosis

Background or PurposeAlthough human umbilical cord blood-derived mesenchymal stem cell transplantation (HUCB-MSCT) resulted in a good short-term therapeutic effect on patients with decompensated liver cirrhosis (DLC), the long-term survival remained unclear. This study aimed to evaluate the impact of HUCB-MSCT on long-term outcomes in patients with DLC. MethodsThis retrospective cohort study included hospitalized patients with decompensated cirrhosis in Liuzhou Hospital of Traditional Chinese Medicine between November 2010 and February 2013. The primary outcome was overall survival (OS). The secondary outcomes were 3-year and 5-year survival rates and the occurrence rate of hepatocellular carcinoma (HCC). ResultsA total of 201 subjects were enrolled, including 36 patients who underwent HUCB-MSCT (SCT group) and 165 patients who did not (non-SCT group). After PSM (1:2), there were 36 patients in the SCT group and 72 patients in non-SCT group. The 3-year and 5-year survival rates of the two groups were 83.3% vs. 61.8% and 63.9% vs. 43.6%, and median OS time was 92.50 and 50.80 months, respectively. HUCB-MSCT treatment was found to be an independent beneficial factor for patient OS (hazard ratio = 0.47; 95% CI: 0.29–0.76; P = 0.002). There was no significant difference in the occurrence rate of HCC between the two groups (P = 0.410). Discussion or ConclusionsHUCB-MSCT may improve long-term OS without increasing the occurrence of HCC in patients with DLC. Trial RegistrationThe Chinese Clinical Trial Registry (ChiCTR2100047550).

Short-term outcome of plasma adsorption therapy in amyotrophic lateral sclerosis.

To observe the short-term outcome of plasma adsorption PA therapy in amyotrophic lateral sclerosis (ALS). 28 cases of als patients were recruited in this study, of which 20 were male and 8 were female with a mean age of 53.21±9.07 years and the average course of 33±23.35 months. The clinical manifestations were limb weakness (N=27), muscular atrophy (N=27), muscular tremor (N=5), dysphagia (N=12) and dysarthria (N=12). The clinical data of the patients recruited were graded by Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRSR) : <10 (N=1), 11-20 (N=4), 21-30 (N=6), 31-40 (N=12), >40 (N=5). All patients received PA therapy once a week for three successive times after examining the conditions of blood coagulation and virus infection. PA therapy was supplemented with neurotrophic therapy meanwhile. All patients' clinical manifestations and scores of ALSFRSR before treatment and one week after treatment were evaluated and compared. The levels of serum superoxide dismutase (SOD), interleukin-10 (IL-10), serum creatine kinase (CK) and lactate dehydrogenase (LDH) before and after treatment were compared. After PA therapy, 14 patients have improved obviously in muscle strength, 4 patients in hypermyotonia partially, 3 patients in muscular tremor, 5 patients in dysarthria, 3 patients in salivation to some extent and 2 patients in swallowing function. The score of ALSFRSR after PA treatment (31.89±10.36) was remarkably higher than that before PA treatment (30.68±10.52) (P<0.01). The levels of SOD (155.10±21.87 IU/L) and IL-10 (138.06±185.88 pg/mL) after PA treatment were significantly higher than the levels before PA treatment (143.08.3±19.16 IU/L and 46.34±75.31 pg/mL, respectively) (P<0.05). The levels of CK (168.86±113.50 IU/L) and LDH (152.07±32.65 IU/L) after PA treatment were significantly lower than the levels before PA treatment (356.68±250.30 IU/L and 181.36±33.74 IU/L respectively) (P<0.01). At the end of follow-up period (November, 2019), five patients died of respiratory failure 16-21 months after PA treatment and two patents died of respiratory infection 15-20 months after PA treatment. 7 patients were still alive. The score of ALSFRS-R of these patients who survived at the end of follow-up (13.00±13.37) were significantly lower than before PA treatment (36.71±8.56) (P<0.05) and after PA treatment (38.14±8.82) (P<0.05). Plasma adsorption (PA) therapy has shortterm therapeutic effects on als. The effects might be attributed to the anti-oxygen free radical effect by increasing SOD level and the anti-inflammation effect by increasing IL-10 level. As the efficacy of PA therapy was obtained in a small sample size and short follow-up period, the longterm observation of PA efficacy in treating als should be further investigated.

Identification and antibiotic susceptibility evaluation of Mycoplasma synoviae isolated from chickens in central China

Mycoplasma synoviae (M. synoviae) infections have become an increasingly serious concern in China because they cause huge economic losses to the poultry industry. Antibiotic treatment is one of control strategies that can be used to contain clinical outbreaks in M. synoviae-free flocks, especially because the bacteria can be transmitted through eggs. To understand M. synoviae infection status in farms of central China and the antibiotic susceptibility of the circulating strains in vivo and in vitro, 485 samples were collected from five provinces from 2019 to 2021. Fifty-two strains were isolated and identified. Determination of the minimum inhibitory concentration (MIC) of eight antibiotics (tylvalosin, tiamulin, tilmicosin, lincomycin, enrofloxacin, chlortetracycline, doxycycline and tylosin) for isolates showed that tylvalosin, doxycycline and tiamulin were effective against 52 clinical isolates (MIC values ≤ 0.0625–0.25 μg/mL, ≤0.0625–1 μg/mL, and 0.25–2 μg/mL, respectively). Tilmicosin, enrofloxacin and lincomycin had high MIC90 values (>32 μg/mL). An artificial M. synoviae infection model was established in chickens for evaluation of the short-term therapeutic effect of these antibiotics. After 5 days of medication, doxycycline (200 mg/L) showed a superior ability to inhibit M. synoviae compared with other groups, as did tylvalosin (200 mg/L). Furthermore, the therapeutic efficacy of tylvalosin (0.4 μg/mL) on intra-embryo-injected M. synoviae was higher than that of tiamulin at the same dose. A combination of MIC values determined in vitro and therapeutic effects observed in vivo revealed that tylvalosin and doxycycline had the best therapeutic effects. Tylvalosin also showed better inhibitory effects on the vertical transmission of M. synoviae than tiamulin.

Clinical Study on the Efficacy of Bevacizumab in Combination with Pembrolizumab on Cellular Immune Function in the Treatment of Driver Gene-Negative Stage IV Lung Adenocarcinoma.

To explore the efficacy of bevacizumab in combination with PD-1 immune drug pembrolizumab on cellular immune function in the treatment of driver gene-negative stage IV lung adenocarcinoma and its short-term survival effect. From February 2020 to December 2021, 85 patients with driver gene-negative stage IV lung adenocarcinoma were admitted to our hospital and treated with first-line therapy, and their clinical records were reviewed retrospectively. According to the treatments, the patients were separated into two groups the combination group (n = 45) and the control group (n = 40). The treatment regimen of the control group was an AP chemotherapy regimen (pemetrexed combined with cisplatin) + PD-1 immune drug pembrolizumab. The treatment regimen of the combination group was AP chemotherapy regimen + PD-1 immune drug pembrolizumab combined with bevacizumab. We evaluated the pre- and post-treatment cellular immunological function of the two patient groups and discussed the difference between them. There was a substantial difference in the overall effective rate and the disease control rate between the two groups, with the former being 27.50% compared to 48.89% and the latter being 72.50% compared to 93.33% among these 85 patients studied. The KPS for the combination group improved and stayed at 91.11% after treatment, which is considerably better than the KPS for the control group, which was 42.50% (χ 2 = 23.09, P < 0.05). There was no significant difference (P > 0.05) in the numbers of CD3+, CD4+, CD19+, CD8+, or CD4+/CD8+ cells pretreatment between the two groups, but after treatment, the combination group had significantly higher numbers of all these cells. Neither the CD8+ nor the CD19+ level was significantly different between the control and combination groups (P > 0.05). Furthermore, the incidence of common clinical side effects was similar between the two groups (P > 0.05). Proteinuria, tiredness, increased alanine aminotransferase, hypertension, immunological pneumonia, muscle pain, arthralgia, hypothyroidism, etc. were the most common side effects reported among both groups throughout therapy. A grade IV side effect is rare. After follow-up until March 2022, the median PFS for the control group was 9.00 ± 1.65 months (95% CI, 5.76-12.24) and the mean PFS was 11.48 ± 0.91 months (95% CI, 9.69-13.26). Comparison of the median PFS of the combination group (13.00 ± 1.10) months (95% CI: 10.84-15.16) with the average PFS of the group (15.52 ± 0.88) months (95% CI = 13.79-17.25) reveals a statistically significant difference (P < 0.05). Combining bevacizumab with the PD-1 immune medication pembrolizumab to treat patients with stage IV lung adenocarcinoma improves the quality of life, short-term therapeutic effectiveness, immune function, and PFS.

Intensity-modulated proton and carbon-ion radiation therapy in the management of major salivary gland carcinomas

Primary major salivary gland carcinomas (SGCs) present with diverse histological types that are known to be largely radioresistant with a high tendency to develop distant metastasis (DM). Photon-based radiotherapy (RT) is limited in terms of its therapeutic effect and toxicities. In view of the physical and biological advantages of intensity-modulated proton and/or carbon-ion radiation therapy, we aimed to evaluate the short-term therapeutic effect and toxicities in patients with major SGCs treated with this form of radiation therapy. Between August 2015 and November 2019, a total of 55 consecutive and non-selected major SGC patients who received particle RT at the Shanghai Proton and Heavy Ion Center (SPHIC) were retrospectively analyzed. The 2-year overall survival (OS), progression-free survival (PFS), local-regional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) rates, as well as prognostic factors were analyzed. Additionally, acute and late toxicities were also analyzed. With a median follow-up time of 24 (range, 6-57) months, the 2-year OS, PFS, LRRFS, and DMFS rates were 91.6%, 78.6%, 94.2%, and 83.9%, respectively. At the time of this analysis, four patients had developed local or regional recurrence, and seven additional patients had developed DM. Three patients had died due to disease progression, and another patient with recurrence experienced a late Grade 5 event (hemorrhage) at 9 months after re-irradiation with carbon ion and subsequently died. Otherwise, none of the patients had grade 3 or higher treatment-induced acute or late adverse effects except one who developed grade 3 acute mucositis. Overall, intensity-modulated proton and/or carbon-ion radiation therapy provided satisfactory therapeutic effectiveness in our major SGCs patients with a low incidence of acute and late toxicities.

Native T1 Mapping-Based Radiomics for Noninvasive Prediction of the Therapeutic Effect of Pulmonary Arterial Hypertension.

(1) Background: Novel markers for predicting the short-term therapeutic effect of pulmonary arterial hypertension (PAH) to assist in the prompt initiation of tailored treatment strategies are greatly needed and highly desirable. The aim of the study was to investigate the role of cardiac magnetic resonance (CMR) native T1 mapping radiomics in predicting the short-term therapeutic effect in PAH patients; (2) Methods: Fifty-five PAH patients who received targeted therapy were retrospectively included. Patients were subdivided into an effective group and an ineffective group by assessing the therapeutic effect after ≥3 months of treatment. All patients underwent CMR examinations prior to the beginning of the therapy. Radiomics features from native T1 mapping images were extracted. A radiomics model was constructed using the support vector machine (SVM) algorithm for predicting the therapeutic effect; (3) Results: The SVM radiomics model revealed favorable performance for predicting the therapeutic effect with areas under the receiver operating characteristic curve of 0.955 in the training cohort and 0.893 in the test cohort, respectively. With the optimal cutoff value, the radiomics model showed accuracies of 0.909 and 0.818 in the training and test cohorts, respectively; (4) Conclusions: The CMR native T1 mapping-based radiomics model holds promise for predicting the therapeutic effect in PAH patients.

Hepatocellular Recovery of Chronic Paraquat Induced Liver Toxicity in Vitamin E and C Treated Male Wistar Rats

Paraquat is an organic compound also known as methyl viologen, a chemical herbicide or weed killer with highly toxic effect on ingestion or exposure. Vitamin E and C are powerful antioxidants that act as initial responder against oxygen reactive species called free radicals which attack and destroy the tissues. The aim of this study was to determine a short term therapeutic effect of vitamin E and C combination on liver enzymes parameters of paraquat induced liver toxicity in male albino rats. 200 male albino rats were used for the study. The 200 rats were divided into four main groups (A, B, C, D) consisting of 50 rats in each group. The Groups were further divided into two subgroups having 25 rats in each subgroup. “A” group was not induced with paraquat while “B”, ‘C” and “D” groups were induced with increasing dose of 0.02g, 0.04g and 0.06g of paraquat respectively. “A” group had two subgroups; “Ao” and “AVEC” which represented the sub-group not treated with Vit E and the subgroup treated with Vit E (500mg) respectively. This also applied to group “B”, “C” and “D” paraquat was administered every forth night followed by treatment with the vitamins for one month. Blood samples were collected and analysed for liver function (SGOT, SGPT, ALT And GGT). There was a significant increase in the level of the liver enzymes among the “Ao”, “Bo”, “Co” and “Do”, p-value&lt;0.05 and also among the “AVEC”, “BVEC”, “CVEC” and “DVEC”, p-value&lt;0.05. The result also showed that there were significant differences in intra-group comparison in all the liver enzyme parameters, p-value&lt;0.05 while there was no significant difference among the AO and AVEC subgroups for all parameters. This study has shown that vitamin E and C combination has a therapeutic effect in male albino rats on one month of weekly treatment. Therefore, a weekly treatment with Vit E and C may treat liver disease toxicity associated with paraquat toxicity in rats.

First-line immunotherapy of neuronal surface antibody-mediated autoimmune encephalitis: Assessment of therapeutic effectiveness and cost-efficiency

ObjectiveTo evaluate the therapeutic effectiveness and cost-efficiency of first-line immunotherapies on neuronal surface antibody-mediated autoimmune encephalitis (AE) based on a real-world observational study in China. MethodsOur study retrospectively collected the clinical and paraclinical data of patients with definite neuronal surface antibody-mediated AE between July 2014 and July 2020. Regular follow-up was performed after administering standard regimens of first-line immunotherapies, including intravenous methylprednisolone (IVMP) and / or intravenous immunoglobulin (IVIG). Therapeutic effectiveness was reflected by modified Rankin Scale scores. The health resource utilization and direct medical costs were extracted to analyze the cost-efficiency. ResultsAmong the 78 eligible patients, 48 (61.5%) were males with a median age of 40 years. More than half (56, 71.8%) were treated with combination therapy, with the rest receiving IVMP and IVIG monotherapy (both of 11, 14.1%). Related objective variables, i.e., sex, onset age, disease course, onset symptoms, antibody types, abnormal paraclinical results, disease severity, and the health insurance, showed insignificant differences on the selection of therapy. Each therapy showed similar short-term (4-week) and long-term (1-year) therapeutic effects. Yet the single or combination of IVIG had a slightly better effectiveness but higher cost than the monotherapy of IVMP. ConclusionThe combination of IVMP and IVIG was used more frequently than either alone, which may be associated with neurologist's personal experience and patient's wishes. Though with similar therapeutic effectiveness, the use of IVMP alone might be a better choice with a better cost-efficiency.