Poor Curative Effect Research Articles

Tanshinone I inhibits the functions of T lymphocytes and exerts therapeutic effects on delayed-type hypersensitivity reaction via blocking STATs signaling pathways

Delayed-type hypersensitivity (DTH) reactions are a kind of chronic inflammatory diseases initiated by antigens and antigen-specific T cells. Currently, the therapy of DTH reactions is limited by the poor curative effects and serious adverse reactions of existing agents. In this study, we investigated the regulatory effects of tanshinone Ⅰ, a natural compound isolated from Salvia miltiorrhiza, on the functions of multiple immune cells and its therapeutic effects on DNFB-induced DTH reaction, and then explored its immunosuppressive mechanisms. The results showed that tanshinone Ⅰ at 5 to 20 μM moderately inhibited the activation of macrophages and dendritic cells, but did not weaken the activation of neutrophils. Tanshinone Ⅰ at 1 to 4 μM intensively suppressed the activation, proliferation, and differentiation of CD4+ and CD8+ T cells, and slightly affected the functions of B cells. Tanshinone Ⅰ administration markedly alleviated the edema, inflammatory response, and the infiltrations of CD4+ T cells, CD8+ T cells, and CD11b+ cells in ear tissues of mice which were induced DTH reactions by DNFB. Transcriptome analysis revealed that tanshinone Ⅰ strongly inhibited CD4+ T cells to express genes involving in cell proliferation, metabolism, activation, and differentiation. Furthermore, immunoblotting analysis showed that tanshinone Ⅰ selectively inhibited the phosphorylation of STAT3 and STAT5 in CD4+ T cells stimulated by anti-CD3e and anti-CD28 antibodies or IL-2. Collectively, tanshinone Ⅰ can strongly inhibit the functions of T lymphocytes, exert therapeutic effects on DTH reaction by blocking STATs signaling pathways, and has potential to be developed into therapeutic drug for DTH reactions.

Analysis of therapeutic effects and influencing factors of ICIs in lung-cancer patients.

The aim of this retrospective study was to analyze the efficacy and risk factors of immune checkpoint inhibitors (ICIs) in lung cancer patients. One hundred lung cancer patients who were treated in our hospital from May 2021 to May 2023 were selected as the study subjects and divided into chemotherapy group (n = 50) and ICIs group (n = 50), in which the chemotherapy group was given the combined treatment of vincristine and cisplatin (NP), while the ICIs group was given ICIs for treatment. The therapeutic effect and adverse reactions (hypertriglyceridemia, anemia, hypertension and hypoproteinemia) of the two groups were compared, and fasting venous blood was collected. The levels of carcinoembryonic antigen (CEA) and cancer antigen 199 (CA199) were compared between the two groups before and after treatment. According to the therapeutic effect, 100 patients with lung cancer were divided into complete remission (CR) + partial remission (PR) group (n = 52) and stable (SD) + progressive (PD) group (n = 48). The clinical data and pathologic data of the two groups were compared. The rates of objective effective rate (ORR) in chemotherapy group and ICIs group were 36.00% and 68.00% respectively, and the level of ORR in ICIs group was significantly higher than that in chemotherapy group, with statistical significance (P < 0.05). There was no significant difference in serum CEA and CA199 levels between the two groups before operation (P > 0.05). Three months after operation, the serum CEA and CA199 levels in ICIs group were significantly lower than those in chemotherapy group, and the difference was statistically significant (P < 0.05). The adverse reactions of hypertriglyceridemia, anemia, hypertension and hypoproteinemia in chemotherapy group and ICIs group during treatment were all grade 1-2, and the incidence of adverse reactions was similar between the two groups (P > 0.05). There was no significant difference in sex, age, anatomic position, pathologic type, smoking history and differentiation between the two groups (P > 0.05). In SD + PD group, the preoperative maximum tumor diameter > 4cm, tumor node metastasis (TNM) stage IV, lactate dehydrogenase (LDH) ≥ 183 U/L, and tumor volume ≥ 120m3 were significantly higher than those in CR + PR group, and the prognostic nutritional index (PNI) ≥ 41.8 and the proportion of ICIs were significantly lower than those in CR + PR group, with statistical significance (P < 0.05). Multifactorial logistic regression analysis showed that preoperative maximum tumor diameter > 4cm and LDH ≥ 183U/L were risk factors for poor lung cancer outcome, and PNI ≥ 41.8 and ICIs treatment were protective factors for poor lung cancer outcome (P < 0.05). ICIs is effective in the treatment of lung cancer, which can obviously reduce the tumor load and has high safety. In addition, the maximum tumor diameter and LDH are risk factors that affect the poor curative effect of lung cancer. High PNI level and ICIs treatment are helpful to improve the effect of lung cancer, and early monitoring is helpful to guide the treatment plan and evaluate the treatment effect.

Efficacy of Microneedle as an Assisted Therapy for Melasma: A Meta-analysis and Systematic Review of Randomized Controlled Trials.

Melasma is a common hyperpigmentary disorder, it has variety of treatment options, but it usually has a poor curative effect and high recurrence rate. Microneedles have shown certain prospects in the treatment of melasma as an assisted therapy, but there is no consensus on its efficacy and safety. To evaluate the efficacy and safety of microneedles as an adjuvant treatment for melasma. Statistical tools were used to adjust the improvement of MASI scores in all studies to obtain standardized mean differences (SMD), and then, meta-analysis were performed. Risk ratio (RR) was utilized to assess adverse reactions, clinical effectiveness, and patient satisfaction. The effects of microneedle-assisted treatment for melasma begin to manifest at the 4th week, with optimal results observed at the 24th week, and with a high patient satisfaction. Compared with oral medication alone, microneedle-assisted therapy began to be more effective at week 12 and continued by 24weeks. Compared with laser therapy alone, microneedle-assisted therapy also showed stronger efficacy, at the 8th week, microneedle-assisted treatment was significantly more effective, reaching its peak at the 12th week. Finally, in the comparison of microneedle and microinjection therapy, microneedle has always been more significant than micro-injection. Microneedle is a valuable adjunctive therapy for melasma treatment. It enhances long-term clinical outcomes compared to monotherapy and is associated with high patient satisfaction. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

An Effect of Chronic Negative Stress on Hippocampal Structures and Functional Connectivity in Patients with Depressive Disorder.

Depressive disorder is a mental health disorder with complicated etiopathogenesis. Environmental stress and neurodevelopment combined with other factors contribute to the occurrence of depression. Especially for the depressive disorder with chronic negative stress, it has characteristics of recurrence and poor curative effect because of unclear mechanism. Here, we investigated the hippocampal structures and functional connectivity (FC) according to resting-state functional magnetic resonance imaging in patients with depression who underwent chronic negative stress. A total of 65 patients with depression (34 underwent chronic negative stress and 31 non-underwent chronic negative stress) and 30 healthy controls who did not undergo chronic negative stress were included in the study. The volumes of hippocampal subfields, seed-based FCs between hippocampus and the whole brain voxels, and ROI-wise-based FC between hippocampal subfields were compared among the three groups. In the patients with depression who underwent chronic negative stress, the volumes of right_GC-ML-DG-head, right_CA4-head and right_CA3-head increased, FCs between Temporal_Mid_R, Precuneus_R, Frontal_Sup_R, Temporal_Sup_R, Angular_L, Frontal_Inf_Tri_R, Supp_Motor_Area_R, Precentral_L and hippocampus increased, and FCs between parasubiculum and CA3, and presubiculum and CA1 decreased. When compared to the patients who did not undergo chronic negative stress, the patients who underwent chronic negative stress had larger volumes of right_GC-ML-DG-head and right_CA3-head, higher FCs between Frontal_Sup_R, Frontal_Inf_Tri_R and hippocampus, and lower FCs between presubiculum and CA1. The depression underwent chronic negative stress may experience disrupted hippocampal structures and functional connectivity. It may be one of potential depressive disorder subtypes.

Role of innate lymphoid cells in oral squamous cell carcinoma microenvironment

Oral squamous cell carcinoma (OSCC) is the most common oral malignancy. It has a high incidence, strong invasion ability, easy metastasis, poor curative effect, and poor prognosis. Innate lymphoid cells (ILCs) are an important part of immune cells located in the mucosal barrier, which play an important role in the occurrence, development and outcome of tumors. ILCs are the key cells for decoding the regulatory mechanism of tumor microenvironment and the signatures for tumor progression. This paper reviewed the latest progress on ILCs, summarized the possible characteristics and functions of ILCs in the microenvironment of OSCC, and explored the relationship between ILCs and the occurrence, development and immunotherapy of OSCC.

Leptin receptor deficiency impedes metabolic surgery related-weight loss through inhibition of energy expenditure in db/db mice

BackgroundRoux-en-Y gastric bypass (RYGB) surgery is an effective metabolic surgery against diabetes and obesity. Clinical evidence indicates that patients with severe obesity have a poor curative effect in losing weight if they suffer from leptin or its receptor deficiency, but the underlying mechanism remains elusive. Here, we investigated the effect of leptin receptor deficiency on metabolic dysfunction in db/db mice treated by RYGB surgery.MethodsThe db/db mice and their heterozygote control db/m mice were subjected to RYGB or sham surgery. Body weight, blood glucose, food intake and glucose tolerance were evaluated. Micro-PET/CT and histological analysis were performed to examine the glucose uptake of tissues and the fat changes in mice. The key factors in glucose and fatty acid metabolism were detected by western blot analysis.ResultsCompared with the sham group, the db/db mice in the RYGB group showed more significant weight regain after surgical recovery and improvement in hyperinsulinemia and glucose tolerance. However, the total body fat and multiple organ lipid deposition of RYGB-treated db/db mice was increased. The underlying mechanism studies suggested that the activation of AMPK regulated GLUT4 to increase glucose uptake, but AMPK could not promote fatty acid oxidation through the JAK2/STAT3 pathway under leptin receptor deficiency in db/db mice.ConclusionWe conclude that leptin receptor deficiency impedes the AMPK activation-mediated fat catabolism but does not affect AMPK-related glucose utilization after metabolic surgery in db/db mice. This result helps select surgical indications for patients with obesity and diabetes.

Use of biologics in patients with psoriasis - A retrospective analysis based on real-world data.

To summarize and analysis the application of biologic agents in patients with psoriasis in the real world. Relying on collected data from June 2020 to September 2021 in the database of China Psoriasis Standardized Diagnosis and Treatment Center, 2529 cases of psoriasis patients treated with biologic agents in 188 different tertiary hospitals across China were retrospective analyzed. The collected information mainly includes demographic data (age, gender, psoriasis history), curative effectiveness of used biologics drug withdrawal and its reason. According to the collected information, condition of the usage for each category of biologics and influencing factor of biologics replacement were analyzed. A total of 2529 patients were analyzed, which included 1626 male (64.29%) and 903 female (35.71%) with an average age of 42.12±14.70 (17∼85) years old; 2336 (92.37%) patients were aged from 19 to 60 years old. Within these patients, 2362 of them (93.40%) had a psoriasis area and severity index (PASI) score, and 1776 of these patients had moderate to severe cases (75.19%). According to the patient's self-evaluation of the past efficacy of biological agents, secukinumab was chosen by the most people to have the highest efficacy (1140 cases, 93.60%). The main reason for the withdrawal of secukinumab is that the disease is already well controlled at the time of withdrawal (67 cases, 38.95%); for TNF- α inhibitor is the poor curative effect; for ustekinumab and ixekizumab were the non-affordable price. In the current biotherapy of psoriasis in China, the efficacy of secukinumab is thought by most people to be the highest. Secukinumab is the first choice when the needs of changing biologics appear.

Using Herbal-Cake-Separated Moxibustion for the Treatment of Rats with Chronic Renal Failure.

In the process of moxibustion in clinical practice, subjects need to be in a stable mood and comfortable posture to avoid problems such as moxa ash falling, scalding skin, and poor curative effect. Such problems also exist in the rat moxibustion experiment. To simulate clinical practice, it is necessary to introduce an experimental instrument in animal experiments, that is, a moxibustion device with fixed rats and moxibustion treatment synchronization, which can make experimental rats receive moxibustion treatment quietly and comfortably under non-anesthesia. Our research group designed a rat moxibustion experimental platform. The device was framed by a wooden board with a supporting base plate, multiple fixed components, and partitioned components. The device can achieve the operation mode of moxibustion in rats without binding, avoiding anesthesia and scalding and simultaneously exposing multiple acupoints on the back. This operation can avoid physical and mental injury to rats and operators, which improves the research efficiency and further promotes the development and research of moxibustion animal experiments. The device has a simple structure, is easy to operate and popularize, is comprehensively and innovatively designed, reusable, and is suitable for rat experiments mainly based on moxibustion. This article mainly introduces the structure of the experimental platform device for rat moxibustion, the basic procedure of herbal-cake-separated-moxibustion in experimental rats using the device and describes the establishment of a rat model of chronic renal failure (CRF) and representative experimental results.

Prognosis Influence of Additional Chromosome Abnormalities in Newly Diagnosed Acute Promyelocytic Leukemia with t(15;17)(q22;q21)

The therapeutic advancements over the last decade have dramatically improved the prognosis and decreased the mortality of acute promyelocytic leukemia (APL). Some patients still recur repeatedly, and the poor curative effect of some patients has become a challenging issue. Survival may be impacted by additional concurrent mechanisms linked to additional chromosome abnormalities (ACA) as a potential pathogenic factor. Therefore, to confirm the role of ACA, we retrospectively analyzed the characteristics and prognostic impact of ACA in a series of newly diagnosed APL patients with t(15;17)(q22;q21). First, we assessed the characteristics of chromosomal abnormalities. Of these 268 patients, 208 (77.6%) had the t(15;17) as the only abnormality and 60 (22.4%) had the t(15;17) with ACA. Based on the number of ACA, the evaluable cohort of APL patients with t(15;17) was further divided into four groups: no ACA, one ACA, two ACA, and three or more ACA, with respective frequencies of 77.24%, 13.81%, 5.22%, and 3.73%. Trisomy 8 was the most frequently observed ACA, alone or combined with other anomalies in 23 cases (39.0%). Second, there was no significant difference presented in main clinical characteristics and response to therapy between the groups t(15;17) with alone and t(15;17) with ACA ( p＞0.05). Similarly, no significant impact was observed in clinical features and response to therapy, such as median white blood cells, platelets, hemoglobin, and the rate of hematologic complete remission between patients with trisomy 8 and patients with other ACA ( p＞0.05). Third, the influence of ACA on prognosis in APL patients with a median follow-up time of 47 months (range 1-89 months) was analyzed. There was still no significant difference in APL patients between the group t(15;17) alone and the group t(15;17) with ACA for the incidence of 5-year overall survival(OS) (90.8% vs. 86.8%, p=0.531) and 5-year disease-free survival (DFS) (89.7% vs. 85.8%, p=0.301). Interestingly, patients in APL with trisomy 8 had a poorer 5-year OS than those with other ACA (91.8% vs. 69.6%, p=0.033) and unaffected 5-year DFS (88.9% vs. 88.2%, p=0.919). The OS and DFS were similar between patients with 0 to 2 ACA and patients with 3 or more ACA ( p=0.294, p=0.283, respectively). Otherwise, no statistical difference was demonstrated for the incidence of OS ( p=0.515) and DFS (p=0.383) among the groups based on the number of ACA besides t(15;17). Finally, the old patients with age ≥60 years were shown to have lower 5-year OS compared with young patients(67.9% vs. 94.0%, p ＜0.001) and unaffected 5-year DFS (94.3% vs. 87.8%, p=0.430). The association between age and ACA on the prognosis of APL was observed. Either Cox analysis of age and ACA or combined with age and trisomy 8, it was all indicated that age ≥60 years was only an adverse prognostic factor for survival ( p＜0.001, HR = 4.627, 95% CI: 2.144-9.982; p＜0.001, HR = 4.412, 95% CI: 2.037-9.553, respectively). It should be noted that OS significantly among the following groups of patients: ＜60 years without ACA, ≥60 years without ACA,＜60 years with ACA, and ≥60 years with ACA ( p＜0.001). The 5-year OS rates were 92.9%, 97.9%, 80.6%, and 52.5%. Overall, the group≥60 years with ACA had worse OS compared to the groups ≥60 years without ACA and＜60 years without ACA ( p＜0.001, p＜0.001, respectively ). The group＜60 years with ACA had lower OS compared to the group ≥60 years without ACA ( p＜0.001). Our results suggested that trisomy 8 as the most common ACA seemed to be an adverse but not independent predictive factor in APL with t(15;17), while the ACA besides t(15;17) did not confer poor prognosis in APL. Elderly patients with ACA appeared to have worse OS.

The trend of changes in spine-pelvic sagittal parameters before and after surgery in patients with double-segment lumbar spondylolisthesis and their evaluating for surgery efficacy

To explore the trend of changes in the parameters of the spine-pelvic sagittal plane before and after surgery in patients with double-segment lumbar spondylolisthesis (LSL) and to evaluate the value of the surgical effect. A retrospective analysis of 95 double-segment lumbar spondylolisthesis patients treated with posterior lumbar interbody fusion from October 2019 to October 2020 were analyzed, including 31 males and 64 females;age ranging from 41 to 63 years old, with an average of (52.10±4.35) years old;degree of lesion, 47 patients with gradeⅠand 48 patients with gradeⅡ. The surgical efficacy was evaluated according to the Oswestry dysfunction index(ODI) improvement rate at 3 months after operation. ODI improvement rate ≥50% was considered good, and <50% was considered bad. Ninety-five patients were divided into good curative effect group (74 cases) and poor curative effect group (21 cases) according to surgical curative effect. The clinical data, such as gender, age, body mass index, course of disease, degree of disease, operation time, intraoperative blood loss, and comorbidities were compared between two groups were compared. The parameters of spine pelvis sagittal plane were observed before and 3 months after operation, including spine sacral angle (SSA), T1 pelvic angle (TPA), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS). Clinical symptoms were evaluated using visual analogue scale (VAS) and ODI. The correlation between the changes of spine pelvis sagittal plane parameters and the changes of VAS and ODI before and after surgery were analyzed, and the value of spine pelvis sagittal plane parameters in evaluating the surgical efficacy of patients with double level lumbar spondylolisthesis at 3 months after surgery was evaluated. The courses of disease and surgical time in the group with poor efficacy were longer than those in the group with good efficacy, and the degree of lesion was higher in the group with poor efficacy (P<0.05). The SSA, TPA, LL, and SS of the group with good efficacy were higher than those of the group with poor efficacy before and 3 months after surgery, while the PT was lower than that of the group with poor efficacy (P<0.05). The changes in SSA, TPA, LL, PT, and SS before and after surgery in the group with good efficacy were greater than those in the group with poor efficacy (P<0.05). The VAS and ODI of both groups were lower at 3 months after surgery than before, and the group with good efficacy was lower(P<0.05). The changes in VAS and ODI before and after surgery in the group with good efficacy were greater than those in the group with poor efficacy (P<0.05). The changes in SSA, TPA, LL, PT, SS before and after surgery were positively correlated with the changes in VAS and ODI (P<0.05). Three months after surgery, SSA, TPA, LL, PT, and SS were used to evaluate the surgical efficacy of patients with dual level lumbar spondylolisthesis. The area under the curve (AUC) was 0.868, 0.797, 0.875, 0.822, and 0.853, respectively. The combined evaluation of all indicators resulted in the highest AUC, 0.927, and the best sensitivity and specificity were 90.50% and 91.89%, respectively. The spine pelvis sagittal plane parameters SSA, TPA, LL, and SS of patients with double level lumbar spondylolisthesis before and after surgery show an upward trend;PT shows a downward trend;PI do not change significantly. And the changes of SSA, TPA, LL, SS, and PT are closely related to the patient's pain level and the improvement of lumbar function, which can be used as parameters to evaluate the surgical efficacy.

Axial Convex-Shaped Hematoma was Associated with Poor Curative Effect of Surgical Treatment for Traumatic Posterior Fossa Epidural Hematoma in Children.

Posterior fossa epidural hematoma (PFEDH) is rare which accounts for just 4-12.9% of all EDH cases. Since its frequently subtle and nonspecific clinical presentation, CT scan has great importance for early diagnosis and treatment of PFEDH. However, indications for surgery depending on the findings of CT image are still controversial. We retrospectively analyzed 40 pediatric cases of PFEDH. Their baseline characteristic, clinical presentation, imaging findings and outcomes were collected and analyzed. The ellipsoid volume equation X × Y × Z/2 was used to measure the hematoma volume. The Glasgow Outcome Scale (GOS) was used to assess the neurologic functional outcome. A total of 40 pediatric PFEH patients were included with 8 patients having poor outcome and 32 patients having a relatively good prognosis. GCS score showed a significant difference between good and poor outcome groups (p < 0.001). Y value on CT image was significantly bigger in poor outcome group than good outcome group (p < 0.01). Similar results were got in X/Z value (p < 0.05) and Y/Z value (p < 0.01) which reflected the shape of hematoma. A predictive model with Y + X/Z showed the largest area under the ROC curve with a sensitivity of 75.0% and specificity of 93.7%. GCS score at admission was closely related to the prognosis of the pediatric patients with PFEDH. The morphometry of PFEDH has a crucial role in judging the prognosis. Axial convex-shaped hematoma was associated with poor curative effect of surgical treatment.

ROS-Responsive Janus Au/Mesoporous Silica Core/Shell Nanoparticles for Drug Delivery and Long-Term CT Imaging Tracking of MSCs in Pulmonary Fibrosis Treatment.

Mesenchymal stem cell (MSC) therapy has been proven to be a potentially effective approach for idiopathic pulmonary fibrosis (IPF) treatment. However, this strategy is currently limited by the poor curative effect and an insufficient comprehension of the in vivo condition of the transplanted MSCs in the remedy of IPF. To address these issues, herein, a nanosystem composed of Janus Au/mesoporous silica core/shell nanoparticles (Janus NPs) is designed for effective therapeutic and real-time tracing of MSCs in MSC-based IPF therapy. The Janus NPs consist of a Au core and a pirfenidone (PFD)-loaded mesoporous silica shell asymmetrically decorated with two targeting moieties: one is reactive oxygen species (ROS)-sensitive thioketal grafted methoxy poly(ethylene glycol) (mPEG-TK), and the other is 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE). The asymmetric decoration on each side of the particle allows long-term anchoring of the Janus NPs on the cell membrane to facilitate the responsive release of PFD in the ROS environment of the fibrotic lung, thereby enhancing the therapeutic efficacy of the transplanted MSCs by improving the microenvironment. Following drug release, the Janus NPs quickly enter into MSCs, achieving long-term computed tomography (CT) imaging tracing of MSCs in IPF model mice for an in-depth comprehension of the cell therapy mechanism. Overall, this work reports on Janus Au/PFD-loaded mesoporous silica core/shell NPs that combine the drug delivery and imaging tracking of MSCs, which may provide a strategy for the stem cell-based treatment of IPF.

Anti-ovarian cancer actions and pharmacological targets of plumbagin.

Ovarian cancer is a gynecological malignancy characterized with increasing death rate in the world. It is clinically reported that chemotherapy against ovarian cancer is still found with poor curative effect and potential side effect. Plumbagin is an emerging anti-cancer compound. Although some experimental findings of plumbagin anti-ovarian cancer activity are described, the pharmacological targets should be further explored. In this study, we aimed to investigate the underlying pharmacological activities and targets of plumbagin against ovarian cancer in vitro. As results, in silico docking analysis suggested plumbagin potently treating ovarian cancer through regulating pharmacological targets, including octamer-binding transcription factor 4 (OCT4) and Kruppel-like factor 4 (KLF4). The preliminary experimental data showed that plumbagin treatment inhibited cell growth and induced apoptosis in cancer cells. In addition, decreased mRNA expressions of intracellular OCT4, PCNA, and elevated KLF4 mRNA activation were detected in plumbagin-treated cancer cells. Furthermore, immunostaining determination showed reduced OCT4-positive cells and increased KLF4-positive cells were observed following plumbagin treatments. To sum up, our current findings have preliminarily showed the anti-ovarian cancer benefits of plumbagin, and the pharmacological targets may be identified as KLF4 and OCT4 pathway. Thus, we conclude that plumbagin may be a bioactive compound for ovarian cancer treatment.

Clinical Features of Nontuberculous Mycobacterial Pulmonary Disease in the Yangtze River Delta of China: A Single-Center, Retrospective, Observational Study.

With increased focus on nontuberculous mycobacterial pulmonary disease (NTM-PD), and the improvement in detection methods, the global incidence continues to increase every year, but the diagnosis and treatment are difficult with a high misdiagnosis rate and poor curative effect. This study aimed to analyze the clinical indicators of different pathogenic NTM in the Yangtze River Delta. The study retrospectively analyzed the medical records of patients with NTM-PD, who resided in the Yangtze River Delta and were diagnosed using sputum or bronchial lavage fluid and hospitalized in Shanghai Pulmonary Hospital from March 2017 to February 2019. The clinical data of confirmed patients were collected. Among the 513 cases of NTM-PD, 482 cases were infected by four common bacteria: Mycobacterium intracellulare (224, 46.5%), M. abscessus (138, 28.6%), M. kansasii (84, 17.4%), and M. avium (36, 7.5%). The analysis found that different NTM strains have their corresponding positive and negative correlation factors (p &lt; 0.05). M. intracellulare, M. abscessus, M. kansasii, and M. avium were the main pathogenic bacteria isolated from patients with NTM-PD in the Yangtze River Delta were. Different strains resulted in different clinical features, assisting in the early diagnosis and treatment of NTM-PD.

Experimental study on stromal vascular fraction mediated inhibition of skin pigmentation in guinea pigs

Pigment disorder dermatoses are common diseases with complex mechanisms. There are various methods for the clinical treatment of pigmentation diseases, but these have a poor curative effect and many adverse reactions. Currently, looking for safe and effective whitening agents is a popular research topic. Stromal vascular fractions (SVFs) are a compound cell component of adipose-derived stem cells (ADSCs) that can promote tissue regeneration, healing, and vascularization. The purpose of this experiment was to investigate the inhibitory effect of SVFs on pigmentation in guinea pigs. After guinea pig subcutaneous fat was digested and centrifuged, SVFs were isolated and quantified. SVF was injected into the pigmentation area of the prepared guinea pig pigmentation model. The amount of inducible nitric oxide synthase (iNOS) was determined using immunohistochemical analysis, histopathological staining, and the Fontana-Masson (F-M) method for measuring melanin formation. The skin of the guinea pigs obtained stable and homogenous coloration following three treatments with narrow-band ultraviolet B (NB-UVB). Hematoxylin-eosin (HE) staining revealed that compared to the control group, the cuticle, granular layer, and spinous layer were thicker and the number of epidermal melanocytes and melanin granules increased. While the quantity of pigment granules in the treated group dramatically decreased, it did not significantly change in the blank control group. F-M staining revealed that melanin granules greatly expanded following ultraviolet irradiation and were continuously distributed in basal cells and spinous layers. The entire epidermis was evenly covered in melanin granules. The level of melanin dramatically decreased following therapy. According to immunohistochemical labeling, epidermal cells' cytoplasm and membranes are where iNOS is primarily found. In the epidermis of the irradiated group, iNOS expression was much higher than in the control group, and following treatment, it decreased in the experimental group. SVFs have a reliable treatment effect on ultraviolet B (UVB)-induced pigmentation in guinea pig skin. SVFs can significantly inhibit pigmentation, effectively shorten the fading time of pigmentation, and play a role in skin whitening, providing a new breakthrough for the treatment of pigmentation diseases.

Recent advances in the progress of immune checkpoint inhibitors in the treatment of advanced gastric cancer: A review.

Most patients with advanced gastric cancer were treated with palliative therapy, which had a poor curative effect and a short survival time. In recent years, the clinical research of immune checkpoint inhibitors in advanced gastric cancer has made a breakthrough and has become an important treatment for advanced gastric cancer. The modes of immune checkpoint inhibitors in the treatment of advanced gastric cancer include single drug, combined chemotherapy, radiotherapy, and multiple immune drug combination therapy, among which combination therapy shows better clinical efficacy, and a large number of trials are currently exploring more effective combination therapy programs. In this paper, the new clinical research progress of immune checkpoint inhibitors in the treatment of advanced gastric cancer is reviewed, with an emphasis on combination therapy.

Clinical significance and intervention strategy of gastrointestinal psychiatry

With the development of global economy and society,the number of patients who suffer from functional gastrointestinal disorders (FGID) and mental illness is growing. In recent years, a substantial amount of high-quality research evidence shows that these two kinds of diseases often coexist, and they are mutually causal, and their common pathophysiology is the abnormal interaction of "bacteria-gut-brain axis". In clinical practice, there are some problems, such as insufficient recognition and attention of both doctors and patients to its clinical manifestations, lack of understanding of pathophysiological mechanism, and lack of overall and integrated views of intervention methods, which may be the main factors of poor curative effect at present. Therefore, according to the global research progress and the author's clinical experience, we put forward a new viewpoint of "gastrointestinal psychiatry", it concluded that clinical intervention strategies needed to include dietary and lifestyle changes as well as multidisciplinary interventions such as probiotics, prebiotic, fecal microbiota transplantation and cognitive psychology. On the basis of gastrointestinal psychiatry, this paper systematically elaborated the diagnosis and treatment of this kind of diseases.

Logistic Regression Analysis of Risk Factors and Improvement of Clinical Treatment of Traumatic Arthritis after Total Hip Arthroplasty (THA) in the Treatment of Acetabular Fractures.

Objective Logistic regression was adopted to analyze the risk factors of traumatic arthritis after total hip arthroplasty (THA) in the treatment of acetabular fractures, and the clinical treatment was enhanced. Methods A total of 200 patients with acetabular fractures treated in our hospital from February 2019 to April 2021 were enrolled for THA. According to the occurrence of traumatic arthritis after operation, the patients were divided into control group and study group. The control group was patients without traumatic arthritis (n = 165), and the study group was patients with traumatic arthritis after operation (n = 35). The general data were analyzed, the risk factors of traumatic arthritis after THA for acetabular fractures were analyzed by logistic regression, and the clinical treatment methods were promoted. Results First of all, there exhibited no significant difference in the general data such as sex, age, medical history, and operation site (P > 0.05). There were significant differences in the general data of whether the patients had a job, rehabilitation exercise, and osteoarthritis before operation (P < 0.05). Secondly, we compared the curative effects between two groups. The effective rate in the study group was higher compared to the control group (P < 0.05). After treatment, the Harris hip function score of the study group at discharge, 1 month, 3 months, and 6 months after discharge was higher compared to that of the control group (P < 0.05). The incidence of postoperative complications in the study group was significantly higher compared to that in the control group (P < 0.05). The presence of osteoarthritis, curative effect, poor reduction of fracture, injury of articular cartilage, entry of internal fixation into the joint, avascular necrosis of the femoral head, and infection before operation were significantly correlated with traumatic arthritis after THA in the treatment of acetabular fractures (P < 0.05). Logistic regression analysis indicated that poor reduction, curative effect, articular cartilage injury, entry of internal fixation into the joint, avascular necrosis of the femoral head, infection, and preoperative osteoarthritis were the risk factors of traumatic arthritis after THA in the treatment of acetabular fractures (P < 0.05). Conclusion Poor fracture reduction, curative effect, articular cartilage injury, internal fixation into the joint, avascular necrosis of the femoral head, infection, and the presence of osteoarthritis before operation are the risk factors of traumatic arthritis after THA in the treatment of acetabular fractures. When performing THA for patients with acetabular fracture, attention should be paid to the presence of osteoarthritis before operation, and for those with poor curative effect, attention should be paid to the occurrence of poor fracture reduction, articular cartilage injury, internal fixation into the joint, avascular necrosis of the femoral head, and combined infection, and timely intervention measures should be taken to reduce the risk of traumatic arthritis after operation.

The genetic duet of BRAF V600E and TERT promoter mutations predicts the poor curative effect of radioiodine therapy in papillary thyroid cancer.

The BRAF V600E and TERT promoter mutations are well known to be associated with poor clinical outcomes of papillary thyroid cancer (PTC). Radioactive iodide (RAI)-refractory can be evaluated in advance of treatment, for which predictive biomarkers may be helpful. The present study is to analyze the correlation of both mutations with the curative effect of radioiodine therapy. A total of 126 patients who underwent RAI therapy from October 2016 to August 2019 were recruited. Treatment and follow-up were defined according to criteria used in the 2015 ATA guidelines. The RAI response of patients was assessed as excellent response (ER) and RAI-refractory at the end of follow-up. When dividing the 126 patients into 4 groups, the no mutation, only BRAF V600E mutation, only TERT promoter mutation, and coexistence of two mutation groups were found in 15.8%, 68.3%, 2.4%, and 13.5% patients. RAI-refractory was found in 52.9% (9/17) patients with the coexisting BRAF and TERT mutations. In logistic regression analysis, M1, BRAF, and TERT mutation were confirmed to be independent factors predicting the RAI-refractory. Moreover, 35.3%, 41.2%, and 23.5% of patients in the BRAF and TERT mutation group were assessed as ER, SIR, and BIR respectively. Kaplan-Meier analyses revealed that the genetic duet of BRAF V600E and TERT promoter mutations was associated with a lower ER reached time. We found that BRAF V600E and TERT promoter mutation is significantly correlated with the poor curative effect of RAI therapy in PTC. ClinicalTrials.gov Identifier: ChiCTR1800018760.

Effects of transcranial direct current stimulation on cough reflex and urge-to-cough in healthy young adults

BackgroundChronic cough is prevalent in the clinic. The existing therapies are mostly limited to medical treatment, with poor curative effects and serious side effects. Studies have suggested that the right dorsolateral prefrontal cortex (rDLPFC) may play an active role in the inhibitory pathway of cough elicitation. Thus, this study explored the effect of transcranial direct current stimulation (tDCS) on the rDLPFC activation in relation to cough reflex and urge-to-cough sensitivity.MethodsTwenty-three healthy young adults completed the experiment. Participants randomly received tDCS anodal stimulation, cathodal stimulation, and sham stimulation, and the interval between every two stimuli was at least one week. The tDCS (2 mA, 30 min) stimulated brain rDLPFC region. After tDCS intervention, cough reflex threshold and urge-to-cough were evaluated immediately by inhalation of citric acid-saline solution.ResultsCompared with sham stimulation, the cough reflex thresholds logC2 and logC5 have increased under tDCS anodal stimulation (1.78 ± 0.55 g/L vs. 1.57 ± 0.57 g/L, p < 0.05; 1.92 ± 0.53 g/L vs. 1.67 ± 0.56 g/L, p < 0.05), accompanied by the increase of the urge-to-cough threshold LogCu (0.76 ± 0.53 g/L vs. 0.47 ± 0.44 g/L, p < 0.05). In contrast, the urge-to-cough sensitivity expressed as UTC slope was not significantly changed (1.21 ± 0.86 point·L/g vs. 1.00 ± 0.37 point·L/g, p > 0.05), and there were no apparent changes in cough reflex thresholds Log C2 and logC5, urge-to-cough threshold LogCu, and urge-to-cough sensitivity UTC slope under tDCS cathodal stimulation, compared with sham stimulation.ConclusionsThis study found that anodal tDCS stimulation of rDLPFC could significantly decrease cough reflex sensitivity, accompanied by the increase of urge-to-cough threshold. Further investigations targeting different brain regions using multiple central intervention techniques to explore the underlying mechanisms are warranted.Trial registration The study protocol was registered for the clinical trial in China (registration number: ChiCTR2100045618)