National Medical Journal of China
Volume 100 · Issue 26 · 2020
Natl Med J China
Population medicine: a newly emerging subject healing the schism between preventive medicine and clinical medicine
In medical practice, the rift between preventive medicine and clinical medicine has a long history. The root factor is that the two kinds of disciplines have been developing in parallel, which weakens the cultivation of medical students' awareness of great health and solidifies their thinking. In recent years, the concept of group medicine has been put forward internationally, and ideas have been put forward to make up for this crack. Through reviewing the definition, development, discipline construction, talent training and practice of group medicine, this paper believes that the current implementation of the Healthy China strategy in China must promote the transformation from "treatment as the center" to "people's health as the center" through the discipline construction of group medicine. The specific measures include establishing a complete group medicine education and training system covering academic education, post-graduation education and continuing education, instilling the idea of group medicine in clinical and public health practice, establishing a group medicine demonstration base, and carrying out publicity and advocacy to promote the development of group medicine in the whole country.
Gut microbiota: an overlooked factor that plays a significant role in male infertility
The symbiotic intestinal flora is called the second gene pool of the human body, which exhibits different structural and functional characteristics at different periods. The disorder of intestinal flora and its metabolites will affect physiological processes such as energy metabolism, immune regulation, digestion and absorption, and then affect the function of host gonads. Recent studies have found that the imbalance of intestinal flora is directly related to male infertility, but this factor is often overlooked in clinical practice. This paper briefly introduces the process of intestinal flora and spermatogenesis in adult males, and the underlying mechanism by which intestinal flora influences spermatogenesis by mediating endotoxemia, inflammation and down-regulating the expression of spermatogenesis-related genes. This not only opens up a new field for the study of the mechanism of male infertility, but also provides a new direction and choice for the clinical diagnosis and treatment of the so-called idiopathic male infertility with unknown etiology.
The relationship between surgical strategies for benign prostatic hyperplasia and complications
Benign prostatic hyperplasia is a common disease in middle-aged and elderly men, and the treatment method based on surgery has the problem of more postoperative complications. Current studies have shown that the incidence of postoperative complications is related to the surgical mode and prostate volume. This paper discusses the similarities and differences of different surgical methods in the treatment of postoperative complications of different volumes of prostate from the two dimensions of surgical mode and prostate volume, and intends to find the best surgical mode suitable for different patients.
Imaging findings of CT pulmonary angiography in patients with chronic thromboembolic pulmonary hypertension
To investigate the imaging findings of CT pulmonary angiography (CTPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH).
Consecutive CTEPH cases admitted to receive CTPA in China-Japan Friendship Hospital from December 2015 to December 2019 were enrolled with prospective data collected. The medical histories, imaging manifestation and hemodynamic parameters were analyzed. Patients were divided into proximal lesions group and distal lesions group according to the site of thrombus, and imaging findings were compared between these two groups.
In 135 cases of CTEPH, CTPA showed thrombus in both lungs in the majority of patients (133 cases, 98.5%) with location of thromboembolic disease in level Ⅰ, Ⅱ and Ⅲ for most patients, only 8 cases with level Ⅳ(7.3%) and no level 0 patients. The most common signs of chronic thrombus were vessel cutoffs (134 cases, 99.3%), eccentric wall-adherent filling defects (111 cases, 88.2%), web or bands (80 cases, 59.3%), stenosis (41 cases, 30.4%). Compared to patients with distal lesions, eccentric wall-adherent filling defects, irregular vessel wall were more common in patients with proximal lesions, stenosis was more common in distal lesions, all P<0.05. The most common lung parenchymal signs were mosaic attenuation (104 cases, 77.0%), and pulmonary infarction (79 cases, 58.5%). Pulmonary infarction included pleura-based consolidation opacity (35/79, 44.3%), linear opacities (23/79, 29.1%), or both (13/79, 16.5%). Pulmonary artery enlargement (132 cases, 97.8%) and right ventricular hypertrophy (130 cases, 96.3%) were common, other signs included contrast reflux into the inferior vena cava (70 cases, 51.9%), enlargement of bronchial arteries (68 cases, 50.3%). No differences were found for all the secondary signs between patients with proximal lesions and those with distal lesions, all P>0.05.
Vessel cutoffs, eccentric wall-adherent filling defects, web or bands are the most common CTPA findings of chronic thrombus in CTEPH. Secondary signs include mosaic attenuation, pulmonary infarction, pulmonary artery enlargement, right ventricular hypertrophy and enlargement of bronchial arteries. Eccentric wall-adherent filling defects are more common in patients with proximal lesions than those with distal lesions.
Analysis of metastatic colorectal cancer patients treated with regorafenib in real-world practice
To evaluate the dose, efficacy and tolerability of regorafenib in a real-world clinical setting of metastatic colorectal cancer patients.
The clinical data of patients with metastatic colorectal cancer who had received at least two previous treatment lines treated with regorafenib from May 2018 to December 2019 at National Cancer Center/Cancer Hospital was retrospectively analyzed. Patients′demographics, treatment, dosimetry, safety and survival data were collected. The primary endpoint was overall survival (OS).
A total of 114 patients were enrolled in this study, including male 83 and female 31, with a median age of 61.Of all patients, 83 were treated with regorafenib and 31 were given combination therapy with regorafenib. Starting dose was 80 mg in 57 (50.0%) patients, 120 mg in 24 (21.1%) patients, and 160 mg in 28 (24.6%) patients. Dose increases were observed in 30.9% (25/81) of patients receiving 80 mg and 120 mg as the initial dose. Forty-five (39.5%) and 36 (31.6%) patients took the last daily dose of 80 mg and 120 mg, respectively. Median follow-up time was 8.5 months.Objective response rate (ORR) and disease control rate(DCR) were 1.0% and 52.1%, respectively. The median progression free survivalrate (PFS) was 2.4 moths (95%CI: 0.80-10.57), median OS was 11.0 moths(95%CI: 9.03-not available). The difference of the PFS and OS in the different dose groups was not statistically significant. But patients who received 120 mg regorafenib showed much longer survival with a median OS of 16.7 month. The difference of survival between the regorafenib group and combination group was not statistically significant either. Twenty patients continued with regorafenib as treatment even after progression. These patients had longer survival compared with those (n=52) who stopped regorafenib with median OS of 16.7 month vs 9.1 month (χ2=2.305, P=0.116), respectively.There were 7.9%(9/114) of the patients who discontinued regorafenib therapy because of the adverse event, such as hand-foot skin reaction (HFSR), gastrointestinal bleeding, proteinuria and liver function injury.
Patients with advanced colorectal cancer who failed to respond to standard therapy have a good survival benefit. The initial dose of 120 mg of regorafenib has a better risk/benefit ratio and is more suitable for patients with advanced colorectal cancer.
Analysis of the safety and efficacy of bronchial thermoplasty for severe asthma with the first second forced expiratory volume (FEV1) as a percentage of the predicted value (FEV1%pred)<60%
To investigate the efficacy and safety of bronchial thermoplasty (BT) in severe asthma patients with the first second forced expiratory volume (FEV1) as a percentage of the predicted value (FEV1%pred) <60%.
A retrospective analysis was performed on 75 patients with asthma who were treated with BT at Shenzhen University Hospital of the Chinese Academy of Sciences from January 2016 to January 2018. The patients were divided into two groups based on the FEV1%pred before treatment: FEV1%pred <60% group (39 cases) and FEV 1%pred ≥60% group (36 cases). Comparative analysis of glucocorticoid consumption, times of acute attack, asthma control test (ACT) score, changes in lung function, and adverse reactions at 3 weeks after treatment were performed between the two groups of patients.
Before BT treatment, the consumption of oral prednisone, the amount of budesonide inhaled, and the times of acute attack [M (Q1, Q3)] in the FEV1%pred <60% group were significantly greater than those in the FEV 1%pred ≥60% group, and the ACT score was significantly lower than the FEV1%pred ≥60% group [10.00 (0, 20.00) vs 0(0, 3.75) mg/d, 960 (320, 960) vs 320 (320, 640) μg/d, 5(4, 8) vs 4 (4, 5) times/year, 13 (9, 15) vs 17 (13, 19) scores] (all P<0.05). Except that the oral prednisone dosage in the FEV1%pred<60% group was still higher 1 year after treatment [0 (0, 5.00) vs 0 (0, 0) mg/d] (P=0.009), there was no significant difference in the remaining indicators between the two groups 1 year after treatment and 2 years after treatment (all P>0.05). After 1 year and 2 years of treatment, all indicators in the two groups were better than before treatment (all P<0.05). The inhaled budesonide amount and the times of acute exacerbation in the FEV1%pred <60% group 2 years after treatment were less than those 1 year after treatment [320 (320, 320) vs 320 (320, 640) μg/d, 0 (0, 0) vs 0(0, 1) times/year] (all P<0.05), and there was no significant difference in the remaining indicators. In the FEV1%pred ≥60% group, there was no significant difference between 2 years after treatment and 1 year after treatment in the above indicators except the amount of inhaled budesonide (all P>0.05). In the FEV1%pred <60% group, FEV 1 and the FEV1%pred were significantly lower than the FEV1%pred ≥60% group before treatment, 1 year after treatment and 2 years after treatment [FEV1:(1.21±0.41) vs (2.26±0.80)L, (1.84±0.73) vs (2.30±0.78)L, (1.70±0.66) vs (2.38±0.76)L; FEV1%pred:46.2 (38.5, 53.7)% vs 80.8(66.5, 93.6)%, 60.1 (48.2, 71.6)% vs 87.4 (68.5, 96.5)%, 58.5 (48.6, 74.8)% vs 86.6 (73.0, 97.3)%] (all P<0.05). In the FEV1%pred <60% group, FEV 1 and FEV1%pred 1 year after treatment and 2 years after treatment were all increased compared with before treatment (all P<0.05). In the FEV1%pred ≥60% group, there was no statistical difference in FEV1 at each time point before and after treatment (all P>0.05), but the FEV1%pred at 2 years after treatment was higher than before treatment (P<0.05). There were no significant differences in adverse events between the two groups (all P>0.05).
BT can significantly improve the lung function, reduce the times of acute attack and the dosage of glucocorticoids in severe asthma patients with FEV1% pred<60%, which is safe and effective.
Clinical analysis of kidney injury in patients with COVID-19
To investigate the relationship between novel coronavirus pneumonia (COVID-19) and kidney injury.
A retrospective analysis was performed on confirmed COVID-19 patients in the Central Theater Command General Hospital of Chinese PLA on March 12, 2020. A total of 87 hospitalized confirmed COVID-19 patients were enrolled in the study, and they were hospitalized for at least one week. The recorded information included clinical data and indicators of kidney-related laboratory tests.
The average age of patients was (65.2±17.1) years, and 34.5% (30/87) patients were ≥ 75 years old and 31.0% (27/87) patients were 60-74 years old. Male and female patients accounted for 59.8% (52/87) and 40.2% (35/87), respectively. There were 29.9% (26/87) and 12.6% (11/87) patients who had already showed mild elevation of blood urea nitrogen (BUN) and serum creatinine (SCr) at admission. Moreover, 25.3% (22/87) and 4.6% (4/87) patients still exhibited mild elevation of BUN and SCr one week after admission. However, 28.7% (25/87) patients showed an elevation of BUN one week later after admission, though their BUN levels were normal at admission. Likewise, 16.1% (14/87) patients showed an elevation of SCr one week later after admission, while their SCr levels were normal at admission. Only two patients had an increase of SCr ≥26.5 μmol/L, and both of them were over 75 years old.
COVID-19 patients with severe acute kidney injury are uncommon. However, attention should be paid to acute kidney injury of the elderly patients in the diagnosis and treatment of COVID-19.
The influence and clinical significance of proteasome inhibitor on serum bone metabolite markers in patients with myeloma bone disease
To investigate the influence and clinical significance of proteasome inhibitor on serum bone metabolite markers including tartrate-resistant acid phosphatase 5b isoenzyme (TRACP-5b), type I collagen carboxy terminal peptide β(β-CTX), type I procollagen amino terminal prolongation peptide (PINP) and vitamin D3 in patients with myeloma bone disease (MBD).
From April 2015 to June 2018, 68 patients with newly diagnosed MBD who admitted to our hospital were treated with proteasome inhibitor-based regimen. Serum concentration of TRACP-5b、β-CTX、PINP and vitamin D3 were measured before treatment and after 4 and 8 cycles of chemotherapy, and imaging changes were observed.
After 4 and 8 cycles of chemotherapy, serum levels of TRACP-5b, β-CTX and vitamin D3 were decreased significantly ( P<0.05). The serum concentration of PINP was (78.1±44.9) ng/L before chemotherapy, while after 4 cycles, it turned to (94.5±56.1) ng/L without significant difference (t=-1.871, P=0.063). Moreover, it increased to (173.3±80.5) ng/L after 8 cycles of chemotherapy with significant difference (t=-8.272, P<0.001). The proportion of imaging classification ≥3 among all patients was 66.2%, and it decreased to 60.3% after 4 cycles of chemotherapy without significant difference (χ2=0.569, P=0.477). The proportion of imaging classification ≥3 after 8 cycles of chemotherapy decreased to 44.5%, which was significantly lower than that before treatment (χ2=6.260, P=0.012). After 8 cycles of chemotherapy, 63 patients were evaluable, of which 50 were effective and 13 were ineffective. Serum concentration of PINP in the effective group was higher than that in the ineffective group ((190.7±78.5) ng/L vs (106.5±47.3) ng/L,t=5.762, P<0.001), and the serum concentration of vitamin D3 in the effective group was lower than that in the ineffective group ((11.7±4.8) μg/L vs (15.6±5.5) μg/L, t=-2.478, P=0.016). The proportion of patients with more than grade 3 bone disease of the effective group was also significantly lower than that of the ineffective group (38.0% vs 69.2%, χ 2=4.076, P=0.044). There was no significant difference in the serum concentration of TRACP-5b and β-CTX between two groups.
After treatment with the proteasome inhibitor -based regimen, the serum concentrations of TRACP-5b, β-CTX and vitamin D3, which reflect osteoclast activity in MBD patients were decreased, the serum concentration of PINP indicating osteoblast activity was increased, and the grade of imaging of bone disease was decreased.
Establishment and primary clinical application of metabolic evaluation database of urolithiasis
To establish the metabolic evaluation database of urolithiasis, perform metabolic evaluation, and provide instructions for treatment and prevention of urolithiasis.
This metabolic evaluation database was developed by JAVA and was established by Oracle11g database and Browser/Server framework. We extracted the clinical data of all patients who had complete information, and analyzed their risk factors of stone formation, stone-related medical history, blood and urine tests results and 24-hour urine analysis.
A total of 360 patients diagnosed as urolithiasis were included in this research. Male to female ratio was 1.9∶1, and the urolithiasis was first diagnosed at (35.5±13.5) years old. Family history was positive in 39.7% of patients. Metabolic syndrome occurred in 35.0% of patients. Overweight or obesity occurred in 73.2% and 50.0% of male patients, respectively. Abdominal obesity in 62.3% and 56.1% of male and female patients, respectively. Among all patients, 67.5% had high urine sodium, 53.6% had hypercalciuria, 41.1% had hypocitraturia, 29.7% had hyperuricosuria, 22.5% had hypomagnesuria, 15.8% had hyperoxaluria, 11.7% had hyperphosphoraturia, and 36.4% had low urinary volume.
The prevalence of overweight or obesity, abdominal obesity, hypertension, diabetes, and metabolic syndrome in stone patients were significantly higher than those in general population. The number of 24-hour urinary abnormalities was positively associated with body mass index. The interventions on high urinary sodium, low urinary volume, obesity and metabolic syndrome were important to the treatment of urolithiasis. This database would facilitate the metabolic evaluation, provide evidence for the treatment and prevention of urolithiasis, and lay foundation for finding important controllable risk factors of urinary stone.
Early efficacy of islet transplantation in the treatment of adult advanced diabetes
To evaluate the safety and efficacy of islet transplantation for patients with advanced diabetes.
Five cases of islet allotransplantation were performed on 4 adult recipients. The same blood type adult brain-dead pancreas donors were selected and the islets were prepared in GMP laboratory. The prepared islet suspension was slowly injected into the liver of the recipients within 30-60 minutes. The immunosuppressive regimen was a combination of basiliximab, tacrolimus and mycophenolate mofetil and TNF-alpha monoclonal antibody was used to reduce the post-transplant inflammatory response. Insulin was temporarily applied to control blood glucose after surgery, and the dosage of insulin was adjusted to decrease according to the blood glucose level until it was discontinued.
A total of 5 islet transplants were performed in 4 patients, including 1 patient who received the second islet transplantations. All operations were succeed and the blood glucose and portal pressure were stable during the operation. Exogenous insulin was continued to keep blood glucose level stable (4-12 mmol/L) after surgery. Four cases (including the one who received two islet transplantation) started to stop using insulin at the third to fourth week, and the insulin dosage of the other case was 74% lower than that before the operation, and no hypoglycemic reaction occurred in all patients after islet transplantation. The C-peptide level in 3 patients reached the normal range, and the level in one patient with type I diabetes (without insulin release) remained at 0.45-0.6 μg/L (0.15-0.2 nmol/L). In addition, one patient showed a rise in blood glucose again and continued to use insulin half a year after insulin discontinuation. Then, he was performed the second islet transplantation which showed good effect and stopped taking insulin in 10 days after surgery. There were 3 cases of liver puncture bleeding after opeation, of which 2 cases were treated with ultrasound radiofrequency ablation to stop bleeding, 1 case stopped spontaneously, and no other complications were found.
Islet transplantation is effective in the treatment of advanced diabetes patients with small trauma and high safety, which is worthy of more promotion. Long-term efficacy and maintenance therapy still need further investigation.
Application of urethral pressure profilometry in artificial urinary sphincter implantation
To investigate the changes of maximum urethral pressure (MUP) and maximum urethral closure pressure (MUCP) after artificial urethral sphincter (AUS) implantation and their prognostic value.
The clinical data of patients who had undergone AUS implantation in multiple medical centers between March and July 2019 were retrospectively analyzed. Data of urethral pressure profilometry, pad usage, related scores and complications related to surgery were collected and compared. The primary endpoint was social continence (defined as 0-1 pad/d) 1 month after activation of the pump.
A total of five male patients were included in this study. Two underwent transurethral resection of the prostate for benign prostatic hyperplasia, two underwent radical prostatectomy for prostate cancer, and one underwent urethral reunion, urethral stricture dilatation and cystostomy due to trauma from traffic accident. All patients had different degrees of urinary incontinence. The results of preoperative urethral profilometry test showed that the MUP of five patients were 52, 53, 88, 32, and 66 cmH2O(1 cmH2O=0.098 kPa), respectively, and the MUCP were 17, 52, 62, 27, and 40 cmH2O, respectively. AUS implantation was performed. The intraoperative urethral pressure profilometry showed that the MUP were 53, 113, 50, 77, and 89 cmH2O in the inactivated state, and the MUCP were 50, 97, 31, 71, and 51 cmH2O, respectively. In the activated state, the MUP were 112, 174, 193, 121, and 120 cmH2O, and the MUCP were 109, 160, 175, 114, and 92 cmH2O, respectively. All patients met the social continence (0-1 pad/d) criterion. No complications were reported during the follow-up.
The relationship between the range of intraoperative urethral pressure and the effect of urinary control can be gained by measuring the specific values of MUP and MUCP during AUS implantation and the post-operative effects, which provides as a data basis for standardizing AUS implantation.
The effect of blocking penile blood drainage on stem cells therapy for rats with erectile dysfunction
To investigate the effect of blocking penile blood drainage at the root of the rat penis on cell retention, penile erectile function, and histopathological changes when erectile dysfunction (ED) is treated by intracavernous injection (ICI) of stem cells.
Thirty male SD rats were randomly divided into sham operation group (n=6), ED model group (n=6), treatment group A (blockade group, n=9) and treatment group B (non-blockade group, n=9). Twenty-four hours after the model was established, group A and group B were treated by ICI of 1 × 106 adipose-derived stem cells (ADSCs). Before ICI, the penile blood drainage in group A was temporarily blocked with a rubber tourniquet at the root of the penis which was removed 5 minutes after the injection. The dynamic changes of the local fluorescent signal of the penis and the expression of the fluorescent signal in the lung were detected after ICI. The maximum intracavernous pressure/mean arterial pressure (ICPmax/MAP) was measured to evaluatethe erectile function, and histopathological changes of the penis were observed after 28 days.
At different time points (0, 10 and 60 min), the intensity of the bioluminescent signal (×106·p·s-1·sr·cm-2) in group A had a similar trend when compared with that in group B, and the differences were not statistically significant (8.76±1.17 vs 8.16±1.12, 6.45±1.47 vs 6.72±0.69, 3.77±0.30 vs 3.36±1.06, all P>0.05). A large number of ADSCs could be found in the lungs in both treatment groups after 60 min of ICI. There was no statistically significant difference in erectile function (0.44±0.11 vs 0.43±0.07) and histopathological change (0.08±0.02 vs 0.08±0.03) regardless of the occlusion of blood drainage at the root of the penis (all P>0.05).
Temporarily blocking of penile blood drainage has no obvious advantage in improving cell retention and efficacy when ADSCs are used to treat ED of rat models.
Screening of phenylketonuria and analysis of phenylalanine hydroxylase gene in 380 996 newborns from Hainan province
To investigate the incidence of phenylketonuria and distribution characteristics of phenylalanine hydroxylase (PAH) gene in newborns from Hainan province.
Dry blood spot specimens of heels from 380 996 newborns in Hainan province from January 2017 to December 2019 were collected. Phenylalanine (Phe) concentrations in these dry blood spots were measured by the fluorescence method to screen phenylketonuria (PKU). A second dry blood spot sample will be collected if suspicious samples were detected after initial screening. Tandem mass spectrometry were used to detect the concentrations of Phe and tyrosine. Urine samples of the suspected newborns were sent out for urotrexate spectrum analysis and tetrahydrobiopterin loading test. PCR and flow-through rapid hybridization method were employed to detect PAH gene mutations. Meanwhile, peripheral blood samples of suspicious newborns of PKU and their parents were collected to perform gene sequencing.
Among the 380 996 newborns, 39 were suspected and 14 were diagnosed with PKU, including 11 cases of PAH deficiency and 3 cases of tetrahydrobiopterin deficiency. Of 14 confirmed cases, there were 8 male cases and 6 female cases. In the newborn population of Hainan province, the annual incidence of PKU was 1.22/100 000. Thirteen PAH gene mutations were detected in confirmed cases: c.728G>A, c.158G>A, c.1238G>C, c.611A>G, c.1068C>A, c.706+5G>A, c.740G>T, c.1081A>T, c.793T>G, c.1223G>A, c.721C>T, c.331C>T and c.1174T>A.
PKU has a high incidence in newborn population of Hainan province in the past three years. The PAH gene has a wide spectrum of mutations. Two rare mutations were also found: c.793T>G and c.706+5G>A.
Case 509: Cutaneous purpura-lymphadenopathy-multi-serous effusion
Cryoglobulinemia is a clinical syndrome with multisystem involvement that can be secondary to a variety of diseases. The detection of cryoglobulin requires high temperature at the time of detection, which is not a routine clinical project, and sometimes misses the diagnosis. A critical case of cryoglobulinemia with cutaneous purpura, renal impairment, respiratory failure and pericardial effusion was reported. The condition was significantly relieved after rituximab treatment.
Case 510 short stature-hypokalemia-hypomagnesemia-hypophosphatemia-metabolic acidosis
This article reports a rare case of Gitelman syndrome complicated with Fanconi syndrome. This patient visited our hospital due to hypokalemia. The patient was short in stature since childhood, and had various electrolyte disorders, including hypokalemia, hyponatremia, hypophosphatemia and hypomagnesemia. Blood gas analysis showed mild metabolic acidosis, and examination showed urinary acidification disorder, renal potassium loss, renal phosphorus loss, urinary amino acid positive, and blood uric acid decreased, which was in line with the diagnosis of Fanconi syndrome. The etiology of hypokalemia seems to be diagnosed as Fanconi syndrome, but the patient's blood gas analysis in an outside hospital 2 years ago showed mild metabolic alkalosis, and finally the detection of SLC12A3 gene showed the presence of pathogenic mutation, which confirmed the diagnosis of Gitelman syndrome. Fanconi syndrome is considered as a manifestation of hypokalemic nephropathy caused by long-term severe hypokalemia.
Immune checkpoint inhibitor-induced type 1 diabetes mellitus
Immune checkpoint inhibitors can produce immune-related adverse events while achieving tumor immunotherapy. One of the rare adverse reactions is the development of type 1 diabetes, accompanied by life-threatening diabetic ketoacidosis, mainly related to anti-programmed cell death protein 1 (PD-1) /PD-1 ligand (PD-L1) treatment, which is called immune checkpoint inhibitor-induced type 1 diabetes (ICIT1D). Due to the popularity of tumor immunotherapy, ICIT1D is increasing. This article reviews the prevalence, clinical manifestations, immunogenetic characteristics, pathogenesis and monitoring and treatment of ICIT1D, so as to improve clinicians' understanding of the disease.
Research progress of a new anti-tuberculosis drug putomanil
pretomanid (PA-824) is a new anti-tuberculosis drug approved by the U.S. Food and Drug Administration (FDA) on August 14, 2019. It has highly effective anti-Mycobacterium tuberculosis activity and good safety. In this paper, the research progress of the drug in structural characteristics, mechanism of action, pharmacokinetics, pharmacokinetics and clinical trials were reviewed.
Advances in diagnosis and treatment of gastric cancer complicated with multiple primary carcinomas
Gastric cancer is a malignant disease that seriously threatens human health. With the aging of society, the progress of diagnostic technology and the development of comprehensive treatment, the survival time of gastric cancer patients is gradually prolonged, and the incidence of gastric cancer combined with multiple primary cancers is gradually increasing. A large number of studies have shown that the prognosis of multiple primary cancers is similar to that of single primary cancers. However, when encountering such patients in clinical work, many of our medical workers often lose confidence in the prognosis of patients and mainly focus on palliative care. This article summarizes the incidence, etiology, diagnosis, treatment and prognosis of gastric cancer combined with multiple primary carcinomas, hoping to provide some reference for future clinical work.
SARS-CoV-2 and SARS-CoV-2 disease
As of April 2, 2020, the number of 2019 novel coronavirus (2019-nCoV) infections worldwide has exceeded one million, with a high proportion of medical professionals. As many as 20 percent of those infected are medical professionals, according to initial reports from state health departments in the U.S. states of Ohio and Minnesota. This article presents the experience of the United States on the characteristics of 2019-nCoV, the characteristics of pathogenic infection, and the protection of susceptible populations, individuals, and neurological professionals.
Application of broad-spectrum antibiotics in the diagnosis of pulmonary tuberculosis in adults
Antibiotic tests have been widely used for the diagnosis of bacterionegative pulmonary tuberculosis for over 30 years, especially in low-resource countries. It is estimated that at least 26.5 million courses of antibiotics are prescribed each year as a result of this practice, which may increase antibiotic exposure and the occurrence of resistance. To assess the diagnostic efficacy of antibiotic tests, the researchers conducted a systematic review and meta-analysis of the relevant literature. By searching the Medline, Embase, and Global Health databases for literature as of March 15, 2019 on the diagnostic efficacy of antibiotic tests in adult patients with suspected tuberculosis, the risk of bias was assessed using the QUADAS-2 tool, and the pooled sensitivity and specificity of antibiotic tests were estimated using a bivariate random effects model, usingI2Statistics were analyzed for heterogeneity. Eight final studies were included in the meta-analysis, with a total of 2 786 patients from 7 countries in Africa, South America, and Asia. The results showed that the combined sensitivity of antibiotic test in the diagnosis of pulmonary tuberculosis was 67% (95%CI: 42-85), with a specificity of 73% (95%CI:58~85)。 The study showed that antibiotic tests were less efficacious in the diagnosis of tuberculosis, with estimates of sensitivity and specificity well below the internationally recommended diagnostic criteria. Given the dire situation of antibiotic resistance, current policies and practices regarding this trial seem inappropriate and its use should be limited and further studies undertaken.
Impairment of spermatogenesis and sperm motility in gut microbial metabolic disorders induced by high-fat diet
Between 1973 and 2011, male sperm density in western countries dropped rapidly by more than 50%, and there is currently no effective treatment to slow down its decline. More and more clinical studies and animal experiments have shown that obesity and metabolic syndrome mediated by high-fat diet can reshape intestinal flora, and then affect physiological functions such as energy metabolism, intestinal mucosal barrier, host immunity, and prevention of pathogens. In order to understand whether high-fat diet affects male reproduction through intestinal flora, the intestinal flora of mice fed on normal diet was transplanted into 6 mice fed on normal diet (group 1), and the intestinal flora of mice fed on high-fat diet was transplanted into another 6 mice fed on normal diet (group 2). After 15 weeks, it was detected that the sperm production, sperm motility, the number of spermatogonial stem cells in seminiferous tubules and spermatocytes in group 2 mice were significantly decreased, and the blood endotoxin increased nearly 2 times, but the above indexes of group 1 mice did not change significantly. Further exploration of the mechanism found that the disordered intestinal flora transplantation triggered the infiltration of intestinal T lymphocytes and macrophages and the significant increase of epididymal pro-inflammatory factors. In order to explore which microorganisms have this effect on the reproductive system, this study used 16S-rDNA sequencing to find that the bacterial flora in the two groups of mice appeared intragroup clustering at the genus level, that is, the abundance of Bacteroides and Progenitor in Group 2 mice increased significantly, so it is speculated that the increased abundance of Bacteroides and Progenitor is the cause of endotoxemia. RNA sequencing of spermatogenesis-related genes in mice testis showed that the expression of genes involved in sperm cell meiosis and regulating testicular mitochondrial function was significantly reduced in mice testis in group 2 compared with group 1. At the same time, the study also collected blood and fecal samples from 12 healthy men and 48 oligoasthenospermia men aged 22 to 45 years for analysis, and found that it was consistent with the results of animal experiments: the abundance of Bacteroides and Probacterium in human specimens was negatively correlated with sperm motility (r=-0.28,P=0.029), circulating endotoxin levels were positively correlated with Bacteroides abundance (r=0.30,P=0.021), which indicates that the unbalanced intestinal flora may be directly involved in the occurrence and development of male infertility diseases.
Type 1 Diabetes Circulating CD4+/CD8+The expression level of PD-1/PD-L1 on T cells normalized during partial remission
The honeymoon period of type 1 diabetes mellitus (T1D), also known as the partial remission period (PR), is mainly manifested by a transient recovery of self-islet function and a reduction in exogenous insulin requirement, accompanied by downregulation of autoimmune response. PR is a short "clinical cure stage", and inducing and prolonging PR is the common research goal of domestic and foreign scholars. Programmed cell death protein-1 (PD-1) and its ligand PD-L1 are important immunosuppressive molecules. Monoclonal antibodies to PD-1 and PD-L1 are widely used in the field of oncology and are closely related to the pathogenesis of T1D. However, its expression changes in the PR phase of T1D patients are completely unknown. In order to investigate the correlation between the expression levels of PD-1 and PD-L1 in peripheral blood T lymphocytes of T1D patients and PR, 98 T1D patients and 49 healthy controls who were regularly visited by the outpatient clinic of Xiangya Second Hospital were included in this study. The onset age of T1D patients was 12.9 (1.9-65.7) years and the course of diabetes was 4.2 (0-23.7) months. According to PR status, T1D patients were divided into 4 groups: no PR (n =39), before PR (n =15), in PR (n =30) and after PR (n =14). PR was defined as C-peptide ≥300 pmol/L or insulin-corrected glycosylated hemoglobin (IDAA1c) ≤9. Twenty-nine newly diagnosed patients who had not yet entered PR were followed up for 1 year. Detection of CD4 in peripheral blood mononuclear cells (PBMC) by flow cytometry+/CD8+Dynamic changes of PD-1/PD-L1 expression on T cells, regulatory T cells (Treg) and IL-35+Frequency changes in Treg cells. The results showed that the expression level of PD-1 in peripheral T cells of T1D patients was significantly lower than that of healthy controls. PD-1 and PD-L1 proteins in circulating CD4+/CD8+The expression on T cells showed dynamic changes around PR: the expression level of PD-1/PD-L1 was the lowest before PR, and the expression of PD-1/PD-L1 returned to close to the level of normal healthy control after entering PR, but decreased again after PR. However, this expression pattern of PD-1/PD-L1 is not present in patients who do not develop PR. In addition, CD8+PD-1+T cell frequency was positively correlated with PR duration. Circulating Treg and IL-35+There was no significant correlation between Treg cell frequency and PR. It can be seen that the occurrence of PR is related to CD4+/CD8+PD-1+/PD-L1+It suggests that PD-1/PD-L1 protein may be a potential biological target to induce or prolong PR in T1D patients, which provides a new idea for the prevention and treatment of T1D.
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